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Sample records for subacute oral toxicity

  1. Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

    African Journals Online (AJOL)

    Purpose: To assess Alchornea cordifolia, a medicinal plant with numerous biological actions and uses in traditional medicine, for possible toxicity in rats. Methods: The probable effect of the ethanol extract of Alchornea cordifolia (250 - 2000 mg/kg, p.o.) by gavage was evaluated on blood cellular elements and chemistry, ...

  2. Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

    African Journals Online (AJOL)

    Erah

    2010-10-21

    Oct 21, 2010 ... Purpose: To assess Alchornea cordifolia, a medicinal plant with numerous biological actions and uses in traditional medicine, for possible toxicity in rats. Methods: The probable effect of the ethanol extract of Alchornea cordifolia (250 - 2000 mg/kg, p.o.) by gavage was evaluated on blood cellular elements ...

  3. Alternative acute oral toxicity assessment under REACH based on sub-acute toxicity values.

    Science.gov (United States)

    Gissi, Andrea; Louekari, Kimmo; Hoffstadt, Laurence; Bornatowicz, Norbert; Aparicio, Alberto Martin

    2017-01-01

    The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one ton per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies. Proving this hypothesis would allow avoiding acute toxicity oral testing whenever a sub-acute oral toxicity study is required or available and indicates low toxicity. ECHA conducted an analysis of the REACH database and found suitable studies on both acute oral and sub-acute oral toxicities for 1,256 substances. 415 of these substances had low toxicity in the sub-acute toxicity study (i.e., NO(A)EL at or above the limit test threshold of 1,000 mg/kg). For 98% of these substances, low acute oral toxicity was also reported (i.e., LD50 above the classification threshold of 2,000 mg/kg). On the other hand, no correlation was found between lower NO(A)ELs and LD50. According to the REACH Regulation, this approach for predicting acute oral toxicity needs to be considered as part of a weight of evidence analysis. Therefore, additional sources of information to support this approach are presented. Ahead of the last REACH registration deadline, in 2018, ECHA estimates that registrants of about 550 substances can omit the in vivo acute oral toxicity study by using this adaptation.

  4. Subacute (90 days) oral toxicity studies of Kombucha tea.

    Science.gov (United States)

    Vijayaraghavan, R; Singh, M; Rao, P V; Bhattacharya, R; Kumar, P; Sugendran, K; Kumar, O; Pant, S C; Singh, R

    2000-12-01

    Kombucha tea (KT) is a popular health beverage and is used as an alternative therapy. KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment. The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria. KT is consumed in several countries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments, viz., intestinal disorders, arthritis, ageing and stimulation of immunological system. Though KT is used in several parts of the world its beneficial effects and adverse effects have not been scientifically evaluated. Since there are no animal toxicological data on KT, subacute oral toxicity study was carried out. Five groups of rats were maintained: (a) control group given tap water orally, (b) KT given 2 ml/kg orally, (c) plain tea (PT) given 2 ml/kg orally, (d) KT given in drinking water, 1% (v/v) and (e) PT given in drinking water, 1% (v/v). The rats were given this treatment daily for a period of 90 days. Weekly records of weight, feed intake, water intake and general behaviour were monitored. There was no significant difference in the growth of the animals as evidenced by the progressive body weight change. The organ to body weight ratio and histological evaluation did not show any toxic signs. The haematological and biochemical variables were within the clinical limits. The study indicates that rats fed KT for 90 days showed no toxic effects.

  5. Evaluation of Acute and Subacute Oral Toxicity of the Ethanol ...

    African Journals Online (AJOL)

    Toxicity tests of 95% ethanol extract of the root of Antidesma acidum were studied in male and female rats. The oral acute toxicity test at 5,000 mg/kg revealed that the ethanol extract did not produce toxic effects on signs, general behavious, mortality and gross appearance of internal organs of rats. Furthermore, the oral ...

  6. Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats

    DEFF Research Database (Denmark)

    Hadrup, Niels; Löschner, Katrin; Bergström, Anders

    2012-01-01

    Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 $, 6 #); Ag-NP at doses: 2...

  7. Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats.

    Science.gov (United States)

    Al-Afifi, Nashwan Abdullah; Alabsi, Aied Mohammed; Bakri, Marina Mohd; Ramanathan, Anand

    2018-02-05

    Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. This study demonstrates tolerability of DC

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

    Science.gov (United States)

    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 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. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Acute and subacute oral toxicity evaluation of Tephrosia purpurea extract in rodents

    Directory of Open Access Journals (Sweden)

    Talib Hussain

    2012-04-01

    Full Text Available Objective: To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea in rodents. Methods: The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/ kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose, p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results: In the acute toxicity study, T. purpurea was found to be well tolerated upto 2 000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions: These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent

  10. Haematolohical Profile of Subacute Oral Toxicity of Molybdenum and Ameliorative Efficacy of Copper Salt in Goats

    OpenAIRE

    Kusum; Raina, R.; Verma, P. K.; Pankaj, N. K.; Kant, V.; Kumar, J.; Srivastava, A. K.

    2010-01-01

    Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline i...

  11. Subacute (28-day) toxicity of furfural in Fischer 344 rats: a comparison of the oral and inhalation route.

    Science.gov (United States)

    Arts, Josje H E; Muijser, Hans; Appel, Marko J; Frieke Kuper, C; Bessems, Jos G M; Woutersen, Ruud A

    2004-09-01

    The subacute oral and inhalation toxicity of furfural vapour was studied in Fischer 344 rats to investigate whether route-to-route extrapolation could be employed to derive the limit value for inhalation exposure from oral toxicity data. Groups of 5 rats per sex were treated by gavage daily for 28 days at dose levels of 6-192 mg/kg bw/day, or exposed by inhalation to concentrations of 20-1280 mg/m3 (6 h/day, 5 days/week) or 160-1280 mg/m3 (3 h/day, 5 days/week) for 28 days. Controls received vehicle (corn oil) or were exposed to clean air. Daily oral treatment with the highest dose of furfural (initially 192 mg/kg bw/day, later reduced to 144 mg/kg bw/day and finally to 120 mg/kg bw/day) resulted in mortality, and in increases in absolute and relative kidney and liver weight in surviving females of this group. Exposure of rats by inhalation for 6 h/day, 5 days/week for 28 days induced mortality at concentrations of 640 mg/m3 and above within 1-8 days. At 640 mg/m3 (3 h/day) and at 320 mg/m3 (3 and 6 h/day) and below, however, exposure was tolerated without serious clinical effects. In contrast, histopathological nasal changes were seen even at the lowest concentration of 20 mg/m3. With increasing exposure concentration, the nasal effects increased in incidence and severity and also expanded from the anterior part to the posterior part, including the olfactory epithelium. It was concluded that the no-observed-adverse-effect level (NOAEL) for oral toxicity was 96 mg/kg bw/day. The NOAEL for systemic inhalation toxicity was comparable, i.e. 92 mg/kg bw/day (corresponding to 320 mg/m3 (6 h/day) or 640 mg/m3 (3 h/day)) assuming 100% absorption. The presence of the histopathological nasal changes at the lowest tested concentration of 20 mg/m3 (corresponding to 6 mg/kg bw/day) proves that for locally acting substances like furfural extrapolation from the oral to the inhalation route is not valid.

  12. Haematolohical profile of subacute oral toxicity of molybdenum and ameliorative efficacy of copper salt in goats.

    Science.gov (United States)

    Kusum; Raina, R; Verma, P K; Pankaj, N K; Kant, V; Kumar, J; Srivastava, A K

    2010-07-01

    Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils.

  13. Subacute toxicity of propyl gallate

    NARCIS (Netherlands)

    Strik JJTWA; Danse LHJC; Helleman PW; van Leeuwen FXR; Speijers GJA; Vaessen HAMG

    1986-01-01

    The 4 week oral toxicity of propyl gallate in rats, exposed to 0, 1000, 5000 and 25000 mg/kg feed, was investigated. Parameters studied comprised growth, food and water intake, biochemistry, hematology, organ weights and histopathology. In the highest dose group both females and males gained less

  14. Subacute toxicity assessment of annatto in rat

    OpenAIRE

    Bautista, Ana Rita Pedreira Lapa; E.L.T. Moreira; Batista, Márcio Santos; Miranda, M.S.; Gomes, I. C. S.

    2004-01-01

    Texto completo:acesso restrito. p. 625-629 Increased human use of annatto (Bixa orellana L), a red yellow food colorant, demands generation of toxicity data. The toxic effects of annatto powder (bixin 27%) have been assessed following administration of a subacute regimen (4 weeks, 20 doses) in Wistar male and female rats. A full study with three dose levels was considered unnecessary since no sign of toxicity had been noted in a preliminary experiment with 1000 mg/kg body weight/day as ...

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

    2010-03-26

    As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -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 {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-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 TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} 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 TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  17. Subacute toxicity assessment of annatto in rat.

    Science.gov (United States)

    Bautista, A R P L; Moreira, E L T; Batista, M S; Miranda, M S; Gomes, I C S

    2004-04-01

    Increased human use of annatto (Bixa orellana L), a red yellow food colorant, demands generation of toxicity data. The toxic effects of annatto powder (bixin 27%) have been assessed following administration of a subacute regimen (4 weeks, 20 doses) in Wistar male and female rats. A full study with three dose levels was considered unnecessary since no sign of toxicity had been noted in a preliminary experiment with 1000 mg/kg body weight/day as was recommended by the OECD guideline. In this study, annatto administered by gavage at a dose level of 2000 mg/kg/day decreased male body weight gain, but had no effect on either food intake or food conversion efficiency. Haematological and plasma biochemical examination as well necropsy performed at the end of administration (29th day) and observation (43rd day) periods revealed no alterations related with annatto administration. Kidney apoptosis occurred in 20% treated female rats in restricted areas without proliferation or tubular segments modification. The precise nature of apoptosis was not investigated in the present study. These findings suggest that annatto was no toxic to the rat.

  18. Sub-acute toxicity evaluation of ethanol extract of rheumatic tea ...

    African Journals Online (AJOL)

    Sub-acute toxicity profile of Rheumatic Tea Formula (RTF), a polyherbal tea consisting of Salix alba, Eucalyptus globulus and Albizia chevalieri was investigated in wistar rats of both sexes. Wistar rats were orally administered three different doses of ethanol extract of RTF for 28 days after which the effect on body weight, ...

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

    Science.gov (United States)

    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.

  20. Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

    Directory of Open Access Journals (Sweden)

    Idris Bello

    2016-03-01

    Full Text Available Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD rats. The methanolic extract of Alstonia scholaris stem bark (ASME was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.. Histopathological studies revealed slight degeneration (lesion and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg. The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged.

  1. Biocompatible lutein-polymer-lipid nanocapsules: Acute and subacute toxicity and bioavailability in mice.

    Science.gov (United States)

    Ranganathan, Arunkumar; Hindupur, Ravi; Vallikannan, Baskaran

    2016-12-01

    Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were prepared (henceforth referred as lutein nanocapsules) and studied for acute, subacute oral toxicity and bioavailability of lutein in mice. Prior to examining the safety of lutein nanocapsules, particle size, zeta potential, surface morphology and interaction between lutein, PLGA and PL were studied. In acute study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10 and 100mg/kg body weight (BW) and examined for 2weeks, while in subacute study, daily mice were gavaged with a dose of 1 and 10mg/kg BW for 4weeks. Results revealed that mean size and zeta value of lutein nanocapsules were 140nm and -44mV, respectively. Acute and subacute toxicity studies did not show any mortality or treatment related adverse effect in clinical observations, ophthalmic examinations, body and organ weights. No toxicity related findings were observed in hematology, histopathology and other blood and tissue clinical chemistry parameters. In subacute study, no observed adverse effect level (NOAEL) of lutein nanocapsules was found to be at a dose of 10mg/kg BW. Feeding lutein nanocapsules resulted in a significant (plutein level in plasma and tissue compared to the control group. Lutein nanocapsules did not cause toxicity in mice. However, human trials are warranted. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Evaluation of acute and subacute toxicities of aqueous ethanolic ...

    African Journals Online (AJOL)

    We investigated the acute and subacute toxicities of hydro-ethanolic extract of leaves of Senna alata (L.) Roxb. in Swiss mice and Wistar albino rats. The mice were divided into 6 groups of 10 animals and each group received once by intra gastric gavages 0, 4, 8, 12, 16, 20 times 1000 mg/kg dose of extract. Distilled water ...

  3. Acute and Subacute Toxic Study of Aqueous Leaf Extract of ...

    African Journals Online (AJOL)

    HP

    Results: For the acute toxicit test, no death and signs of poisoning were observed in the treated groups. In the subacute .... Subcute toxicity test. The animals were divided into six groups of six animals each. The treatments were given by intraperitoneal injection. Group 1 served ... produce significant changes in behavior,.

  4. Acute and subacute toxicities of defatted ethanolic extract of Moringa ...

    African Journals Online (AJOL)

    Moringa oleifera seeds are widely accepted as a nutritional supplement. The seeds are consumed and are sold on the shelf of nature, herbal shops, pharmacy and supermarkets. They are consumed as herbal remedy for various diseases. This study was designed to evaluate the acute and sub-acute toxicity of defatted ...

  5. Subacute toxicity evaluation of KR-33493, FAF1 inhibitor for a new anti-parkinson's disease agent, after oral administration in rats and dogs.

    Science.gov (United States)

    Jeong, Jong-Woo; Yu, Changsun; Lee, Jong-Hwa; Moon, Kyoung-Sik; Kim, Eunhee; Yoo, Sung-Eun; Koo, Tae-Sung

    2016-11-01

    KR33493, a newly developed FAS-associated factor 1 (FAF1) inhibitor for Parkinson's disease, is being evaluated in a Phase I clinical trial. In the present study, the subchronic toxicity of KR33493 in Sprague-Dawley (SD) rats and beagle dogs was investigated at various oral doses for 28 and 14 days, respectively. During the study, food consumption, body weights, organ weights, gross findings, and mortality were examined; and ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, histopathology, and toxicokinetics were performed. In rats, weight gain decreased in both sexes at 500 mg/kg/day, with no significant differences. In dogs, some significant differences compared with the control were found during the trial; however, at the end of recovery periods, these were no longer observed and there was no dose correlation. Some histopathological findings were observed, but these were considered as incidental changes. Since no other significant changes were observed, doses above 500 and 1000 mg/kg KR33493 in rat and dogs, respectively, caused no observed adverse effects. Therefore, based on these results, the Phase 1 clinical trial for KR33493 was approved by the Korean Food & Drug Administration. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

    Directory of Open Access Journals (Sweden)

    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

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

    Directory of Open Access Journals (Sweden)

    Akram Ghadirkhomi

    2016-08-01

    Full Text Available 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 (pConclusion: 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.

  8. Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

    African Journals Online (AJOL)

    Erah

    2010-10-21

    Oct 21, 2010 ... Histopathological assessment of liver sections of treated-rats showed normal architecture at doses < ... to provoke hepatic damage in mice [10]. In view of ..... 6. Olaleye MT, Adegboye OO, Akindahunsi AA. Alchornea cordifolia extract protects Wistar albino rats against acetaminophen-induced liver damage.

  9. Acute and subacute (28-day) toxicity studies of ionic liquid, didecyldimethyl ammonium acesulfamate, in rats.

    Science.gov (United States)

    Jodynis-Liebert, Jadwiga; Nowicki, Michał; Adamska, Teresa; Ewertowska, Małgorzata; Kujawska, Małgorzata; Petzke, Ewelina; Konwerska, Aneta; Ostalska-Nowicka, Danuta; Pernak, Juliusz

    2009-01-01

    The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD(50) cut-off value of 500 mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100 mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10 mg/kg/day.

  10. Assessment of acute and subacute toxic effects of the Saudi folk herb Retama raetam in rats

    Directory of Open Access Journals (Sweden)

    Mardi M. Algandaby

    2015-12-01

    Conclusion: Repeated administration of methanolic extract of RR (250 mg/kg has a low nephrotoxic subacute toxicity potential, while it might have hepatotoxic, nephrotoxic, and mutagenic effects at higher doses.

  11. [Studies on distribution, excretion and subacute toxicity of squalane in dogs].

    Science.gov (United States)

    Kamimura, H; Koga, N; Oguri, K; Yoshimura, H; Inoue, H; Sato, K; Ohkubo, M

    1989-05-01

    In the previous papers, we demonstrated, by using rats, that squalane (2,6,10,15,19,23-hexamethyltetracosane) could stimulate the fecal excretion of 2,3,4,7,8-pentachlorodibenzofuran, which was regarded as the most important etiologic agent of yusho among PCB and PCDF congeners found in the causal rice oil. We also reported that, in rats, squalane was not essentially absorbed from the gastrointestinal tract, and did not show any appreciable side effects during the 3-month treatment. In the present paper, we have investigated the distribution, excretion and subacute toxicity of squalane in beagle dogs. The fecal excretion of squalane accounted for about 83% of dose during the initial 2 days after administration at a single oral dose of 1,200 mg/kg to male dogs. On day 3, absorbed squalane was mostly distributed to the hair and the skin, and the concentrations in these tissues were decreased on day 6. These results suggested that most of squalane administered orally was not absorbed from the gastrointestinal tract, but a part was absorbed and excreted through the hair. In addition, squalane distributed into the liver was found to be eliminated rather slowly. A long-term (13-week) treatments with squalane orally at doses of 400 mg/kg/day or 1,200 mg/kg/day in male and female dogs, resulted also in accumulation of squalane in the liver at a level of about 3% (400 mg/kg) or about 6% (1,200 mg/kg) of the daily dose. This accumulation of squalane in the liver was highest among all the tissues. Nevertheless, no appreciable toxic signs were observed in the serum biochemical tests and the hepatic functional test for squalane groups. Therefore, squalane accumulating in the liver, did not seem to disturb the hepatic physiological functions. It was suggested also in a long-term treatment that the skin and the hair played the most important role in the elimination of squalane. In conclusion, the present studies on subacute toxicity tests suggested that squalane did not give any

  12. Evaluation of acute and subacute toxicity of aqueous extract of Crassocephalum rubens leaves in rats.

    Science.gov (United States)

    Adewale, Olusola B; Onasanya, Amos; Anadozie, Scholastica O; Abu, Miriam F; Akintan, Idowu A; Ogbole, Catherine J; Olayide, Israel I; Afolabi, Olakunle B; Jaiyesimi, Kikelomo F; Ajiboye, Bashir O; Fadaka, Adewale O

    2016-07-21

    Crassocephalum rubens is found throughout tropical Africa including the Indian Ocean islands. The leaves are commonly eaten in form of soups and sauces in South-Western Nigeria, also in other humid zones of Africa. Traditionally, it is used as an antidote against any form of poisoning; used to treat stomach and liver complaints; and externally to treat burns, sore eyes, earache, leprosy and breast cancer. In this study, acute and subacute toxicity of aqueous extract of C. rubens leaves was evaluated in rats in order to assess its safety profile. In acute toxicity study, rats were given a single oral administration of aqueous extract of C. rubens leaves at graded doses (250-5000mg/kg). The animals were monitored for behavioural changes and possible mortality over a period of 24h and thereafter, for 14 days. In the subacute toxicity study, rats of both sexes were administered C. rubens orally at doses of 250mg/kg, 500mg/kg, 750mg/kg and 1000mg/kg body weight daily, for 28 days. Rats were observed weekly for any changes in general behaviour and body weights. In addition, other relevant parameters were assayed at the end of the main and reversibility study periods. There was no observed adverse effect; including mortality in the animals. The extract caused no significant difference in the body weights as well as organs weights of treated groups when compared with the control groups. Haematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological assessments were normal in liver and kidney. It can therefore be suggested based on the results from this study that aqueous extract of C. rubens leaves, at dosage levels up to 1000mg/kg, is non-toxic and could also offer protection on some body tissues. Aqueous extract of C. rubens could therefore, be considered safe. This study supports the application of Crassocephalum rubens in traditional medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Acute and sub-acute toxicity study of Clerodendrum inerme, Jasminum mesnyi Hance and Callistemon citrinus

    OpenAIRE

    Bharat Bhushan; Satish Sardana; Gulshan Bansal

    2014-01-01

    Objective: To study acute and sub-acute toxicity study of Clerodendrum inerme (C. inerme), Jasminum mesnyi (J. mesnyi) Hance and Callistemon citrinus (C. citrinus). Methods: The acute toxicity test was conducted in Swiss albino mice. The extracts of C. inerme, J. mesnyi Hance and C. citrinus was administered in single dose of 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0 g/kg and observed for behavioral changes and mortality, if any. In sub-acute toxicity study, Wistar rats of either sex were administer...

  14. Comparative in vivo assessment of the subacute toxicity of gold and silver nanoparticles

    Science.gov (United States)

    Rathore, Mansee; Mohanty, Ipseeta Ray; Maheswari, Ujjwala; Dayal, Navami; Suman, Rajesh; Joshi, D. S.

    2014-04-01

    In spite of the projected therapeutic potentials of gold nanoparticles (GNP) and silver nanoparticles (SNP), very limited data are available on the interaction of nanoparticles with the biological systems. The present investigation was designed to evaluate as well as compare the subacute toxicity of GNP and SNP. Stable suspensions of GNP and SNP with mean particle diameter 10 and 25 nm, respectively, were prepared. Wistar rats were orally fed SNP (3 mg/kg) or GNP (20 μg/kg), once a day for 21 days. Biochemical indices (creatinine phosphokinase-MB, urea, blood urea nitrogen, aspartate transaminase, alkaline alanine transferase) and histopathological features of the liver, heart, brain, lungs, and kidney were evaluated for signs of toxicity. A significant decline in hepatic and renal function in the GNP treated group was observed as compared to SNP. GNP was found to be relatively more toxic on the lungs and SNP on the myocardial tissue as compared to SNP and GNP treatments, respectively. Interestingly, neither SNP nor GNP adversely affected the basal architecture of the brain as compared to sham. The present study demonstrated that GNP was significantly more noxious on the liver and kidney as compared with SNP.

  15. Evaluation of acute and subacute toxicity of Alstonia congensis ...

    African Journals Online (AJOL)

    The extract demonstrated good hypoglycaemic effects by lowering the plasma sugar level and also had some beneficial and reduction effects on cardiovascular risk factors. There was no evidence of drug-induced symptoms or death at all the doses of the extract administered in acute study but subacute results revealed a ...

  16. Evaluation of acute and subacute toxicity of hydroethanolic extract of Dolichandra unguis-cati L. leaves in rats.

    Science.gov (United States)

    Calil Brondani, Juliana; Reginato, Fernanda Ziegler; da Silva Brum, Evelyne; de Souza Vencato, Marina; Lima Lhamas, Cibele; Viana, Carine; da Rocha, Maria Izabel Ugalde Marques; de Freitas Bauermann, Liliane; Manfron, Melânia Palermo

    2017-04-18

    Dolichandra unguis-cati L. is a native climbing plant of Brazil, popularly known as "unha de gato". It has been traditionally used mainly as an antipyretic, anti-inflammatory and anti-tumor agent, yet little toxicological information is found in the literature. To identify the chemical composition of the hydroethanolic extract obtained from the leaves of Dolichandra uniguis-cati and to evaluate the acute and subacute toxicity in male and female rats, in order to assess the safety profile of this plant. In the acute study, a single dose (2000mg/kg) of the extract was orally administered to male and female rats. In the subacute study, the extract was orally administered to male and female rats at doses 100, 200 and 400mg/kg for 28 days. Behavioral changes, catalase and tbars evaluations, biochemical, hematological and histopathological analysis were determined. The extract' chemical composition was accessed through UHPLC/MS. Chlorogenic acid, caffeic acid, ferulic acid, vanillinic acid, p-coumaric acid, rosmarinic acid, trans-cinnamic acid, luteolin, apigenin, quercitrin and quercetin were identified in the extract. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. In relation to the subacute study, females showed a reduction in AST (100, 200 and 400mg/kg), ALT (200mg/kg) and BUN (100 and 200mg/kg) levels, while male rats 400mg/kg presented an increase in AST levels. The Chol dosage significantly decreased in female rats in a dose-dependent manner, whereas for male rats this parameter showed no statistically significant reductions. No behavioral and histopathological changes were recorded. Our results indicate that the hydroethanolic extract of Dolichandra unguis-cati leaves did not present relevant toxic effects when administered orally to male and female rats. The extract also showed a potential hypocholesterolemic activity. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Subacute Toxicity Profile of Lacidipine Nanoformulation in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Rupesh Shirodkar

    2015-01-01

    Full Text Available The present study was aimed at investigating the safety of Lacidipine (LCDP loaded nanostructured lipid carriers (NLCs in Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during 28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrificed on the 29th day. Study revealed no signs or symptoms of toxicity or morbidity. No significant changes in the body weight were observed between treated and control group. Significant increase in left testis weight and liver weight was observed in male and female rats, respectively. Haematological estimation revealed significant decrease in haemoglobin count in male rats while female rats showed significant increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological changes were observed. No delayed effect was noted in satellite group. The results indicate that developed LCDP loaded NLCs are safe when administered orally in rats.

  18. Sub-acute toxicity study on the aqueous extract of Albizia zygia stem ...

    African Journals Online (AJOL)

    Sub-acute toxicity study on the aqueous extract of Albizia zygia stem bark. ... Morphological (body weight and organ weight indices), haematological {white blood cell (WBC), red blood cell (RBC), haemoglobin, haematocrit, and platelet counts}, biochemical {alanine aminotransferase (ALT), aspartate amino transferase ...

  19. Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study.

    Science.gov (United States)

    Patel, Shruti B; Rao, Nirav J; Hingorani, Lal L

    2016-03-01

    The use of Withania somnifera is increasing due to a number of its chemical constituents found useful for health. The present study was carried out to investigate the potential adverse effects (if any) of a standardized Withania somnifera extract (WSE) in rats following acute and sub chronic administration. The toxicity study was performed in Wistar rats by oral administration. An acute toxicity study was done at the dose of 2000 mg/kg. In the sub-acute study, Wistar rats (10/sex/group) were administered via gavage 0 (control), 500, 1000, 2000 mg/kg body weight/day of WSE for 28 days. Among two additional satellite groups, one group did not receive any drug while the second group received 2000 mg/kg/day for 28 days. At the end of study, the animals sacrificed and their body weight, hematology, serum chemistry, and histopathology evaluation was done. In acute toxicity studies, oral LD50 of WSE in Wistar rats was greater than 2000 mg/kg body weight. Compared to the control group in sub-acute toxicity study, administration of extract did not show any toxicologically significant treatment related changes in clinical observations, ophthalmic examination, body weight gain, feed consumption, clinical pathology evaluation, and organ weight. Hematological and serum chemistry parameters were within the normal limits. Terminal necropsy did not reveal any treatment related gross or histopathological findings. Based on this study, the no-observed-adverse-effect-level of WSE is 2000 mg/kg body weight, the highest level tested. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  20. Oral toxicity of elephant foot yam (Amorphophallus paeoniifolius tuber in mice

    Directory of Open Access Journals (Sweden)

    Yadu Nandan Dey

    2017-02-01

    Full Text Available Context: Amorphophallus paeoniifolius tuber is an important constituent of Ayurvedic system of medicine. The tuber of this plant has high medicinal value and is consumed as a food. It is associated with acridity (itchy sensation in mouth and throat upon oral consumption and presence of high oxalates raphides. Aims: To evaluate the acute and subacute oral toxicity studies of methanolic (APME and aqueous (APAE extracts of Amorphophallus paeoniifolius tuber in Swiss albino mice according to OECD guidelines. Methods: In acute oral toxicity study, the mice were orally administered a single dose of APME or APAE (2000 mg/kg and clinical signs and mortality were observed for 14 days. In subacute (repeated dose oral toxicity study, the mice were administered once daily, orally with APME or APAE (1000 mg/kg up to 28 days. The parameters assessed were behavior, clinical signs, body weight, feed and water consumption, urinary, biochemical, hematological and major organ weights and histology. Results: In acute toxicity study, there was no treatment related mortality and morbidity in any of the group. In subacute toxicity study, there were no significant changes in behavior, body weight, feed and water consumption, urinary, biochemical, hematological and organ weight and histological parameters compared to vehicle treated group. There was no treatment related mortality or morbidity. Conclusions: Administration of methanolic and aqueous extracts of Amorphophallus paeoniifolius tuber, individually in acute and 28 days repeated dose in mice, did not exhibit any toxicity or adverse effect at the doses used.

  1. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

    Science.gov (United States)

    Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

    2007-09-25

    Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

  2. Acute and Subacute Toxic Study of Aqueous Leaf Extract of ...

    African Journals Online (AJOL)

    kg and observed continuously for the first 4 h, then hourly for the next 24 h, and finally, 6-hourly for 72 h. Control animals received orally normal saline. The rats were observed carefully for mortality, pain as well as respiratory movements.

  3. Subacute toxicity assessment of water disinfection byproducts on zebrafish.

    Science.gov (United States)

    Rácz, Gergely; Csenki, Zsolt; Kovács, Róbert; Hegyi, Arpád; Baska, Ferenc; Sujbert, László; Zsákovics, Ivett; Kis, Renáta; Gustafson, Ryan; Urbányi, Béla; Szende, Béla

    2012-07-01

    Disinfection of raw water is essential to the production of drinking water. However, by-products of disinfection may exert toxic effects. The potential toxic effects of two of these compounds, 4-ethylbenzaldehyde (EBA) and 2,4-difluoroaniline (DFA) were investigated using the zebrafish (Danio rerio) model. The two compounds, dissolved, were introduced in duplicate aquariums containing zebrafish in two different concentrations based on LC50 values. The aquarium water containing EBA or DFA was changed every 96 h throughout the 3 months of treatment. Behavior of the fish in each replicate was inspected twice daily. In course of treatment with both concentrations, fish exposed to DFA displayed behavior associated with visible anxiety, while EBA treated were lethargic and did not evade capture. Application of both concentrations of each component into the aquarium water resulted in dystrophic lesions in the liver, kidney and skin of the fish while preneoplastic lesions and tumors were not observed.

  4. Evaluation of the subacute and subchronic toxicity of inhaled EDS hydrotreated naphtha in the rat.

    Science.gov (United States)

    McKee, R H; Hinz, J P

    1987-07-01

    Inhalation studies were conducted to assess the subacute and subchronic toxicity of EDS hydrotreated naphtha (HN). In the subacute toxicity study, male and female Sprague-Dawley rats were exposed to various concentrations of HN vapor (0.2, 1.0, and 5.0 g/m3) 6 hr/day for 5 consecutive days. Following 2 recovery days, the animals were exposed for 4 additional days and then sacrificed on the 12th study day. In the subchronic toxicity study, a similar protocol was utilized; however, the animals were exposed 5 days/week for 13 weeks. Following a 2-week recovery period, the animals were sacrificed. Parameters examined in both studies included survival, growth, clinical observations, urinalysis, blood chemistry at necropsy, and microscopic examination of selected tissues. There was some evidence of systemic effects associated with repeated inhalation exposure to HN, although these effects were mild and were primarily confined to the high-exposure groups. The major systemic effect appeared to be renal toxicity in male rats as evidenced by increased urinary excretion of renal epithelial cells, creatinine, glucose, and protein and decreased urine osmolality. However, the absence of consistent pathologic changes in the kidneys of these animals suggested that the lesions were either slight or reversible during the 2-week recovery period.

  5. Toxic effects of ackee oil (Blighia sapida L) following subacute administration to rats.

    Science.gov (United States)

    Singh, P; Gardner, M; Poddar, S; Choo-Kang, E; Coard, K; Rickards, E

    1992-03-01

    Subacute intraperitoneal administration of the lipid portion of the unripe ackee arillus, referred to as "ackee oil", resulted in marked neutropenia (p less than 0.001) and increase in platelets (p less than 0.01) without anaemia, in rats. Blood urea, sodium and aspartate aminotransferase levels were significantly decreased but glucose and bilirubin levels were similar to those of controls. The lungs showed areas of petechial haemorrhages and a dose-related perivascular and peribronchial mononuclear cell infiltration. The pulmonary toxicity may be interpreted as a hypersensitive reaction to ackee oil. Further research is in progress on the neutropenic effects of ackee oil.

  6. Oral Chromium Exposure and Toxicity

    Science.gov (United States)

    Sun, Hong; Brocato, Jason

    2015-01-01

    Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

  7. Subacute toxicity of nano-selenium compared to other selenium species in mice.

    Science.gov (United States)

    Benko, Ilona; Nagy, Gabor; Tanczos, Bence; Ungvari, Eva; Sztrik, Attila; Eszenyi, Peter; Prokisch, Jozsef; Banfalvi, Gaspar

    2012-12-01

    Sixteen groups of mice were fed diets containing different selenium species to compare their toxicity. Inorganic sodium selenate and sodium hydroselenite, elementary nanoSe, organic Sel-Plex, and Lacto-MicroSelenium were administered for 14 d at concentrations of 0.5, 5, and 50 ppm Se, equivalent to 0.5, 5, and 50 mg Se/kg food, corresponding to an estimated 4, 40, and 400 µg/kg body weight/d Se uptake, respectively. At the end of the treatment, body, liver, spleen, kidney, heart, and brain weights were measured, mice were subjected to necropsy, and histological examinations were performed on the liver. At lower Se doses (0.5 and 5 ppm) a moderate reduction was observed in the number of bone marrow and white blood cells and in granulocyte-macrophage colony-forming units (GM-CFUs) relative to the untreated control group of mice. A comparison of lowest toxic doses of sodium selenite in mice (0.5 ppm) and mallard (10 ppm) indicates that birds are more resistant to Se than rodents. In mice, a small but measurable weight loss was observed after 5 ppm selenate and LactoMicroSe treatment. The most significant changes took place after 50-ppm administration in body and spleen weight, hematology, and liver histology. Toxicity was more pronounced when inorganic Se was applied than after subacute application of Sel-Plex, nanoSe, or LactoMicroSe. To summarize the effects, the authors' 14-d murine subacute toxicity study showed that the toxicity of Se species decreased in the following order: selenate > selenite > nanoSe > Sel-Plex > LactoMicroSe. Copyright © 2012 SETAC.

  8. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    Science.gov (United States)

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. The Study on Acute and Subacute Toxicity and Anti-Cancer Effects of cultivated wild ginseng Herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Ki-Rok, Kwon

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled in mice and rats. Methods : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute LD50 toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture

  10. Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model

    Directory of Open Access Journals (Sweden)

    O'Shaughnessy Patrick T

    2011-01-01

    Full Text Available Abstract Background There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure. Results In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m3, 4 hours/day, 10 days, 5 ± 2 nm primary size. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published in vitro studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our in vivo study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma - optical emission spectroscopy (ICP-OES was 31 μg/g lung (dry weight immediately after the final exposure, 10 μg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu. Conclusions Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.

  11. [Oral treatment of vitamin B12 deficiency in subacute combined degeneration].

    Science.gov (United States)

    Wellmer, J; Sturm, K-U; Herrmann, W; Hoever, J; Klockgether, T; Linnebank, M

    2006-10-01

    Vitamin B12 deficiency due to malnutrition or malabsorption may lead to pernicious anemia and neurological disorders. Although randomized prospective studies have shown that pernicious anemia can be safely treated with oral vitamin B12 even in the absence of intrinsic factor, it is still common practice to treat patients with neurological symptoms with intramuscular cyancobalamin injections. We report the successful oral treatment of subacute combined degeneration of the spinal cord in a 24-year-old woman closely monitored clinically with MRI and plasma levels of vitamin B12, homocysteine, and methylmalonic acid. We suggest monitored oral substitution therapy as first-line therapy for neurological disorders related to vitamin B12 deficiency.

  12. Acute and Sub-Acute Toxicity of Aqueous Extract of Nauclea ...

    African Journals Online (AJOL)

    Purpose: To determine the dose – toxicity profile of the aqueous extract of Nauclea latifolia stem bark. (AQE). Methods: .... filtered and lyophilized and the dried residue was diluted appropriately with water for oral administration to the experimental animals. Acute toxicity test ..... the removal of metabolic wastes from the blood.

  13. Phytochemical, sub-acute toxicity, and antibacterial evaluation of Cordia sebestena leaf extracts.

    Science.gov (United States)

    Osho, Adeleke; Otuechere, Chiagoziem A; Adeosun, Charles B; Oluwagbemi, Tolu; Atolani, Olubunmi

    2016-03-01

    In Nigeria, Cordia sebestena (Boraginaceae), an understudied medicinal plant, is used in traditional medicine for the treatment of gastrointestinal disorders. In this study, we investigated the chemical composition, antibacterial potential, and sub-acute toxicity of C. sebestena leaves. Ethyl acetate extracts were analyzed using thin layer chromatography (TLC) and Fourier transform infrared (FTIR) spectrophotometry. The antibacterial potential of the extracts was tested against five standard bacteria, namely Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Clinical observations and blood parameters were used to evaluate the possible toxicity of C. sebestena. The TLC profile yielded 39 fractions, which were pooled to nine combined sub-fractions (A-I). The FTIR spectrum of sub-fraction H indicated the presence of aliphatic C-H stretching vibration at 2922 and 2850 cm-1, C=O stretch at 1734 and 1708 cm-1, and C=C stretch of aromatics and aliphatics at 1464 and (shoulder) 1618 cm-1, respectively. The fractions of the C. sebestena ethyl acetate leaf extract showed antibacterial potential across board, but fraction H had the highest antibacterial activity against B. cereus and S. aureus. The study also indicated the relatively low toxicity profile of the ethyl acetate leaf extract of C. sebestena in the liver of rats. The study showed that C. sebestena leaves have strong antibacterial potential and low toxicity, thereby underlying the scientific basis for their folkloric use in the management of microbial infections and its associated complications.

  14. Subacute toxicity study on sup(99m)Tc stannous glucoheptonate injection

    Energy Technology Data Exchange (ETDEWEB)

    Belbeck, L.; Bowen, B.M.; Jeu, J.; Richardson, M. (McMaster Univ., Hamilton, Ontario (Canada))

    1981-07-01

    A subacute toxicity study on sup(99m)Tc stannous glucoheptonate was performed with rats, dogs and rabbits, injected intravenously at ten to 100 times the human dose on a body weight basis. There were no abnormalities in the clinical status of any of the animals. No changes were found in urinalysis, blood chemistry or hematology in the rabbits nor in gross examination, renal histology or bone marrow smears in rats and rabbits. Hepatic histology was also done. A focal area of necrosis in a liver of one rabbit that had been injected with 100 times the human dose was observed using light microscopy. Examination by electron microscopy in another group of rats and rabbits was prompted by the observation of that lesion. This revealed vacuolated and dilated smooth endoplasmic reticulum and degranulated and vesiculated rough endoplasmic reticulum in all the test livers. X-ray microanalysis indicates that the ultrastructural changes are linked to the deposition of tin.

  15. Preliminary Phytochemical Screening, Acute Oral Toxicity and ...

    African Journals Online (AJOL)

    Purpose: To investigate the preliminary phytochemical properties, acute oral toxicity and anticonvulsant activity of the berries of Solanum nigrum Linn (S. nigrum) Methods: Phytochemicals from the ethanol berry extract were screened by standard methods. Acute oral toxicity study was conducted as per Organisation for ...

  16. Acute and Subacute Oral Toxicity of Periodate in Rats

    Science.gov (United States)

    2014-11-17

    Transient increases in gastrointestinal pH and degeneration of parietal cells, hemolytic effects including hemoglobinuria and hemosiderin deposits in...and degeneration of parietal cells, hemolytic effects including hemoglobinuria and hemosiderin deposits in the kidneys, and non-specific fatty changes

  17. Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids.

    Science.gov (United States)

    Şeremet, Oana Cristina; Bărbuceanu, Florica; Ionică, Floriana Elvira; Margină, Denisa Marilena; GuŢu, Claudia Maria; Olaru, Octavian Tudorel; Ilie, Mihaela; Gonciar, Veaceslav; Negreş, Simona; ChiriŢă, Cornel

    2016-01-01

    Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs. The aim of the paper was to assess the safety of some dry extracts obtained from these species. For the determination of acute toxicity, Organization for Economic Cooperation and Development (OECD) Guideline No. 423 was used. For the determination of repeated dose oral toxicity, Senecionis vernalis herba and Symphyti radix extracts (250 mg÷kg) were administrated, by gavage, for 28 days, and their effects on animal weight, liver and biliary functions, hepatic tissue and oxidative stress were investigated. After the acute toxicity testing, the dry extracts were placed in the GHS Category V (LD50>5000 mg÷kg, p.o.). For the subacute toxicity testing, no death or any signs of toxicity were observed. Also, no significant differences in biochemical parameters were observed between control and treated groups. The observed histopathological lesions were non-specific and were not consistent with the data reported in the literature for PAs exposure. In conclusion, the administration for 28 days, of the tested extracts, in a dose which correspond to a PAs concentration over the limits imposed in some countries, produced no hepatic and biliary toxic effects. Further studies, extended over a longer period of time, are needed in order to determine the safety of plant extracts containing PAs.

  18. Acute and Sub-acute Toxicity Profile of Aqueous Leaf Extract of ...

    African Journals Online (AJOL)

    Methods: Acute toxicity study was performed by administering a single oral dose of 5000 mg/kg body weight of the extract to 5 rats while distilled water was given to another 5 ... Histopathology did not reveal any sign of lesions or pathological changes in the organs that could be attributed to treatment with the plant extract.

  19. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles.

    Science.gov (United States)

    Sharma, Vyom; Singh, Poonam; Pandey, Alok K; Dhawan, Alok

    2012-06-14

    Zinc oxide (ZnO) nanoparticles are finding applications in a wide range of products including cosmetics, food packaging, imaging, etc. This increases the likelihood of human exposure to these nanoparticles through dermal, inhalation and oral routes. Presently, the majority of the studies concerning ZnO nanoparticle toxicity have been conducted using in vitro systems which lack the complex cell-cell, cell-matrix interactions and hormonal effects found in the in vivo scenario. The present in vivo study in mice was aimed at investigating the oral toxicity of ZnO nanoparticles. Our results showed a significant accumulation of nanoparticles in the liver leading to cellular injury after sub-acute oral exposure of ZnO nanoparticles (300 mg/kg) for 14 consecutive days. This was evident by the elevated alanine aminotransferase (ALT) and alkaline phosphatase (ALP) serum levels and pathological lesions in the liver. ZnO nanoparticles were also found to induce oxidative stress indicated by an increase in lipid peroxidation. The DNA damage in the liver and kidney cells of mice was evaluated by the Fpg-modified Comet assay which revealed a significant (plesions in liver indicating oxidative stress as the cause of DNA damage. The TUNEL assay revealed an induction of apoptosis in the liver of mice exposed to ZnO nanoparticles compared to the control. Our results conclusively demonstrate that sub-acute oral exposure to ZnO nanoparticles in mice leads to an accumulation of nanoparticles in the liver causing oxidative stress mediated DNA damage and apoptosis. These results also suggest the need for a complete risk assessment of any new engineered nanoparticle before its arrival into the consumer market. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Mammalian Toxicological Evaluation of TNT Wastewaters. Volume II. Acute and Subacute Mammalian Toxicity of TNT and LAP Mixture

    Science.gov (United States)

    1979-06-01

    lContinued) ’ in rats; subacute toxicity in mice; anemia; testicular atrophy; uterine U hypoplasia; hemosiderosis ; SGPT; cholesterol; unscheduled DNA...food intake, mild to moderate hemolytic anemia, 5. enlarged splee s and (usually) livers, hemosiderosis of the spleen, and colored urine.! Testicular...temporary with mice); mild to moderate anemia; alterations in organ weights, including enlarged spleens and (usually) livers; hemosiderosis of the spleen

  1. Combined subacute toxicity of copper and antiparasitic albendazole to the earthworm (Eisenia fetida).

    Science.gov (United States)

    Gao, Yuhong; Li, Hongshuang; Li, Xuemei; Sun, Zhenjun

    2016-03-01

    Copper (Cu) is one of the most common metal contaminants, and albendazole (ABZ) is a veterinary drug with a high efficacy against helminthes. It is believed that the two may co-exist in soil. In this study, the combined subacute toxicity of Cu exposure (0, 80, 120, 160 mg kg(-1)) and ABZ exposure (0, 3, 9 mg kg(-1)) in earthworms (Eisenia fetida) were observed using three approaches, namely chronic growth and reproduction, antioxidant enzyme activity, and earthworm Cu residue. The results have shown that the toxicity of Cu on cocoon hatching success and biomass was alleviated by presence of low concentrations of ABZ (3 mg kg(-1)) during a 56-day exposure period. However, the sensitivity of the earthworms' reproduction to Cu increased with the presence of high concentrations of ABZ (9 mg kg(-1)), indicating a reduction beginning at a Cu concentration of 80 mg kg(-1), in the cocoon number, hatching success, and biomass. In addition, the three enzyme activities exhibited different responsive patterns, indicating inducement in the catalase and glutathione peroxidase, and inhibition in the superoxide dismutase, which were dependent on the exposure times and concentrations. In regard to the earthworm Cu residue, when increasing Cu exposure concentrations, the internal Cu concentrations tended to level off, exhibited a linear pattern at the Cu concentration range of 40 to 120 mg kg(-1), and showed a stable trend above 120 mg kg(-1). The results of the present study can potentially provide important information regarding the combined toxicity of the veterinary drugs and the heavy metals in soil.

  2. Evaluation of subacute toxicity of methanolic/aqueous preparation of aerial parts of O. sanctum in Wistar rats: Clinical, haematological, biochemical and histopathological studies.

    Science.gov (United States)

    Raina, P; Chandrasekaran, C V; Deepak, M; Agarwal, A; Ruchika, K-G

    2015-12-04

    Ocimum sanctum, commonly known as Holy Basil or Tulsi has been used in Ayurveda as a demulcent, stimulant, expectorant; in the treatment of bronchitis, skin infections, malaria, diarrhoea, dysentery, arthritis, gastric and inflammatory disorders. We have previously shown that methanolic/aqueous extract of O. sanctum did not induce genotoxicity and other toxic effects in acute oral toxicity study. In the present report, we have performed sub-acute toxicity of methanolic/aqueous preparation of O. sanctum in Wistar rats to evaluate whether it induced any chronic toxic effects. In subacute toxicity study, animals received O. sanctum extract (OSE) by oral gavage at the doses of 250, 500 and 1000 mg/kg/day (n=5/group/sex) for 28 days. At the end of the study, the animals were sacrificed and evaluated for the effect of OSE on clinical, haematological, biochemical and histopathological parameters. The rats treated with OSE did not show any change in body weight, food and water consumption, motor activity, sensory reactivity and foot splay measurements. There were no significant changes in haematological, pathological and biochemical parameters; and histopathology of tissues (liver, kidney, spleen, heart, and testis/ovary) among rats of either sex. OSE at a dose of 1000 mg/kg showed significant increase of Mean corpuscular hemoglobin (MCH) (19.8 ± 0.8; 18.7 ± 0.5) and mean corpuscular hemoglobin concentration (MCHC) (41.8 ± 1.1; 39.3 ± 0.7) in male and female rats in comparison to their respective controls (MCH: 17.7 ± 0.3; 17.4 ± 0.3; MCHC: 37.8 ± 0.5; 36.1 ± 0.2). Urine parameters (appearance, blood, nitrate, leucocyte, glucose, ketone, pH, protein and specific gravity) in both the male and female rats were comparable to their respective controls. In addition, no changes were observed in the vital organs of rats at macroscopic and microscopic levels. Our results showed that oral administration of OSE was not toxic to male and female Wistar rats upto the highest

  3. Iron and nickel complexes with heterocyclic ligands: stability, synthesis, spectral characterization, antimicrobial activity, acute and subacute toxicity.

    Science.gov (United States)

    Bouchoucha, Afaf; Terbouche, Achour; Zaouani, Mohamed; Derridj, Fazia; Djebbar, Safia

    2013-07-01

    The synthesis and characterization by elemental analysis, emission atomic spectroscopy, TG measurements, magnetic measurements, FTIR, (1)H NMR, UV-visible spectra and conductivity of a series of iron (II) and nickel (II) complexes with two heterocyclic ligands (L(1)(SMX): sulfamethoxazole and L(2)(MIZ): metronidazole) used in pharmaceutical field and with a new ligand derived benzoxazole (L(3)(MPBO): 2-(5-methylpyridine-2-yl)benzoxazole), were reported. The formulae obtained for the complexes are: [M(L(1))2 Cl2]·nH2O, [M(L(2))2Cl2(H2O)2]·H2O and [M(L(3))2(OH)2]·nH2O. Stability constants of these complexes have been determined by potentiometric methods in water-ethanol (90:10, v/v) mixture at a 0.2 mol L(-1) ionic strength (NaCl) and at 25.0±0.1 °C. Sirko program was used to determine the protonation constants as well as the binding constants of three species [ML2H2](2+), [ML2] and [ML](2+). The antimicrobial activity of the ligands and complexes was evaluated in vitro against different human bacteria and fungi using agar diffusion method. Iron sulfamethoxazole complex showed a remarkable inhibition of bacteria growth especially on Staphylococcus aureus and P. aeruginosa. The iron metronidazole complex is active against yeasts especially on Candida tropicalis strain. Nickel complexes presented different antibacterial and antifungal behavior's against bacteria and fungal. The acute toxicity study revealed that the iron complexes are not toxic at 2000 mg/kg dose orally administrated. LD50 for nickel complexes was determined using graphical method. No significant differences in the body weights between the control and the treated groups of both rat sexes in subacute toxicity study using for iron complexes. Hematological and clinical blood chemistry analysis revealed no toxicity effects of the iron complexes. Pathologically, neither gross abnormalities nor histopathological changes were observed for these complexes. Copyright © 2013 Elsevier GmbH. All rights

  4. Preliminary Phytochemical Screening, Acute Oral Toxicity and ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. ... PTZ-induced seizure mice in at the dose of 300 mg/kg p.o. The extract also reduced the frequency of convulsion and provided up to .... Oral acute toxicity test. Acute toxicity of the plant extract was carried out.

  5. Subacute pulmonary toxicity of copper indium gallium diselenide following intratracheal instillations into the lungs of rats.

    Science.gov (United States)

    Tanaka, Akiyo; Hirata, Miyuki; Shiratani, Masaharu; Koga, Kazunori; Kiyohara, Yutaka

    2012-01-01

    The aim of this study was to clarify the pulmonary toxicity of copper indium gallium diselenide (CIGS) solar cells on 62 8-wk-old rats. Male Wistar rats were given 0.5, 5 or 50 mg/kg of CIGS particles, intratracheally, 3 times for a week. Control rats were given vehicle, distilled water, only. These rats were euthanized 0, 1 or 3 wk after the final instillation serially, and toxicological effects were determined. None of the CIGS-treated groups exhibited suppression of body weight gain compared with the control group. The relative lung weight in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups were significantly increased compared with that in the control group throughout the observation period. Although serum copper (Cu) and selenium (Se) concentrations were not affected by instillations of CIGS particles, the indium (In) levels increased with the passage of time in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups. However, the serum gallium (Ga) levels decreased in the CIGS 50 mg/kg-treated group from 0 to 3 wk. The content of each metal in the lung increased depending on the dose instilled and was constant during observation periods. Histopathologically, foci of slight to severe pulmonary inflammatory response and exudation were present among all the CIGS-treated groups, and the severity of these lesions worsened with the passage of time. The present results clearly demonstrate that CIGS particles caused subacute pulmonary toxicity and that dissolution of CIGS particles in the lung was considerably slow when repeated intratracheal instillations were given to rats.

  6. [On the subacute toxicity of labetalol (AH5158): a combined alpha-and beta-adrenoceptor blocking agent (author's transl)].

    Science.gov (United States)

    Shimpo, K; Yokoi, Y; Fujiwara, S; Togashi, H; Tanabe, T

    1980-11-01

    Subacute toxicity and recovery tests of labetalol hydrochloride, alpha- and beta-adrenoceptor blocking agent, were carried out using male and female Wistar strain rats. The drug was orally administered at 50, 150, 450 or 1000 mg/kg/day for 1 month. In all the drug-treated groups, increase in salivation was observed from immediately to 15 minutes after dosing through the treatment period. Eight of the 10 males and 9 of the 10 females in the group treated with 1000 mg/kg/day died of intoxication. Suppression of body weight gain was observed in male rats in the 450 and 1000 mg/kg/day groups and in female rats in the 1000 mg/kg/day group. In the 150 mg/kg/day and higher dose groups, water consumption showed a tendency to increase as compared with that of control group. Increase in urine volume was observed in female rats in the 450 mg/kg/day group. In the serum biochemical examination, slight elevation in potassium levels was noted in the 150 and 450 mg/kg/day groups. In histopathological findings, some abnormalities were found in the groups treated at 150 mg/kg/day and higher. Major abnormalities found in organs were; congestion and hypremia of various organs due to vasodilation, swelling of parenchymatous cells in liver and kidneys, and loose arrangement and change in the thickness of muscle fibers in cardiac and skeletal muscles. None of these abnormal findings was found in any examination in recovery tests.

  7. Acute and Subacute Toxicity In Vivo of Thermal-Sprayed Silver Containing Hydroxyapatite Coating in Rat Tibia

    Directory of Open Access Journals (Sweden)

    Masatsugu Tsukamoto

    2014-01-01

    Full Text Available To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA containing silver (Ag. This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2–4 days after treatment and subacute phase (4–12 weeks after treatment. Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation.

  8. Acute and subacute toxicity in vivo of thermal-sprayed silver containing hydroxyapatite coating in rat tibia.

    Science.gov (United States)

    Tsukamoto, Masatsugu; Miyamoto, Hiroshi; Ando, Yoshiki; Noda, Iwao; Eto, Shuichi; Akiyama, Takayuki; Yonekura, Yutaka; Sonohata, Motoki; Mawatari, Masaaki

    2014-01-01

    To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2-4 days after treatment) and subacute phase (4-12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation.

  9. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    Science.gov (United States)

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  10. Determination of toxicity of subacute treatment of some plant growth regulators on rats.

    Science.gov (United States)

    Celik, Ismail; Tuluce, Yasin

    2007-12-01

    potential enzyme MPO activity significantly increased in the spleen of rats treated with both doses of NAA and TIBA whereas ADA activity significantly decreased in the spleen of rats treated with 100 ppm dose of NAA and TIBA. The observations presented led us to conclude that the administrations of subacute NAA, 2,4-D, and TIBA promote MDA content, inhibit the antioxidative defense system and activate or inhibit immune potential enzymes in the rat's spleen and lung tissues. These data suggest that PGRs produced substantial organ toxicity in the lung and spleen during the period of a 25-day subacute exposure.

  11. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis.

    Science.gov (United States)

    Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho; Torres-Santos, Eduardo Caio

    2016-06-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Subacute toxicity of titanium dioxide (TiO2) nanoparticles in male rats: emotional behavior and pathophysiological examination.

    Science.gov (United States)

    Younes, Naima Rihane Ben; Amara, Salem; Mrad, Imen; Ben-Slama, Imen; Jeljeli, Mustapha; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

    2015-06-01

    Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in many fields (paint, industry, medicine, additives in food colorants, and nutritional products). Over the past decade research, TiO2 NPs have been focused on the potential toxic effects of these useful materials. In the present study, we investigated the effects of subacute exposure to TiO2 NPs on emotional behavior in adult Wistar rats, the biochemical parameters, and the histology of organs. Animals were injected intraperitoneally (ip) with TiO2 NPs (20 mg/kg body weight) every 2 days for 20 days. The elevated plus-maze test showed that subacute TiO2 NPs treatment increased significantly the anxious index (AI) compared to control group. The toxicological parameters were assessed 24 h and 14 days after the last injection of TiO2 NPs. Subacute exposure to nanoparticles increased the AST/ALT enzyme ratio and LDH activity. However, the blood cell count remained unchanged, except the platelet count increase. Histological examination showed a little inflammation overall. Moreover, our results provide strong evidence that the TiO2 NPs can induce the liver pathological changes of rats. The intraperitoneal injection of TiO2 NPs increased the accumulation of titanium in the liver, lung, and the brain. The results suggest that TiO2 NPs could alter the neurobehavioral performance of adult Wistar rats and promotes alterations in hepatic tissues.

  13. Preclinical toxicity profile of oral bilastine.

    Science.gov (United States)

    Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

    2012-06-01

    As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

  14. The Study on Acute and Subacute Toxicity and Sarcoma-180 Anti-cancer Effects of Carthami Tinctor-Fructus Herbal-acupuncture(CF

    Directory of Open Access Journals (Sweden)

    Chang-Suk An

    2002-02-01

    Full Text Available Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with Carthami- Tinctorii fructus (CF in mice and rats. Method: Balb/c mice were injected intraperitoneally with Carthami - Tinctorii fructus (CF for LD50 and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Carthami- Tinctorii fructus (CF for subacute toxicity test. The Carthami- Tinctorii fructus herbal-acupuncture was injected on Chung-wan (CV12 of mice with Sarcoma-180 cancer cell line. Results: 1. LD50 was uncountable as none of the subjects expired during the test. 2. In acute toxicity test, toxic symptoms were not detected, but the body weight of mice was increased in treatment Ⅰ, treatment Ⅱ groups, compared to the normal group.(p<0.05 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment Ⅰ and treatment Ⅱ groups, total cholesterol was increased in treatment I group, GOT was decreased in treatment Ⅱ group, and GPT was decreased in treatment Ⅰ group, compared to the normal group.(p<0.05 4. The clinical signs and the body weight of mice treated with 0.1 cc, 0.2cc Carthami- Tinctorii fructus (CF were not affected during the subacute toxicity test. 5. In subacute toxicity test, treatment groups didn't show significant changes in complete blood count test (CBC of rats, compared to the nonnal group.(p<0.05 6. In subacute toxicity test of serum biochemical values of rats, uric acid was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the nonnal group, triglyceride was decreased in treatment I group, compared to the normal group, GOT and GPT were decreased in treatment I and treatment Ⅱ groups, and alkaline phosphatase was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the normal group.(p<0.05 7. Median survival time was increased in all the treatment groups for Sarcoma-180 cancer cell

  15. Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: Biochemical and histopathological studies.

    Science.gov (United States)

    Abdel-Daim, Mohamed; El-Bialy, Badr E; Rahman, Haidy G Abdel; Radi, Abeer M; Hefny, Hany A; Hassan, Ahmed M

    2016-02-01

    Spirulina platensis (SP); a microalga with high antioxidant and anti-inflammatory activities, acts as a food supplement in human and as many animal species. Deltamethrin (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to DLM leads to hepatotoxic, nephrotoxic and neurotoxic side effects for human and many species, including birds and fish. The present study was undertaken to examine the potential hepatoprotective, nephroprotective, neuroprotective and antioxidant effects of SP against sub-acute DLM toxicity in male mice. DLM intoxicated animals revealed a significant increase in serum hepatic and renal injury biomarkers as well as TNF-α level and AChE activity. Moreover, liver, kidney and brain lipid peroxidation and oxidative stress markers were altered due to DLM toxicity. Spirulina normalized the altered serum levels of AST, ALT, APL, LDH, γ-GT, cholesterol, uric acid, urea, creatinine AChE and TNF-α. Furthermore, it reduced DLM-induced tissue lipid peroxidation, nitric oxide and oxidative stress in a dose-dependent manner. Collectively, that Spirulina supplementation could overcome DLM-induced hepatotoxicty, nephrotoxicity and neurotoxicity by abolishing oxidative tissue injuries. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Mucopenetrating nanoparticles for enhancement of oral bioavailability of furosemide: In vitro and in vivo evaluation/sub-acute toxicity study.

    Science.gov (United States)

    Radwan, Salma El-Sayed; Sokar, Magda Samir; Abdelmonsif, Doaa Ali; El-Kamel, Amal Hassan

    2017-06-30

    The aim of this study was to formulate and evaluate chitosan (CS)/alginate (ALG) nanoparticles (NPs) loaded with furosemide (FSM) in an attempt to enhance its release, permeability and bioavailability. Non-everted gut sac method was used to evaluate the ex vivo permeation of FSM from its suspension and the selected CS/ALG NPs formulation. The pharmacokinetic parameters of FSM subsequent to oral administration of the selected formulation were assessed in rats. In vivo subacute toxicity study of the prepared blank and FSM loaded formulations was evaluated in rats. The selected optimized formulation (F3) showed optimum particle size (PS), polydispersity index (PDI), zeta potential (ZP) and acceptable percentage entrapment efficiency (%EE) of 253.8nm±4.6, 0.25±0.03, -35mV±1 and 96%±1, respectively. The release profile of FSM from the selected formulation was characterized by initial burst effect in 0.1N HCl. Scanning electron microscope (SEM) demonstrated a smooth surface and spherical shape for the lyophilized optimized NPs. Selected CS/ALG NPs (F3) presented a significant enhancement (p≤0.01) in permeation parameters of FSM as well as in T max , C max , AUC 0-24 and AUC 0-∞ . Subacute toxicity study results revealed that the selected formulation was safe and nontoxic. The histopathological inspection of the stomach and small intestine tissues of the loaded NPs (F3) and blank groups reflected no obvious signs of cellular toxicity or inflammatory reaction. CS/ALG NPs loaded with FSM enhanced both drug release and mucus-penetrating ability leading to an overall increase in FSM bioavailability. In addition, the in vivo subacute toxicity study results indicated the safety of the prepared NPs for oral drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Huso huso Acute and subacute toxicity study of ethanolic extract of ...

    African Journals Online (AJOL)

    acute toxicity profiles of ... body weight changes, haematology, plasma biochemical parameters, relative organ weight (ROW) were evaluated. ... to ascertain its effect on the male reproductive system as well as its effect on chronic administration.

  18. Acute and subacute toxicity tests of madder root, natural colorant extracted from madder (Rubia tinctorum), in (C57BL/6 X C3H)F1 mice.

    Science.gov (United States)

    Ino, N; Tanaka, T; Okumura, A; Morishita, Y; Makita, H; Kato, Y; Nakamura, M; Mori, H

    1995-01-01

    As part of the safety assessment of madder root (MR), a food colorant extracted from madder (Rubia tinctorum), toxicity tests were undertaken using (C57BL/6 x C3H)F1 mice of both sexes. An acute toxicity test was performed by 14-day administration of MR dissolved in distilled water by gavage at doses of 0, 500, 2000, 3500, and 5000 mg/kg body weight to groups of each sex. One male mouse dosed at 5000 mg/kg body weight was dead before the end of the study, indicating that the maximum tolerated dose of MR was between 3500 and 5000 mg/kg body weight. A subacute toxicity test of MR was performed using 62 mice of each sex, mixing their diets with MR at concentrations of 0, 0.3, 0.6, 1.25, 2.5, and 5% for 90 days. All mice tolerated these doses of MR well. The body weight gains of either sex were not affected by the treatment. None of the mice treated with MR showed clinical signs of toxicity. Histopathological examinations showed retention cysts of the kidneys and epidermal vaginal cysts in a few of the treated or control mice. No hyperplastic, preneoplastic, and neoplastic lesions and no pathological findings of toxicity were found. These results suggest that dietary exposure of MR at these doses has no acute or subacute toxic effects on mice.

  19. Antimicrobial evaluation, acute and sub-acute toxicity studies of Allium sativum

    Directory of Open Access Journals (Sweden)

    Bashir Lawal

    2016-07-01

    Conclusions: The extract caused selective changes in some biochemical parameters of organ function; however, since only mild alteration was observed at a dose of 300 mg/kg, the garlic bulb may be considered to be relatively safe and could be explored as an oral remedy at this dose.

  20. Sub-acute toxicity and biochemical effects of extracts of Anaphe ...

    African Journals Online (AJOL)

    Ataxia syndrome which is characterized by sudden onset of severe muscular tremor and gait ataxia has been shown to be associated with the consumption of the larvae of Anaphe venata in South Western part of Nigeria. In this report, the sub -acute toxicity and biochemical effects of polar and nonpolar extracts of Anaphe ...

  1. Oral acute toxicity study of selected botanical pesticide plants used ...

    African Journals Online (AJOL)

    Oral acute toxicity study of selected botanical pesticide plants used by subsistence farmers around the Lake Victoria Basin. M Kamatenesi-Mugisha, JP Buyungo, P Ogwal, A Kasibante, AL Deng, JO Ogendo, MJ Mihale ...

  2. Effects of SiC nanoparticles orally administered in a rat model: Biodistribution, toxicity and elemental composition changes in feces and organs

    Energy Technology Data Exchange (ETDEWEB)

    Lozano, Omar, E-mail: omar.lozanogarcia@fundp.ac.be [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Research Centre for the Physics of Matter and Radiation (PMR-LARN), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Laloy, Julie; Alpan, Lütfiye [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Mejia, Jorge [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Research Centre for the Physics of Matter and Radiation (PMR-LARN), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Rolin, Stéphanie [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Toussaint, Olivier [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Laboratory of Biochemistry and Cellular Biology (URBC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Dogné, Jean-Michel [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); and others

    2012-10-15

    Background: Silicon carbide (SiC) presents noteworthy properties as a material such as high hardness, thermal stability, and photoluminescent properties as a nanocrystal. However, there are very few studies in regard to the toxicological potential of SiC NPs. Objectives: To study the toxicity and biodistribution of silicon carbide (SiC) nanoparticles in an in vivo rat model after acute (24 h) and subacute (28 days) oral administrations. The acute doses were 0.5, 5, 50, 300 and 600 mg·kg{sup −1}, while the subacute doses were 0.5 and 50 mg·kg{sup −1}. Results: SiC biodistribution and elemental composition of feces and organs (liver, kidneys, and spleen) have been studied by Particle-Induced X-ray Emission (PIXE). SiC and other elements in feces excretion increased by the end of the subacute assessment. SiC did not accumulate in organs but some elemental composition modifications were observed after the acute assessment. Histopathological sections from organs (stomach, intestines, liver, and kidneys) indicate the absence of damage at all applied doses, in both assessments. A decrease in the concentration of urea in blood was found in the 50 mg·kg{sup −1} group from the subacute assessment. No alterations in the urine parameters (sodium, potassium, osmolarity) were found. Conclusion: This is the first study that assesses the toxicity, biodistribution, and composition changes in feces and organs of SiC nanoparticles in an in vivo rat model. SiC was excreted mostly in feces and low traces were retrieved in urine, indicating that SiC can cross the intestinal barrier. No sign of toxicity was however found after oral administration. -- Highlights: ► SiC nanoparticles were orally administered to rats in acute and subacute doses. ► SiC was found in low traces in urine. It is mostly excreted in feces within 5 days. ► SiC excretion rate, feces and organ elemental composition change with time. ► No morphological alteration were found on GI tract, liver, kidneys

  3. Subchronic oral toxicity studies with α-cyclodextrin in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The toxicity of α-cyclodextrin (α-CD), a cyclic polymer of six α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, more specifically a water-soluble dietary fiber, was examined in a 4-week range finding study and a 13-week oral toxicity study in rats. In the 4-week

  4. Oral toxicity of bacterial toxins against thrips species

    NARCIS (Netherlands)

    Gerritsen, L.J.M.; Visser, J.H.; Jongsma, M.A.

    2004-01-01

    The oral toxicity of excretion products of several Photorhabdus and Xenorhabdus strains was tested on two thrips species: Frankliniella occidentalis and Thrips tabaci. Out of 46 Photorhabdus isolates and 6 Xenorhabdus isolates only 6 North American P. temperata isolates were toxic to the thrips

  5. Potential fluoride toxicity from oral medicaments: A review

    Directory of Open Access Journals (Sweden)

    Rizwan Ullah

    2017-08-01

    Full Text Available The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

  6. Acute and subacute toxicity of copper sulfate pentahydrate (CuSO(4)5.H(2)O) in the guppy (Poecilia reticulata).

    Science.gov (United States)

    Park, Keehae; Heo, Gang-Joon

    2009-03-01

    Chemicals are used for treatment of aquatic diseases, but there is little data available about copper sulfate in small ornamental fish. The aim of the present study was to determine the TLm(24h) and evaluate the toxicity of copper sulfate in the guppy (Poecilia reticulata). The fish were subjected to an acute toxicity test for 24 hr, and the results showed a TLm(24h) value of 1.17 ppm. Severe hyperplasia and exfoliation of the epithelial cells of gill lamellae and obstruction of the internal cavities of renal tubules with necrotized renal epithelial cells sloughed from the basement membrane were observed. However, no significant changes, except for mild curling of gill lamellae, were found in a subacute toxicity test in which fish were exposed to 1/10 of the TLm(24h) value for 1 week. Therefore, use of less than 0.12 ppm of copper sulfate may be recommended as a therapeutic level.

  7. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hussin Muhammad

    2012-04-01

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

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

    Science.gov (United States)

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

    2012-04-10

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

  9. Masticatory function in subacute TMD patients before and after treatment.

    NARCIS (Netherlands)

    Pereira, L.J.; Steenks, M.H.; Wijer, A. de; Speksnijder, C.M.; Bilt, A. van der

    2009-01-01

    Masticatory function can be impaired in temporomandibular disorders (TMDs) patients. We investigated whether treatment of subacute non-specific TMD patients may influence oral function and clinical outcome measures. Fifteen patients with subacute TMD participated in the study. We quantified

  10. Anti-diabetic effects of Inonotus obliquus polysaccharides-chromium (III) complex in type 2 diabetic mice and its sub-acute toxicity evaluation in normal mice.

    Science.gov (United States)

    Wang, Cong; Chen, Zhongqin; Pan, Yuxiang; Gao, Xudong; Chen, Haixia

    2017-10-01

    Polysaccharides are important bioactive ingredients from Inonotus obliquus. This study aimed to synthesize and characterize a novel I. obliquus polysaccharides-chromium (III) complex (UIOPC) and investigate the anti-diabetic effects in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) mice and sub-acute toxicity in normal mice. The molecular weight of UIOPC was about 11.5 × 10 4 Da with the chromium content was 13.01% and the chromium was linked with polysaccharides through coordination bond. After treatment of UIOPC for four weeks, the body weight, fasting blood glucose (FBG) levels, plasma insulin levels of the diabetic mice were significantly reduced when compared with those of the diabetic mice (p < 0.05). The results on serum profiles and antioxidant enzymes activities revealed that UIOPC had a positive effect on hypoglycemic and antioxidant ability. Histopathology results showed that UIOPC could effectively alleviate the STZ-lesioned tissues in diabetic mice. Furthermore, high dose administration of UIOPC had no obviously influence on serum profiles levels and antioxidant ability of the normal mice and the organ tissues maintained organized and integrity in the sub-acute toxicity study. These results suggested that UIOPC might be a good candidate for the functional food or pharmaceuticals in the treatment of T2DM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    McFarland, Craig A., E-mail: craig.a.mcfarland@us.army.mi [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Quinn, Michael J. [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Boyce, John [Biotechnics, LLC, Hillsborough, NC 27278 (United States); LaFiandra, Emily M.; Bazar, Matthew A. [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Talent, Larry G. [Oklahoma State University, Department of Natural Resource Ecology and Management, Stillwater, OK 74078 (United States); Johnson, Mark S. [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States)

    2011-02-15

    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{sub 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. - Research highlights: Oral LD{sub 50} (mg/kg) values were 1406 for male and 1867 for female lizards. Dose-dependent hepatocellular transdifferentiation was observed at {>=}5 mg/kg-d. Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

  12. Oral Exposure and Absorption of Toxicants

    Science.gov (United States)

    This chapter provides an overview of the toxicokinetics of orally absorbed xenobiotics. This includes a description of the basic anatomy and physiology of the digestive tract most relevant to the absorption process. In addition, differences in anatomy and physiology between human...

  13. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  14. Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam. Merr. in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Muhammad Kifayatullah

    2015-10-01

    Conclusions: The result indicates that the oral administration of Pericampylus glaucus (Lam. Merr. extract did not produce any significant toxic effect in BALB/c mice. Hence, the extract can be utilized safely for therapeutic use in pharmaceutical formulations.

  15. Preliminary Investigation Into The Acute Oral Toxicity Of Tephrosia ...

    African Journals Online (AJOL)

    An investigation was carried out on the acute toxicity of the crude methanolic leaf extract of Tephrosia vogelii Hook. f. (Fabaceae) in mice following oral administration of the extract at doses ranging from 10 to 10,000 mg per kg body weight. Propylene glycol was used as vehicle of administration. Clinical signs observed ...

  16. Oral acute toxicity study of selected botanical pesticide plants used ...

    African Journals Online (AJOL)

    aghomotsegin

    Key words: Oral acute toxicity, biopesticide, plant extracts, Lake Victoria Basin. ... Asia in the upland forest areas and open waste areas. It is used .... freeze like water. The essential oils were kept in a fridge so as to minimize their volatile behavior which is catalyzed by relatively high temperature including room temperature.

  17. Acute oral toxicity test and phytochemistry of some west african ...

    African Journals Online (AJOL)

    Background: Although there is increased acceptance and utilization of medicinal plants worldwide, many are used indiscriminately without recourse to any safety test. Thus, the need for toxicity tests to determine the safe dose for oral consumption. Objective: LD and phytochemistry of four medicinal plants 50 of West Africa ...

  18. Oral acute toxicity study of selected botanical pesticide plants used ...

    African Journals Online (AJOL)

    aghomotsegin

    used plants were identified and selected for biosafety assessments namely: Ocimum gratissimum,. Tithonia diversifolia, Eucalyptus ... Key words: Oral acute toxicity, biopesticide, plant extracts, Lake Victoria Basin. INTRODUCTION. There is a ..... breathing (hyperventilation), excess loss of saliva. (salivation) and death of ...

  19. Experimental oral lead toxicity in young dogs

    Energy Technology Data Exchange (ETDEWEB)

    Stowe, H.D.; Goyer, R.A.; Krigman, M.M.; Wilson, M.; Cates, M.

    1973-02-01

    Litter-mate male pups were fed a calcium-and-phosphorus-low purified diet with and without 100 ppm of lead as lead acetate from age 6 to 18 weeks. Lead-toxic dogs exhibited cyclic but terminally severe anorexia and cachexia, significant anemia, normoblastocytosis and leukopenia within six weeks, hypoproteinemia, decreased serum albumin, ..cap alpha../sub 1/-globulin, ..beta../sub 2/-globulin, alkaline phosphatase and lactic dehydrogenase 1, elevated serum glutamic oxaloacetic and pyruvic transaminases, delayed closure of the thoracic vertebral epiphyses, lead lines in the distal radii and thoracic spinous processes, enlargement of liver, kidney, and brain, hepatic fatty metamorphosis, focal proximal renal tubular necrosis, hydropic degeneration of spermatognia, and lead inclusion body formation. Approximately 97% of the tissue lead was estimated to be skeletal; the greatest concentration of lead in the brain was found in the occipital gray matter.

  20. Acute and subacute toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the shallow-water coral Porites divaricata: Application of a novel exposure protocol.

    Science.gov (United States)

    Renegar, D Abigail; Turner, Nicholas R; Riegl, Bernhard M; Dodge, Richard E; Knap, Anthony H; Schuler, Paul A

    2017-01-01

    Previous research evaluating hydrocarbon toxicity to corals and coral reefs has generally focused on community-level effects, and results often are not comparable between studies because of variability in hydrocarbon exposure characterization and evaluation of coral health and mortality during exposure. Toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the coral Porites divaricata was assessed in a constant exposure toxicity test utilizing a novel toxicity testing protocol uniquely applicable to shallow-water corals, which considered multiple assessment metrics and evaluated the potential for post-exposure mortality and/or recovery. Acute and subacute effects (gross morphological changes, photosynthetic efficiency, mortality, and histologic cellular changes) were evaluated during pre-exposure (4 wk), exposure (48 h), and post-exposure recovery (4 wk) periods. Coral condition scores were used to determine a 48-h median effective concentration of 7442 μg/L. Significant physical and histological changes resulted from exposure to 640 μg/L and 5427 μg/L 1-methylnaphthalene, with a 1-d to 3-d delay in photosynthetic efficiency effects (ΔF/Fm). Pigmented granular amoebocyte area was found to be a potentially useful sublethal endpoint for this species. Coral mortality was used to estimate a 48-h median lethal concentration of 12 123 μg/L. Environ Toxicol Chem 2017;36:212-219. © 2016 SETAC. © 2016 SETAC.

  1. European medicinal and edible plants associated with subacute and chronic toxicity part I: Plants with carcinogenic, teratogenic and endocrine-disrupting effects.

    Science.gov (United States)

    Kristanc, Luka; Kreft, Samo

    2016-06-01

    In recent decades, the use of herbal medicines and food products has been widely embraced in many developed countries. These products are generally highly accepted by consumers who often believe that "natural" equals "safe". This is, however, an oversimplification because several botanicals have been found to contain toxic compounds in concentrations harmful to human health. Acutely toxic plants are in most cases already recognised as dangerous as a result of their traditional use, but plants with subacute and chronic toxicity are difficult or even impossible to detect by traditional use or by clinical research studies. In this review, we systematically address major issues including the carcinogenicity, teratogenicity and endocrine-disrupting effects associated with the use of herbal preparations with a strong focus on plant species that either grow natively or are cultivated in Europe. The basic information regarding the molecular mechanisms of the individual subtypes of plant-induced non-acute toxicity is given, which is followed by a discussion of the pathophysiological and clinical characteristics. We describe the genotoxic and carcinogenic effects of alkenylbenzenes, pyrrolizidine alkaloids and bracken fern ptaquiloside, the teratogenicity issues regarding anthraquinone glycosides and specific alkaloids, and discuss the human health concerns regarding the phytoestrogens and licorice consumption in detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Wuen Yew Teoh

    2013-01-01

    Full Text Available 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.

  3. Safety Assessment of Lactobacillus helveticus KLDS1.8701 Based on Whole Genome Sequencing and Oral Toxicity Studies.

    Science.gov (United States)

    Li, Bailiang; Jin, Da; Etareri Evivie, Smith; Li, Na; Yan, Fenfen; Zhao, Li; Liu, Fei; Huo, Guicheng

    2017-09-24

    Lactobacillus helveticus KLDS1.8701 isolated from Chinese traditional fermented dairy product has been shown earlier to possess probiotic potentials but it is important to evaluate its safety in view of its possible use as a probiotic. The aim of the present study is to critically assess the safety of L. helveticus KLDS1.8701 through multiple perspectives. The complete genome of L. helveticus KLDS1.8701 was sequenced to mine for safety-associated genes. The minimum inhibitory concentrations of 15 antimicrobials and the adverse metabolites were determined. Standard acute oral and subacute toxicity studies were conducted in rats. The results in silico disclosed that the genome of L. helveticus KLDS1.8701 carries no transferable antibiotic resistance genes, no virulence factors and only 3 genes related to adverse metabolites. In vitro results showed that L. helveticus KLDS1.8701 was resistant against 6 antimicrobials and did not raise safety concerns about biogenic amine, D-lactic acid and nitroreductase. The results in vivo revealed that no adverse effects on experimental rats were observed in the oral toxicity tests. Overall, findings from this study suggest that L. helveticus KLDS1.8701 is safe and can be used as a potential probiotic for human consumption.

  4. Determination of acute toxicity and the effects of sub-acute concentrations of CuO nanoparticles on blood parameters in Rutilus rutilus

    Directory of Open Access Journals (Sweden)

    Abdolreza Jahanbakhshi

    2015-07-01

    Full Text Available Objective(s:Copper oxidenanoparticles have different industrial applications so it is inevitable that nanoparticulate products finally find their way into aquatic ecosystems. Nevertheless there is little information available about their effects on some of edible fish. The present study aims to determine the acute toxicity and evaluate the effect of two sub-acute concentrations (50 and 70% 96 h LC50 of CuO-NPs on some hematological and biochemical parameters of R. rutilus. Materials and Methods:225 healthy specimen of R. rutilus (mean weight 5.52±1.2 g; mean length 6.20±0.2 cm were transported to the laboratory. In order to prepare the stock solution, CuO-NPs was dispersed in pure water with ultrasonication (50-60 kHz for 15 min every day before dosing. At first, R. rutilus was exposed to CuO-NPs to determine the lethal concentration (LC50 value. Following acute test, fish were treated with sub-acute concentrations of CuO-NPs (50 and 70% 96 h-LC50 at with one control group (no CuO-NPs for a week to determine the changes in the level of some plasma hematological and biochemical parameters. Results:The 96 h-LC50 values of CuO-NPs was 2.19±0.003 mg/l. R. rutilus exhibited significantly lower RBC count, Hb and Hct values and a significant increase in the WBC numbers, MCH, MCHC and MCV indices (p

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

    Science.gov (United States)

    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.

  6. Large Dataset of Acute Oral Toxicity Data Created for Testing ...

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are being developed due to animal welfare and resource considerations. We compiled a large dataset of oral rat LD50 values to assess the predictive performance currently available in silico models. Our dataset combines LD50 values from five different sources: literature data provided by The Dow Chemical Company, REACH data from eChemportal, HSDB (Hazardous Substances Data Bank), RTECS data from Leadscope, and the training set underpinning TEST (Toxicity Estimation Software Tool). Combined these data sources yield 33848 chemical-LD50 pairs (data points), with 23475 unique data points covering 16439 compounds. The entire dataset was loaded into a chemical properties database. All of the compounds were registered in DSSTox and 59.5% have publically available structures. Compounds without a structure in DSSTox are currently having their structures registered. The structural data will be used to evaluate the predictive performance and applicable chemical domains of three QSAR models (TIMES, PROTOX, and TEST). Future work will combine the dataset with information from ToxCast assays, and using random forest modeling, assess whether ToxCast assays are useful in predicting acute oral toxicity. Pre

  7. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    National Research Council Canada - National Science Library

    Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

    2014-01-01

    Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation...

  8. 35__200 - 204__Musa - Toxicity

    African Journals Online (AJOL)

    User

    ABSTRACT. Sub-acute toxicity profile of Rheumatic Tea Formula (RTF), a polyherbal tea consisting of Salix alba, Eucalyptus globulus and Albizia chevalieri was investigated in wistar rats of both sexes. Wistar rats were orally administered three different doses of ethanol extract of RTF for 28 days after which the effect on ...

  9. Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment.

    Science.gov (United States)

    Máté, Zsuzsanna; Horváth, Edina; Kozma, Gábor; Simon, Tímea; Kónya, Zoltán; Paulik, Edit; Papp, András; Szabó, Andrea

    2016-05-01

    Incomplete information on toxicological differences of micro- and nanometer-sized particles raised concerns about the effects of the latter on health and environment. Besides chemical composition, size and surface-to-volume ratio of nanoparticles (NPs) can affect toxicity. To investigate size-dependent toxicity differences, we used particles made of dioxide of the neurotoxic heavy metal manganese (Mn), typically found in inhaled metal fumes, in three size ranges (size A, 9.14 ± 1.98 nm; size B, 42.36 ± 8.06 nm; size C, 118.31 ± 25.37 nm). For modeling the most frequent route of exposure to Mn, NPs were given to rats for 6 weeks by intratracheal instillation. Of each NP size, 3 or 6 mg/kg body weight was given while control animals were vehicle treated. Neurotoxicity was assessed by measuring spontaneous locomotor activity in an open field and by recording spontaneous and evoked electrical activity from the somatosensory cortical area. Mn content of brain, lung, and blood, measured by ICP-MS, were correlated to the observed functional alterations to see the relationship between Mn load and toxic effects. Body weight gain and organ weights were measured as general toxicological indices. The toxicity of size A and size B NPs proved to be stronger compared to size C NPs, seen most clearly in decreased body weight gain and altered spontaneous cortical activity, which were also well correlated to the internal Mn dose. Our results showed strong effect of size on NP toxicity, thus, beyond inappropriateness of toxicity data of micrometer-sized particles in evaluation of NP exposure, differentiation within the nano range may be necessary.

  10. Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Stoeger, Tobias; van den Brule, Sybille

    2015-01-01

    .5 and 25μg on a range of parameters. However, mice that survived a high dose (50μg; 2.7mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results......Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were...... prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100μg; ≥1.4mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6μg; ≥0.3mg/kg) elicited acute toxicity in terms of reduced weight gain...

  11. Acute and Subacute Inhalation Toxicity Study in Rats Exposed to Pyrotechnically-Disseminated M18 Red Smoke

    Science.gov (United States)

    2017-04-12

    Command USEPA: United States Environmental Protection Agency VMD: Veterinary Medicine Division I. NON-TECHNICAL SYNOPSIS The inhalation toxicity of a...staff will provide the Veterinary Medicine Office a current emergency contact roster. In an emergency, the animal care staff will phone the numbers...uniquely identified by number via cage card and tail marking. (CD® is a registered trademark of Charles River Laboratories International , Inc.; Teklad® and

  12. Epstein-Barr virus (HHV-4) inoculation to rabbits by intranasal and oral routes results in subacute and/or persistent infection dissimilar to human disease.

    Science.gov (United States)

    Rajčáni, Julius; Szenthe, Kalman; Durmanová, Vladimira; Tóth, Agnes; Asványi, Balazs; Pitlik, Ervin; Stipkovits, Laszlo; Szathmary, Susan

    2014-01-01

    We report the infection of New Zealand white rabbits with Epstein-Barr virus (EBV). EBV prepared in B95-8 (producer) cells was inoculated to rabbits by combined intranasal and oral routes. Blood and white blood cell (WBC) samples were taken before infection, then on days 8, 28 and 98 post-infection (p.i.). Administration of either 3 × 10(8) (group A, 11 rabbits) or 1 × 10(9) (group B, 10 rabbits) EBV DNA copies per animal induced subacute and/or persistent infection. The IgG antibodies in plasma were detected by ELISA as well as by immunoblot (IB). The IB bands showed mainly antibodies to the BZRF1/Zta transactivation polypeptide (69.2%), the p54 early protein (53.4%) and to the p23 capsid protein (35.8%). No anti-EBNA1 antibody was detected throughout. Viral DNA could be detected by PCR in WBCs and/or spleen of 7 out of 21 infected rabbits (30%), while 60-80% of them showed serologic response. The transiently present EBV DNA was accompanied by LMP1 antigen. Rabbits developed persistent EBV infection in the absence of EBNA1 antibodies and by the lack of typical infectious mononucleosis-like syndrome. The absence of EBNA1 antibody may reflect the lack of EBNA1 in B cells of EBV-inoculated rabbits. © 2014 S. Karger AG, Basel

  13. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  14. Can TiC nanoparticles produce toxicity in oral administration to rats?

    Directory of Open Access Journals (Sweden)

    Julie Laloy

    2014-01-01

    Conclusion: No sign of toxicity was found after oral administration. TiC was excreted mostly in feces producing mineral absorption alterations. Low traces were retrieved in urine, indicating that TiC can cross the intestinal barrier.

  15. Acute and subacute toxicity tests of onion coat, natural colorant extracted from onion (Allium cepa L.), in (C57BL/6 x C3H)F1 mice.

    Science.gov (United States)

    Kojima, T; Tanaka, T; Mori, H; Kato, Y; Nakamura, M

    1993-01-01

    The toxicity test of onion coat colorant (OC), a food colorant extracted from onion (Allium cepa L.), was undertaken using (C57BL/6 x C3H)F1 mice of both sexes for the safety assessment of this product. The acute toxicity test was performed by administration of OC suspended in corn oil by gavage at doses of 2500, 5000, 7500, and 10,000 mg/kg body weight to groups of 5 or 6 males and 6 or 7 females, maintained for 14 d. Six of 12 females dosed at 10,000 mg/kg body weight and 3 of 11 females dosed at 7500 mg/kg body weight were dead before the end of the study, indicating that the tolerated dose of OC was between 7500 and 5000 mg/kg body weight. The subacute toxicity test of OC was examined using 123 mice of both sexes (62 males and 61 females) by feeding a diet mixed with OC at concentrations of 5, 2.5, 1.25, 0.6, and 0.3% for 90 d. All mice tolerated these doses of OC well. The body weight gains of male and female mice were not affected by the treatment. Histopathological examinations showed that hyperplastic changes in the esophagus, forestomach, pancreas, cervix, and endometrium of mice were found in treated and control mice. However, their incidences were not related to the dose of OC. Moreover, only a spontaneous ovarian teratoma was found in an OC-treated mouse. These results suggest that OC has no acute and subacute toxic effects in mice.

  16. [The role of an information booklet or oral information about back pain in reducing disability and fear-avoidance beliefs among patients with subacute and chronic low back pain. A randomized controlled trial in a rehabilitation unit].

    Science.gov (United States)

    Coudeyre, E; Givron, P; Vanbiervliet, W; Benaïm, C; Hérisson, C; Pelissier, J; Poiraudeau, S

    2006-11-01

    To compare the efficacy of an information booklet or oral information about back pain in reducing disability and fear-avoidance beliefs among patients with subacute and chronic low back pain referred to a rehabilitation department. An alternate-month design was used for 142 patients with subacute or chronic low back pain who were hospitalized for treatment. Seventy-two patients received written standardized information about back pain (the "back book") and usual physical therapy (intervention group), and 70 received usual physical therapy only along with nonstandardized oral information (control group). The main outcome measure was disability (measured on the Quebec back-pain disability scale), and secondary outcome measures were pain intensity (measured on a visual analog scale), fear-avoidance beliefs (measured on the Fear-Avoidance Beliefs Questionnaire [FABQ] Physical component), and knowledge of the relation of back pain to physical activity assessed at baseline, just before discharge from the hospital and 3 months after discharge. Satisfaction related to the information received was assessed on the day of discharge. Receiving the "back book" had a significant impact on disability at 3 months, from 48.40+/-14.55 to 34.57+/-18.42 in the intervention group and from 52.17+/-16.88 to 42.40+/-14.95 in the control group (p=0.03). Receipt of the book also had a significant impact on patients' knowledge and satisfaction about information but a nonsignificant effect on fear-avoidance beliefs. Providing an information booklet about back pain to patients with subacute and chronic low back pain referred to a rehabilitation unit contributes to reduced disability in these patients.

  17. Oral and Topical Toxicity of Fipronil to Melon Fly and Oriental Fruit Fly (Diptera: Tephritidae)

    Science.gov (United States)

    BACKGROUND: The objective of this study was to develop basic oral and topical toxicity data for Fipronil in Solulys protein bait to wild melon fly, Bactrocera cucurbitae (Coquillett) and the oriental fruit fly, Bactrocera dorsalis (Hendel). RESULTS: For the oral study, both females and males were ...

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

    Science.gov (United States)

    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 americana is safe on sub-acute basis but extremely high doses may not be advisable.

  19. Acute oral toxicity and cytotoxicological evaluation of the ethanol ...

    African Journals Online (AJOL)

    Acute toxicity and cytotoxicity of ethanol extract of Samanea tubulosa (EESt) pods were evaluated in Swiss mice. Acute toxicity studies were conducted based on OECD guidelines 420, where the limit test dose was 5000 mg/kg. Observation was made and recorded systemically for 1, 2, 4 and 24 h after the administration of ...

  20. Sacha Inchi (Plukenetia volubilis L. powder: acute toxicity, 90 days oral toxicity study and micronucleus assay in rodents

    Directory of Open Access Journals (Sweden)

    Idania Rodeiro

    2018-02-01

    Full Text Available Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied. Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L. Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5% used. Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice. Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.

  1. Acute Oral Toxicity (LD(50)) of CHF1 in Rats.

    Science.gov (United States)

    1982-04-01

    submitted by SRI International, the U.S. Department of Agriculture (USDA) , and private industry, against a variety of mosquitoes , sand flies, fleas...required for registration of a new insect repellent are prescribed by the Environmental Protection Agency ( EPA ). The basic animal toxicity tests required...0.5 t 5.0 gm /kg)(2). For this reason CHF1 is best classified as "slightly toxic." The slope of the dose response curve was greater for female rats

  2. Evaluation of toxicity profile of leaf base extract of Sorghum bicolor ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-01-19

    Jan 19, 2009 ... acute and sub-acute toxicity effects of mature dry leaf base of S. bicolor to ... The test routes were both intraperitoneal and oral. The administration of the extract in both rats and mice was done in phases. The first phase involved the administration of widely differing ..... Ethanol-induced gastric lesions in rats.

  3. Toxicity of Bromkal 70-5DE, a technical mixture of polybrominated diphenyl ethers, following 28 d of oral exposure in rats and impact of analysed impurities.

    Science.gov (United States)

    Oberg, Mattias; Westerholm, Emma; Fattore, Elena; Stern, Natalia; Hanberg, Annika; Haglund, Peter; Wiberg, Karin; Bergendorff, Anders; Håkansson, Helen

    2010-06-01

    The subacute toxicity of a commercial polybrominated diphenyl ether (PBDE) preparation, Bromkal 70-5DE, was investigated. In addition to a vehicle control, the mixture was given orally to male and female Sprague-Dawley rats for 28 d at three dose levels; 2.5, 25 and 250 mg kg(-1) b.w.d(-1). The observed effects include increased hepatic EROD activity (from 2.5 mg kg(-1)d(-1)); increased liver weight (males), increased PROD activity and depletion of hepatic retinoids (from 25 mg kg(-1)d(-1)); and increased liver weight (females), marked histological changes in the liver and lungs, as well as increased serum parameters such as total protein, cholesterol and albumin (from 250 mg kg(-1)d(-1)). Chemical analysis of the PBDE mixture with gas chromatography/mass spectrometry (GS/MS) showed impurities of polybrominated dibenzofurans and to a lesser extent dibenzodioxins, in total levels of about 7.0 microg g(-1) of Bromkal technical mixture. The animals were thereby exposed to an estimated dose of dioxin-like equivalents corresponding to 1.3-131 ng TEQ kg(-1) b.w.d(-1). It cannot be ruled out that this level of impurities can explain the hepatic EROD induction and hepatic retinoid depletion, which are considered typical markers of toxicity mediated via the aryl hydrocarbon receptor (AhR). Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  4. Oral bioaccessibility of potentially toxic elements (PTEs) in urban ...

    African Journals Online (AJOL)

    A literature survey has shown that no study has investigated the oral bioaccessibility of PTEs in Nigeria dusts. Studies on human health risk of PTEs from urban Nigeria dust have been based only on total elemental concentrations. Whilst this protocol is useful in assessing human health of PTEs, it could lead to an over ...

  5. Oral Toxicity Studies of Hydroalcohol Leaf Extract of Ageratum ...

    African Journals Online (AJOL)

    Erah

    Bordeaux, France. Abstract. Purpose: Ageratum conyzoides is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. The objective of this study was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats.

  6. Oral Toxicity of Agro-Fungicides: Tilt (Propiconazole), Bayleton ...

    African Journals Online (AJOL)

    Introduction: The hazard use of pesticides, emergence of many diseases with high prevalence e.g (cancer, kidney failure and hepatic problems) urged the need for research on fungicides which are continuously received by human in Sudan via fruit and vegetables. Objective: To detect the toxicity of these fungicides in ...

  7. Acute and Subchronic Oral Toxicity Assessment of the Ethanolic ...

    African Journals Online (AJOL)

    oil from turmeric (Curcuma longa L.). Food Chem. Toxicol 2013; 53: 52–61. 20. Saravanan N, Nalini N. Hemidesmus indicus protects against ethanol-induced liver toxicity. Cell Mol Biol. Lett 2008; 13: 20–37. 21. Ramaiah SK. Preclinical safety assessment: Current gaps, challenges, and approaches in identifying translatable ...

  8. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Science.gov (United States)

    2010-07-01

    ... mg/kg.) If compound-related mortality is produced in the limit test, further study may need to be... sufficient to produce a dose-response curve and permit an acceptable estimation of the LD50. Range finding... death after dosing. (iv) Dose-response curves for mortality and other toxic effects (when permitted by...

  9. Acute oral toxicity and cytotoxicological evaluation of the ethanol ...

    African Journals Online (AJOL)

    Lucas Nicolau

    2015-02-02

    Feb 2, 2015 ... Acute toxicity studies were conducted based on OECD guidelines 420, where the limit test dose was 5000 mg/kg. Observation was made and recorded systemically for 1, 2, 4 and 24 h after the administration of dose for skin changes, morbidity, aggression and sensitivity of the behavior of the animals.

  10. Acute and Subchronic Oral Toxicity Assessment of the Ethanolic ...

    African Journals Online (AJOL)

    Purpose: To investigate the toxicological profile of the ethanol extract of Oncoba spinosa (EEOS) after acute and sub-chronic administration to rodents. Methods: In the acute toxicity study, a single administration of the extract at doses of 2000 and 5000 mg/kg, respectively, was given to the mice. Mice were observed for ...

  11. Charge Affects the Oral Toxicity of Poly(amido amine) Dendrimers

    Science.gov (United States)

    Thiagarajan, Giridhar; Greish, Khaled; Ghandehari, Hamidreza

    2013-01-01

    Poly(amido amine) (PAMAM) dendrimers have been evaluated for the influence of surface functionality and size on the epithelial barrier of the gut with the goal of identifying safe carriers that can be used for oral drug delivery. Limited studies are conducted to date however to assess the toxicity of PAMAM dendrimers in vivo when administered by the oral route. The goal of this research was to conduct an oral acute toxicity study of PAMAM dendrimers as a function of size and charge in immune competent CD-1 mice. Maximum tolerated doses (MTD) of PAMAM dendrimers as a function of size and surface functionality were established and clinical signs of toxicity monitored. Results demonstrate that positively charged dendrimers caused more toxicity whereas their anionic counterparts were tolerated at ten times higher doses. Severe signs of toxicity observed for large (G7) cationic amine- or hydroxyl-terminated dendrimers include hemobilia and spleenomegaly. The MTD for these dendrimers ranged from 30mg/kg to 200mg/kg. Anionic G6.5 or smaller molecular weight carboxyl-, amine- or hydroxyl-terminated dendrimers (G3.5-COOH, G4-NH2, G4-OH) on the other hand were tolerated at doses of upto 500mg/kg (300mg/kg in some cases) with minimal or no signs of toxicity. Establishing the MTD of orally delivered PAMAM dendrimers and the influence of surface functionality and size on toxicity, aids in the rational design of PAMAM-drug conjugates for oral drug delivery applications. PMID:23419816

  12. Brine shrimp lethality and acute oral toxicity studies on Swietenia mahagoni (Linn.) Jacq. seed methanolic extract

    Science.gov (United States)

    Sahgal, Geethaa; Ramanathan, Surash; Sasidharan, Sreenivasan; Mordi, Mohd. Nizam; Ismail, Sabariah; Mansor, Sharif Mahsufi

    2010-01-01

    Background: The seeds of Swietenia mahagoni have been applied in folk medicine for the treatment of hypertension, diabetes, malaria, amoebiasis, cough, chest pain, and intestinal parasitism. Here we are the first to report on the toxicity of the Swietenia mahagoni crude methanolic (SMCM) seed extract. Methods: SMCM seed extract has been studied for its brine shrimp lethality and acute oral toxicity, in mice. Results: The brine shrimp lethality bioassay shows a moderate cytotoxicity at high concentration. The LC50 for the extract is 0.68 mg/ml at 24 hours of exposure. The LD50 of the SMCM seed extract for acute oral toxicity in mice is greater than 5000 mg/kg. Conclusion: This study demonstrates that Swietenia mahagoni crude methanolic seed extract may contain bioactive compounds of potential therapeutic significance which are relatively safe from toxic effects, and can compromise the medicinal use of this plant in folk medicine. PMID:21808570

  13. Effects of Oral Administration of Aloe Vera Plus on the Heart and ...

    African Journals Online (AJOL)

    Alasia Datonye

    Effects of Oral Administration of Aloe Vera Plus on the Heart and Kidney: A Subacute Toxicity Study in Rat Models. O.C. Koroye* I.M. Siminialayi ** E.N. Etebu *. *Federal Medical Center, Yenagoa, Bayelsa State and **Department of Pharmacology, College of Health Sciences, University of Port Harcourt. ABSTRACT.

  14. The Acute Oral Toxicity of Commonly Used Pesticides in Iran, to Honeybees (Apis Mellifera Meda

    Directory of Open Access Journals (Sweden)

    Rasuli Farhang

    2015-06-01

    Full Text Available The honey bee is credited with approximately 85% of the pollinating activity necessary to supply about one-third of the world’s food supply. Well over 50 major crops depend on these insects for pollination. The crops produce more abundantly when honey bees are plentiful. Worker bees are the ones primarily affected by pesticides. Poisoning symptoms can vary depending on the developmental stage of the individual bee, and the kind of chemical employed. The oral toxicity of these insecticides: (phosalone and pirimicarb, acaricide (propargite, insecticide and acaricide (fenpropathrin, fungicides, and bactericides (copper oxychloride and the Bordeaux mixture, were evaluated for the purposes of this research. The results showed that fenpropathrin had high acute oral toxicity (LC50-24h and LC50-48 were 0.54 and 0.3 ppm, respectively. Propargite had 7785 ppm (active ingredient for LC50-24h and 6736 ppm (active ingredient for LC50-48h in honeybees and is therefore, non-toxic to Apis mellifera. On the other hand, copper oxychloride had minimum acute oral toxicity to honeybees (LC50-24h and LC50-48 were 4591.5 and 5407.9 ppm, respectively and was therefore considered non-toxic. Also, the Bordeaux mixture was safe to use around honeybees. Phosalone and primicarb were considered highly and moderately toxic to honeybees, respectively.

  15. Toxicidad aguda oral de la o-vainillina Acute oral toxicity of o-vanillin

    Directory of Open Access Journals (Sweden)

    Yamisleydi Alonso Moreno

    2008-04-01

    Full Text Available El 2-hidroxi-3-metoxibenzaldehído (o-vainillina posee una probada actividad anti sickling y una baja actividad hemolítica sobre hematíes SS y normales, por lo que puede ser eficaz en el tratamiento de la anemia drepanocítica, enfermedad genética de alta prevalencia a nivel global. En este sentido se desarrolló un estudio de toxicidad aguda oral, con el objetivo de determinar sus efectos adversos. Se administró una dosis de 2 000 mg/kg de peso corporal a un grupo de ratas (3 hembras y 3 machos y el vehículo a otro grupo utilizado como control. Los animales se mantuvieron en observación durante 14 días, se determinaron las variaciones de peso, la presencia o no de síntomas y signos clínicos, y la necropsia al finalizar el estudio. Como resultado no se observó disminución del peso corporal en ninguno de los grupos experimentales, presentaron síntomas como: piloerección, respiración acelerada, actividad disminuida, acicalamiento, aislamiento a la esquina de la caja y la muerte de un animal. El análisis macroscópico de los órganos no detectó variación alguna. La DL50 de la o-vainillina se encuentra por encima de 2 000 mg/kg de peso corporal, según el sistema global armonizado2-hydroxy-3-methoxybenzaldehyde (o-vanillin has a proven anitsickling activity and a low haemolytic activity on SS and normal red corpuscles, so it may be efficient in the treatment of drepanocytic anemia, a genetic disease of high prevalence at the world level. In this sense, an acute oral toxicity study was conducted aimed at determining its adverse effects. A dose of 2 000 mg/kg of body weight was administered to a group of rats (3 females and 3 males, where the vehicle was given to the control group. The animals were observed for 14 days. The variations of weight, the presence or not of symptoms and clinical signs, and the necropsy at the end of the study were determined. Body weight reduction was not observed in any of the experimental groups. They

  16. Effects of extracts of toxic fescue given orally to rats.

    OpenAIRE

    Daniels, L B; Nelson, T S; Beasley, J. N.

    1981-01-01

    Fresh fescue (Festuca arundinacea) was obtained from farms where toxicity was encountered in cattle grazing the fescue. The fescue was dried in a forced draft oven at 60 degrees C and then ground. The dry ground fescue was extracted with ether and then re-extracted with either 1% sodium bicarbonate (NaHCO3), sodium hydroxide or hydrochloric acid. The residual ether was evaporated and the residue resuspended in ethyl alcohol diluted with water 1% (control) and 1 mL of the above extracts of fes...

  17. Oral glucose loading for detection of mitochondrial toxicity during HAART in HIV-infected patients.

    NARCIS (Netherlands)

    Hofstede, H.J.M. ter; Borm, G.F.; Koopmans, P.P.

    2007-01-01

    Nucleoside reverse transcriptase inhibitors used in antiretroviral therapy may cause mitochondrial toxicity. Mitochondrial dysfunction leads to disturbance of the glucose metabolism, resulting in an accumulation of L-lactate. We tested the hypothesis that an oral glucose tolerance test (OGTT) can be

  18. Acute and sub-chronic oral toxicity studies of methanol extract of ...

    African Journals Online (AJOL)

    Acute and sub-chronic oral toxicity studies of methanol extract of Clinacanthus nutans in mice. Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Norhafizah Mohtarrudin, Arifah Abdul Kadir, Manraj Singh Cheema, Zuraini Ahmad, Ching Siew Mooi, Siti Farah Md. Tohid ...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 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. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zakiah Ismail

    2014-01-01

    Full Text Available The subchronic toxicity effect of the leaf extract of Carica papaya Linn. in Sprague Dawley (SD rats was investigated in this study. The extract was prepared by dissolving the freeze dried extract of the leaves in distilled water and was administered orally to SD rats (consisted of 10 rats/sex/group at 0 (control, 0.01, 0.14, and 2 g/kg body weight (BW for 13 weeks. General observation, mortality, and food and water intake were monitored throughout the experimental period. Hematological and biochemical parameters, relative organ weights, and histopathological changes were evaluated. The study showed that leaf extract when administered for 13 weeks did not cause any mortality and abnormalities of behavior or changes in body weight as well as food and water intake. There were no significant differences observed in hematology parameters between treatment and control groups; however significant differences were seen in biochemistry values, for example, LDH, creatinine, total protein, and albumin. However, these changes were not associated with histopathological changes. In conclusion, the results suggested that daily oral administration of rats with C. papaya leaf extract for 13 weeks at a dose up to fourteen times the levels employed in traditional medicine practice did not cause any significant toxic effect.

  2. Quantum chemistry based quantitative structure-activity relationships for modeling the (sub)acute toxicity of substituted mononitrobenzenes in aquatic systems

    NARCIS (Netherlands)

    Zvinavashe, E.; Murk, A.J.; Vervoort, J.; Soffers, A.E.M.F.; Freidig, A.; Rietjens, I.M.C.M.

    2006-01-01

    Fifteen experimental literature data sets on the acute toxicity of substituted nitrobenzenes to algae (Scenedesmus obliquus, Chlorella pyrenoidosa, C. vulgaris), daphnids (Daphnia magna, D. carinata), fish (Cyprinus carpio, Poecilia reticulata), protozoa (Tetrahymena pyriformis), bacteria

  3. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

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

    Science.gov (United States)

    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

  5. One Year Oral Toxicity Study of WR238605 Succinate in Dogs. Volume 1

    Science.gov (United States)

    1997-07-18

    and Mead, D.C. Clin. Chem. 20, 586, 1974. Haptoelobin Antigen- antibody method Ciba-Corning 550 Express Clinical Chemistry System Atlantic... Antibodies Test Kit B-4 ’ £• ET •^ !• Tk ir\\. a f HEMATOLOGY Ervthrocyte Count Electronic counting procedure SysmexKlOOO Hematology Analyzer...100X C-19 ONE YEAR ORAL TOXICITY STUDY OF WR23 8605 SUCCINATE IN DOGS 1 Shf INCIDENCE OF OBSERVATIONS SEX: MALE STUDY: 219 PERIOD D0SE:(mg

  6. Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

    OpenAIRE

    Vandenberg, Laura N.; Welshons, Wade V.; vom Saal, Frederick S.; Toutain, Pierre-Louis

    2014-01-01

    For decades, hazard assessments for environmental chemicals have used intra-gastric gavage to assess the effects of ‘oral’ exposures. It is now widely used – and in some cases required – by US federal agencies to assess potential toxicity of endocrine disrupting chemicals (EDCs). In this review we enumerate several reasons why gavage is not appropriate for the assessment of EDCs using bisphenol A (BPA) as a main example. First, whereas human dietary exposures interact with the oral mucosa, ga...

  7. ADMET evaluation in drug discovery: 15. Accurate prediction of rat oral acute toxicity using relevance vector machine and consensus modeling.

    Science.gov (United States)

    Lei, Tailong; Li, Youyong; Song, Yunlong; Li, Dan; Sun, Huiyong; Hou, Tingjun

    2016-01-01

    Determination of acute toxicity, expressed as median lethal dose (LD50), is one of the most important steps in drug discovery pipeline. Because in vivo assays for oral acute toxicity in mammals are time-consuming and costly, there is thus an urgent need to develop in silico prediction models of oral acute toxicity. In this study, based on a comprehensive data set containing 7314 diverse chemicals with rat oral LD50 values, relevance vector machine (RVM) technique was employed to build the regression models for the prediction of oral acute toxicity in rate, which were compared with those built using other six machine learning approaches, including k-nearest-neighbor regression, random forest (RF), support vector machine, local approximate Gaussian process, multilayer perceptron ensemble, and eXtreme gradient boosting. A subset of the original molecular descriptors and structural fingerprints (PubChem or SubFP) was chosen by the Chi squared statistics. The prediction capabilities of individual QSAR models, measured by q ext (2) for the test set containing 2376 molecules, ranged from 0.572 to 0.659. Considering the overall prediction accuracy for the test set, RVM with Laplacian kernel and RF were recommended to build in silico models with better predictivity for rat oral acute toxicity. By combining the predictions from individual models, four consensus models were developed, yielding better prediction capabilities for the test set (q ext (2) = 0.669-0.689). Finally, some essential descriptors and substructures relevant to oral acute toxicity were identified and analyzed, and they may be served as property or substructure alerts to avoid toxicity. We believe that the best consensus model with high prediction accuracy can be used as a reliable virtual screening tool to filter out compounds with high rat oral acute toxicity. Graphical abstractWorkflow of combinatorial QSAR modelling to predict rat oral acute toxicity.

  8. Cytotoxicity and oral acute toxicity studies of Lantana camara leaf extract.

    Science.gov (United States)

    Pour, Badakhshan Mahdi; Latha, Lachimanan Yoga; Sasidharan, Sreenivasan

    2011-05-03

    The objective of this study was to investigate the toxicity of Lantana camara methanol extract. In order to evaluate the toxicity of Lantana camara, the acute toxicity of the methanolic extract on adult mice and cytotoxicity test on Vero cell line were investigated. A fixed large dose of 2 g/kg body weight of L. camara leaf extract was administrated by a single oral gavage according to the OECD procedure. In 2 weeks, L. camara leaf extract showed no obvious acute toxicity. While female mice lost body weight after being treated with single dose of leaf extract in acute toxicity test, male ones lost organ mass, particularly for heart and kidney. The biochemical liver function tests showed significantly elevated TBIL and ALT in the L. camara leaf extract treated female mice group compared with the control group. Cytotoxicity effect of leaf extract of L. camara was estimated through a MTT assay. Cytotoxicity tests on Vero cell line disclosed that leaf extract at concentrations up to 500 µg/mL inhibited the growth of cells 2.5 times less than did Triton 100 × 1%. More interestingly, the cytotoxicity initiated to decline at elevated concentrations of this extract. The results of both tests confirm that L. camara shows a pro toxic effect.

  9. Cytotoxicity and Oral Acute Toxicity Studies of Lantana camara Leaf Extract

    Directory of Open Access Journals (Sweden)

    Badakhshan Mahdi Pour

    2011-05-01

    Full Text Available Background: The objective of this study was to investigate the toxicity of Lantana camara methanol extract. Methods: In order to evaluate the toxicity of Lantana camara, the acute toxicity of the methanolic extract on adult mice and cytotoxicity test on Vero cell line were investigated. A fixed large dose of 2 g/kg body weight of L. camara leaf extract was administrated by a single oral gavage according to the OECD procedure. Results: In 2 weeks, L. camara leaf extract showed no obvious acute toxicity. While female mice lost body weight after being treated with single dose of leaf extract in acute toxicity test, male ones lost organ mass, particularly for heart and kidney. The biochemical liver function tests showed significantly elevated TBIL and ALT in the L. camara leaf extract treated female mice group compared with the control group. Cytotoxicity effect of leaf extract of L. camara was estimated through a MTT assay. Cytotoxicity tests on Vero cell line disclosed that leaf extract at concentrations up to 500 µg/mL inhibited the growth of cells 2.5 times less than did Triton 100× 1%. More interestingly, the cytotoxicity initiated to decline at elevated concentrations of this extract. Conclusions: The results of both tests confirm that L. camara shows a pro toxic effect.

  10. The interaction between oral melphalan and gastric antisecretory drugs: Impact on clinical efficacy and toxicity.

    Science.gov (United States)

    Kitazawa, Fumiaki; Kado, Yoko; Ueda, Kumi; Kokufu, Takatoshi; Fuchida, Shin-Ichi; Okano, Akira; Hatsuse, Mayumi; Murakami, Satoshi; Nakayama, Yuko; Takara, Kohji; Shimazaki, Chihiro

    2016-02-01

    The aim of the present study was to clarify whether gastric antisecretory drugs affect the clinical efficacy and toxicity of orally administered melphalan in patients with multiple myeloma. A total of 10 patients receiving bortezomib plus oral melphalan and prednisolone (VMP) therapy between December 2011 and November 2014 were analyzed retrospectively. The patients were divided into a control group (seven patients) and a concomitant group (three patients, who were also administered with gastric antisecretory drugs). The gastric antisecretory drugs included rabeprazole sodium (two patients) and famotidine (one patient). No significant differences between the groups were observed in either the characteristics of the patients or the VMP regimen. The levels of monoclonal protein (M protein) in the control group tended to decrease (with a VMP cycle-dependency), although they were primarily stable in the concomitant group. During the second and third VMP cycles, the levels of M protein were markedly lower in the control group compared with the concomitant group. All the patients in the control group achieved a partial response, whereas those in the concomitant group exhibited stable disease. Hematological toxicity levels were revealed to be comparable between the two groups, whereas gastrointestinal toxicity was more prevalent in the control group. In conclusion, the results of the present study suggested that the clinical efficacy of melphalan may be reduced by the co-administration of gastric antisecretory drugs. This interaction may result in decreased toxicity and clinical efficacy of melphalan.

  11. Acute Oral Toxicity and Brine Shrimp Lethality of Elaeis guineensis Jacq., (Oil Palm Leaf Methanol Extract

    Directory of Open Access Journals (Sweden)

    Yeng Chen

    2010-11-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Copyright © 2010 Elsevier GmbH. All rights reserved.

  14. Enzymatic extract from Ecklonia cava: Acute and subchronic oral toxicity and genotoxicity studies.

    Science.gov (United States)

    Yun, Jun-Won; Kim, Seung-Hyun; Kim, Yun-Soon; You, Ji-Ran; Cho, Eun-Young; Yoon, Jung-Hee; Kwon, Euna; Yun, In-Jue; Oh, Je-Hun; Jang, Ja-June; Park, Jin-Sung; Che, Jeong-Hwan; Kang, Byeong-Cheol

    2018-02-01

    Ecklonia cava (EC) is known to have antioxidant, anti-inflammatory, antidiabetic, and anticancer properties. Despite its wide use and beneficial properties, comprehensive toxicological information regarding EC extract is currently limited. Therefore, the purpose of this study was to investigate acute toxicity, subchronic toxicity, and genotoxicity of enzymatic EC extract according to test guidelines published by Organization for Economic Cooperation and Development. The acute oral LD50 values of this EC extract administered to rats and dogs were estimated to be more than 3000 mg/kg BW. In an oral 13-week toxicity study, changes in body weights of rats exposed to the EC extract up to 3000 mg/kg BW were found to be normal. In addition, repeated doses of EC extract failed to influence any systematic parameters of treatment-related toxic symptoms such as food/water consumption, mortality, urinalysis, hematology, serum biochemistry, organ weight, or histopathology. These results indicated that the no-observed-adverse-effect level for the EC extract was 3000 mg/kg/day for male and female rats. Data obtained from Ames test, chromosome aberration assay, and micronucleus assay indicated that EC extract was not mutagenic or clastogenic. Taken together, these results support the safety of enzymatic EC extract as a potential therapeutic for human consumption against various diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

    Science.gov (United States)

    Fort, Douglas J; Mathis, Michael B; Kee, Faith; Whatling, Paul; Clerkin, David; Staveley, Jane; Habig, Clifford

    2017-09-02

    Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2017;9999:1-15. © 2017 SETAC. © 2017 SETAC.

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

    Science.gov (United States)

    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.

  17. Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

    NARCIS (Netherlands)

    Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.; Fernandez-Tejedor, Margarita; Tediosi, Alice; Kotterman, Michiel; Heuvel, van den Fredericus H.M.; Robbens, Johan; Fernandes, José O.; Romme Rasmussen, Rie; Sloth, Jens J.; Marques, António

    2017-01-01

    The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60%

  18. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

    Science.gov (United States)

    Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

    2017-11-01

    Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p  790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

  19. Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate oligonucleotides, following subacute intradermal administration in Sprague-Dawley rats.

    Science.gov (United States)

    Henry, S P; Grillone, L R; Orr, J L; Bruner, R H; Kornbrust, D J

    1997-01-15

    The systemic toxicity of two phosphorothioate oligonucleotides specific for herpes simplex viruses (ISIS 1082) and human papiloma virus (ISIS 2105) were evaluated following repeated intradermal injections of vehicle control, 0.33, 2.17, or 21.7 mg/kg daily to Sprague-Dawley rats (10/sex/group) for 14 days. Animals were sacrificed 1 day after the last dose, except for a portion of the ISIS 1082-treated animals (5/sex/group) which were maintained for an additional 14-day recovery period. The profile of alterations noted for both compounds was very similar. Other than local signs of irritation at the site of injection, there were no clinical signs of toxicity or treatment-related mortality, but there was a slight decrease in body weight gain for the 21.7 mg/kg dose groups. Alterations in hematology parameters included dose-dependent thrombocytopenia and anemia. Alterations in serum chemistry parameters were suggestive of mild alterations in hepatic metabolism, with increases in liver transaminases and bilirubin, along with decreases in albumin and cholesterol. Both spleen and liver weights were significantly elevated in a dose-dependent fashion. Histopathological alterations noted in liver, kidney, lung, injection site skin, and spleen were characterized as perivascular and interstitial infiltrates of macrophages and monocytes. Additional microscopic alterations in the spleen included mild lymphoid hyperplasia (seen in lymph nodes as well), and extramedullary hematopoiesis. Treatment-related cytopenias were likely related to mild, focal hypocellularity in the bone marrow. Alterations in ISIS 1082-treated animals were only partially reversed following the 14-day treatment-free period. In conclusion, repeated intradermal administration of ISIS 1082 and ISIS 2105 produced a similar spectrum of toxicities, with liver, kidney, spleen, and bone marrow being identified as target tissues.

  20. Malnutrition in subacute care

    OpenAIRE

    Collins, Jorja Claire

    2017-01-01

    Malnutrition is a significant problem across all healthcare settings because of its high prevalence and association with adverse outcomes for patients and increased healthcare costs. There is a paucity of research considering subacute patients’ nutritional status and how this changes throughout inpatient stay. Additionally, a stronger evidence base for strategies to prevent and treat malnutrition specifically in this setting is required. This thesis aimed to address these research gaps to con...

  1. Acute Oral Toxicity Study of GAL-57 (Bentazon + Dicamba Herbicide in Rats

    Directory of Open Access Journals (Sweden)

    Dragica Brkić

    2009-01-01

    Full Text Available An acute oral toxicity study of the herbicide GAL-57 (Avalon, a mixture of bentazon and dicamba as active ingredients, was conducted to assess its acute oral toxicity to rats, using a new method that has been used in the past several years (2001. Clinical observations were performed for all animals after different time intervals, and gross necropsy was performed at termination of examination. Clinical symptoms (decreased activity, prone position, abnormal limb position, decreased righting reflex, decreased grip and limb tone, decreased body and abdominal tone and dyspnoea from mild to marked degree were noted after administration of 2000 mg/kg. Animals were found dead 30 minutes to one hour after the treatment. GAL-57 did not cause any clinical sings at single 300 mg/kg bw dose. The physical condition and behaviour of animals were normal during the 14-day observation period. The acute oral LD-50 value of the GAL-57 proved to be between 300 and 2000 mg/kg body weight in rats and was ranked into Poison group III according to Serbian criteria, category 4 of the Global Harmonized Classification System and Category III of the EPA classification.

  2. Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    Science.gov (United States)

    Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

    2017-07-01

    Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Raghunath Pariyani

    2015-01-01

    Full Text Available 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.

  5. Drinking water toxicity study of the environmental contaminant--Bromate.

    Science.gov (United States)

    Dongmei, Liu; Zhiwei, Wang; Qi, Zhu; Fuyi, Cui; Yujuan, Shan; Xiaodong, Liu

    2015-12-01

    Bromate is a byproduct of water disinfection that is produced when waters contain bromide treated with ozone. To investigate the level of the toxicity of bromate and find the most sensitive indicators in a short time, a series of toxicological assessments were conducted including the acute toxicity, cumulative toxicity, genetic toxicity and subacute toxicity of bromate (using Potassium Bromate to represent bromate). The LD50 of orally administered Potassium Bromate was 215 mg/kg in Wistar rats and 464 mg/kg in ICR mice. The cumulative toxicity of Potassium Bromate was not obvious. The Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test did not indicate mutagenicity. The results of the subacute study did not exhibit significant differences in most of the parameters, except the white blood cell count, which was significantly decreased in male rats. In addition, Potassium Bromate influenced the albumin, creatinine, total cholesterol, triglycerides and glucose levels in male rats to various extents. A thorough analysis of the above tests clearly demonstrates that bromate has toxicity, not obvious cumulative toxicity and the white blood cell count can be used as an indicator to reflect the toxicity of bromate and investigate bromate's toxic mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Investigation of neurotoxic and immunotoxic effects of some plant growth regulators at subacute and subchronic applications on rats.

    Science.gov (United States)

    Isik, Ismail; Celik, Ismail

    2015-12-01

    The present study was aimed to investigate the effects of subacute and subchronic treatment of some plant growth regulators (PGRs), such as abscisic acid (ABA) and gibberellic acid (GA3), on neurological and immunological biomarkers in various tissues of rats. The activities of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) were selected as biomarkers for neurotoxic biomarkers. Adenosine deaminase (ADA) and myeloperoxidase (MPO) were measured as indicators for immunotoxic investigation purpose. Wistar albino rats were orally administered with 25 and 50 ppm of PGRs ad libitum for 25-50 days continuously with drinking water. The treatment of PGRs caused different effects on the activities of enzymes. Results showed that the administrations of ABA and GA3 increased AChE and BChE activities in some tissues of rats treated with both the dosages and periods of ABA and GA3. With regard to the immunotoxic effects, ADA activity fluctuated, while MPO activity increased after subacute and subchronic exposure of treated rat tissues to both dosages when compared with the controls. The observations presented led us to conclude that the administrations of PGRs at subacute and subchronic exposure increased AChE, BChE, and MPO activities, while fluctuating the ADA activity in various tissues of rats. This may reflect the potential role of these parameters as useful biomarkers for toxicity of PGRs. © The Author(s) 2013.

  7. Oral toxicity of silver ions, silver nanoparticles and colloidal silver – a review

    DEFF Research Database (Denmark)

    Hadrup, Niels; Lam, Henrik Rye

    2014-01-01

    Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin......, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts...... and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least...

  8. TRANSEPITHELIAL TRANSPORT AND TOXICITY OF PAMAM DENDRIMERS: IMPLICATIONS FOR ORAL DRUG DELIVERY

    Science.gov (United States)

    Sadekar, S.; Ghandehari, H.

    2011-01-01

    This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer – drug conjugates, as a function of physicochemical properties will further need to be assessed. PMID:21983078

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

    Science.gov (United States)

    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

  10. Oral toxic exposure of titanium dioxide nanoparticles on serum biochemical changes in adult male Wistar rats

    Directory of Open Access Journals (Sweden)

    Dasal Vasantharaja

    2015-01-01

    Full Text Available Objective(s: Titanium dioxide (TiO2 nanoparticles (NPs are widely used in commercial food additives and cosmetics worldwide. Uptake of these nanoparticulate into humans by different routes and may exhibit potential side effects, lags behind the rapid development of nanotechnology. Thus, the present study designed to evaluate the toxic effect of mixed rutile and anatase TiO2 NPs on serum biochemical changes in rats. Materials and Methods: In this study, adult male Wistar rats were randomly allotted into the experimental and control groups (n=6, which were orally administered with 50 and 100 mg/kg body weight of TiO2 NPs. Toxic effects were assessed by the changes of serum biochemical parameters such as glucose, total protein, albumin, globulin, cholesterol, triglyceride, high density lipoprotein, alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, blood urea nitrogen, uric acid and creatinine. All the serum biochemical markers were experimented in rats, after 14-days of post exposure. Results: Changes of the serum specific parameters indicated that liver and kidney were significantly affected in both experimental groups. The changes between the levels of total protein, glucose, aspartate transaminase, alanine transaminase and alkaline phosphatase indicate that TiO2 NPs induces liver damage. Significant increase in the blood urea nitrogen and uric acid indicates the renal damage in the TiO2 NPs treated rats. Conclusion: The data shows that the oral administration of TiO2 NPs (

  11. Safety assessment of dietary bamboo charcoal powder: a 90-day subchronic oral toxicity and mutagenicity studies.

    Science.gov (United States)

    Zhenchao, Jia; Yuting, Zhong; Jiuming, Yan; Yedan, Lu; Yang, Song; Jinyao, Chen; Lishi, Zhang

    2015-01-01

    Vegetable carbon has been used as food additive in EU (E153) and China for many years; however, no experimental data have been available on its dietary safety. This study was designed to evaluate the subchronic toxicity and genotoxicity of bamboo charcoal powder (BCP). In the study of subchronic oral toxicity, BCP was administered orally at doses of 2.81, 5.62, and 11.24 g/kg BW for 90 days to SD rats. Additional satellite groups from the control group and high dose group were observed for a 28-day recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples were collected. The toxicological endpoints observed included clinical signs, food consumption, body and organ weights, hematological and biochemical parameters, macroscopic and microscopic examinations. The results showed no significant differences between the BCP treated groups and control group. The genotoxicity of BCP was assessed with the Salmonella typhimurium mutagenicity assay (Ames test) and a combination of comet assay and mammalian erythrocyte micronucleus protocol. The results did not reveal any genotoxicity of BCP. Based on our study, the no-observed-adverse-effect level (NOAEL) for BCP is 11.24 g/kg BW/day. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Oral glucose loading for detection of mitochondrial toxicity during HAART in HIV-infected patients.

    Science.gov (United States)

    ter Hofstede, Hadewych J M; Borm, George F; Koopmans, Peter P

    2007-07-01

    Nucleoside reverse transcriptase inhibitors used in antiretroviral therapy may cause mitochondrial toxicity. Mitochondrial dysfunction leads to disturbance of the glucose metabolism, resulting in an accumulation of L-lactate. We tested the hypothesis that an oral glucose tolerance test (OGTT) can be used to detect mitochondrial toxicity in patients on antiretroviral nucleoside analogues. An OGTT was performed in 30 subjects: 16 HIV-infected treated patients without adverse events (group 1) and 14 HIV-infected patients with adverse events related to nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity (group 2). Lactate was measured at baseline and 60 and 120 min after glucose loading. At all time points the lactate levels were higher in the adverse events group compared to the other group, with the highest levels of lactate at t = 60 min (mean 1912 micromol/L, SD +/- 609); mean lactates in the group without adverse events was 1429 micromol/L (SD +/- 464). When levels above the upper limit of normal of 1800 micromol/L were used as an indication for mitochondrial toxicity, the sensitivity and specificity were 57% and 81%, respectively. The area under the ROC curve was 0.75. For L-lactate levels > 2000 micromol/L the specificity was 90%. An OGTT with measurement of lactate at baseline and one hour after glucose loading can detect (occult) hyperlactataemia in patients with mitochondrial impairment. From our study we suggest to perform an OGTT as an additional test in patients with symptoms suspect for adverse events to discern mitochondrial toxicity.

  13. Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism

    Directory of Open Access Journals (Sweden)

    Hsu CH

    2015-05-01

    Full Text Available Chih-Hsiang Hsu,1 Ching-Lung Lin,1 Sheue-Er Wang,1 Shuenn-Jyi Sheu,2 Chiang-Ting Chien,1 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, 2Brion Research Institute of Taiwan, Taipei, Taiwan Abstract: The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group and the B401 (50 mg/kg group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO production, levels of neuronal nitric oxide synthase (nNOS and endothelial nitric oxide synthase (eNOS, expression levels of factors governing angiogenesis (vascular endothelial growth factor, oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal, inflammation (tumor necrosis factor alpha, apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3 were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in

  14. Susceptibility of young and adult rats to the oral toxicity of titanium dioxide nanoparticles.

    Science.gov (United States)

    Wang, Yun; Chen, Zhangjian; Ba, Te; Pu, Ji; Chen, Tian; Song, Yanshuang; Gu, Yongen; Qian, Qin; Xu, Yingying; Xiang, Kun; Wang, Haifang; Jia, Guang

    2013-05-27

    Titanium dioxide nanoparticles (TiO2 NPs) have potential applications as food additives, but concerns persist about their safety. Children are identified as having the highest exposure and may face the greatest health risks. However, the toxicological sensitivity of TiO2 NPs in different ages is not clear. Here, a comparative toxicity study of TiO2 NPs in 3-week (youth) and 8-week (adult) old Sprague-Dawley rats is reported following oral exposure at doses of 0, 10, 50, 200 mg kg(-1) body weight per day for 30 days. The organ mass and histology, blood biochemistry and redox state, intestinal function, and biodistribution of NPs are characterized. The results show that TiO2 NPs induce different toxic effects on young and adult rats. The liver edema, heart injuries and non-allergic mast cell activation in stomach tissues are found in young rats. On the other hand, only slight injury in the liver and kidney and decreased intestinal permeability and molybdenum contents are found in adult rats. Furthermore, TiO2 NP exposure can provoke reductive stress (i.e., increased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios) in plasmas through enhancing the glucose and GSH levels in young rats or reducing the glutathione peroxidase (GSH-Px) acitivity and GSSG levels in adult rats. These results suggest that different ages may require different biomarkers for identifying and monitoring oral toxicity of nanoparticles. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. A subchronic 90-day oral toxicity study of Origanum vulgare essential oil in rats.

    Science.gov (United States)

    Llana-Ruiz-Cabello, M; Maisanaba, S; Puerto, M; Pichardo, S; Jos, A; Moyano, R; Cameán, A M

    2017-03-01

    Oregano essential oil (Origanum vulgare L. virens) (OEO) is being used in the food industry due to its useful properties to develop new active packaging systems. In this concern, the safety assessment of this natural extract is of great interest before being commercialized. The European Food Safety Authority requests different in vivo assays to ensure the safety of food contact materials. One of these studies is a 90 days repeated-dose oral assay in rodents. In the present work, 40 male and 40 female Wistar rats were orally exposed to 50, 100 and 200 mg/kg body weight (b.w.) OEO during 90 days following the OECD guideline 408. Data revealed no mortality and no treatment-related adverse effects of the OEO in food/water consumption, body weight, haematology, biochemistry, necropsy, organ weight and histopathology. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of this OEO is 200 mg/kg b.w. in Wistar rats, the highest dose tested. In conclusion, the use of this OEO in food packaging appears to be safe based on the lack of toxicity during the subchronic study at doses 330-fold higher than those expected to be in contact consumers in the worst scenario of exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    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. © 2015 SETAC.

  18. Assessment of acute oral and dermal toxicity of 2 ethyl-carbamates with activity against Rhipicephalus microplus in rats.

    Science.gov (United States)

    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 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.

  19. Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

    Science.gov (United States)

    Pepper, Ruth; Campbell, Neil; Yaqoob, Magdi M; Roberts, Norman B; Fan, Stanley L-S

    2011-10-12

    Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water. HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies. 39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested.No patients had unexplained EPO resistance or biochemical evidence of adynamic bone. Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R² = 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.

  20. Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

    Directory of Open Access Journals (Sweden)

    Roberts Norman B

    2011-10-01

    Full Text Available Abstract Background Aluminium (Al toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water. Methods HD patients only treated with Reverse Osmosis(RO treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies. Results 39 patients (34 anuric were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration and the total amount of Al ingested. No patients had unexplained EPO resistance or biochemical evidence of adynamic bone. Conclusions Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R2 = 0.07 and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.

  1. Dietary safety of a dual-enzyme preparation for animal feed: Acute and subchronic oral toxicity and genotoxicity studies.

    Science.gov (United States)

    Dillon, G P; Gaffney, M A; Curran, C M; Moran, C A

    2017-08-01

    Animal feed is routinely supplemented with exogenous enzymes to improve nutrient utilization, such as proteases to enhance protein hydrolysis in vivo and xylanases to alleviate feed related anti-nutritional factors. The present studies were conducted to evaluate the potential oral toxicity and genotoxicity of a dual-enzyme preparation, Vegpro® concentrate (VPr-C). Acute oral toxicity studies were conducted in adult male and female Sprague-Dawley Crl CD rats and CHS Swiss ICO:OFI (IOPS Caw) mice. Thirteen week preliminary and final subchronic oral toxicity studies were conducted in male and female rats. Genotoxicity was evaluated through a bacterial reverse mutation test (Ames test), an in-vitro mammalian chromosomal aberration test, and a mammalian micronucleus test. The LD50 was >2000 mg/kg of BW in mice and rats. In the 13-week oral toxicity study, the No Observed Adverse Effects Level (NOAEL) was 1000 mg/kg BW per day for females and 300 mg/kg BW per day for males. VPr-C showed no mutagenic activity in Salmonella typhimurium, did not induce significant chromosomal aberrations in cultured human lymphocytes, and did not increase the frequency or proportion of micronucleated immature erythrocytes in mice. There was no evidence of acute or subchronic toxicity or genotoxicity associated with the test article at these test dosages. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles.

    Science.gov (United States)

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Moon, Changjong; Kim, Je-Hein; Kim, Hyoung-Chin; Kim, Jong-Choon

    2016-10-28

    Copper nanoparticles (Cu NPs) have great potential in electronics and biomedical fields because of their efficient thermodynamic and anti-microbial properties. However, their potential toxic effects and kinetic data following repeated exposure are still unclear. We evaluated the physicochemical properties of Cu NPs (25 nm) and copper microparticles (Cu MPs, 14-25 μm). Comparative in vivo toxicity of Cu NPs and Cu MPs was evaluated by conducting a 28-day repeated oral dose study at equivalent dose levels of 0, 100, 200, and 400 mg/kg/day (vehicle, 1 % hydroxypropyl methylcellulose). We determined Cu levels in the blood, tissues, urine, and feces by using inductively coupled plasma mass spectrometry. The solubility of Cu NPs and Cu MPs was 84.5 and 17.2 %, respectively, in an acidic milieu; however, they scarcely dissolved in vehicle or intestinal milieus. The specific surface area of Cu NPs and Cu MPs was determined to be 14.7 and 0.16 m(2)/g, respectively. Cu NPs exhibited a dose-dependent increase of Cu content in the blood and tested organs, with particularly high levels of Cu in the liver, kidney, and spleen. Only for liver and kidney increased Cu levels were found in Cu MPs-treated rats. Cu NPs caused a dose-related increase in Cu levels in urine, whereas Cu MPs did not affect the urine Cu levels. Extremely high levels of Cu were detected in the feces of Cu MPs-treated rats, whereas much lower levels were detected in the feces of Cu NPs-treated rats. A comparative in vivo toxicity study showed that Cu NPs caused damages to red blood cells, thymus, spleen, liver, and kidney at ≥200 mg/kg/days, but Cu MPs did not cause any adverse effects even at the highest dose. Overall, the in vivo repeated dose toxicity study of Cu NPs and Cu MPs demonstrated that large surface area and high solubility in physiological milieus could directly influence the toxicological responses and biodistribution of Cu particles when administered orally. Under these experimental

  3. Surge of subacute sclerosing panencephalitis

    National Research Council Canada - National Science Library

    Lisel V Richter-Joubert; Donovan Jacobs; Tracy Kilborn

    2017-01-01

    Subacute sclerosing panencephalitis (SSPE) is a poorly understood complication of measles infection, presenting in up to 1 in 2500 infected children, resulting in devastating neurocognitive outcomes and a high mortality rate...

  4. Dialysis anaemia caused by subacute zinc toxicity.

    Science.gov (United States)

    Petrie, J J; Row, P G

    1977-06-04

    Nine out of ten patients dialysed in a satellite dialysis unit became severely anaemic over a 2-month period. The onset of anaemia coincided with the installation of a new galvanised-iron water softener in the dialysate water-supply system. An activated carbon filter was installed and haemoglobin levels returned towards previous values. Two patients on home dialysis showed similar falls in haemoglobin after the installation of galvanised iron piping in their dialysate water-supply systems; these problems also resolved after carbon filtration of the dialysis water. It is suggested that elution of zinc from galvanised iron can cause anaemia in dialysis patients. Carbon filtration removes of 95-99% of the zinc eluted.

  5. Acute toxicity of various oral doses of dried Nerium oleander leaves in sheep.

    Science.gov (United States)

    Ada, S E; Al-Yahya, M A; Al-Farhan, A H

    2001-01-01

    The acute toxicity of dried Nerium oleander leaves to Najdi sheep is described in 12 sheep assigned as untreated controls, N. oleander-treated once at 1 and 0.25 g/kg body weight and N. oleander-treated daily at 0.06 g/kg body weight by drench. Single oral doses of 1 or 0.25 g of dried N. oleander leaves/kg body weight caused restlessness, chewing movements of the jaws, dyspnea, ruminal bloat, incoordination of movements, limb paresis, recumbency and death 4-24 hr after dosing. Lesions were widespread congestion or hemorrhage, pulmonary cyanosis and emphysema, hepatorenal fatty change and catarrhal abomasitis and enteritis. The daily oral doses of 0.06 g dried N. oleander leaves/kg body weight caused less severe signs and death occurred between days 3 and 14. In these animals, the main lesions were hepatonephropathy and gelatinization of the renal pelvis and mesentry and were accompanied by significant increases in serum AST and LDH activities, in bilirubin, cholesterol and urea concentrations and significant decreases in total protein and albumin levels, anemia and leucopenia.

  6. Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

    Science.gov (United States)

    Vandenberg, Laura N; Welshons, Wade V; Vom Saal, Frederick S; Toutain, Pierre-Louis; Myers, John Peterson

    2014-06-25

    For decades, hazard assessments for environmental chemicals have used intra-gastric gavage to assess the effects of 'oral' exposures. It is now widely used--and in some cases required--by US federal agencies to assess potential toxicity of endocrine disrupting chemicals (EDCs). In this review we enumerate several reasons why gavage is not appropriate for the assessment of EDCs using bisphenol A (BPA) as a main example. First, whereas human dietary exposures interact with the oral mucosa, gavage exposures avoid these interactions, leading to dramatic differences in absorption, bioavailability and metabolism with implications for toxicokinetic assumptions and models. Additionally, there are well acknowledged complications associated with gavage, such as perforation of the esophagus that diminish its value in toxicological experiments. Finally, the gavage protocol itself can induce stress responses by the endocrine system and confound the assessment of EDCs. These serious flaws have not been taken into account in interpreting results of EDC research. We propose the exploration of alternatives to mimic human exposures when there are multiple exposure routes/sources and when exposures are chronic. We conclude that gavage may be preferred over other routes for some environmental chemicals in some circumstances, but it does not appropriately model human dietary exposures for many chemicals. Because it avoids exposure pathways, is stressful, and thus interferes with endocrine responses, gavage should be abandoned as the default route of administration for hazard assessments of EDCs.

  7. Acute toxicity of phorate oxon by oral gavage in the Sprague-Dawley rat.

    Science.gov (United States)

    Snider, Thomas H; McGarry, Kevin G; Babin, Michael C; Jett, David A; Platoff, Gennady E; Yeung, David T

    2016-01-01

    The oral toxicity of phorate oxon (PHO), with emphasis on gender- and age-related effects, was characterized in the Sprague-Dawley rat. The oral LD50 (95% fiducial limits) for PHO in corn oil was 0.88 (0.79, 1.04) mg/kg in males and 0.55 (0.46, 0.63) mg/kg in females with a probit slope of 15. Females had higher baseline blood cholinesterase titers, but males were significantly more tolerant. Younger rats generally had lower absolute cholinesterase blood titers. However as PHO challenges increased, baseline-normalized cholinesterase inhibition was independent of age and gender. Butyrylcholinesterase (BChE) and especially acetylcholinesterase (AChE) in brains of younger females were affected more than that in either males or older females. In summary, while female rats, especially older females, had higher titers relative to males, female rats were more susceptible in terms of absolute cholinesterase inhibition and 24-hr lethality data, but the differences were not observed when titers were normalized to baseline levels.

  8. Inadvertent provocative oral ondansetron use leading to toxic epidermal necrolysis in an HIV-infected patient

    Directory of Open Access Journals (Sweden)

    Punit P Saraogi

    2012-01-01

    Full Text Available Toxic epidermal necrolysis (TEN is a severe cutaneous adverse reaction to drugs, characterized by extensive detachment of epidermis and mucous membranes with a mortality of 30-40%. An increased occurrence of cutaneous drug reactions is seen in patients with human immunodeficiency virus (HIV infection. We present this case of TEN caused by ondansetron in an HIV-infected patient. A 24-year-old HIV-1-infected man on antitubercular therapy and cotrimoxazole, presented with extensive and confluent erosions involving the face, trunk, extremities and mucous membranes following the intake of oral ondansetron, ofloxacin and ornidazole. All the drugs were withdrawn and he was treated with intravenous dexamethasone and antibiotics with consequent healing of the erosions. However, the lesions recurred on inadvertent intake of oral ondansetron. He was treated with intravenous antibiotics, fluid resuscitation and supportive care. The skin lesions healed completely over 2 months with postinflammatory depigmentation and scarring, and the eye lesions healed with corneal opacities. We would like to emphasize that the drug most frequently associated with adverse drug reactions may be innocent in a given patient and the physician dealing with a suspected drug reaction must always remain unbiased regarding the causative drug.

  9. Evaluation of ATC as an Orally Administered Drug in Treatment of Cadmium Toxicity of Rat Organs

    Directory of Open Access Journals (Sweden)

    S. Nabilaldine Fatemi

    2009-01-01

    Full Text Available The effect of N-tetramethylene dithiocarbamate (ATC as a chelating agent on the excretion of cadmium was evaluated in cadmium-poisoned Wistar rats following administration through food and drink. The present research aimed to characterize the potential efficiency of ATC as an orally administered chelator drug after cadmium administration for 60 days. This chelator significantly enhanced the urinary and biliary excretion of cadmium and restored the altered levels of iron. Cadmium and iron concentrations in different tissues were determined by graphite furnace and flame atomic absorption spectrometry (GF AAS and F AAS methods, respectively. The chelation therapy results show that ATC is able to remove cadmium ions from different tissues while iron concentration returned to the normal level and the clinical symptoms were also reduced. In summary, we conclude that ATC is able to mobilize and promote the excretion of cadmium in rat organs and reduce the side effects and general symptoms of toxicity caused by cadmium and might be useful for preliminary testing of the efficacy of chelating agents in human body. However, these results should be confirmed in different experimental models before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in cadmium toxicity.

  10. Blood Parameters and Toxicity of Chromium Picolinate Oral Supplementation in Lambs.

    Science.gov (United States)

    Dallago, Bruno Stéfano Lima; Braz, ShélidaVasconcelos; Marçola, Tatiana Guerrero; McManus, Concepta; Caldeira, Denise Ferreira; Campeche, Aline; Gomes, Edgard Franco; Paim, Tiago Prado; Borges, Bárbara Oliveira; Louvandini, Helder

    2015-11-01

    The effects of oral supplementation of chromium picolinate (CrPic) on various blood parameters and their possible toxicity on the liver, kidneys, lungs, heart, and testis were investigated. Twenty-four Santa Inês (SI) lambs were treated with four different concentrations of CrPic (six animals/treatment): placebo, 0.250, 0.375, and 0.500 mg CrPic/animal/day for 84 days. The basal diet consisted of hay Panicum maximum cv Massai and concentrate. Blood and serum were collected fortnightly for analysis. On day 84, the animals were euthanized, and histopathological analysis in the liver, kidney, heart, lung, and testis was made. The liver and kidney were also submitted to electronic microscopy analysis. Differences between treatments (P < 0.05) were observed for packed cell volume (day 84), hemoglobin (day 84), total plasm protein (day 56 and day 84), and triglycerides (day 70). There was no statistically significant relationship between Cr supplementation and histopathology findings, although some animals treated with supplementary Cr showed morphological changes in the liver, kidney, and testis. Thus, the effectiveness of supplementation with Cr remains in doubt as to its physiological action and toxicity in sheep.

  11. Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies.

    Science.gov (United States)

    Andreani, Tatiana; Kiill, Charlene P; de Souza, Ana Luiza R; Fangueiro, Joana F; Fernandes, Lisete; Doktorovová, Slavomira; Santos, Dario L; Garcia, Maria L; Gremião, Maria Palmira D; Souto, Eliana B; Silva, Amélia M

    2014-11-01

    The present work aimed at studying the interaction between insulin and SiNP surfaced with mucoadhesive polymers (chitosan, sodium alginate or polyethylene glycol) and the evaluation of their biocompatibility with HepG2 and Caco-2 cell lines, which mimic in vivo the target of insulin-loaded nanoparticles upon oral administration. Thus, a systematic physicochemical study of the surface-modified insulin-silica nanoparticles (Ins-SiNP) using mucoadhesive polymers has been described. The surfacing of nanoparticle involved the coating of silica nanoparticles (SiNP) with different mucoadhesive polymers, to achieve high contact between the systems and the gut mucosa to enhance the oral insulin bioavailability. SiNP were prepared by a modified Stöber method at room temperature via hydrolysis and condensation of tetraethyl orthosilicate (TEOS). Interaction between insulin and nanoparticles was assessed by differential scanning calorimetry (DSC), X-ray and Fourier-transform infrared (FTIR) studies. The high efficiency of nanoparticles' coating resulted in more stable system. FTIR spectra of insulin-loaded nanoparticles showed amide absorption bands which are characteristic of α-helix content. In general, all developed nanoparticles demonstrated high biocompatible, at the tested concentrations (50-500 μg/mL), revealing no or low toxicity in the two human cancer cell lines (HepG2 and Caco-2). In conclusion, the developed insulin-loaded SiNP surfaced with mucoadhesive polymers demonstrated its added value for oral administration of proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

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

    Science.gov (United States)

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

    2009-02-01

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

  14. Developmental toxicity of N-methylaniline following prenatal oral administration in rats

    Directory of Open Access Journals (Sweden)

    Krystyna Sitarek

    2016-06-01

    Full Text Available Objectives: The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA administered by gavage to pregnant female rats. Material and Methods: Pregnant female rats were administered N-methylaniline in corn oil by gavage at daily doses of 0.8 mg/kg of body weight (b.w., 4 mg/kg b.w., 20 mg/kg b.w. and 100 mg/kg b.w. from implantation (the 5th day post mating to the day prior to the scheduled caesarean section (the 20th day of pregnancy. General behavior, body weight, food and water consumption, hematological, biochemical analyses and pathomorphological changes of the dams were recorded. Results: All the females survived until the end of the study. The test substance was toxic to pregnant females, even at the lowest of the used doses, i.e., 0.8 mg/kg b.w./day. Lower weight gain during pregnancy and significantly higher NMA-dose-dependent absolute weight of the organs were noted in the exposed females. The females from the groups exposed at doses of 20 mg/kg b.w./day and 100 mg/kg b.w./day developed anemia and showed higher concentrations of free thyroxine (FT3 and free triiodothyronine (FT4 thyroid hormones. Total protein concentration exhibited an increase in all the exposed groups of females. In the prenatal toxicity study, administration of N-methylaniline throughout the embryonic and fetal periods produced embryotoxic effects at doses ranging 4–100 mg/kg b.w./day. Conclusions: Considering the data obtained in this study, it is reasonable to assume that N-methylaniline administered orally to pregnant rats is toxic for mothers even at a low dose of 0.8 mg/kg b.w./day. However, this dose was not associated with any significant effects to their offspring. This prenatal exposure level may be considered as no-observed-adverse-effect level (NOAEL for the progeny and a dose of 4 mg/kg b.w./day as the lowest-observed-adverse-effect level (LOAEL for the progeny.

  15. Physicochemical analysis and repeated-dose 90-days oral toxicity study of nanocalcium carbonate in Sprague-Dawley rats.

    Science.gov (United States)

    Sung, Jae Hyuck; Park, Soo Jin; Jeong, Min Sook; Song, Kyung Seuk; Ahn, Kyu Sup; Ryu, Hyun Ryol; Lee, Han; Song, Mi Ryoung; Cho, Myung-Haing; Kim, Jun Sung

    2015-01-01

    In our previous studies of nanocalcium carbonate, in which we performed physicochemical analysis, genotoxicity, acute single-dose and repeated-dose 14-day oral toxicity testings in Sprague-Dawley (SD) rats, nanocalcium carbonate did not show a difference in toxicity compared to vehicle control. Here, we provide the first report of a repeated-dose 90-day oral toxicity test of nanocalcium carbonate in Sprague-Dawley rats, with physicochemical comparison of micro and nanocalcium carbonate. We find that the two particles differ in size, hydrodynamic size, and specific surface area, with no differences in components, crystalline structure and radical production. In terms of ionization ability, nanocalcium carbonate was slightly more ionized within 1% than microcalcium carbonate at pH 5 and pH 7. In the repeated-dose 90-day oral toxicity test of nanocalcium carbonate, there was no significant toxicity, and similar blood concentrations of Ca(2+) compared to the vehicle control group. Based on our results, although nanocalcium carbonate has different physicochemical properties, nanocalcium carbonate does not differ from microcalcium carbonate in terms of toxicity. Based on the results, we suggest that the no-observed-adverse-effect level (NOAEL) of nanocalcium carbonate is 1000 mg kg(-1) day(-1) in SD rats according to the maximum dose (OECD guideline 408). However, the NOAEL might be higher than 1000 mg kg(-1) day(-1) because there were no adverse effects revealed by consistent pathological findings or biochemical parameter changes. To justify a safe concentration of nanocalcium carbonate, which is a low toxicity chemical, more data is required on dose levels above 1000 mg kg(-1). Our findings may be useful for creating safety guidelines for the use nanocalcium carbonate.

  16. Copper pellets simulating oral exposure to copper ammunition: Absence of toxicity in American kestrels (Falco sparverius)

    Science.gov (United States)

    Franson, J. Christian; Lahner, Lesanna L.; Meteyer, Carol U.; Rattner, Barnett A.

    2012-01-01

    To evaluate the potential toxicity of copper (Cu) in raptors that may consume Cu bullets, shotgun pellets containing Cu, or Cu fragments as they feed on wildlife carcasses, we studied the effects of metallic Cu exposure in a surrogate, the American kestrel (Falco sparverius). Sixteen kestrels were orally administered 5 mg Cu/g body mass in the form of Cu pellets (1.18–2.00 mm in diameter) nine times during 38 days and 10 controls were sham gavaged on the same schedule. With one exception, all birds retained the pellets for at least 1 h, but most (69%) regurgitated pellets during a 12-h monitoring period. Hepatic Cu concentrations were greater in kestrels administered Cu than in controls, but there was no difference in Cu concentrations in the blood between treated and control birds. Concentration of the metal-binding protein metallothionein was greater in male birds that received Cu than in controls, whereas concentrations in female birds that received Cu were similar to control female birds. Hepatic Cu and metallothionein concentrations in kestrels were significantly correlated. Histopathologic alterations were noted in the pancreas of four treated kestrels and two controls, but these changes were not associated with hepatic or renal Cu concentrations, and no lesions were seen in other tissues. No clinical signs were observed, and there was no treatment effect on body mass; concentrations of Cu, hemoglobin, or methemoglobin in the blood; or Cu concentrations in kidney, plasma biochemistries, or hematocrit. Based on the parameters we measured, ingested Cu pellets pose little threat to American kestrels (and presumably phylogenetically related species), although the retention time of pellets in the stomach was of relatively short duration. Birds expected to regurgitate Cu fragments with a frequency similar to kestrels are not likely to be adversely affected by Cu ingestion, but the results of our study do not completely rule out the potential for toxicity in

  17. Subacute bacterial endocarditis (SBE due to Streptococcus gordonii

    Directory of Open Access Journals (Sweden)

    Raffaella Battista

    2009-12-01

    Full Text Available Endocarditis is an inflammatory state of the endothelium that promotes thrombus formation and tissue damage on the surface of heart valves. Recent studies have reported endocarditis mortality rates ranging from 12% to 46% (2008. The Streptococcus gordonii is a normal inhabitant of the human oral cavity. It is a component of the microbial communities responsible of plaque formation, associated with dental caries and also regarded as the main causative agent in the development of subacute bacterial endocarditis (SBE.

  18. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  19. Acute and twenty-eight days repeated oral dose toxicity study of besifloxacin in Wistar albino rats.

    Science.gov (United States)

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

    2011-07-01

    The purpose of this study was to investigate the potential acute and 28-day repeated oral toxicities of besifloxacin (BAF) in Wistar albino rats. In oral acute and repeated dose study, BAF was administered to both sex of rats, at dose levels of 0, 300, 600, 900 mg/kg/day and 0, 100, 200, 500 mg/kg/day, respectively. In the acute study, total white blood cell (WBC) (male, 43.74%; female, 42.60%) and total bilirubin (T-BIL) (male, 80%; female, 60%) were significantly increase, total protein (TP) (male, 23.24%; 27.80%) was significantly decreased, and significant incidence of pericholangitis (male, 83.33%; female, 75%) was shown in males and females of high-dose groups. In repeated oral dose toxicity study, similar type effects were also observed after serum hematological and serum biochemical analysis, whereas additionally sever hepatic injury and focal ulceration in gastric mucosa also observed in high dose groups of both sexes after histopathological analysis. However these toxic effects of besifloxacin were transient and reversible and no-observed adverse effect level (NOAEL) were 300 mg/kg/day for acute and 100 mg/kg/day for repeated dose toxicity study, respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Phool Chandra

    2012-01-01

    Full Text Available 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. LD 50 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.

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

    Science.gov (United States)

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

    2012-04-01

    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. LD(50) 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.

  2. A 90 days oral toxicity of imidacloprid in female rats: morphological, biochemical and histopathological evaluations.

    Science.gov (United States)

    Bhardwaj, Shipra; Srivastava, M K; Kapoor, Upasana; Srivastava, L P

    2010-05-01

    A 90 days oral toxicity study of imidacloprid was conducted in female rats with doses of 0, 5, 10, 20mg/kg/day. Decrease in the body weight gain was observed at 20mg/kg/day and at necropsy the relative body weights of liver, kidney and adrenal was also significantly increased at this dose level. No mortality occurred during treatment period while food intake was reduced at high dose level. In clinical chemistry parameters high dose of imidacloprid has caused significant elevation of serum GOT, GPT, glucose and BUN and decreased the activity of AChE in serum and brain. The spontaneous locomotor activity was also decreased at highest dose exposure where as there were no significant changes in hematological and urine parameters. The brain, liver and kidney of rats exposed with high dose of imidacloprid had showed mild pathological changes. Based on the morphological, biochemical, hematological and neuropathological studies it is evident that imidacloprid has not produced any significant effects at 5 and 10mg/kg/day doses but induced toxicological effects at 20mg/kg/day to female rats. Hence, 10mg/kg/day dose may be considered as no observed effect level (NOEL) for female rats. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Subacute sclerosing panencephalitis in pregnancy.

    Science.gov (United States)

    Chiu, Michael H; Meatherall, Bonnie; Nikolic, Ana; Cannon, Kristine; Fonseca, Kevin; Joseph, Jeffrey T; MacDonald, Judy; Pabbaraju, Kanti; Tellier, Raymond; Wong, Sallene; Koch, Marcus W

    2016-03-01

    We present a case of subacute sclerosing panencephalitis that developed in a previously healthy 29-year-old pregnant woman who had returned from a trip to rural India shortly before the onset of symptoms. She was admitted to hospital at 27 weeks' gestation with a history of cognitive decline and difficulty completing simple tasks. She had no clinical signs of infection. The working diagnosis was autoimmune encephalitis, although extensive investigations did not lead to a final classifying diagnosis. The patient became comatose and developed hypertension, and an emergency caesarean section was done at 31 weeks to deliver the child, who seemed healthy. The patient died about 6 weeks after the onset of symptoms. The patient was found to have had subacute sclerosing panencephalitis at autopsy. In this Grand Round, we review the clinical features and treatment of subacute sclerosing panencephalitis, and the epidemiological and public health aspects of the case. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Subacute sclerosing panencephalitis and chronic viral encephalitis.

    Science.gov (United States)

    Anlar, Banu

    2013-01-01

    Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system associated with the presence of mutant measles virus in the brain. It presents as a progressive, usually fatal disease. The diagnosis is based on clinical criteria and an elevated titer of measles antibodies in the cerebrospinal fluid (CSF). Electroencephalography and imaging studies provide supportive laboratory data. A brain biopsy is indicated only when CSF serology is negative or equivocal in a suspected case to assess the presence of inclusion bodies, measles virus antigens, or viral RNA. Among many drugs and methods tried in the treatment, the highest rate of stabilization or improvement was obtained with intraventricular human lymphoblastoid interferon-α and oral inosiplex. Further research for more available and efficient therapeutic regimens is warranted. Measles and SSPE are preventable by maintenance of high rates of immunization in the population. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    María Guadalupe Prado-Ochoa

    2014-01-01

    Full Text Available 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.

  6. Comparison of the up-and-down method and the fixed-dose procedure for acute oral toxicity testing.

    Science.gov (United States)

    Yam, J; Reer, P J; Bruce, R D

    1991-04-01

    The acute oral toxicity data for 10 compounds, generated by using two alternative methods in rats, the up-and-down method and the fixed-dose procedure, were compared with those obtained from the classical LD50 test. In this evaluation, both alternative methods offered a reduction in animal use, while providing adequate information to rank the compounds according to the EEC classification for acute oral toxicity. In addition to the ranking, these alternative methods also provided useful information on signs of toxicity and gross autopsy findings, although the results varied depending on the method used. Of the three methods, the up-and-down method required the fewest animals. Although the up-and-down method used only females, the LD50 values obtained were in good agreement with those obtained by the classical method, which used both sexes. It is concluded that the up-and-down method and the fixed-dose procedure are acceptable alternative methods to the classical LD50 test, and the choice of method depends on the type of toxicity information required.

  7. Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

    KAUST Repository

    Alves, Ricardo N.

    2017-11-17

    The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60% (monkfish). Arsenic (>64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73%) and iodine (71%) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according to species. For example, methylmercury bioaccessibility decreased significantly after steaming in all species, while zinc bioaccessibility increased in fish (tuna and plaice) but decreased in molluscs (mussel and octopus).Together with human exposure assessment and risk characterization, this study could contribute to the establishment of new maximum permissible concentrations for toxic elements in seafood by the European food safety authorities, as well as recommended intakes for essential elements.

  8. Acute Oral Toxicity and Brine Shrimp Lethality of Methanol Extract of ...

    African Journals Online (AJOL)

    kidney and lung tissues of the rats. Histopathological examination also did not reveal any toxicity ... Keywords: Mentha spicata, Acute toxicity, Brine shrimp, Histopathology, Haematological. Tropical Journal of Pharmaceutical Research is ... rheumatism, toothache, muscle pain. Mint possesses antimicrobial and antioxidant.

  9. Biochemical and hematological effects of acute and sub-acute administration to ethyl acetate fraction from the stem bark Scutia buxifolia Reissek in mice.

    Science.gov (United States)

    da Silva, Andreia R H; Moreira, Laís da R; Brum, Evelyne da S; de Freitas, Mayara L; Boligon, Aline A; Athayde, Margareth L; Roman, Silvane S; Mazzanti, Cinthia M; Brandão, Ricardo

    2014-05-14

    Scutia buxifolia is a native tree of Southern Brazil, Uruguay, and Argentina, which is popularly known as "coronilha" and it is used as a cardiotonic, antihypertensive and diuretic substance. The aim of this study was to assess the acute and sub-acute toxicity of the ethyl acetate fraction from the stem bark Scutia buxifolia in male and female mice. The toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). In an acute study, a single dose of 2000 mg/kg of Scutia buxifolia was administered orally to male and female mice. Mortality, behavioral changes, and biochemical and hematological parameters were evaluated. In the sub-acute study, Scutia buxifolia was administered orally to male and female mice at doses of 100, 200, and 400mg/kg/day for 28 days. Behavioral changes and biochemical, hematological, and histological analysis were evaluated. The acute administration of Scutia buxifolia did not cause changes in behavior or mortality. Male and female mice presented decreased levels of platelets. Female mice presented decreased levels of leukocytes. On the other hand, in a sub-acute toxicity study, we observed no behavioral changes in male or female mice. Our results demonstrated a reduction in glucose levels in male mice treated to 200 and 400mg/kg of Scutia buxifolia. Aspartate aminotransferase (ASAT) activity was increased by Scutia buxifolia at 400mg/kg in male mice. In relation to the hematological parameters, male mice presented a reduction in hemoglobin (HGB) and hematocrit (HCT) when treated to 400mg/kg of plant fraction. Female mice showed no change in these parameters. Histopathological examination of liver tissue showed slight abnormalities that were consistent with the biochemical variations observed. Scutia buxifolia, after acute administration, may be classified as safe (category 5), according to the OECD guide. However, the alterations observed, after sub-acute

  10. Thirteen Week Oral Toxicity Study of WR238605 with a Thirteen Week Recovery Period in Dogs. Volume 1

    Science.gov (United States)

    1993-06-11

    included extramedullary hematopoiesis and hemosiderin pigment in high dose and to a lesser extent in mid dose males and females. Hemosiderin pigment...DAMD17-92-C-2001 Task Order No.: UIC-5A UIC/TRL Study No.: 097 In the iiver, hemosiderin deposits, Kupffer cell hypertrophy, and subacute...inflammation occurred together in mid and high dose animals sacrificed at the end of the dosing period. Hemosiderin deposits and subacute inflammation of

  11. Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients

    NARCIS (Netherlands)

    Brand, W.; Schutte, M.E.; Williamson, G.; Zanden, J.J. van; Cnubben, N.H.P.; Groten, J.P.; Bladeren, P.J. van; Rietjens, I.M.C.M.

    2006-01-01

    The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be

  12. Acute and subchronic oral toxicities of Pu-erh black tea extract in Sprague-Dawley rats.

    Science.gov (United States)

    Wang, Di; Xu, Kunlong; Zhong, Ying; Luo, Xiao; Xiao, Rong; Hou, Yan; Bao, Wei; Yang, Wei; Yan, Hong; Yao, Ping; Liu, Liegang

    2011-03-08

    Pu-erh black tea, which is obtained by first parching crude green tea leaves and then undergoes secondary fermentation with microorganisms, has been believed to be beneficial beverages for health for nearly 2000 years in China, Japan and Taiwan area. But its potential toxicity when administered at a high dose as concentrated extracts has not been completely investigated. The present study was aimed at evaluating potential toxicity of Pu-erh black tea extracts (BTE) from acute and sub-chronic administration to male and female Sprague-Dawley (SD) rats. A single BTE dose of 10,000 mg/kg of body weight was administered by oral gavage for acute toxicity in SD rats. Four groups (10 males and 10 females per group) of dose levels of 1250, 2500, and 5,000 mg/kg/day of the test article, as well as controls (distilled water) were tested as the subchronic toxicity study. No deaths and signs of toxicity occurred during the 14 days of the study. There were no test article related mortalities, body weight gain, feed consumption, clinical observation, organ weight changes, gross finding, clinical or histopathological alterations during the 91-day administration. The LD(50) of BTE can be defined as more than 10,000 mg/kg, and a dose of 5,000 mg/kg/day was identified as the no-observed-adverse-effect-level (NOAEL) in this study. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Sub-chronic (13-week) oral toxicity study in rats with recombinant human lactoferrin produced in the milk of transgenic cows

    NARCIS (Netherlands)

    Appel, M.J.; Veen, H.A. van; Vietsch, H.; Salaheddine, M.; Nuijens, J.H.; Ziere, B.; Loos, F. de

    2006-01-01

    The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of transgenic cows was investigated in Wistar rats by daily administration via oral gavage for 13 consecutive weeks, 7 days per week. The study used four groups of 20 rats/sex/dose. The control group received

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  16. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats

    Directory of Open Access Journals (Sweden)

    Seol-Hee Moon

    Full Text Available A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study. Keywords: γ-Oryznaol, Rice, Rat, Repeated-dose oral toxicity study, NOAEL

  17. Subacute thyroiditis--61 cases review.

    Science.gov (United States)

    Hwang, S C; Jap, T S; Ho, L T; Ching, K N

    1989-02-01

    To examine the hospitalized patients with available data suggesting subacute thyroiditis, we have reviewed 80 hospital charts over the last 11 years and the data demonstrated 61 patients (48 females, 13 males, Aged 22-75 years) had evidence of subacute thyroiditis clinically or pathologically. Fifty seven of those patients had the clinical manifestation of severe tenderness over the neck, and others were painless. The thyroid function test were abnormal in 53% (30/57) of cases. All had rapid sedimentation rate (46/46). The thyroid antibodies were positive in 26% (10/39) of cases. Sixteen patients received unnecessary thyroid operation and complicated with hypothyroidism with or without hypoparathyroidism in two cases. In conclusion, all patients with painful or painless goiter should be appreciated carefully with additional study such as aspiration cytology to avoid misdiagnosis and inappropriate management.

  18. Acute and sub-chronic oral toxicity studies of the extracts from herbs ...

    African Journals Online (AJOL)

    The variables included were body weights; feed consumption, organ weights, hematology and blood clinical chemistry, and histopathology were performed. Acute toxicity test revealed that, the limit dose of 2,000 mg/kg did not cause any mortality or symptoms of toxicity in all rats during the observation period. In the ...

  19. Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V. [Division of Pharmaceutical Technology, Defence Research Laboratory, Assam (India); Department of Life Sciences, Defense Research Development and Organization, New Delhi (India)

    2012-07-01

    The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ({sup 99m} Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of {sup 99m}Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

  20. Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

    Directory of Open Access Journals (Sweden)

    P Chattopadhyay

    2012-01-01

    Full Text Available The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m (99m Tc-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma-scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99mTc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation.

  1. Subacute sclerosing panencephalitis: A clinical appraisal

    National Research Council Canada - National Science Library

    Jagtap, Sujit Abajirao; Nair, M D; Kambale, Harsha J

    2013-01-01

    Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis affecting primarily children and young adults, caused by a persistent infection of immune resistant measles virus...

  2. Acute toxicities of adjuvant treatment in patients of oral squamous cell carcinoma with and without submucous fibrosis: A retrospective audit.

    Science.gov (United States)

    Chakrabarti, Swagnik; Mishra, Aseem; Agarwal, Jai Prakash; Garg, Apurva; Nair, Deepa; Chaturvedi, Pankaj

    2016-01-01

    To assess the severity of acute toxicities of postoperative adjuvant therapy on oral squamous cell carcinoma (OSCC) patients with and without submucous fibrosis (SMF). The study population comprised treatment naïve OSCC patients who underwent curative intent surgical resection from June 2010 to April 2011 followed by adjuvant treatment. Patients whose treatment details including toxicity profile were available were included in the study. One-hundred nine patients met the inclusion criteria of whom 36 had associated SMF and 73 no SMF. Overall, 35 patients received chemotherapy (CT) with radiotherapy (RT) and the rest only RT. Forty-two patients had centralized and 67 lateralized lesions. All patients with centralized lesions and 3 with lateralized lesion received radiation to bilateral face and neck. All others received ipsilateral radiation. The severity of mucositis, xerostomia, and skin toxicity (as per radiation therapy oncology group scale of acute toxicity) was compared between the SMF and non-SMF groups and patients with centralized and lateralized lesions. CT in addition to RT did not add significant to the assessed toxicities. Severe mucositis as well as treatment breaks were more in SMF group as compared to non-SMF group (P = 0.001 and lesions (P = 0.002 and 0.00 respectively). In subgroups of lateralized as well as centralized lesions, severe mucositis was more common in SMF patients than those without SMF (P = 0.01 and 0.02 respectively). OSCC patients with SMF have worse toxicity with adjuvant therapy and require good supportive care.

  3. Oral lesions associated with Nevirapine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A report of 10 cases.

    Science.gov (United States)

    Reddy, Ramana Bv; Shekar, P Chandra; Chandra, K Lalith Prakash; Aravind, Rs

    2013-09-01

    Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are closely related severe, acute mucocutaneous reactions usually caused by drugs. They are acute life-threatening conditions and cause widespread necrosis of the epithelium. There is persistence of a high risk of SJS or TEN in relation to human immunodeficiency virus (HIV) infection associated with exposure to nevirapine (NVP). In this article, we present nine cases of SJS and one case of TEN in HIV-seropositive individuals who developed cutaneous, oral, ocular and genital lesions while being treated with NVP.

  4. Acute and sub-acute toxicological assessment of the aqueous seed ...

    African Journals Online (AJOL)

    Experiments were conducted to determine the oral median lethal dose (LD50) 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 ...

  5. Subacute Budd-Chiari syndrome associated with polycythemia vera and factor V Leiden mutation

    NARCIS (Netherlands)

    Simsek, S; Verheesen, RV; Haagsma, EB; Lourens, J

    We describe a 48-year-old caucasian woman with a subacute Budd-Chiari syndrome attributed to the presence of polycythaemia vera, heterozygosity for the factor V Leiden mutation and the use of an oral contraceptive pill. Two diagnostic pitfalls were encountered. First, on CT scanning of the abdomen

  6. Masticatory function in subacute TMD patients before and after treatment.

    Science.gov (United States)

    Pereira, L J; Steenks, M H; de Wijer, A; Speksnijder, C M; van der Bilt, A

    2009-06-01

    Masticatory function can be impaired in temporomandibular disorders (TMDs) patients. We investigated whether treatment of subacute non-specific TMD patients may influence oral function and clinical outcome measures. Fifteen patients with subacute TMD participated in the study. We quantified masticatory performance, maximum voluntary bite force, muscle activity and chewing cycle duration before and after treatment. Masticatory performance and bite force of patients were compared with the results obtained for an age- and gender-matched group of subjects without TMD complaints. Furthermore, we determined possible changes in anamnestic and clinical scores from questionnaires (mandibular function impairment questionnaire; MFIQ), pain scores and clinical outcome measures. Maximum bite force significantly increased, although the values after treatment were still significantly lower than those of the subjects without TMD complaints. The corresponding electromyography values did not show significant change after treatment. The masticatory performance of the patients remained unaltered; patients chewed significantly less efficient than controls. The average duration of chewing cycles significantly decreased after treatment. We observed a significant improvement in MFIQ scores. During the clenching and chewing tasks, the visual analogue scale scores were significantly higher than before these tasks. We may conclude that subacute temporomandibular joint disorders negatively influence chewing behaviour. Bite force, chewing cycle duration and also perceived mandibular function significantly improved after treatment, although the masticatory performance remained unaltered.

  7. Guidance for Reviewing OCSPP 850.2100 Avian Oral Toxicity Studies Conducted with Passerine Birds

    Science.gov (United States)

    Guidance based on comparison of results from the TG223 validation studies to results from avian acute oral studies previously submitted to EPA for two test chemicals following EPA's 850.2100 (public draft) guidelines.

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

    Science.gov (United States)

    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...

  9. Estimation of daily intake of potentially toxic elements from urban street dust and the role of oral bioaccessibility testing.

    Science.gov (United States)

    Okorie, Alexander; Entwistle, Jane; Dean, John R

    2012-02-01

    The pseudo-total and oral bioaccessible concentration of six potentially toxic elements (PTEs) in urban street dust was investigated. Typical pseudo-total concentrations across the sampling sites ranged from 4.4 to 8.6 mg kg(-1) for As, 0.2-3.6 mg kg(-1) for Cd, 25-217 mg kg(-1) for Cu, 14-46 mg kg(-1) for Ni, 70-4261 mg kg(-1) for Pb, and, 111-652 mg kg(-1) for Zn. This data compared favourably with other urban street dust samples collected and analysed in a variety of cities globally; the exception was the high level of Pb determined in a specific sample in this study. The oral bioaccessibility of PTEs in street dust is also assessed using in vitro gastrointestinal extraction (Unified Bioaccessibility Method, UBM). Based on a worst case scenario the oral bioaccessibility data estimated that Cd and Zn had the highest % bioaccessible fractions (median >45%) while the other PTEs i.e. As, Cu, Ni and Pb had lower % bioaccessible fractions (median PTEs in the samples has been compared to estimated tolerable daily intake values based on unintentional soil/dust consumption. Cadmium, Cu and Ni are well within the oral tolerable daily intake rates. With respect to As and Pb, only the latter exceeds the TDI(oral) if we model ingestion rate based on atmospheric 'dustiness' rather than the US EPA (2008) unintentional soil/dust consumption rate of 100 mg d(-1). We consider it unlikely that even a child with pica tendencies would ingest as much as 100mg soil/dust during a daily visit to the city centre, and in particular to the sites with elevated Pb concentrations observed in this study. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2015-09-01

    Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  12. Rapidly progressive subacute sclerosing panencephalitis presenting with acute loss of vision.

    Science.gov (United States)

    Ekici, Bariş; Calişkan, Mine; Tatli, Burak; Aydinli, Nur; Ozmen, Meral

    2011-12-01

    A 10-year-old male presented with vision loss and behavioral changes. He had midpoint pupils with no reaction to light and normal funduscopic examination. Cranial magnetic resonance imaging revealed bilateral cortical lesions at parieto-occipital lobes. Elevated measles antibody titers in the cerebrospinal fluid confirmed the diagnosis of subacute sclerosing panencephalitis. Despite oral inosiplex and supportive care, patient developed generalized seizures with frequent myoclonic jerks and rapidly progressed into coma. Cortical blindness in subacute sclerosing panencephalitis can be an early indicator for fulminant course.

  13. Hippocratic screening and subchronic oral toxicity assessments of the methanol extract of Vatairea macrocarpa heartwood in rodents

    Directory of Open Access Journals (Sweden)

    Neyres Z. T. Jesus

    2012-07-01

    Full Text Available Vatairea macrocarpa (Benth. Ducke, Fabaceae, is popularly known as 'angelim'. Its heartwood macerate is used to treat inflammation, gastric ulcer, diabetes and infections. The oral acute and subchronic toxicity of the methanol extract of V. macrocarpa heartwood (MEVm was evaluated. In the Hippocratic screening, a single administration of MEVm was given orally to mice at doses ranging from 100 to 5000 mg/kg. In the subchronic study, MEVm was given orally as a daily administration for thirty days to Wistar rats at doses of 20, 100 and 500 mg/kg. In Hippocrtaic screening, doses of MEVm up to 5000 mg/kg did not cause any relevant behavioral changes or deaths thus making it impossible to establish the LD50. In subchronic assay, body weight gains and food intake were significantly reduced at the last week of treatment with 20 and 500 mg/kg dose. Serum triacylglycerides, total proteins and γ-glutamyltransferase activity were significantly reduced, while alkaline phosphatase activity was elevated. In hematological parameters, MEVm increased the percentage of segmented neutrophils cells at the highest dose. All alterations observed were minor in nature and were not accompanied by any relevant clinical signs or any histopathological changes. In conclusion, the results demonstrate relative safety profile of MEVm in the experimental animals.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats

    NARCIS (Netherlands)

    Jonker, D.; Kuper, C.F.; Fraile, N.; Estrella, A.; Rodríguez Otero, C.

    2003-01-01

    Lycopene, as a suspension in sunflower oil (20% w/w), was tested for subchronic toxicity by administration at dietary concentrations of 0, 0.25, 0.50, and 1.0% to groups of 20 male and 20 female Wistar rats for a period of 90 days. The lycopene examined in this study was derived from a fungal

  16. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Science.gov (United States)

    2010-07-01

    ...) Clinical pathology. Hematology and clinical chemistry examinations must be made on all animals, including..., ovaries, female mammary gland. (G) Others—all gross lesions and masses, skin. (12) Histopathology. (i) The... Pathology Testing in Toxicity and Safety Studies. Fundam. & Appl. Toxicol. 29:198-201. (1996) ...

  17. Oral two-generation reproduction toxicity study with NM-200 synthetic amorphous silica in Wistar rats

    NARCIS (Netherlands)

    Wolterbeek, A.; Oosterwijk, T.; Schneider, S.; Landsiedel, R.; Groot, D. de; Ee, R. van; Wouters, M.; Sandt, H. van de

    2015-01-01

    Synthetic amorphous silica (SAS) like NM-200 is used in a wide variety of technological applications and consumer products. Although SAS has been widely investigated the available reproductive toxicity studies are old and do not cover all requirements of current OECD Guidelines. As part of a

  18. Role of diet in absorption and toxicity of oral cadmium- A review of ...

    African Journals Online (AJOL)

    The role of diet or its components in the absorption, distribution and toxicity of cadmium (Cd) has received attention in recent times. Experimental evidence in literature strongly suggests that the absorption of Cd is dependent on factors such as age, pH, diet and intestinal metallothionein (MT) production. The chemical forms ...

  19. A one-year oral toxicity study of sodium stearoyl lactylate (SSL) in rats

    NARCIS (Netherlands)

    Lamb, J.; Hentz, K.; Schmitt, D.; Tran, N.; Jonker, D.; Junker, K.

    2010-01-01

    The toxicity of sodium stearoyl lactylate (SSL) was examined in Wistar rats fed diets containing 0, 1.25, 2.5, and 5% SSL for one year, equivalent to mean daily intakes of 558, 1115, and 2214. mg/kg/day in males and 670, 1339, and 2641. mg/kg/day in females, respectively. SSL was well tolerated at

  20. Acute Oral Toxicity and Brine Shrimp Lethality of Methanol Extract of ...

    African Journals Online (AJOL)

    Purpose: To determine, in Sprague Dawley rats, the toxicity profile of the methanol extract of Mentha spicata, a plant used in folklore medicine for the treatment of various forms of pain. Methods: The plant extract, at concentrations ranging from 100 - 0.07 mg/ml, was used to determine the median lethal concentration (LC50) ...

  1. Large Dataset of Acute Oral Toxicity Data Created for Testing in Silico Models (ASCCT meeting)

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are ...

  2. Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic.

    Science.gov (United States)

    Cerdá, Begoña; Cerón, José J; Tomás-Barberán, Francisco A; Espín, Juan Carlos

    2003-05-21

    The water-soluble ellagitanin punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (> or =2 g/L), the present study evaluated the possible toxic effect of punicalagin in Sprague-Dawley rats upon repeated oral administration of a 6% punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found in treated rats in any blood parameter analyzed (including the antioxidant enzymes gluthatione peroxidase and superoxide dismutase) with the exception of urea and triglycerides, which remained at low values throughout the experiment. Although the reason for the decrease is unclear, it could be due to the lower nutritional value of the punicalagin-enriched diet with respect to the standard rat food. Histopathological analysis of liver and kidney corroborated the absence of toxicity. In principle, the results reported here, together with the large safety margin considered, indicate the lack of toxic effect of punicalagin in rats during the 37 day period investigated. However, taking into account the high punicalagin content of pomegranate-derived foodstuffs, safety evaluation should be also carried out in humans with a lower dose and during a longer period of intake.

  3. Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

    OpenAIRE

    Douglas Rossi Jesus; Lorena Neris Barbosa; Thiago Bruno Lima Prando; Leonardo Franco Martins; Francielli Gasparotto; Karla Moraes Rocha Guedes; Douglas Cardoso Dragunski; Emerson Luiz Botelho Lourenço; Paulo Roberto Dalsenter; Arquimedes Gasparotto Junior

    2015-01-01

    The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameter...

  4. Oral Mucosa Dose Parameters Predicting Grade ≥3 Acute Toxicity in Locally Advanced Nasopharyngeal Carcinoma Patients Treated With Concurrent Intensity-Modulated Radiation Therapy and Chemotherapy: An Independent Validation Study Comparing Oral Cavity versus Mucosal Surface Contouring Techniques.

    Science.gov (United States)

    Li, Kaixin; Yang, Ling; Hu, Qiang-Ying; Chen, Xiao-Zhong; Chen, Ming; Chen, Yuanyuan

    2017-10-01

    To determine whether volumes based on the contours of the mucosal surface instead of the oral cavity can be used to predict grade ≥3 acute oral mucosa toxicity in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. A standardized method for the oral cavity (oral cavity contours, OCC) and a novel method for the mucosal surface (mucosal surface contours, MSC) were developed for the oral mucosa and prospectively applied to the radiation treatment plans of 92 patients treated with concurrent IMRT and chemotherapy for LANPC. Dose-volume histogram (DVH) data were extracted and then toxicity was analyzed. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Grade ≥3 acute oral mucosa toxicity occurred to 20.7% (19/92) of patients in the study. A highly significant dose-volume relationship between oral mucosa irradiation and acute oral mucosa toxicity was supported by using both oral cavity and mucosal surface contouring techniques. In logistic regression, body weight loss was an independent factor related to grade ≥3 acute toxicity for OCC and MSC (P=.017 and 0.005, respectively), and the independent factor of dosimetric parameters for OCC and MSC were V30Gy (P=.003) and V50Gy (P=.003) respectively. In the receiver operating characteristics curve, the areas under V30Gy of the OCC curves was 0.753 (P=.001), while the areas under V50Gy of MSC curves was 0.714 (P=.004); the cut-off value was 73.155% (sensitivity, 0.842; specificity, 0.671) and 14.32% (sensitivity, 0.842; specificity, 0.575), respectively. DVH analysis of mucosal surface volumes accurately predicts grade ≥3 acute oral mucosa toxicity in patients with LANPC receiving concurrent IMRT and chemotherapy, but in clinical practice the MSC method appears no better than the OCC one. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights

  5. Oral Mucosa Dose Parameters Predicting Grade ≥3 Acute Toxicity in Locally Advanced Nasopharyngeal Carcinoma Patients Treated With Concurrent Intensity-Modulated Radiation Therapy and Chemotherapy: An Independent Validation Study Comparing Oral Cavity versus Mucosal Surface Contouring Techniques

    Directory of Open Access Journals (Sweden)

    Kaixin Li

    2017-10-01

    Full Text Available PURPOSE: To determine whether volumes based on the contours of the mucosal surface instead of the oral cavity can be used to predict grade ≥3 acute oral mucosa toxicity in patients with locally advanced nasopharyngeal carcinoma (LANPC treated with concurrent intensity-modulated radiation therapy (IMRT and chemotherapy. METHODS AND MATERIALS: A standardized method for the oral cavity (oral cavity contours, OCC and a novel method for the mucosal surface (mucosal surface contours, MSC were developed for the oral mucosa and prospectively applied to the radiation treatment plans of 92 patients treated with concurrent IMRT and chemotherapy for LANPC. Dose–volume histogram (DVH data were extracted and then toxicity was analyzed. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. RESULTS: Grade ≥3 acute oral mucosa toxicity occurred to 20.7% (19/92 of patients in the study. A highly significant dose–volume relationship between oral mucosa irradiation and acute oral mucosa toxicity was supported by using both oral cavity and mucosal surface contouring techniques. In logistic regression, body weight loss was an independent factor related to grade ≥3 acute toxicity for OCC and MSC (P = .017 and 0.005, respectively, and the independent factor of dosimetric parameters for OCC and MSC were V30Gy (P = .003 and V50Gy (P = .003 respectively. In the receiver operating characteristics curve, the areas under V30Gy of the OCC curves was 0.753 (P = .001, while the areas under V50Gy of MSC curves was 0.714 (P = .004; the cut-off value was 73.155% (sensitivity, 0.842; specificity, 0.671 and 14.32% (sensitivity, 0.842; specificity, 0.575, respectively. CONCLUSION: DVH analysis of mucosal surface volumes accurately predicts grade ≥3 acute oral mucosa toxicity in patients with LANPC receiving concurrent IMRT and chemotherapy, but in clinical practice the MSC method appears no better than

  6. Oral dietary developmental toxicity study with polyvinyl acetate phthalate (PVAP) in the rat.

    Science.gov (United States)

    DeMerlis, C C; Schoneker, D R; Borzelleca, J F

    2014-10-01

    Polyvinyl acetate phthalate (PVAP) was evaluated in a developmental toxicity study with Crl:CD(SD) rats. Female rats were provided continual access to the formulated diets on days 6 through 20 of presumed gestation (DGs 6 through 20) at concentrations of 0%, 0.75%, 1.5% and 3%. All surviving rats were sacrificed and Caesarean-sectioned on DG 21. The following parameters were evaluated: viability, clinical observations, body weights, feed consumption, necropsy observations, Caesarean-sectioning and litter observations, including gravid uterine weights, fetal body weights and sex, and fetal gross external, soft tissue and skeletal alterations. There were no treatment-related adverse effects reported in the developmental toxicity study. The maternal and developmental no-observable-adverse-effect level (NOAEL) of PVAP was the highest concentration administered, i.e., 3.0% (equivalent to 2324mgPVAP/kg/day). Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats

    OpenAIRE

    Damiana Diniz Rosa; Maria do Carmo Gouveia Peluzio; Tania Pérez Bueno; Ernesto Vega Cañizares; Lilian Sánchez Miranda; Betty Mancebo Dorbignyi; Dainé Chong Dubí; Ivette Espinosa Castaño; Łukasz Marcin Grześkowiak; Célia Lucia de Luces Fortes Ferreira

    2014-01-01

    Introduction: Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. Objective: The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Methods: Wistar rat...

  8. Oral toxicity of the microcystin-containing cyanobacterium Planktothrix rubescens in European whitefish (Coregonus lavaretus)

    OpenAIRE

    Ernst, Bernhard; Höger, Stefan J.; O'Brien, Evelyn; Dietrich, Daniel R.

    2006-01-01

    The microcystin-producing cyanobacterium Planktothrix is one of the most widespread genera amongst toxin producing cyanobacteria in European lakes. In particular, the metalimnic blooms of Planktothrix rubescens have been associated with growing problems in the professional freshwater fishery as a decrease in yearly yields in the important coregonids fishery often coincides with the appearance of P. rubescens. P. rubescens is a cyanobacterial species known to produce toxic compounds, e.g. micr...

  9. Oral toxic exposure of titanium dioxide nanoparticles on serum biochemical changes in adult male Wistar rats

    OpenAIRE

    Dasal Vasantharaja; Venugopal Ramalingam; Gaddam Aadinaath Reddy

    2015-01-01

    Objective(s): Titanium dioxide (TiO2) nanoparticles (NPs) are widely used in commercial food additives and cosmetics worldwide. Uptake of these nanoparticulate into humans by different routes and may exhibit potential side effects, lags behind the rapid development of nanotechnology. Thus, the present study designed to evaluate the toxic effect of mixed rutile and anatase TiO2 NPs on serum biochemical changes in rats. Materials and Methods: In this study, adult male Wistar rats were randomly ...

  10. oral

    African Journals Online (AJOL)

    association between oral candidosis and. AIDS; the first documented patient with. AIDS had oral candidosis.3 A sub- stantial amount of data now emphasise its high prevalence in HIV-infected individuals. The manifestations of candidal infection in HIV-infected persons are restricted to superficial mucosal lesions of varying ...

  11. Survey of subacute sclerosing panencephalitis in Japan.

    Science.gov (United States)

    Abe, Yusaku; Hashimoto, Koichi; Iinuma, Kazuie; Ohtsuka, Yoko; Ichiyama, Takashi; Kusuhara, Koichi; Nomura, Keiko; Mizuguchi, Masashi; Aiba, Hideo; Suzuki, Yasuhiro; Mizusawa, Hidehiro; Hosoya, Mitsuaki

    2012-12-01

    Investigators conducted a retrospective epidemiological study of subacute sclerosing panencephalitis, a fatal disease caused by measles infection, over the past few years in Japan. Data on 118 cases obtained from a questionnaire sent to attending physicians were analyzed. The annual incidence of subacute sclerosing panencephalitis was approximately 0.03 cases per million from 2001 to 2005. Children infected with measles at a young age (panencephalitis, and those infected before 6 months of age showed earlier onset. Because a positive correlation was found between the prevalence of measles and the onset of subacute sclerosing panencephalitis, particularly among children infected at an early age, it is vital to eradicate measles infection by vaccination.

  12. Cytotoxicity and Acute Gastrointestinal Toxicity of Bacterial Cellulose-Poly (acrylamide-sodium acrylate Hydrogel: A Carrier for Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Manisha Pandey 1,2 * , Hira Choudhury 1, Mohd Cairul Iqbal Mohd Amin 2

    2016-12-01

    Full Text Available Background: Preliminary safety evaluation of polymer intended to use as drug delivery carrier is essential. Methods: In this study polyacrylamide grafted bacterial cellulose (BC/AM hydrogel was prepared by microwave irradiation initiated free radical polymerization. The synthesized hydrogel was subjected to in vitro cytotoxicity and acute gastrointestinal toxicity studies to evaluate its biological safety as potential oral drug delivery carrier. Results: The results indicate that hydrogel was non cytotoxic and did not show any histopathological changes in GI tract after a high dose of oral administration. Conclusion: The results revealed that hydrogel composed of bacterial cellulose and polyacrylamide is safe as oral drug delivery carrier.

  13. Short-term toxicity study of ST-20 (NSC-741804) by oral gavage in Sprague-Dawley rats.

    Science.gov (United States)

    Terse, Pramod S; Johnson, Jerry D; Hawk, Michael A; Ritchie, Glenn D; Ryan, Michael J; Vasconcelos, Daphne Y; Contos, Denise A; Perrine, Susan P; Peggins, James O; Tomaszewski, Joseph E

    2011-06-01

    ST-20 (sodium 2,2-dimethylbutyrate) is a potential therapeutic agent for treatment of β-thalassemia and sickle cell disease. A subchronic oral toxicity study was conducted in Sprague-Dawley rats (10/sex/dose) at gavage dosages of 0 (vehicle control), 200, 600, or 1,000 mg/kg, once daily for up to 15 days followed by a 14-day recovery. Ataxia (females), rough coat/thin appearance (males), and decreased body weights were observed at 1,000 mg/kg. Functional observational battery (FOB) deficits were observed more frequently in females and included decreased body tone, rectal temperature, emotional reactivity, neuromotor-neuromuscular activity (as exhibited by a deficit in visual/tactile placing accuracy, ataxia, hind limb dragging, and decreased grip strength), and rearing. ST-20 caused a decrease in WBC/RBC counts and RBC parameters; increase in reticulocytes and red cell inclusion bodies; decrease in total protein, globulin, and glucose; and increase in AG ratio. Micronucleated polychromatic erythrocytes of the bone marrow increased significantly in males at 1,000 mg/kg. Mean liver and kidney weights increased, and hepatocellular hypertrophy was observed in males at 1,000 mg/kg. Toxicologic findings were fully recovered during the 14-day recovery period. In conclusion, the no-observed adverse effect level for FOB and general toxicity was 200 mg/kg following gavage administration of ST-20 for up to 15 consecutive days.

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

    Science.gov (United States)

    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.

  15. Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children.

    Science.gov (United States)

    Aljebab, Fahad; Choonara, Imti; Conroy, Sharon

    2017-01-01

    Long courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels. A literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included. One hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths). Weight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.

  16. Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children.

    Directory of Open Access Journals (Sweden)

    Fahad Aljebab

    Full Text Available Long courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels.A literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included.One hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths.Weight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.

  17. MRI in subacute sclerosing panencephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Tuncay, R. [Department of Neurology, Istanbul Medical Faculty, University of Istanbul (Turkey); Akman-Demir, G. [Department of Neurology, Istanbul Medical Faculty, University of Istanbul (Turkey); Goekyigit, A. [Department of Neurology, Istanbul Medical Faculty, University of Istanbul (Turkey); Eraksoy, M. [Department of Neurology, Istanbul Medical Faculty, University of Istanbul (Turkey); Barlas, M. [Department of Neurology, Istanbul Medical Faculty, University of Istanbul (Turkey); Tolun, R. [Department of Neurology, Istanbul Medical Faculty, University of Istanbul (Turkey); Guersoy, G. [Department of Neurology, Istanbul Medical Faculty, University of Istanbul (Turkey)

    1996-10-01

    Subacute sclerosing panencephalitis (SSPE) is a progressive, slow virus infection of the brain, caused by the measles virus, attacking children and young adults. We investigated 15 patients with SSPE by MRI, with 5 normal and 10 pathological results. In the early period, lesions were in the grey matter and subcortical white matter. They were asymmetrical and had a predilection for the posterior parts of the hemispheres. Later, high-signal changes in deep white matter and severe cerebral atrophy were observed. Parenchymal lesions significantly correlated with the duration of disease. A significant relationship between MRI findings and clinical stage was observed in the 1st year of the disease. (orig.). With 4 figs., 1 tab.

  18. A 6-week oral gavage toxicity study of a novel galacto-oligosaccharide in juvenile rats.

    Science.gov (United States)

    Kobayash, T; Ishida, S; Kaneko, K; Onoue, M

    2014-07-01

    A novel galacto-oligosaccharide (GOS) was administered by gavage to groups (10 males and 10 females) of Sprague-Dawley specific pathogen-free rats for 6 weeks from day 4 after birth at doses of 0, 500, 1000, or 2000 mg/kg/day. Each pup was subjected to a variety of observations to examine for development effects/changes after birth: general condition, clinical signs, functional examinations, grip strength and spontaneous movement, body weight and feed consumption, external differentiation, ophthalmological examination, urinalysis (including water consumption), hematology, blood chemistry, necropsy, organ weight, and histopathology. During the study period, no deaths occurred in any group and there were no observed effects from administration of GOS. Therefore, it was concluded that GOS had no effects on the development of animals 4 days after birth. Since, there were no abnormalities due to administration of GOS in the macroscopic examination, organ weight or histopathology of the reproductive organs or differentiation (incisor eruption and eyelid opening) of males or females, it was concluded that repeated oral administration of GOS at 2000 mg/kg/day for 6 weeks from day 4 after birth had : no effects on postnatal development. The no observed effect level of GOS by repeated oral administration for 6 weeks from day 4 after birth was 2000 mg/kg/day for both males and females under the conditions of this study. © The Author(s) 2014.

  19. Towards a test to predict 5-fluorouracil toxicity: Pharmacokinetic data for thymine and two sequential metabolites following oral thymine administration to healthy adult males

    NARCIS (Netherlands)

    Duley, John A.; Ni, Ming; Shannon, Catherine; Norris, Ross L.; Sheffield, Lesley; Harris, Marion; van Kuilenburg, Andre B. P.; Mead, Scott; Cameron, Andrew; Helsby, Nuala; George, Rani; Charles, Bruce G.

    2016-01-01

    The fluoropyrimidine drugs 5-fluorouracil and its oral prodrug capecitabine remain first line therapy for solid tumours of the neck, breast and colon. However, significant and unpredictable toxicity affects about 10-25% of patients depending upon the mode of 5-fluorouracil delivery. The

  20. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

  1. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement

    NARCIS (Netherlands)

    Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Sottocornola, Lara; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Paganelli, Corrado; Majorana, Alessandra; Gastaldi, Giorgio; Bossi, Paolo; Berruti, Alfredo; Pavanato, Giovanni; Nicolai, Piero; Maroldi, Roberto; Barasch, Andrei; Russi, Elvio G.; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M.

    2016-01-01

    Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis,

  2. Familial subacute sclerosing panencephalitis associated with short latency.

    Science.gov (United States)

    Sharma, Vinod; Gupta, Vineet B; Eisenhut, Michael

    2008-03-01

    The familial recurrence of subacute sclerosing panencephalitis is rare. The study of such cases and a comparison of intrafamilial with sporadic cases of subacute sclerosing panencephalitis may shed light on important pathogenetic factors. We report on the occurrence of subacute sclerosing panencephalitis in two brothers from rural India, who contracted measles infection simultaneously at ages 3 and 11 years. They developed subacute sclerosing panencephalitis 21 and 37 months later, respectively. A diagnosis of subacute sclerosing panencephalitis was based on history, electroencephalographic changes, and significantly raised levels of cerebrospinal-fluid anti-measles virus immunoglobulin G. A comparison of intrafamilial with sporadic cases of subacute sclerosing panencephalitis revealed that latency in familial subacute sclerosing panencephalitis involved a median of 6.4 years (range, 1.0-10.9), significantly (P panencephalitis from the Indian subcontinent. We confirmed a more rapid manifestation of subacute sclerosing panencephalitis after measles virus infection in intrafamilial compared with sporadic subacute sclerosing panencephalitis.

  3. Hematological and biochemical changes due to short-term oral administration of imidacloprid

    OpenAIRE

    Balani, Tarun; Agrawal, Seema; A M Thaker

    2011-01-01

    Subacute toxicity of repeated (28 day) oral administration of imidacloprid in male White Leghorn (WLH) chicks was assessed. One hundred and twenty-five birds were divided into five groups, with each group containing 25 birds. The birds of group C1 were given no treatment and served as control. Group C2 was administered groundnut oil (1 ml/kg) and served as control (vehicle). Group I1 was given 1/40th of apparent LD50 (ALD50) (1.25 mg/kg), and group I2 was put on 1/30th of ALD50 (1.67 mg/kg), ...

  4. Clinical effectiveness, toxicity, and failure patterns of helical tomotherapy for postoperative oral cavity cancer patients

    Directory of Open Access Journals (Sweden)

    Hsieh CH

    2014-03-01

    Full Text Available Chen-Hsi Hsieh,1–3 Pei-Wei Shueng,1,4 Li-Ying Wang,5 Li-Jen Liao,6 Yu-Chin Lin,7 Ying-Shiung Kuo,8 Wu-Chia Lo,6 Chien-Fu Tseng,8 Hui-Ju Tien,1 Hsiu-Ling Chou,9,10 Yen-Ping Hsieh,11 Le-Jung Wu,1 Yu-Jen Chen3,12–14 1Department of Radiation Oncology, Far Eastern Memorial Hospital, 2Department of Medicine, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Department of Radiation Oncology, National Defense Medical Center, 5School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, 6Department of Otolaryngology, 7Division of Medical Oncology and Hematology, Department of Internal Medicine, 8Department of Dentistry and Oral Surgery, 9Department of Nursing, Far Eastern Memorial Hospital, 10Department of Nursing, Oriental Institute of Technology, Taipei, 11Department of Senior Citizen Service Management, National Taichung University of Science and Technology, Taichung, 12Department of Radiation Oncology, 13Department of Medical Research, Mackay Memorial Hospital, 14Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan Background: The outcome of postoperative high- and intermediate-risk oral cavity cancer (OCC patients receiving helical tomotherapy (HT remains limited. Materials and methods: Between November 2006 and November 2012, 53 postoperative high- and intermediate-risk OCC patients treated with HT were enrolled. Results: The 4-year locoregional, local, and regional control rates were 66%, 76.4%, and 94.3%, respectively. The 4-year locoregional control rates of oral tongue and buccal mucosa cancer were 88.3% and 37.1%, respectively (P=0.012. Eleven (20.8% patients experienced locoregional failure. In-field failure occurred in six of 53 (11.3% in the primary area and three of 53 (5.7% in the regional lymph-node area. No marginal failure was noted. Two of 53 (3.8% experienced out-of-field failure. The rates of grade 3 dermatitis

  5. Pseudotumor cerebri secondary to subacute sclerosing panencephalitis.

    Science.gov (United States)

    Ayçiçek, Ali; Işcan, Akin; Ceçe, Hasan

    2009-05-01

    Unusual presentations are not rare in subacute sclerosing panencephalitis. Five patients initially diagnosed with pseudotumor cerebri were ultimately determined to have pseudotumor cerebri secondary to subacute sclerosing panencephalitis. The present study retrospectively reviewed 56 cases history, neurologic symptoms, and clinical and laboratory data, as well as the outcomes. On admission, five patients (group 1) presenting with pseudotumor cerebri exhibited bilateral papilledema, and in each of them cranial magnetic resonance imaging revealed small lateral ventricles, effacement of the subarachnoid space, and no mass lesion. On admission, 51 patients (group 2) had no pseudotumor cerebri findings. The year of original measles infection, the interval between measles and onset of subacute sclerosing panencephalitis, and initial neurologic symptoms were similar, but length of symptoms before diagnosis of subacute sclerosing panencephalitis was shorter in group 1, and the clinical stage of subacute sclerosing panencephalitis on admission was more advanced in group 2. Cerebrospinal fluid mean open pressure was 378 +/- 22 H(2)O in group 1 and 146 +/- 28 H(2)O in group 2; cerebrospinal fluid antibody was 2038 +/- 768 U/L in group 1 and was 664 +/- 214 U/L in group 2. Only three of the five patients with pseudotumor cerebri had typical periodic discharges on electroencephalographic examination. These findings suggest that subacute sclerosing panencephalitis can cause pseudotumor cerebri.

  6. Toxic effects of orally ingested oil from the Deepwater Horizon spill on laughing gulls.

    Science.gov (United States)

    Horak, K E; Bursian, S J; Ellis, C K; Dean, K M; Link, J E; Hanson-Dorr, K C; Cunningham, F L; Harr, K E; Pritsos, C A; Pritsos, K L; Healy, K A; Cacela, D; Shriner, S A

    2017-12-01

    The explosion of the Deepwater Horizon oil rig released, millions of gallons of oil into the environment, subsequently exposing wildlife, including numerous bird species. To determine the effects of MC252 oil to species relevant to the Gulf of Mexico, studies were done examining multiple exposure scenarios and doses. In this study, laughing gulls (Leucophaeus atricilla, LAGU) were offered fish injected with MC252 oil at target doses of 5 or 10mL/kg bw per day. Dosing continued for 27 days. Of the adult, mixed-sex LAGUs used in the present study, ten of 20 oil exposed LAGUs survived to the end of the study; a total of 10 of the oil exposed LAGUs died or were euthanized within 20 days of initiation of the study. Endpoints associated with oxidative stress, hepatic total glutathione (tGSH), oxidized glutathione (GSSG) and reduced glutathione (rGSH) significantly increased as mean dose of oil increased, while the rGSH:GSSG ratio showed a non-significant negative trend with oil dose. A significant increase in 3-methyl histidine was found in oil exposed birds when compared to controls indicative of muscle wastage and may have been associated with the gross observation of diminished structural integrity in cardiac tissue. Consistent with previous oil dosing studies in birds, significant changes in liver, spleen, and kidney weight when normalized to body weight were observed. These studies indicate that mortality in response to oil dosing is relatively common and the mortality exhibited by the gulls is consistent with previous studies examining oil toxicity. Whether survival effects in the gull study were associated with weight loss, physiologic effects of oil toxicity, or a behavioral response that led the birds to reject the dosed fish is unknown. Published by Elsevier Inc.

  7. Acetylcysteine in the treatment of subacute sinusitis: A double-blind placebo-controlled clinical trial.

    Science.gov (United States)

    Bahtouee, Mehrzad; Monavarsadegh, Gholamhosein; Ahmadipour, Mohammadjavad; Motieilangroodi, Mazyar; Motamed, Niloofar; Saberifard, Jamshid; Eghbali, Seyyedsajjad; Adibi, Hooman; Maneshi, Hesam; Malekizadeh, Hasan

    2017-01-01

    Sinusitis is a common disease with harmful effects on the health and finances of patients and the economy of the community. It is easily treated in most of its acute stages but is associated with some management difficulties as it goes toward chronicity. Therefore, we tried to improve the treatment of subacute sinusitis by using acetylcysteine, which is a safe mucolytic and antioxidant agent. Thirty-nine adult patients with subacute sinusitis proved by computed tomography (CT) were enrolled in a double-blind, placebo-controlled trial. They received oral amoxicillin-clavulanic acid and normal saline nasal drops for 10 days and oral pseudoephedrine for 7 days. In addition, the patients received acetylcysteine (600 mg orally, once daily) in the intervention group or placebo in the control group for 10 days. A paranasal CT scan was taken at baseline and 30 days after patients finished the treatment and was evaluated quantitatively by Lund-Mackay (LM) score. Symptoms and some aspects of quality of life also were assessed at baseline and 14 days after initiation and 30 days after termination of the treatment via the Sino-Nasal Outcome Test questionnaire. The groups showed no significant difference in LM score after treatment. A positive correlation was observed between the LM and SNOT-20 scores. We concluded that adding oral acetylcysteine to amoxicillin-clavulanic acid, pseudoephedrine, and intranasal normal saline has no benefit for the treatment of subacute sinusitis.

  8. In vivo toxicity studies of fusarium mycotoxins in the last decade: a review.

    Science.gov (United States)

    Escrivá, L; Font, G; Manyes, L

    2015-04-01

    This review summarizes the information regarding the in vivo studies of Fusarium mycotoxins in the last decade. The most common studies are classified as subacute toxicity, subchronic toxicity, acute toxicity, toxicokinetic studies and teratogenicity in order of importance. The most used animals in in vivo studies are pigs, rats, chickens and mice. Fumonisin B1, deoxynivalenol, zearalenone, nivalenol and T-2 toxin are the most studied fusarotoxins. Studies with combinations of mycotoxins are also frequent, deoxynivalenol generally being one of them. The predominant route of administration is oral, administered mostly in the form of naturally contaminated feed. Other administration routes also used are intraperitoneal, intravenous and subcutaneous. In vivo research on Fusarium mycotoxins has increased since 2010 highlighting the need for such studies in the field of food and feed safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Comparison of acute and subacute genitourinary and gastrointestinal adverse events of radiotherapy for prostate cancer using intensity-modulated radiation therapy, three-dimensional conformal radiation therapy, permanent implant brachytherapy and high-dose-rate brachytherapy

    NARCIS (Netherlands)

    Morimoto, Masahiro; Yoshioka, Yasuo; Konishi, Koji; Isohashi, Fumiaki; Takahashi, Yutaka; Ogata, Toshiyuki; Koizumi, Masahiko; Teshima, Teruki; Bijl, Henk P; van der Schaaf, Arjen; Langendijk, Johannes A; Ogawa, Kazuhiko

    2014-01-01

    AIMS AND BACKGROUND: To examine acute and subacute urinary and rectal toxicity in patients with localized prostate cancer monotherapeutically treated with the following four radiotherapeutic techniques: intensity-modulated radiation therapy, three-dimensional conformal radiation therapy,

  10. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.

    Science.gov (United States)

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

    Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Wistar rats were randomly divided into three groups (n = 6/group): control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose), and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose). Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  11. Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

    Directory of Open Access Journals (Sweden)

    J.V. Joviano-Santos

    2014-07-01

    Full Text Available It has been demonstrated that carbon nanotubes (CNTs associated with sodium hyaluronate (HY-CNTs accelerate bone repair in the tooth sockets of rats. Before clinical application of HY-CNTs, it is important to assess their biocompatibility. Moreover, cardiac toxicity may be caused by the translocation of these particles to the blood stream. The aim of this study was to evaluate possible changes in cardiovascular function in male Wistar rats whose tooth sockets were treated with either CNTs or HY-CNTs (100 μg/mL, 0.1 mL. Blood pressure and heart rate were monitored in conscious rats 7 days after treatment. Cardiac function was evaluated using the Langendorff perfusion technique. The data showed no changes in blood pressure or heart rate in rats treated with either CNTs or HY-CNTs, and no significant changes in cardiac function were found in any of the groups. To confirm these findings, experiments were conducted in rats injected intraperitoneally with a high concentration of either CNTs or HY-CNTs (0.75 mg/kg. The same parameters were analyzed and similar results were observed. The results obtained 7 days following injection indicate that the administration of low concentrations of CNTs or HY-CNTs directly into tooth sockets did not cause any significant change in cardiovascular function in the rats. The present findings support the possibility of using these biocomposites in humans.

  12. Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Joviano-Santos, J.V.; Sá, M.A.; De Maria, M.L.A.; Almeida, T.C.S. [Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Geraldo, V.; Oliveira, S.; Ladeira, L.O. [Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2014-05-23

    It has been demonstrated that carbon nanotubes (CNTs) associated with sodium hyaluronate (HY-CNTs) accelerate bone repair in the tooth sockets of rats. Before clinical application of HY-CNTs, it is important to assess their biocompatibility. Moreover, cardiac toxicity may be caused by the translocation of these particles to the blood stream. The aim of this study was to evaluate possible changes in cardiovascular function in male Wistar rats whose tooth sockets were treated with either CNTs or HY-CNTs (100 μg/mL, 0.1 mL). Blood pressure and heart rate were monitored in conscious rats 7 days after treatment. Cardiac function was evaluated using the Langendorff perfusion technique. The data showed no changes in blood pressure or heart rate in rats treated with either CNTs or HY-CNTs, and no significant changes in cardiac function were found in any of the groups. To confirm these findings, experiments were conducted in rats injected intraperitoneally with a high concentration of either CNTs or HY-CNTs (0.75 mg/kg). The same parameters were analyzed and similar results were observed. The results obtained 7 days following injection indicate that the administration of low concentrations of CNTs or HY-CNTs directly into tooth sockets did not cause any significant change in cardiovascular function in the rats. The present findings support the possibility of using these biocomposites in humans.

  13. Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate.

    Science.gov (United States)

    Jesus, Douglas Rossi; Barbosa, Lorena Neris; Prando, Thiago Bruno Lima; Martins, Leonardo Franco; Gasparotto, Francielli; Guedes, Karla Moraes Rocha; Dragunski, Douglas Cardoso; Lourenço, Emerson Luiz Botelho; Dalsenter, Paulo Roberto; Gasparotto Junior, Arquimedes

    2015-01-01

    The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm.

  14. Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

    Directory of Open Access Journals (Sweden)

    Douglas Rossi Jesus

    2015-01-01

    Full Text Available The large consumption of biodegradable films from cassava starch acetate (FCSA as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm.

  15. Actividad antiulcerosa y toxicidad aguda oral de celulosa microcristalina suspensión al 12 % Antiulcer activity and oral acute toxicity of microcrystalline cellulose suspension 12 %

    Directory of Open Access Journals (Sweden)

    Pedro Gilberto Barzaga Fernández

    2004-08-01

    Full Text Available La celulosa microcristalina ha sido usada recientemente en el tratamiento de la gastritis alcalina por reflujo biliar duodenogástrico. Se realizó un estudio toxicológico y se evaluó el efecto antiulceroso de celulosa microcristalina suspensión al 12 % en ratas. La determinación de la toxicidad aguda oral se realizó mediante el ensayo de dosis límite, mediante la administración de una dosis de 2 000 mg/kg a animales de uno y otro sexos. El efecto protector sobre la mucosa gástrica se evaluó sobre lesiones inducidas por taurocolato de sodio y se ensayaron las dosis de 240, 360 y 540 mg/kg de la suspensión. Como resultado en el estudio toxicológico, no se produjo mortalidad para la dosis ensayada, por lo que se clasificó la sustancia como no tóxica. Mientras que las diferentes dosis empleadas para el efecto antiulceroso disminuyeron el número y la intensidad de las lesiones significativamente de manera dosis dependiente. La dosis efectiva media fue de 356,8 mg/kg. Tales hallazgos permiten sugerir que el efecto protector de celulosa microcristalina suspensión al 12 % podría estar dado por una inactivación de los ácidos biliares o por una alteración en la cantidad o composición de la capa de moco que recubre la mucosa gástrica.The microcrystalline cellulose has been used recently in the treatment of alkaline gastritis due to duodenogastric biliary reflux. A toxicological study was conducted and the antiulcer effect of microcrystalline cellulose suspension 12 % was evaluated in rats. Acute oral toxicity was determined by the limited dose test through the administration of a dose of 2 000 mg/kg to animals of both sexes. The protective effect over the gastric mucosa was evaluated in the injuries induced by sodium taurocholate. Doses of 240, 360 and 540 mg/kg of the suspension were tested. As a result, no mortality was reported for the tested dose in the toxicological study. Therefore, the substance was clasiffied as non toxic. The

  16. Evaluation of 90-day oral rat toxicity studies on the food additive, gum ghatti.

    Science.gov (United States)

    Maronpot, Robert R; Davis, Jeffrey; Moser, Glenda; Giri, Dipak K; Hayashi, Shim-Mo

    2013-01-01

    Gum ghatti, a polysaccharide of natural origin, is used in foods as a thickening, gelling, emulsifying and stabilizing agent. In a 90-day toxicity study following Organization for Economic Co-operation and Development (OECD) Guideline #408, male and female Sprague-Dawley rats were exposed to 0 (control), 0.5, 1.5 and 5% gum ghatti in AIN-93M basal diet. Expected changes included increased full and empty cecal weights in 5% groups. Incidentally 2/10 females from the 5% gum ghatti group had a single colon ulcer with associated acute inflammation. In a second 90-day study increased cecal weights were present in Sprague-Dawley females exposed to 5% gum ghatti in AIN-93M and NIH-07 basal diets. A single colon ulcer with associated acute inflammation occurred in 1/20 control females given AIN-93M basal diet. The colon ulcers were considered a sporadic change possibly attributable to AIN-93M basal diet. In the second study a few statistically significant alterations in clinical chemistry were considered sporadic and unrelated to treatment. Feed consumption among treated and control groups was similar for each sex. Gum ghatti intake at the 5% dietary level ranged from 3044 to 3825mg/kg body weight/day. The 5% dietary administration was a NOAEL in both studies. NOAELs for males and females in the first study were 3044 and 3309mg/kg/day, respectively. NOAELs for females in the second study were 3670 and 3825mg/kg/day for AIN-93M and NIH-07 diets, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Speech and language therapy for aphasia following subacute stroke

    Directory of Open Access Journals (Sweden)

    Engin Koyuncu

    2016-01-01

    Full Text Available The aim of this study was to investigate the time window, duration and intensity of optimal speech and language therapy applied to aphasic patients with subacute stroke in our hospital. The study consisted of 33 patients being hospitalized for stroke rehabilitation in our hospital with first stroke but without previous history of speech and language therapy. Sixteen sessions of impairment-based speech and language therapy were applied to the patients, 30-60 minutes per day, 2 days a week, for 8 successive weeks. Aphasia assessment in stroke patients was performed with Gülhane Aphasia Test-2 before and after treatment. Compared with before treatment, fluency of speech, listening comprehension, reading comprehension, oral motor evaluation, automatic speech, repetition and naming were improved after treatment. This suggests that 16 seesions of speech and language therapy, 30-60 minutes per day, 2 days a week, for 8 successive weeks, are effective in the treatment of aphasic patients with subacute stroke.

  18. Possible progression of subacute lupus erythematosus--case report.

    Science.gov (United States)

    Brănişteanu, Daciana Elena; Lăbonţu, Andreea; Ciobanu, Delia; Stoleriu, Gabriela; Brănişteanu, D; Oanţă, A

    2014-01-01

    Subacute lupus erythematosus (SLE) is a specific form of lupus erythematosus characterized by prevalently cutaneous manifestations usually with a good prognosis. It is more common in patients aged 15 to 70 years, and there is a female predilection. This form accounts for 10% of all lupus erythematosus cases. We present the case of a 57-year-old male patient diagnosed at age 35 with chronic psoriasiform subacute lupus erythematosus, pathologically confirmed at the Iaşi Dermatology Clinic. At the age of 54 years he had multiple ischemic strokes, followed by deterioration of general status, and at 56 years deep vein thrombosis in the right leg. The patient presented the erythematous-squamous lesions specific to psoriasiform SLE localized both on the upper third of the body and knees and associated with submucosal lesions of the lower lip, oral mucosa and appendages. The patient also presented hypo- and hyperpigmentated atrophic scar-like lesions. Laboratory tests performed during the last two admissions showed the presence of anti-ds DNA and antiphospholipid antibodies, inflammatory syndrome, and nitrogen retention syndrome. Treatment consisted of systemic and local dermatocorticoids and associated medication, emollient lotions and creams with SPF 50+, with slowly favorable progression. The peculiarity of the case lies in the chronic progression without significant systemic involvement for 19 years, and then in 2 years the antiphospholipid antibody syndrome and a shift to systemic lupus erythematosus to occur.

  19. Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith

    Directory of Open Access Journals (Sweden)

    Liberio Silvana A

    2011-11-01

    Full Text Available Abstract Background Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of M. fasciculata geopropolis against oral pathogens, its effects on S. mutans biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on S. mutans and its immunotoxicological potential. Methods Antimicrobial activities of three hydroalcoholic extracts (HAEs of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v and chlorhexidine (0.12%, w/w were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs. Results Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for S. mutans and C. albicans, but presented no activity against L. acidophilus. The MBCs for HAE-2 and HAE-3 against S. mutans were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on S. mutans biofilms after 3 h of treatment. Significant differences (p Conclusions In summary, geopropolis produced by M. fasciculata can exert antimicrobial action against S. mutans and C. albicans, with significant inhibitory activity against S. mutans biofilms. The extract with the highest flavonoid concentration, HAE-2, presented the

  20. Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith.

    Science.gov (United States)

    Liberio, Silvana A; Pereira, Antônio Luís A; Dutra, Richard P; Reis, Aramys S; Araújo, Maria José A M; Mattar, Nadia S; Silva, Lucilene A; Ribeiro, Maria Nilce S; Nascimento, Flávia Raquel F; Guerra, Rosane N M; Monteiro-Neto, Valério

    2011-11-04

    Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of M. fasciculata geopropolis against oral pathogens, its effects on S. mutans biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on S. mutans and its immunotoxicological potential. Antimicrobial activities of three hydroalcoholic extracts (HAEs) of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v) and chlorhexidine (0.12%, w/w) were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs. Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for S. mutans and C. albicans, but presented no activity against L. acidophilus. The MBCs for HAE-2 and HAE-3 against S. mutans were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on S. mutans biofilms after 3 h of treatment. Significant differences (p geopropolis-based gel, but an increase in the production of IL-4 and IL-10, anti-inflammatory cytokines, was detected. In summary, geopropolis produced by M. fasciculata can exert antimicrobial action against S. mutans and C. albicans, with significant inhibitory activity against S. mutans biofilms. The extract with the

  1. Subacute sclerosing panencephalitis: an update.

    Science.gov (United States)

    Gutierrez, Jose; Issacson, Richard S; Koppel, Barbara S

    2010-10-01

    Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis occurring after infection with measles virus. The prevalence of the disease varies depending on uptake of measles vaccination, with the virus disproportionally affecting regions with low vaccination rates. The physiopathology of the disease is not fully understood; however, there is evidence that it involves factors that favour humoral over cellular immune response against the virus. As a result, the virus is able to infect the neurons and to survive in a latent form for years. The clinical manifestations occur, on average, 6 years after measles virus infection. The onset of SSPE is insidious, and psychiatric manifestations are prominent. Subsequently, myoclonic seizures usually lead to a final stage of akinetic mutism. The diagnosis is clinical, supported by periodic complexes on electroencephalography, brain imaging suggestive of demyelination, and immunological evidence of measles infection. Management of the disease includes seizure control and avoidance of secondary complications associated with the progressive disability. Trials of treatment with interferon, ribavirin, and isoprinosine using different methodologies have reported beneficial results. However, the disease shows relentless progression; only 5% of individuals with SSPE undergo spontaneous remission, with the remaining 95% dying within 5 years of diagnosis.

  2. Proton pump inhibitor-induced subacute cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

    Sandholdt, L H; Laurinaviciene, R; Bygum, Anette

    2014-01-01

    Drug-induced subacute cutaneous lupus erythematosus (SCLE) has been known in the literature since 1985 and is increasingly recognized.......Drug-induced subacute cutaneous lupus erythematosus (SCLE) has been known in the literature since 1985 and is increasingly recognized....

  3. A 90-day oral toxicity study of purple corn color, a natural food colorant, in F344 rats.

    Science.gov (United States)

    Nabae, Kyoko; Hayashi, Shim-Mo; Kawabe, Mayumi; Ichihara, Toshio; Hagiwara, Akihiro; Tamano, Seiko; Tsushima, Yoko; Uchida, Koji; Koda, Takatoshi; Nakamura, Mikio; Ogawa, Kumiko; Shirai, Tomoyuki

    2008-02-01

    A subchronic oral toxicity study of purple corn color (PCC), a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.5%, 1.5% and 5.0% for 90 days. No mortalities occurred during the treatment period. No treatment-related changes in the body weight, food and water consumption, ophthalmology, hematology, organ weight data and histopathology were observed. Regarding general conditions and gross pathology, staining of fur and black feces were noted in rats of the 1.5% and 5.0% diet groups. Moreover, brown urine and black material in the stomach, small and large intestine were evident in rats receiving 5.0%. These changes were considered due to the anthocyanin content. On clinical chemistry analysis, total cholesterol, phospholipid and triglyceride were significantly lowered in both sexes of the 5.0% group, but these were not considered to be toxicologically significant. Thus, the No-observed-adverse-effect-level (NOAEL) was judged to be 5.0% in diet for both sexes (male: 3542 mg/kg/day, female: 3849 mg/kg/day) for PCC under the present experimental conditions.

  4. Role of CSF serology in follow-up of subacute Sclerosing Panencephalitis patients on treatment

    Directory of Open Access Journals (Sweden)

    Gupta E

    2006-01-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is a progressive inflammatory disease of the central nervous system with poor prognosis and high mortality. No effective treatment has a proven role; oral isoprinosine and intrathecal administration of a-interferon may prolong survival. We report an unusual case of adult onset SSPE patient on treatment with significant clinical improvement, even in the absence of conversion to seronegativity in either CSF or serum, on follow-up serological examination.

  5. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

    Directory of Open Access Journals (Sweden)

    Paula Abal

    2017-02-01

    Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

  6. A fusion protein containing a lepidopteran-specific toxin from the South Indian red scorpion (Mesobuthus tamulus and snowdrop lectin shows oral toxicity to target insects

    Directory of Open Access Journals (Sweden)

    Fitches Elaine

    2006-03-01

    Full Text Available Abstract Background Despite evidence suggesting a role in plant defence, the use of plant lectins in crop protection has been hindered by their low and species-specific insecticidal activity. Snowdrop lectin (Galanthus nivalis agglutinin; GNA is transported to the haemolymph of insects after oral ingestion, and can be used as a basis for novel insecticides. Recombinant proteins containing GNA expressed as a fusion with a peptide or protein, normally only toxic when injected into the insect haemolymph, have the potential to show oral toxicity as a result of GNA-mediated uptake. Results A gene encoding a toxin, ButaIT, from the red scorpion (Mesobuthus tamulus was synthesised and assembled into expression constructs. One construct contained ButaIT alone, whereas the other contained ButaIT fused N-terminally to a GNA polypeptide (ButaIT/GNA. Both recombinant proteins were produced using the yeast Pichia pastoris as an expression host, and purified. Recombinant ButaIT and ButaIT/GNA were acutely toxic when injected into larvae of tomato moth (Lacanobia oleracea, causing slow paralysis, leading to mortality or decreased growth. ButaIT/GNA was chronically toxic when fed to L. oleracea larvae, causing decreased survival and weight gain under conditions where GNA alone was effectively non-toxic. Intact ButaIT/GNA was detected in larval haemolymph from insects fed the fusion protein orally, demonstrating transport of the linked polypeptide across the gut. Proteolysis of the fusion protein was also observed. ButaIT/GNA was significantly more toxic that GNA alone when fed to the homopteran Nilaparvata lugens (rice brown planthopper in liquid artificial diet. Conclusion The ButaIT/GNA recombinant fusion protein is toxic to lepidopteran larvae both when injected and when fed orally, showing the utility of GNA as a carrier to transport potentially toxic peptides and proteins across the insect gut. Although ButaIT has been claimed to be lepidopteran

  7. SUBACUTE AND MULTIGENERATIONAL TOXICITY EVALUATION OF CASTOR OIL POLYMER INGESTION IN RATS AVALIAÇÃO DA TOXICIDADE SUBAGUDA E MULTIGERACIONAL DA INGESTÃO DE DERIVADO DO POLÍMERO DE MAMONA EM RATOS

    Directory of Open Access Journals (Sweden)

    Gilberto Chierice

    2009-04-01

    Full Text Available Castor oil polymer is a biomaterial that can be used to fill bone defects. Biomaterials should present some characteristics such as: biocompatibility, inert, absence of toxin radical and vapour discharge and permit the organism to recognize them as a part of their structure. The aim of this study was to investigate changes in water ingestion, feed intake, weight gain and toxic effects in rats (Rattus norvegicus after ingestion of 0, 10, 25 and 50% of castor oil polymer (COP, Ricinus communis. In groups that received 10 and 25% of COP the weight gain was smaller than the control group. Feed intake in control group was greater than in groups 10 and 50% COP. The intake of castor oil polymer reduced feed intake and water ingest probably because of the palatability of the product. In the second part of this study (multigenerational there were no toxic effects in the offspring, as external birth defects or alterations incompatible with life, in spite of the fact that lower weight were observed in males and females of the second generation.

    KEY WORDS: Biomaterials, bone defects, polymer, Ricinus communis. Os biomateriais são polímeros artificiais desenvolvidos para substituir tecidos orgânicos danificados e preencherem falhas ósseas. Eles devem apresentar características como a biocompatibilidade, serem inertes, não liberarem vapores e radicais tóxicos e permitirem ao organismo reconhecê-los como parte de sua estrutura. Procurou-se determinar a ingestão de água, o consumo de ração, ganho de peso e possível efeito tóxico decorrentes da ingestão de três doses (10%, 25% e 50% do derivado do polímero de mamona (PM, Ricinus communis, adicionado à água de bebida, em ratos (Rattus norvegicus. Nos grupos que receberam 10% e 25% do PM, o ganho de peso foi menor (P?0,05, quando comparado ao grupo-controle. O consumo de ração nos grupos que receberam 10% e 50% de PM foi menor em relação ao grupo-controle. A ingestão do pol

  8. Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Tanja [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); The Johns Hopkins Hospital School of Medicine, Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Neuroradiology, Baltimore, MD (United States); Thomalla, Goetz [University Medical Center Hamburg-Eppendorf, Department of Neurology, Hamburg (Germany); Goebell, Einar [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); Piotrowski, Anna [The Johns Hopkins University School of Medicine, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD (United States); Yousem, David Mark [The Johns Hopkins Hospital School of Medicine, Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Neuroradiology, Baltimore, MD (United States)

    2015-02-17

    Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis. (orig.)

  9. Short-Term Effects of Oral Administration of Pistacia Lentiscus Oil on Tissue-Specific Toxicity and Drug Metabolizing Enzymes in Mice

    OpenAIRE

    Samir Attoub; Sherif M. Karam; Abderrahim Nemmar; Kholoud Arafat; Annie John; Wafa Al-Dhaheri; Mahmood Ahmed Al Sultan; Haider Raza

    2014-01-01

    Background: Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Methods: Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days. Results: Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant ...

  10. Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract.

    Science.gov (United States)

    Sertié, J A A; Woisky, R G; Wiezel, G; Rodrigues, M

    2005-05-01

    Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.

  11. Genotoxicity and 28-day oral toxicity studies of a functional food mixture containing maltodextrin, white kidney bean extract, mulberry leaf extract, and niacin-bound chromium complex.

    Science.gov (United States)

    Wu, Cheng-Tien; Chiu, Chen-Yuan; Huang, Chun-Fa; Peng, Fu-Chuo; Liu, Shing-Hwa

    2017-11-16

    Steady-fiber granule (SFG) is a functional food mixture that is composed of four major ingredients, resistant maltodextrin, white kidney bean (Phaseolus vulgaris) extract, mulberry leaf (Morus alba L.) extract, and niacin-bound chromium complex. This study focused on determining the safety of SFG. Genotoxicity and 28-day oral toxicity were evaluated. SFG did not induce mutagenicity in the bacterial reverse mutation assay using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) in the presence or absence of metabolic activation (S9 system). SFG also did not induce clastogenic effects in Chinese hamster ovary cells with or without S9 treatment. Similarly, SFG did not induce genotoxicity in a micronucleus test conducted with mice. A dose-dependent 28-day oral toxicity assessment of SFG for rats revealed no significant effects on mortality, body weight, selected organ weights, and behavior. Evaluations of hematology, clinical biochemistry, and histopathology showed no adverse effects in rats treated with SFG. These results suggest that SFG has no significant mutagenic or toxic properties, and the no observed adverse effect level of SFG was defined as at least 5000 mg/kg/day orally for 28 days for male and female rats. Copyright © 2017. Published by Elsevier Inc.

  12. Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model.

    Science.gov (United States)

    Parayath, Neha N; Nehoff, Hayley; Norton, Samuel E; Highton, Andrew J; Taurin, Sebastien; Kemp, Roslyn A; Greish, Khaled

    2016-01-01

    Oral administration of paclitaxel (PTX), a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid) (SMA). Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg) compared to the commercially available PTX formulation (PTX [Ebewe]). In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe). In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer.

  13. Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

    Directory of Open Access Journals (Sweden)

    Rex Munday

    2017-06-01

    Full Text Available Ciguatoxins (CTXs, and possibly maitotoxins (MTXs, are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean. The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia, 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS, and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

  14. 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.

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Effect of aqueous extract of Crocus sativus L. (saffron) stigma against subacute effect of diazinon on specific biomarkers in rats.

    Science.gov (United States)

    Moallem, Seyed Adel; Hariri, Alireza Timcheh; Mahmoudi, Mahmoud; Hosseinzadeh, Hossein

    2014-03-01

    In this study, the effect of aqueous extract of Crocus sativus L. (saffron) stigma was studied against subacute toxicity of diazinon (DZN) on specific biochemical markers in rats. Vitamin E (200 IU/kg) and the aqueous extract of saffron at doses 50, 100 and 200 mg/kg were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Red blood cell (RBC) cholinesterase activity was inhibited by DZN and this effect was not affected by vitamin E or saffron plus DZN. The levels of serum tumor necrosis factor-α (inflammation marker), direct 8-iso-prostaglandin F(2α) (oxidative stress marker) and soluble protein-100 β (S100β, neuronal damage marker) were increased significantly by DZN. The saffron extract inhibited the effect of DZN on these biomarkers levels. However, vitamin E was able to only reduce 8-iso-prostaglandin F(2α) and S100β levels. This study showed that the aqueous extract of saffron prevents DZN-induced rise of several specific inflammation, oxidative stress and neuronal damage biomarkers.

  16. Subacute Sclerosing Panencephalitis: The Foothold in Undervaccination.

    Science.gov (United States)

    Holt, Rebecca L; Kann, Dylan; Rassbach, Caroline E; Schwenk, Hayden T; Ritter, Jana M; Rota, Paul A; Elbers, Jorina

    2016-12-01

    Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles infection. We present a case of a fully vaccinated 3-year-old boy who was diagnosed with and treated for autoimmune encephalitis before arriving at a diagnosis of SSPE. We discuss the challenges of diagnosing SSPE in developed countries. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. [Oral toxicity at 60-days of sacha inchi oil (Plukenetia volubilis L.) and linseed (Linum usitatissimum L.), and determination of lethal dose 50 in rodents].

    Science.gov (United States)

    Gorriti, Arilmi; Arroyo, Jorge; Quispe, Fredy; Cisneros, Braulio; Condorhuamán, Martín; Almora, Yuan; Chumpitaz, Víctor

    2010-09-01

    To evaluate the oral toxicity at 60 days and to determine the lethal dose 50 (LD 50) of raw sacha inchi (Plukenetia volubilis L.) and linseed (Linum ussitatisimum) oils in Holtzman rats and mice of the strain Balb C57 respectively. For the evaluation of the oral toxicity of repeated doses for 60 days, 24 male Holtzman rats were used, divided in three groups of 8 each, the groups were: physiologic saline solution 4 mL/kg (FSS), sacha inchi oil 0.5 mL/kg (SI05) and linseed oil 0.5 mL/kg (L05), during the experiment the body weight was controlled weekly, and signs of toxicity in the research groups, as well as total cholesterol, HDL, glucose, triglycerides and alkaline phosphatase at days 30 and 60 after initiating the experiment. For the evaluation of the LD50 male mice of the Balb C57 strain were used in groups of 10 animals, and they were administered increasing oral doses of raw oils until reaching 1 mL/kg (37 g/kg). The serum parameters in the rats indicated there is no toxicity at 60 days and that the administration of the oils lowered the levels of cholesterol, triglycerides and increased the HDL in comparison with the control group. The LD50 shows that the raw sacha inchi and linseed oils have doses above 37 g/kg of body weight. Sacha inchi and linseed oils are harmless at 60 days and present a LD50 above the 37 g/kg of animal.

  18. Avaliação da toxicidade oral subcrônica da bixina para ratos Oral toxicity assessment of annatto in rats

    Directory of Open Access Journals (Sweden)

    Ana Rita Pedreira Lapa Bautista

    2004-06-01

    Full Text Available A bixina em pó (30% de bixina, proveniente das sementes de urucum (Bixa orellana L., foi administrada, por gavagem, a ratos Wistar, 10 animais de cada sexo, na concentração de 0,01±0,006% de bixina/dia, em óleo de milho, cinco dias por semana, durante 13 semanas, com o objetivo de verificar a toxicidade da substância-teste para essa espécie animal. A grupos controle (10 animais por sexo, foi administrado óleo de milho, para comparação. Durante o período de exposição, foram registrados o peso absoluto corpóreo, o ganho de peso, o consumo de ração e a eficiência alimentar, bem como realizadas as avaliações clínica e oftalmoscópica. Antes da eutanásia, os animais foram anestesiados (éter etílico e submetidos a exames hematológicos de rotina e bioquímicos (glicose, creatinina, colesterol total, triglicérides, asparagina transaminase e g-glutamil transaminase. Durante o exame necroscópico, fígado, rins, baço, adrenais e testículos foram excisados e pesados. O estudo histológico foi realizado em amostras de fígado e rins dos animais expostos e respectivos controles. A análise estatística dos parâmetros de peso, hematológicos e bioquímicos mostrou algumas diferenças significativas entre os grupos teste e controle, as quais não parecem estar relacionadas à exposição. Não foram observadas alterações clínicas, comportamentais, necroscópicas e histológicas. Nas condições do estudo, a bixina não produziu efeitos tóxicos nos animais expostos.The aim of the investigation was to determine the possible health hazards of bixin (30% from annatto (Bixa orellana L. origin to rats. A concentration of 0.01±0.006%/day of bixin in corn oil was administered to 20 Wistar rats (10 per sex, through the oral route (gavage over a period of 13 weeks. A group of untreated animal (10 per sex acting as a control (corn oil was used for comparision. Body weight, body weight gain, feed consumption and feed efficiency were

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

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Toxicity and fetotoxicity of TCDD, TCDF and PCB isomers in rhesus macaques (Macaca mulatta)

    Energy Technology Data Exchange (ETDEWEB)

    McNulty, W.P.

    1985-05-01

    In rhesus macaques (Macaca mulatta), consumption of food containing commercial polychlorinated biphenyl (PCB) mixtures, some pure polychlorobiphenyl congeners, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) caused the same clinical toxic manifestations and histopathologic lesions, although the potencies of the toxicants covered a range of five orders of magnitude. Recovery from poisoning by 3,4,3',4'-tetrachlorobiphenyl (34TCB) or TCDF was rapid, whereas recovery from poisoning by Aroclor 1242, 3,4,5,3',4',5'-hexachlorobiphenyl (345HCB), or TCDD was protracted, if it occurred at all. 34TCB did not appreciably accumulate in body fat, but the level of 345HCB in fat rose steadily during ingestion. Among the symmetrical tetra- and hexachlorobiphenyl isomers tested, subacute oral toxicity could be demonstrated only for those without ortho chlorine substitutions. The principal demonstrable histopathological lesions, bone marrow excepted, were metaplasias in some specialized epithelial structures, such as sebaceous glands, nail beds, gastric mucosa, ameloblast, and thymic corpuscles. These changes were interpreted as toxicant-induced, reversible redirection of differentiation. this aberration was wholly reversible. TCDD and 34TCB caused abortions when given in one or a few oral doses early in pregnancy. At the total doses used (1 or 5 g/kg of body weight for TCDD, 3 or 0.6 mg/kg of body weight for 34TCB), maternal toxicity was frequently apparent subsequent to the abortion.

  1. Subacute Toxicity of RDX and TNT in Dogs

    Science.gov (United States)

    1974-07-19

    observed. Renal microcalculi and bone marrow hemosiderosis are both encountered occasionally in random dog populations. The small group sizes, three per...microcalculi in the renal pelvis was higher in 4 the test animals, in particular, those treated with RDX. The incidence of hemosiderosis of the bone marrow was...microcalculi and of bone marrow hemosiderosis highly precarious. 10 June 1974 WALTER F. LOEB, V.M.D., Ph.D. I •LU BIONETICS Utton A-1 70 LITTON

  2. Subacute Toxicity of RDX and TNT in Monkeys

    Science.gov (United States)

    1974-04-05

    Lil.lililoi * *7.83 1 _ rtPitilr Peur t tli~af. v neuI i f , 1iIcurd (Cervii-aI) MUCsulvIt y b tAMIat LIII - Eye, t ell; _ _ -IIJ3 *37 89 L iv.er -Optjl iL Hkt%46v h5tiItIiioh-5 Abvi~i Iun w I J U I U1ld) = Ut iSu perv v~ltOou

  3. Calendula officinalis: Central depressive effect and subacute toxicity

    OpenAIRE

    Parente, Leila M. L.; Costa, Elson A.; Matos, Lécia G.; Paula, José R.; Cunha, Luiz C.; Júnior, Geraldo V.; Silveira, Nusa A.

    2009-01-01

    Flores da Calendula officinalis L. (calêndula) vêm sendo utilizadas popularmente como cicatrizante, antiinflamatório e sedativo, entre outras atividades. Os principais componentes químicos encontrados nas flores são óleos essenciais, ácido salicílico, carotenóides, flavonóides, taninos e saponinas triterpênicas. Atividades ansiolítica e analgésica foram relatadas em plantas que apresentam flavonóides em sua composição. Nesse trabalho a atividade do extrato etanólico das flores da ...

  4. The economic burden of toxicities associated with cancer treatment: review of the literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and fatigue.

    Science.gov (United States)

    Carlotto, Alan; Hogsett, Virginia L; Maiorini, Elyse M; Razulis, Janet G; Sonis, Stephen T

    2013-09-01

    Side effects or toxicities are frequent, undesirable companions of almost all forms of non-surgical cancer therapy. It is unusual for patients to complete treatment with radiation or chemotherapy without experiencing at least one form of therapy-associated tissue injury or systemic side effect. Often, toxicities do not occur as solitary events; rather, they result in clusters of symptoms that share a common biological aetiology. Like any disease, cancer treatment-related toxicities (CTRTs) vary in their severity. But, in contrast to most diseases in which incidence is described as being present or absent, the current approach to CTRT typically limits reporting to severe cases only. Not only does this dilute the frequency with which CTRTs occur, but it also undermines our ability to determine the full burden of their impact and to accurately assess the cost effectiveness of potential toxicity interventions. In this article, we report the results of a directed literature review for the years 2000-2012, in which we studied and compared three tissue-based toxicities (nausea and vomiting, diarrhoea, and oral mucositis) and one systemic toxicity (fatigue). Our results confirm the heavy burden of resource use and cost associated with CTRTs. The inclusion of fatigue in our analysis provided an opportunity to compare and contrast a toxicity in which there are both acute and chronic consequences. Our findings also demonstrate a number of challenges to, and opportunities for, future study. Among the most obvious are the lack of provider consistency in diagnosis and grading, especially when there is no global agreement on severity scales. Compounding this inconsistency is the disconnect between healthcare providers and patients that exists when describing toxicity severity and impact. In many cases, cancer can be thought of as a chronic disease that requires prolonged but episodic treatment once the acute disease is eradicated. This change reflects increasing treatment

  5. A recombinant fusion protein containing a spider toxin specific for the insect voltage-gated sodium ion channel shows oral toxicity towards insects of different orders.

    Science.gov (United States)

    Yang, Sheng; Pyati, Prashant; Fitches, Elaine; Gatehouse, John A

    2014-04-01

    Recombinant fusion protein technology allows specific insecticidal protein and peptide toxins to display activity in orally-delivered biopesticides. The spider venom peptide δ-amaurobitoxin-PI1a, which targets insect voltage-gated sodium channels, was fused to the "carrier" snowdrop lectin (GNA) to confer oral toxicity. The toxin itself (PI1a) and an amaurobitoxin/GNA fusion protein (PI1a/GNA) were produced using the yeast Pichia pastoris as expression host. Although both proteins caused mortality when injected into cabbage moth (Mamestra brassicae) larvae, the PI1a/GNA fusion was approximately 6 times as effective as recombinant PI1a on a molar basis. PI1a alone was not orally active against cabbage moth larvae, but a single 30 μg dose of the PI1a/GNA fusion protein caused 100% larval mortality within 6 days when fed to 3rd instar larvae, and caused significant reductions in survival, growth and feeding in 4th - 6th instar larvae. Transport of fusion protein from gut contents to the haemolymph of cabbage moth larvae, and binding to the nerve chord, was shown by Western blotting. The PI1a/GNA fusion protein also caused mortality when delivered orally to dipteran (Musca domestica; housefly) and hemipteran (Acyrthosiphon pisum; pea aphid) insects, making it a promising candidate for development as a biopesticide. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. An approach to the toxicity and toxicokinetics of aflatoxin B1 and ochratoxin A after simultaneous oral administration to fasted F344 rats

    OpenAIRE

    Corcuera, L.A. (Laura Ana); Vettorazzi, A. (Ariane); L. Arbillaga; Gonzalez-Peñas, E. (Elena); Lopez-de-Cerain, A. (Adela)

    2012-01-01

    Humans are exposed to the hepatotoxic aflatoxin B1 (AFB1) and nephrotoxic ochratoxin A (OTA) through diet. However, kinetic and toxicological data after their co-administration are scarce. In this study, a single oral dose of AFB1 (0.25mg/kg bw)+OTA (0.5mg/kgbw) was administered to fasted F344 rats. Blood, liver and kidney were harvested at different timepoints for mycotoxins quantification, relative weight calculation, clinical biochemistry and histopathology analysis. Toxicity parameters po...

  7. Mammalian Toxicity of Munition Compounds. Phase 1. Acute Oral Toxicity Primary Skin and Eye Irritation, Dermal Sensitization, and Disposition and Metabolism

    Science.gov (United States)

    1975-07-22

    and mice. Rats and mice receiving toxic doses of nitrotoluenes and nitro- glycerins exhibited ataxia, respiratory depression, and cyanosis. TNT and...CO^-free air at a rate of 250 ml/min. Expired CO2 was collected by bubbling the air through six absorption columns connected in series. Each column...nitrotoluenes and nitro- glycerins are described in detail in Appendix I. 1. Nitrotoluenes The identity of the nitrotoluenes was determined and the purity

  8. The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

    Science.gov (United States)

    Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

    2017-12-01

    Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling.

    Science.gov (United States)

    Xu, Zhi; Huang, Chun-Ming; Shao, Zhe; Zhao, Xiao-Ping; Wang, Meng; Yan, Ting-Lin; Zhou, Xiao-Cheng; Jiang, Er-Hui; Liu, Ke; Shang, Zheng-Jun

    2017-03-01

    Chewing areca nut is closely associated with oral squamous cell carcinoma (OSCC). The current study aimed to investigate potential associations between areca nut extract (ANE) and cisplatin toxicity in OSCC cells. OSCC cells (Cal-27 and Scc-9) viability and apoptosis were analyzed after treatment with ANE and/or cisplatin. The expressions of proteins associated with autophagy and the AMP-activated protein kinase (AMPK) signaling network were evaluated. We revealed that advanced OSCC patients with areca nut chewing habits presented higher LC3 expression and poorer prognosis. Reactive oxygen species (ROS)-mediated autophagy was induced after pro-longed treatment of ANE (six days, 3 μg). Cisplatin toxicity (IC50, 48 h) was decreased in OSCC cells after ANE treatment (six days, 3 μg). Cisplatin toxicity could be enhanced by reversed autophagy by pretreatment of 3-methyladenine (3-MA), N-acetyl-l-cysteine (NAC), or Compound C. Cleaved-Poly-(ADP-ribose) polymerase (cl-PARP) and cleaved-caspase 3 (cl-caspase 3) were downregulated in ANE-treated OSCC cells in the presence of cisplatin, which was also reversed by NAC and Compound C. Collectively, ANE could decrease cisplatin toxicity of OSCC by inducing autophagy, which involves the ROS and AMPK/mTOR signaling pathway.

  10. Brainstem involvement in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Sharma, Pawan; Singh, Dileep; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Kohli, Neera

    2011-01-01

    The parieto-occipital region of the brain is most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. Brainstem involvement is rarely described in SSPE, and usually there is involvement of other regions of the brain. We describe a patient with subacute sclerosing panencephalitis with brain magnetic resonance imaging showing extensive brainstem involvement without significant involvement of other cortical structures. Though rarely described in SSPE, one should be aware of such brainstem and cerebellum involvement, and SSPE should be kept in mind when brainstem signal changes are seen in brain MRI with or without involvement of other regions of brain to avoid erroneous reporting.

  11. Accumulation of Arsenic Speciation and In Vivo Toxicity Following Oral Administration of a Chinese Patent Medicine Xiao-Er-Zhi-Bao-Wan in Rats

    Science.gov (United States)

    Luo, Jiaoyang; Han, Xu; Dou, Xiaowen; Zhang, Lei; Yang, Shihai; Yang, Meihua

    2017-01-01

    Realgar-containing traditional Chinese medicines such as Xiao-Er-Zhi-Bao-Wan (XEZBW), have been widely used for thousands of years. However, events associated with arsenic-induced ailments have increasingly become a public concern. To address the toxicity of XEZBW, we studied the histopathology and blood biochemistry of rats exposed to XEZBW using technology like high-performance liquid chromatography-inductively coupled mass spectrometry to determine arsenic speciation. Our results demonstrated that dimethylarsinic acid (DMA) increased from 18.57 ± 7.45 to 22.74 ± 7.45 ng/g in rat kidney after oral administration for 7 and 14 days, which was 10-fold higher than the levels observed in controls. Trivalent arsenite As(III) showed a large increase on day 7 (26.99 ± 1.98 ng/g), followed by a slight decrease on day 14 (13.67 ± 6.48 ng/g). Total arsenic levels on day 7 (185.52 ± 24.56 ng/g) and day 14 (198.57 ± 26.26 ng/g) were nearly twofold higher than that in the control group (92.77 ± 14.98 ng/g). Histopathological analysis showed mild injury in the liver and kidney of rats subjected to oral administration of realgar for 14 days. As in the XEZBW groups, a mild injury in these organs was observed after administration for 14 days. This study inferred that the toxicity of arsenic was concentration- and time-dependent. The accumulation of DMA, a byproduct of choline metabolism, was responsible for inducing higher toxicity. Therefore, we concluded that measuring the levels of DMA, instead of total arsenic, might be more suitable for evaluating the toxicity of realgar-containing traditional Chinese medicines. PMID:28790918

  12. Accumulation of Arsenic Speciation and In Vivo Toxicity Following Oral Administration of a Chinese Patent Medicine Xiao-Er-Zhi-Bao-Wan in Rats

    Directory of Open Access Journals (Sweden)

    Jiaoyang Luo

    2017-07-01

    Full Text Available Realgar-containing traditional Chinese medicines such as Xiao-Er-Zhi-Bao-Wan (XEZBW, have been widely used for thousands of years. However, events associated with arsenic-induced ailments have increasingly become a public concern. To address the toxicity of XEZBW, we studied the histopathology and blood biochemistry of rats exposed to XEZBW using technology like high-performance liquid chromatography-inductively coupled mass spectrometry to determine arsenic speciation. Our results demonstrated that dimethylarsinic acid (DMA increased from 18.57 ± 7.45 to 22.74 ± 7.45 ng/g in rat kidney after oral administration for 7 and 14 days, which was 10-fold higher than the levels observed in controls. Trivalent arsenite As(III showed a large increase on day 7 (26.99 ± 1.98 ng/g, followed by a slight decrease on day 14 (13.67 ± 6.48 ng/g. Total arsenic levels on day 7 (185.52 ± 24.56 ng/g and day 14 (198.57 ± 26.26 ng/g were nearly twofold higher than that in the control group (92.77 ± 14.98 ng/g. Histopathological analysis showed mild injury in the liver and kidney of rats subjected to oral administration of realgar for 14 days. As in the XEZBW groups, a mild injury in these organs was observed after administration for 14 days. This study inferred that the toxicity of arsenic was concentration- and time-dependent. The accumulation of DMA, a byproduct of choline metabolism, was responsible for inducing higher toxicity. Therefore, we concluded that measuring the levels of DMA, instead of total arsenic, might be more suitable for evaluating the toxicity of realgar-containing traditional Chinese medicines.

  13. Multiple Complications Due to Subacute Suppurative Otitis Media

    OpenAIRE

    Qirjazi, Brikena; Bardhyli, Dolores; Hoxhallari, Xhevair

    2012-01-01

    Subacute otitis media is a well-known pathology of ENT practice which is easily diagnosed and subsequently treated in the outpatient clinic. The rate of complications in acute otitis media is lower than in chronic otitis media. We present here the history of a young patient with subacute otitis media who developed both localized labyrinthitis and facial palsy requiring surgical treatment. We conclude that the treatment of subacute otitis media should be carefully monitored because complicatio...

  14. Subacute Sclerosing Panencephalitis in a Child with Recurrent Febrile Seizures

    OpenAIRE

    Ayşe Kartal; Ayşegül Neşe Çıtak Kurt; Tuğba Hirfanoğlu; Kürşad Aydın; Ayşe Serdaroğlu

    2015-01-01

    Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recu...

  15. Subacute sclerosing panencephalitis in immunized Thai children.

    Science.gov (United States)

    Khusiwilai, Khanittha; Viravan, Sorawit

    2011-12-01

    Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease with high mortality and poor prognosis. This is caused by persistent defective measles virus infection. Clinical presentations are variable including behavioral-cognitive change, myoclonic seizure, visual problem, spasticity or abnormal movement. The authors report a case of 10 year-old boy, previously healthy with complete immunization, presenting with frequent myoclonic jerks, abnormal movements, spasticity and altered mental status. Electroencephalographic (EEG), magnetic resonance imaging (MRI), and laboratory findings are typical for SSPE.

  16. Subacute sclerosing panencephalitis presenting as mania

    Directory of Open Access Journals (Sweden)

    Aggarwal Ashish

    2011-01-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is a rare, invariably fatal degenerative disease of the central nervous system developing after measles infection. Besides neurological symptoms as initial presenting symptoms, rare reports of its presentation with pure psychiatric symptoms have been reported. We here report a case of 14 year old male who initially presented with manic symptoms and then subsequently diagnosed to be suffering from SSPE. Improtance of ruling our organic conditions is emphasized.

  17. Late Onset Subacute Sclerosing Panencephalitis: Presenting Psychosis

    Directory of Open Access Journals (Sweden)

    Yavuz Altunkaynak

    2013-04-01

    Full Text Available Subacute Sclerosing Panencephalitis (SSPE is the late complication of measles and is characterized by seizures, myoclonus, ataxia, behavioral and personality changes, extrapyramidal dysfunctions and vision problems. A 19 year old female patient with SSPE who was followed up at psychiatry clinic with the diagnosis of atypical psychotic disorder was presented. While psychiatric signs and symptoms were dominant, she was diagnosed as SSPE.

  18. Subacute sclerosing panencephalitis: serial electroencephalographic studies.

    Science.gov (United States)

    Wulff, C H

    1982-01-01

    A total of 42 EEGs from five patients with subacute sclerosing panencephalitis were studied. Periodic complexes were noticed in 35 (83%) of these. The interval between the complexes shortened in all patients with progression of the illness. The gradual EEG changes may reflect the increasing number of infected cells as well as an on-going accumulation of immature virus structures. The records without complexes were either from the early onset (one record) or terminal stage (six records). PMID:7086454

  19. Subacute sclerosing panencephalitis presenting as mania

    Science.gov (United States)

    Aggarwal, Ashish; Khandelwal, Ashish; Jain, Manish; Jiloha, R. C.

    2011-01-01

    Subacute sclerosing panencephalitis (SSPE) is a rare, invariably fatal degenerative disease of the central nervous system developing after measles infection. Besides neurological symptoms as initial presenting symptoms, rare reports of its presentation with pure psychiatric symptoms have been reported. We here report a case of 14 year old male who initially presented with manic symptoms and then subsequently diagnosed to be suffering from SSPE. Improtance of ruling our organic conditions is emphasized. PMID:21808475

  20. Multiple Complications Due to Subacute Suppurative Otitis Media

    Directory of Open Access Journals (Sweden)

    Xhevair Hoxhallari

    2012-06-01

    Full Text Available Subacute otitis media is a well-known pathology of ENT practice which is easily diagnosed and subsequently treated in the outpatient clinic. The rate of complications in acute otitis media is lower than in chronic otitis media. We present here the history of a young patient with subacute otitis media who developed both localized labyrinthitis and facial palsy requiring surgical treatment. We conclude that the treatment of subacute otitis media should be carefully monitored because complications may occur. Surgical treatment and pressure release can be efficient for the treatment of a peripheral facial palsy in the course of acute or subacute otitis media.

  1. Subacute sclerosing panencephalitis in a child with recurrent febrile seizures.

    Science.gov (United States)

    Kartal, Ayşe; Çıtak Kurt, Ayşegül Neşe; Hirfanoğlu, Tuğba; Aydın, Kürşad; Serdaroğlu, Ayşe

    2015-01-01

    Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recurrent febrile seizures. The disease progressed with an appearance of myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis.

  2. Subacute Sclerosing Panencephalitis in a Child with Recurrent Febrile Seizures

    Directory of Open Access Journals (Sweden)

    Ayşe Kartal

    2015-01-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is a devastating disease of the central nervous system (CNS caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recurrent febrile seizures. The disease progressed with an appearance of myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis.

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

    National Research Council Canada - National Science Library

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

    2012-01-01

    .... Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C...

  4. Overview of Chronic Oral Toxicity Values for Chemicals Present in Hydraulic Fracturing Fluids, Flowback and Produced Waters

    Science.gov (United States)

    as part of EPA's Hydraulic Fracturing Drinking Water Assessment, EPA is summarizing existing toxicity data for chemicals reported to be used in hydraulic fracturing fluids and/or found in flowback or produced waters from hydraulically fractured wells

  5. Sub-Acute Hepatoxicity of Aqueous Leaf Extract of Eucalyptus ...

    African Journals Online (AJOL)

    Sub–acute toxicity study of the aqueous leaf extract of Eucalyptus camaldulensis was carried out on albino rats. Doses of 250mg, 500mg, 750mg and 1000mg per kilogram body weight of the extract were administered orally for 21 days. The activities of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), ...

  6. Spontaneous and Dosing Route-related Lung Lesions in Beagle Dogs from Oral Gavage and Inhalation Toxicity Studies: Differentiation from Compound-induced Lesions.

    Science.gov (United States)

    Mukaratirwa, Sydney; Garcia, Begonya; Isobe, Kaori; Petterino, Claudio; Bradley, Alys

    2016-10-01

    This study was conducted to characterize lung microscopic lesions in control beagle dogs from inhalation and oral gavage toxicity studies, to determine differences associated with the route of administration, and to discuss distinguishing features from compound-induced lung lesions. Samples from 138 control dogs from oral gavage studies and 124 control dogs from inhalation (vehicle control) studies were evaluated microscopically. There was no significant sex-related difference in the incidence of all lesions. Perivascular mononuclear cell infiltration, centriacinar mixed cell infiltration, bronchopneumonia, subpleural septal fibrosis, and alveolar macrophage accumulation were the most common lesions. Aspiration pneumonia was more common in dogs from gavage studies, suggesting reflux after gavage dosing or accidental administration of test formulation as possible causes. Centriacinar mixed cell infiltration was more common in dogs from inhalation studies, suggesting mild irritation by the vehicles used. Vascular lesions, which included pulmonary arteriopathy and smooth muscle mineralization, were observed in a few animals. Some of the spontaneous lesions are similar to lesions induced by test compounds. Compared to spontaneous lesions, compound-induced lesions tend to be multifocal or diffuse, follow a pattern of distribution (e.g., centriacinar, perivascular, and interstitial), show a dose response in the incidence and severity, and may show cell-specific toxicity. © The Author(s) 2016.

  7. A prospective comparison of common toxicity criteria adverse events Version 3 and 4 in assessing oral mucositis for oral and oropharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    M. Hickman

    2017-03-01

    Conclusion: Differences in grading of mucositis scored by V3 and V4 are frequent. Relationships between biologically effective dose and rates of grade 3 mucositis have historically been based on mucosal appearances. It is not known whether the same relationships apply when mucositis is graded based on symptomatic grading systems. Both V3 and V4 should be used in clinical trials to improve understanding of mucositis and its relationship to quality of life and late mucosal toxicity.

  8. Four Common Pesticides, Their Mixtures and a Formulation Solvent in the Hive Environment Have High Oral Toxicity to Honey Bee Larvae

    Science.gov (United States)

    Zhu, Wanyi; Schmehl, Daniel R.; Mullin, Christopher A.; Frazier, James L.

    2014-01-01

    Recently, the widespread distribution of pesticides detected in the hive has raised serious concerns about pesticide exposure on honey bee (Apis mellifera L.) health. A larval rearing method was adapted to assess the chronic oral toxicity to honey bee larvae of the four most common pesticides detected in pollen and wax - fluvalinate, coumaphos, chlorothalonil, and chloropyrifos - tested alone and in all combinations. All pesticides at hive-residue levels triggered a significant increase in larval mortality compared to untreated larvae by over two fold, with a strong increase after 3 days of exposure. Among these four pesticides, honey bee larvae were most sensitive to chlorothalonil compared to adults. Synergistic toxicity was observed in the binary mixture of chlorothalonil with fluvalinate at the concentrations of 34 mg/L and 3 mg/L, respectively; whereas, when diluted by 10 fold, the interaction switched to antagonism. Chlorothalonil at 34 mg/L was also found to synergize the miticide coumaphos at 8 mg/L. The addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture, the only significant non-additive effect in all tested ternary mixtures. We also tested the common ‘inert’ ingredient N-methyl-2-pyrrolidone at seven concentrations, and documented its high toxicity to larval bees. We have shown that chronic dietary exposure to a fungicide, pesticide mixtures, and a formulation solvent have the potential to impact honey bee populations, and warrants further investigation. We suggest that pesticide mixtures in pollen be evaluated by adding their toxicities together, until complete data on interactions can be accumulated. PMID:24416121

  9. Four common pesticides, their mixtures and a formulation solvent in the hive environment have high oral toxicity to honey bee larvae.

    Directory of Open Access Journals (Sweden)

    Wanyi Zhu

    Full Text Available Recently, the widespread distribution of pesticides detected in the hive has raised serious concerns about pesticide exposure on honey bee (Apis mellifera L. health. A larval rearing method was adapted to assess the chronic oral toxicity to honey bee larvae of the four most common pesticides detected in pollen and wax--fluvalinate, coumaphos, chlorothalonil, and chloropyrifos--tested alone and in all combinations. All pesticides at hive-residue levels triggered a significant increase in larval mortality compared to untreated larvae by over two fold, with a strong increase after 3 days of exposure. Among these four pesticides, honey bee larvae were most sensitive to chlorothalonil compared to adults. Synergistic toxicity was observed in the binary mixture of chlorothalonil with fluvalinate at the concentrations of 34 mg/L and 3 mg/L, respectively; whereas, when diluted by 10 fold, the interaction switched to antagonism. Chlorothalonil at 34 mg/L was also found to synergize the miticide coumaphos at 8 mg/L. The addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture, the only significant non-additive effect in all tested ternary mixtures. We also tested the common 'inert' ingredient N-methyl-2-pyrrolidone at seven concentrations, and documented its high toxicity to larval bees. We have shown that chronic dietary exposure to a fungicide, pesticide mixtures, and a formulation solvent have the potential to impact honey bee populations, and warrants further investigation. We suggest that pesticide mixtures in pollen be evaluated by adding their toxicities together, until complete data on interactions can be accumulated.

  10. Subacute presentation of propionic acidemia.

    Science.gov (United States)

    Delgado, Carmen; Macías, Carlos; de la Sierra García-Valdecasas, Maria; Pérez, Manuel; del Portal, Luis Ruiz; Jiménez, Luis Manuel

    2007-12-01

    Propionic acidemia is a hereditary metabolic disease caused by a deficiency of enzyme propionyl-CoA carboxylase, which is involved in the catabolism of ramified amino acids, odd-chain fatty acids, and other metabolites; the deficiency of this enzyme leads to an accumulation of toxic substances in the body. There are various forms of clinical presentation (severe neonatal, chronic intermittent, or slow and gradual). The case presented in this study was of a slow and insidious evolution form that was diagnosed when the child was 9 months old. Intracranial magnetic resonance imaging showed a slight increase in the signal intensity in sequences measured in T2 in addition to a restriction of the diffusion at the level of both putamens, which, together with biochemical and genetic analyses, confirmed the diagnosis of propionic acidemia. After initiating treatment involving a diet that was low in proteins, carnitine, and biotin, and an open-formula diet of ramified amino acids, the patient made progress, showing signs of improved hypotonia and increased weight gain. His vomiting stopped, and ketoacidosis was corrected.

  11. Evaluation of residual toxic substances in the stomach using upper gastrointestinal endoscopy for management of patients with oral drug overdose on admission: a prospective, observational study.

    Science.gov (United States)

    Miyauchi, Masato; Hayashida, Makiko; Yokota, Hiroyuki

    2015-01-01

    The guidelines on the indications for gastric lavage were published in 1997, and a less-aggressive initial approach has been used for poisoned patients. Clinical studies have shown that the outcomes of retrieval of residual toxic substances in the stomach are variable and that no beneficial effect is obtained. However, the presence of residual toxic substances in the stomach before gastric lavage has not been estimated. The objective of this study was to evaluate the residual stomach contents on admission of patients with oral drug overdoses using upper gastrointestinal endoscopy. A 2-year prospective study of 167 patients with oral drug overdoses was performed. Endoscopy was performed on admission to observe the gastric body, fornix, and pyloric antrum. Patients were classified into 3 groups according to the digestive phase (tablet/food phase, soluble/fluid phase, and reticular/empty phase). The groups were compared with respect to time elapsed since ingestion, and numbers and variety of orally overdosed drugs. The numbers of patients in each phase were as follows: tablet/food phase, 73; soluble/fluid phase, 50; and reticular/empty phase, 44. The tablet/food and soluble/fluid phase groups contained the greatest numbers of patients who presented within 1 to 2 hours since ingestion. In the tablet/food group, only 12 of 73 patients (16%) presented within 1 hour since ingestion, and 3 patients presented >12 hours since ingestion. In the soluble/fluid phase group, only 9 of 50 patients (18%) presented within 1 hour since ingestion, and 2 patients presented >12 hours since ingestion. The reticular/empty phase group contained the greatest number of patients presenting within 2 to 4 hours since ingestion, and 3 patients presented within 1 hour since ingestion. The residual stomach contents before lavage were variable in all of the groups. The residual gastric content before the performance of gastric lavage is variable in overdosed patients on admission. This may

  12. An approach to the toxicity and toxicokinetics of aflatoxin B1 and ochratoxin A after simultaneous oral administration to fasted F344 rats.

    Science.gov (United States)

    Corcuera, L A; Vettorazzi, A; Arbillaga, L; González-Peñas, E; López de Cerain, A

    2012-10-01

    Humans are exposed to the hepatotoxic aflatoxin B1 (AFB1) and nephrotoxic ochratoxin A (OTA) through diet. However, kinetic and toxicological data after their co-administration are scarce. In this study, a single oral dose of AFB1 (0.25 mg/kg bw)+OTA (0.5 mg/kgbw) was administered to fasted F344 rats. Blood, liver and kidney were harvested at different timepoints for mycotoxins quantification, relative weight calculation, clinical biochemistry and histopathology analysis. Toxicity parameters pointed to acute toxicity in liver due to AFB1. No remarkable toxicity was observed in kidneys or immunological organs. Maximum observed concentrations in plasma (Cmax) were at 10 min and 2 h for AFB1 and OTA, respectively. AFB1 plasma concentration could indicate a rapid absorption/ metabolism of the mycotoxin; and AFB1 liver and kidney concentrations were lower than LOQ and LOD, respectively. For OTA, Cmax was 4326.2 μg/L in plasma. In kidney and liver Cmax was reached at 8 h and concentrations were very similar between both organs at all timepoints. Due to the low levels of AFB1, the effect of OTA on AFB1 kinetics could not be assessed. However, AFB1 seems not to affect OTA kinetics, as its profile seems very similar to kinetic studies performed only with OTA in similar conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Comparison of Toxicities Associated with Concomitant Boost and Conventional Fractionated Radiotherapy Regimen in Oral and Oropharyngeal Cancers

    Directory of Open Access Journals (Sweden)

    Abhishek Shrivastava

    2017-10-01

    Full Text Available Introduction: The prevalence of Head and Neck Cancers (HNC is very high in the Indian subcontinent. Radiotherapy is an essential modality in the management of HNC. Aim: The aim of the present study was to compare toxicities of two radiotherapy fractionation regimen (conventional fractionation and concomitant boost technique for the management of HNC. Materials and Methods: A total of 60 patients (n=30 in each arm were assigned to receive either conventional fractionation or concomitant boost radiotherapy. Toxicities were analysed weekly during the treatment, and one and three month after treatment completion. The radiation therapy oncology group acute radiation morbidity scoring system was used to document the severity. Toxicities assessed were mucositis, skin reactions, dysphagia and xerostomia. Statistical analysis was done by the online Graphpad software using Chi-square test. A value of p<0.05 was considered significant. Results: Overall mean age of the patients was 47.35 years (range 23-70 years. There was a male preponderance in both groups (Group A=73.33%, Group B= 76.6%. Most common primary sub site in Group A was tongue (33.3% and in Group B was buccal mucosa (50%. On statistical analysis of toxicity comparison during and post treatment completion, no significant difference in toxicity was found between the two arms in terms of mucositis (p=1, skin reactions (p=0.6404, dysphagia (p=0.7906 and xerostomia (p=0.1066. Conclusion: The concomitant boost technique resulted in no statistically significant difference in toxicity as compared to the conventional fractionation with the added advantage of reduced overall treatment time. This may be a favourable schedule for high volume centers.

  14. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    Directory of Open Access Journals (Sweden)

    Bahareh Amin

    2015-08-01

    Full Text Available Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p. were evaluated using forced swim test (FST. In sub-acute study (21 times with 24-h intervals, antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST. Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg and crocetin (20 and 40 mg/kg produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg. Crocetin (12.5, 25 and 50 mg/kg was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.

  15. Rat Brain Biogenic Amine Levels during Acute and Subacute ...

    African Journals Online (AJOL)

    Rat Brain Biogenic Amine Levels during Acute and Subacute Phosphamidon Treatment with Reference to Behavioral Tolerance. ... African Research Review ... The present study examines if the levels of amine neurotransmitter substances in rat brain regions are altered during acute and sub-acute treatment with an ...

  16. Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats

    Directory of Open Access Journals (Sweden)

    Ćurčić Marijana

    2015-01-01

    Full Text Available Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated diphenyl ether (BDE-209 are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, gama glutamyl transferase (γ-GT], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA, superoxide dismutase (SOD, -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww respectively. Internal doses correlated with external (r = 0.972; p < 0.05 according to equation: internal dose (mg BDE-209/kg of liver ww = 0.0002 x external dose (mg/kg bw/day + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww

  17. Thesaurus for histopathological findings in publically available reports of repeated-dose oral toxicity studies in rats for 156 chemicals.

    Science.gov (United States)

    Nishikawa, Satoshi; Yamashita, Tatsuhiro; Imai, Toshio; Yoshida, Midori; Sakuratani, Yuki; Yamada, Jun; Maekawa, Akihiko; Hayashi, Makoto

    2010-06-01

    Because histopathological findings are often conclusive indicators of the toxicities of chemicals, standardization of nomenclature and construction of a thesaurus for histopathological findings are important for the comparative evaluation of histopathological data from repeated-dose toxicity studies (RTS). However, terms for histopathological findings have not been standardized and different technical terms are used to indicate almost the same thing in RTS. The present study was conducted to construct an easy-to-use thesaurus for histopathological findings in order to facilitate hazard assessments of untested chemicals by the category approach using knowledge of the toxicity of analogue chemicals. We used reports of 28-day RTS, conducted on rats by gavage, which were posted on the websites of the National Institute of Health Sciences (NIHS) and the National Institute of Technology and Evaluation (NITE). The histopathological data were from 156 reports on RTS conducted by 13 institutions in Japan. As a result of this study, major parts of the thesaurus were devoted to the findings in the liver, kidney, stomach, adrenal, thyroid and testis; the first three organs are known to be the main targets of chemicals. We also decided that findings such as swelling and enlargement of hepatocytes should be categorized as synonyms for terms meaning hypertrophy. Our thesaurus will be helpful in assessing or screening new untested chemicals by the category approach using knowledge of the toxicities of analogues of the new chemical. The RTS database with this thesaurus will be made publically available in 2012.

  18. Subacute sclerosing panencephalitis: a case report.

    Science.gov (United States)

    Praticò, A D; Saporito, M; Iacono, O; Castellano-Chiodo, D; Pavone, P

    2011-02-01

    Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence caused by persistent defective measles virus. Clinical manifestations appear many years after the acute measles infection. The incidence of SSPE has substantially declined after the introduction of an effective vaccine. We report a case of a child with SSPE that began with atonia, dysarthria, and intellectual deterioration without the presence of any particular EEG anomalies. We have reported this girl who was affected by this severe affliction in the hope that, because of the rarity of SSPE, it would not go undiagnosed.

  19. Subacute Cutaneous Lupus Erythematosus Triggered by Radiotherapy

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    I. Kolm

    2013-08-01

    Full Text Available Background: The origin of collagen autoimmune diseases is not fully understood. Some studies postulate a mechanism of molecular mimicry or heterologous immunity following viral infections triggering autoimmunity. Apart from infections, other exogenous factors such as visible light or X-rays have been reported to incite autoimmunity. Case Report: We report a case of histologically and serologically confirmed subacute lupus erythematosus (SCLE following radiotherapy for breast cancer. Discussion: The close temporal and spatial correlation between radiotherapy and onset of SCLE in this patient suggests that an autoimmune reaction may have been triggered locally by functionally altering the immune system and breaking self-tolerance.

  20. Cereals Bond Trounces Subacute Rumen Acidosis

    OpenAIRE

    Akbar Nikkhah

    2015-01-01

    This perspective article provides a feasible ideology based on which modern ruminant enterprises will learn to vigilantly include mixtures of hard and soft cereal grains in optimizing rumen environment. Subacute Rumen Acidosis (SARA), variably defined as a common and economically important metabolic disease, occurs arguably when rumen pH declines below 5.8-6 for a long-lasting period of time of several hours. Prolonged SARA reduces high-producing dairy and bee...

  1. Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria) Extracts to Mice

    Science.gov (United States)

    Rangel, Marisa; Martins, Joyce C. G.; Garcia, Angélica Nunes; Conserva, Geanne A. A.; Costa-Neves, Adriana; Sant’Anna, Célia Leite; de Carvalho, Luciana Retz

    2014-01-01

    Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the

  2. Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria Extracts to Mice

    Directory of Open Access Journals (Sweden)

    Marisa Rangel

    2014-01-01

    Full Text Available Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt of the Institute of Botany of Brazil, the acetic acid extracts (AE of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia

  3. Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration.

    Science.gov (United States)

    Choi, Jonghye; Kim, Heyjin; Kim, Pilje; Jo, Eunhye; Kim, Hyun-Mi; Lee, Moo-Yeol; Jin, Seon Mi; Park, Kwangsik

    2015-01-01

    Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage.

  4. Oral lesions associated with Nevirapine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A report of 10 cases

    OpenAIRE

    BV Ramana Reddy; P Chandra Shekar; K Lalith Prakash Chandra; R S Aravind

    2013-01-01

    Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are closely related severe, acute mucocutaneous reactions usually caused by drugs. They are acute life-threatening conditions and cause widespread necrosis of the epithelium. There is persistence of a high risk of SJS or TEN in relation to human immunodeficiency virus (HIV) infection associated with exposure to nevirapine (NVP). In this article, we present nine cases of SJS and one case of TEN in HIV-seropositive individuals ...

  5. Clinical profile of subacute sclerosing panencephalitis.

    Science.gov (United States)

    Akram, Muhammad; Naz, Farrah; Malik, Akbar; Hamid, Haroon

    2008-08-01

    To describe the clinical manifestations of subacute sclerosing panencephalitis in children. Case series. This study was conducted in the Department of Neurology at The Children's Hospital and the Institute of Child Health, Lahore, from April 2005 to April 2007. Fifty patients were diagnosed as subacute sclerosing panencephalitis during the study period. Their diagnosis was based on a detailed history, clinical examination, presence of antimeasles antibodies in Cerebrospinal Fluid (CSF) and typical electroencephalogram (EEG). The findings were described as average, mean and percentages. Fifty patients were included in this study. The average age of the patients was 8 years. Thirty-eight (76%) were males and 12 (24%) were females. The average duration of symptoms before presentation was 66.72 days. History of measles infection was present in 31 patients (62%) and measles vaccination in 43 patients (86%). Motor regression was present in all (100%) patients and cognition decline in 43 patients (86%). Seizures were focal (10%), generalized tonicclonic (16%) and myoclonic (74%). Burst-suppression pattern Electroencephalogram (EEG) and the antimeasles antibody in CSF were positive in 100% of patients. SSPE is an indicator of high incidence of measles infection among the paediatric population even among vaccinated children. Males are more common sufferers. SSPE can present with different types of seizures, cognition decline and motor regression being supported by suggestive EEG and presence of anti-measles antibodies in CSF.

  6. Outcome determinants of subacute low back pain.

    Science.gov (United States)

    Karjalainen, Kaija; Malmivaara, Antti; Mutanen, Pertti; Pohjolainen, Timo; Roine, Risto; Hurri, Heikki

    2003-12-01

    Descriptive prognostic study. To identify outcome determinants of subacute low back pain. The factors predicting recovery from prolonged back pain among working adults are largely unknown. One hundred sixty-four employed patients with subacute (duration of pain 4-12 weeks) daily low back pain were recruited from primary health care to a randomized study. Data on potential predictive factors were collected before randomization. In multiple regressions using repeated measures analysis, the treatment received was adjusted when determining the impact of the predictive factors. Dependent outcome variables used were pain, perceived functional disability, generic health-related quality of life, satisfaction with care, days on sick leave, use of health care, and costs of health care consumption measured, at 3-, 6-, and 12-month follow-ups. Age and intensity of pain at baseline predicted most of the outcomes. The perceived risk of not recovering was a stronger determinant of outcome than gender, education, or self-rated health status (which did not have any predictive value) or body mass index, expectations of treatment effect, satisfaction with work, or the presence of radicular symptoms below the knee (only slight predictive value). The only factors predicting the duration of sick leave were the duration of sick leave at baseline and the type of occupation. Age and intensity of pain are the strongest predictors of outcome. Accumulation of days on sick leave is predicted by the duration of sick leave at entry and the type of work, but not by pain, perceived disability, or satisfaction with work.

  7. Diffuse unilateral subacute neuroretinitis in a young boy: a case report

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    Guan-Fook N

    2012-03-01

    Full Text Available FNg Guan-Fook, Abd Aziz Hayati, Mohd Noor Raja-Azmi, Ahmad Tajudin Liza-Sharmini, Wan Hitam Wan-Hazabbah, Embong ZunainaDepartment of Ophthalmology, School of Medical Science, Universiti Sains Malaysia, Kubang Kerian, Kelantan, MalaysiaAbstract: We report a case of diffuse unilateral subacute neuroretinitis in a young boy with no clinical visualization of nematode. The diagnosis was made based on clinical findings and detection of Toxocara immunoglobulin G by Western blot test. An 11-year-old Malay boy presented with progressive blurring of vision in the left eye for a duration of 1 year. It was associated with intermittent floaters. Visual acuity in the left eye was 6/45 and improved to 6/24 with pinhole. There was positive relative afferent pupillary defect, impaired color vision, and presence of red desaturation in the left eye. There were occasional cells in the anterior chamber with no conjunctiva injection. Posterior segment examination revealed mild-to-moderate vitritis and generalized pigmentary changes of the retina with attenuated vessels. The optic disk was slightly hyperemic with mild edema. There was presence of multiple, focal, gray-white subretinal lesions at the inferior part of the retina. Full blood picture results showed eosinophilia with detection of Toxocara immunoglobulin G by Western blot test. Investigations for other infective causes and connective tissue diseases were negative. The diagnosis of diffuse unilateral subacute neuroretinitis secondary to Toxocara was made based on clinical findings and laboratory results. He was treated with oral albendazole 400 mg daily for 5 days and oral prednisolone 1 mg/kg with tapering doses over 6 weeks. At 1 month follow-up, the inflammation had reduced, and multiple, focal, gray-white subretinal lesions were resolved; however there was no improvement of vision.Keywords: diffuse unilateral subacute neuroretinitis, Toxocara IgG, albendazole

  8. Preliminary safety assessment of Yarrowia lipolytica extracellular lipase: results of acute and 28-day repeated dose oral toxicity studies in rats.

    Science.gov (United States)

    Turki, Saoussen; Jabloun, Zeineb; Mrabet, Ghada; Marouani, Ammar; Thonart, Philippe; Diouani, Mohammed Fethi; Ben Abdallah, Fethi; Amara, Abdelkader; Rejeb, Ahmed; Kallel, Héla

    2010-01-01

    Interest in extracellular lipase sourced from the non conventional yeast Yarrowia lipolytica has increased over the last decade. The enzyme was recently suggested as a good candidate for pancreatic exocrine insufficiency treatment. However, there is still a lack of oral safety evaluation data. In this work, we conducted acute and 28-day repeated dose toxicity studies in rats. Both male and female rats were first orally treated with fungal lipase at either single or repeated doses. The results demonstrated that neither single dose nor chronic administration of lipase was associated with mortality or abnormalities in general conditions, behavior and growth. Except a decrease in urine pH and a dose-unrelated increase of triglycerides observed in males, chronic administration of lipase resulted in similar hematological, blood biochemical and urine parameters to those of untreated animals. Minor histopathological changes were observed in lungs and livers of treated and untreated animals but they were considered of no toxicological significance. This study provides, for the first time, safety data on Yarrowia lipolytica extracellular lipase that support its use as a pharmaceutical. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  9. Sub-chronic (13-week) oral toxicity study in rats with recombinant human lactoferrin produced in the milk of transgenic cows.

    Science.gov (United States)

    Appel, M J; van Veen, H A; Vietsch, H; Salaheddine, M; Nuijens, J H; Ziere, B; de Loos, F

    2006-07-01

    The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of transgenic cows was investigated in Wistar rats by daily administration via oral gavage for 13 consecutive weeks, 7 days per week. The study used four groups of 20 rats/sex/dose. The control group received physiological saline and the three test groups received daily doses of 200, 600 and 2000 mg of rhLF per kg body weight. Clinical observations, growth, food consumption, food conversion efficiency, water consumption, neurobehavioural testing, ophthalmoscopy, haematology, clinical chemistry, renal concentration test, urinalysis, organ weights and gross examination at necropsy and microscopic examination of various organs and tissues were used as criteria for detecting the effects of treatment. Overall, no treatment-related, toxicologically significant changes were observed. The few findings that may be related to the treatment (lower cholesterol in high-dose females, lower urinary pH in high-dose males and females and very slightly higher kidney weight in high-dose females) were considered of no toxicological significance. Based on the absence of treatment-related, toxicologically relevant changes, the no-observed-adverse-effect level (NOAEL) was considered to be at least 2000 mg/kg body weight/day.

  10. Synthesis, Characterization, and Acute Oral Toxicity Evaluation of pH-Sensitive Hydrogel Based on MPEG, Poly(ε-caprolactone, and Itaconic Acid

    Directory of Open Access Journals (Sweden)

    Liwei Tan

    2013-01-01

    Full Text Available A kind of chemically cross-linked pH-sensitive hydrogels based on methoxyl poly(ethylene glycol-poly(caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA, poly(ethylene glycol methyl ether methacrylate (MPEGMA, MEG, N,N-methylenebisacrylamide (BIS, and itaconic acid (IA were prepared without using any organic solvent by heat-initiated free radical method. The obtained macromonomers and hydrogels were characterized by 1H NMR and FT-IR, respectively. Morphology study of hydrogels was also investigated in this paper, and it showed that the hydrogels had good pH-sensitivity. The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10000 mg/kg body weight. No morality or signs of toxicity were observed during the whole 7-day observation period. Compared to the control groups, there were no important adverse effects in the variables of hematology routine test and serum chemistry analysis both in male or female treatment group. Histopathological study also did not show any significant lesions, including heart, liver, lung, spleen, kidney, stomach, intestine, and testis. All the results demonstrated that this hydrogel was nontoxic after gavage. Thus, the hydrogel might be the biocompatible potential candidate for oral drug delivery system.

  11. Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

    Directory of Open Access Journals (Sweden)

    Subramanion L. Jothy

    2013-01-01

    Full Text Available Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

  12. Oral intralipid emulsion use: a novel therapeutic approach to pancreatic β-cell injury caused by malathion toxicity in rats.

    Science.gov (United States)

    Tuzcu, Kasim; Alp, Harun; Ozgur, Tumay; Karcioglu, Murat; Davarci, Isil; Evliyaoglu, Osman; Karakus, Ali; Hakimoglu, Sedat

    2014-07-01

    We aimed to investigate whether oral intralipid emulsion (OIE) reduces pancreatic β-cell injury (PβCI) by chelating with malathion (M), or increases PβCI by increasing M absorption in the stomach. Fifty rats were randomly divided into six groups: control group (C); OIE administered group (L); M-treated group (M); OIE-administered group immediately after given M (M0L); OIE-administered group 6 hours after being given M (M6L) and OIE administered group 12 hours after being given M (M12L). M induced PβCI, hyperglycemia, temporary hyperinsulinemia and oxidative stress (OS). However, there was no significant difference in serum levels of glucose, insulin, total oxidants (TOS) and liver TOS between the M0L group and groups C and L. Also, insulin levels of M12L significantly increased, compared to the M6L group. Biochemical results, which were confirmed by histopathology, indicate that administering OIE after 6 hours and immediately after taking M may markedly prevent PβCI, hyperglycemia and OS. In addition, OIE's effectiveness decreased after 6 hours and was totally ineffective after 12 hours. We concluded that OIE may help to achieve a better prognosis and reduce mortality rate in cases presented to the emergency department, particularly within the first 6 hours, resulting from organophosphate pesticide poisoning by oral ingestion.

  13. Short-term effects of oral administration of Pistacia lentiscus oil on tissue-specific toxicity and drug metabolizing enzymes in mice.

    Science.gov (United States)

    Attoub, Samir; Karam, Sherif M; Nemmar, Abderrahim; Arafat, Kholoud; John, Annie; Al-Dhaheri, Wafa; Al Sultan, Mahmood Ahmed; Raza, Haider

    2014-01-01

    Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days. Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10(-6) - 10(-3)) did not affect the viability (cell death and proliferation) of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues. These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in combination with other pharmacological agents in order

  14. Short-Term Effects of Oral Administration of Pistacia Lentiscus Oil on Tissue-Specific Toxicity and Drug Metabolizing Enzymes in Mice

    Directory of Open Access Journals (Sweden)

    Samir Attoub

    2014-05-01

    Full Text Available Background: Pistacia lentiscus (Anacardiaceae is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Methods: Pistacia lentiscus oil (100µl was administered orally into mice for 5 days. Results: Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10-6 - 10-3 did not affect the viability (cell death and proliferation of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues. Conclusion: These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in

  15. Combined Interferon-α and Inosiplex Treatment of Subacute Sclerosing Panencephalitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Chy-Yuan Han

    2003-08-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is rare in Taiwan. On admission to hospital, a 15-year-old boy was diagnosed with SSPE based on the clinical picture, electroencephalogram, cerebrospinal fluid studies, and brain biopsy. The initial clinical picture was a decline in school performance and a change in personality, followed by progressive tic-like involuntary movements and mental impairment for 8 months, then a rapidly progressive course. After the patient was treated with oral inosiplex and intraventricular interferon-! (IFN-!, his condition stabilized and the neurologic disability index score improved slightly. There were no major side effects during treatment except for a transient initial elevation of body temperature that lasted for several days. Oral inosiplex and intraventricular IFN-! appear to be safe and effective. Early identification and aggressive treatment of SSPE is important.

  16. Subacute sclerosing panencephalitis presenting as neuromyelitis optica.

    Science.gov (United States)

    Raut, Tushar Premraj; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Naphade, Pravin Umakant

    2012-12-14

    Subacute sclerosing panencephalitis (SSPE) is a slowly progressing inflammatory and degenerative disorder of the brain caused by a mutant measles virus. The diagnosis of SSPE is based on characteristic clinical and EEG findings (periodic complexes) and demonstration of elevated antibody titres against measles in cerebrospinal fluid. SSPE can have atypical clinical features at the onset. The authors here report a case of a 3-year-old child who presented with vision loss followed 15 months later by quadriparesis with bladder involvement. These clinical features resembled that of neuromyelitis optica. However, as the disease progressed, appearance of myoclonic jerks, periodic discharges on EEG and positive cerebrospinal fluid serology for measles led to the final diagnosis of SSPE.

  17. Basal ganglia lesions in subacute sclerosing panencephalitis

    Directory of Open Access Journals (Sweden)

    Kelson James Almeida

    Full Text Available ABSTRACT The parieto-occipital region of the brain is the most frequently and severely affected in subacute sclerosing panencephalitis (SSPE. The basal ganglia, cerebellum and corpus callosum are less commonly involved. We describe a patient with SSPE confirmed by neuropathology based on brain magnetic resonance imaging showing extensive basal ganglia involvement and no significant involvement of other cortical structures. Though rarely described in SSPE, clinicians should be aware of this involvement. SSPE should be kept in mind when changes in basal ganglia signal are seen on brain magnetic resonance imaging with or without involvement of other regions of the human brain to avoid erroneous etiological diagnosis of other pathologies causing rapidly progressive dementia.

  18. Subacute Sclerosing Panencephalitis Presenting with Hemidystonia

    Directory of Open Access Journals (Sweden)

    Hepsen Mine Serin

    2014-06-01

    Full Text Available In this paper, we present a case of subacute sclerosing panencephalitis (SSPE in an 11-year-old boy who presented with hemidystonia. Electroencephalogram (EEG revealed periodic epileptiform discharges which did not disappear with diazepam induction. His cranial magnetic resonance imaging was normal. SSPE diagnosis was considered and it was confirmed with the identification of measles antibodies in cerebrospinal fluid. SSPE is a progressive disease. Hemidystonia is not an expected presentation of SSPE. We aimed to emphasize that SSPE may present with different clinical findings such as hemidystonia. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 137-9

  19. Subacute cutaneous lupus erythematosus presenting as poikiloderma.

    LENUS (Irish Health Repository)

    Hughes, R

    2012-02-01

    Subacute cutaneous lupus erythematosus (SCLE) is a recognised variant of lupus erythematosus (LE), which accounts for 10-15% of all cases of cutaneous LE, occurring most commonly in young to middle-aged white women. Diagnosis is based on the detection of anti-Ro\\/SS-A antibodies in the skin and serum, characteristic clinical and histological cutaneous involvement, and relatively mild systemic involvement. Several unusual variants of SCLE have been reported including erythrodermic SCLE, SCLE with vitiligo-like lesions, acral SCLE and bullous SCLE. Poikoilodermatous SCLE is a recognised but rare variant of SCLE. There are currently only two case reports, comprising five individual cases, in the literature. We present a case of SCLE in which the main clinical findings were an extensive photodistributed poikilodermatous rash and alopecia.

  20. Subacute transverse myelitis with Lyme profile dissociation

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    Ajjan, Mohammed

    2008-06-01

    Full Text Available Introduction: Transverse myelitis is a very rare neurologic syndrome with an incidence per year of 1-5 per million population. We are presenting an interesting case of subacute transverse myelitis with its MRI (magnetic resonance imaging and CSF (cerebrospinal fluid findings. Case: A 46-year-old African-American woman presented with decreased sensation in the lower extremities which started three weeks ago when she had a 36-hour episode of sore throat. She reported numbness up to the level just below the breasts. Lyme disease antibodies total IgG (immunoglobulin G and IgM (immunoglobulin M in the blood was positive. Antinuclear antibody profile was within normal limits. MRI of the cervical spine showed swelling in the lower cervical cord with contrast enhancement. Cerebrospinal fluid was clear with negative Borrelia Burgdorferi IgG and IgM. Herpes simplex, mycoplasma, coxiella, anaplasma, cryptococcus and hepatitis B were all negative. No oligoclonal bands were detected. Quick improvement ensued after she was given IV Ceftriaxone for 7 days. The patient was discharged on the 8th day in stable condition. She continued on doxycycline for 21 days. Conclusions: Transverse myelitis should be included in the differential diagnosis of any patient presenting with acute or subacute myelopathy in association with localized contrast enhancement in the spinal cord especially if flu-like prodromal symptoms were reported. Lyme disease serology is indicated in patients with neurological symptoms keeping in mind that dissociation in Lyme antibody titers between the blood and the CSF is possible.

  1. Subacute Thyroiditis Developed in Identical Twins Two Years Apart

    National Research Council Canada - National Science Library

    HAMAGUCHI, Erika; NISHIMURA, Yasuyuki; KANEKO, Shuichi; TAKAMURA, Toshinari

    2005-01-01

    .... Subacute thyroiditis was diagnosed and prednisone was administered. Two years later, her identical twin sister, who lives separately, was referred to our hospital because of neck pain, low-grade fever, and palpitation...

  2. Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

    National Research Council Canada - National Science Library

    Pavan S. Upadhyayula; Jason Yang; John K. Yue; Joseph D. Ciacci

    2017-01-01

    Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine...

  3. Angiosarcoma of the Heart Presenting as Subacute Pericarditis.

    Science.gov (United States)

    Joseph, Alexandra L; Wilklow, Frank E; Olivier, John J; Joseph, Georges J; Glancy, David Luke

    2017-03-15

    A young woman, who presented with what appeared to be subacute pericarditis, was found to have primary angiosarcoma of the heart, a condition that is nearly always fatal regardless of the therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Randomized study of nutritional status and treatment toxicities of oral arginine, glutamine, and Omega-3 fatty acids during concurrent chemoradiotherapy for head and neck cancer patients

    Directory of Open Access Journals (Sweden)

    Imjai Chitapanarux

    2016-03-01

    Full Text Available Background: Patients with head and neck cancer (HNC undergoing concurrent chemoradiotherapy (CCRT are at high risk of dysphagia, malnutrition, and immunosuppression. Arginine, glutamine, and Omega-3 fatty acidsare immune-enhanced nutrition that can promote cellular immunity.We aimed to examine the impact of immunonutrition diet on nutritional status, and CCRT toxicities, in this group of patients. Methods: Forty patients with HNC who treated with curative CCRT were randomized to: group A (n = 20, patients who received a regular diet and dietary counselingby a protocol dietician; group B (n = 20, patients who received a regular diet plus immune-enhanced nutrition supplements and dietary counseling by the same protocol dietician. Outcome measures were weight loss, protein and energy intake, serum pre-albumin and albumin, and toxicities of CCRT were evaluated at baseline, weekly and at the end of treatment. Results:Both groups were well balanced at baseline.One patient from group A (1/20 withdrew consent. Seven patients from group B (7/20 withdrew from the study; 1 patient could not tolerate the side effect of chemotherapy and 6 patients could not tolerate the taste of oral immune-enhanced nutrition.A significant loss in total body weight was observed in group A patients (p<0.001, whereas not significant loss in group B (p=0.109. Median percentage change from baseline of energy intake was 19.6%, and 22.9% at the end of treatment for group A, and B, respectively. The circulating levels of nutritional markers, pre-albumin and albumin decreased after CCRT in both groups. There was a significantly decreased level of albumin in group A more than group B, at the end of treatment. During CCRT; 4 patients (20% in group A and 1 patient(5% in group B developed grade 3 mucositis, respectively. One patient (5% in group A had grade 3 radiation dermatitis. Grade 3 – 4 hematologic toxicities, mainly in absolute neutrophil count (ANC were significant higher in

  5. Developmental toxicity studies with 6 forms of titanium dioxide test materials (3 pigment-different grade & 3 nanoscale) demonstrate an absence of effects in orally-exposed rats.

    Science.gov (United States)

    Warheit, D B; Boatman, R; Brown, S C

    2015-12-01

    Six different commercial forms and sizes of titanium dioxide particles were tested in separate developmental toxicity assays. The three pigment-grade (pg) or 3 ultrafine (uf)/nanoscale (anatase and/or rutile) titanium dioxide (TiO2) particle-types were evaluated for potential maternal and developmental toxicity in pregnant rats by two different laboratories. All studies were conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study). In addition, all test materials were robustly characterized. The BET surface areas of the pg and uf samples ranged from 7 to 17 m(2)/g and 50-82 m(2)/g respectively (see Table 1). The test substances were formulated in sterile water. In all of the studies, the formulations were administered by oral gavage to time-mated rats daily beginning around the time of implantation and continuing until the day prior to expected parturition. In 3 of the studies (uf-1, uf-3, & pg-1), the formulations were administered to Crl:CD(SD) rats beginning on gestation day (GD) 6 through GD 20. In 3 additional studies (uf-2, and pg-2, pg-3 TiO2 particles), the formulations were administered to Wistar rats beginning on GD 5 through 19. The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg/day; control group animals were administered the vehicle. During the in-life portions of the studies, body weights, food consumption, and clinical observations before and after dosing were collected on a daily basis. All dams were euthanized just prior to expected parturition (GD 21 for Crl:CD(SD) rats and GD 20 for Wistar rats). The gross necropsies included an examination and description of uterine contents including counts of corpora lutea, implantation sites, resorptions, and live and dead fetuses. All live fetuses were sexed, weighed, and examined externally and euthanized. Following euthanasia, fresh visceral and head examinations were performed on selected fetuses. The fetal carcasses were then processed and examined for skeletal

  6. Toxicity and antinociceptive effects of Hamelia patens

    Directory of Open Access Journals (Sweden)

    Angel Josabad Alonso-Castro

    Full Text Available Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae, a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg was evaluated in acute (14 days and subacute (28 days assays. In the subacute assay, a blood analysis (both hematology and chemistry was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg were evaluated using thermal-induced nociception (hot plate and the chemical-induced nociceptive tests (acid acetic and formalin. In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o. showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17% and 200 mg/kg (25% showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.

  7. Subacute cannabinoid treatment: anticonvulsant activity and withdrawal excitability in mice.

    OpenAIRE

    Karler, R.; Turkanis, S. A.

    1980-01-01

    1 The effects of subacute treatment with cannabidiol, delta 9-tetrahydrocannabinol (delta 9-THC), phenytoin and phenobarbitone on anticonvulsant activity and on withdrawal excitability in mice were compared in three electrically induced seizure-threshold tests. 2 In the maximal electroshock-threshold test, subacute treatment did not alter the anticonvulsant activity of cannabidiol, phenytoin or phenobarbitone, but tolerance developed to delta 9-THC. 3 In the 60 Hz electroshock-threshold test,...

  8. Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern

    Energy Technology Data Exchange (ETDEWEB)

    Senol, U. [Akdeniz University, Antalya (Turkey). Faculty of Medicine; Haspolat, S. [Akdeniz University, Antalya (Turkey). Dept. of Child Neurology; Cevikol, C. [Akdeniz University, Antalya (Turkey). Dept. of Radiodiagnostics; Saatci, I. [Hacettepe University (Turkey). Medical Faculty

    2000-12-01

    The most common pattern in subacute sclerosing panencephalitis, is in the cerebral hemisphere white matter on T2-weighted images with or without atrophy. Brain-stem lesions are rare. We report brain-stem involvement in two children with subacute sclerosing panencephalitis. A peculiar pattern, with involvement of the pons with extension to both middle cerebellar peduncles and substantia nigra but sparing the pontine tegmentum, is suggested. (orig.)

  9. Serial diffusion-weighted imaging in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Kanemura, Hideaki; Aihara, Masao

    2008-06-01

    Subacute sclerosing panencephalitis may be associated with clinical features of frontal lobe dysfunction. We previously reported that frontal lobe volume falls significantly as clinical stage progresses, using three-dimensional magnetic resonance imaging-based brain volumetry. The hypothesis that frontal volume increases correlate with clinical improvement, however, was not tested in our previous study. Therefore, we reevaluated our patient with subacute sclerosing panencephalitis, to determine whether apparent diffusion coefficient maps can characterize the clinical course of subacute sclerosing panencephalitis. We studied an 8-year-old boy with subacute sclerosing panencephalitis, using serial diffusion-weighted imaging magnetic resonance imaging, and measured the regional apparent diffusion coefficient. The regional apparent diffusion coefficient of the frontal lobe decreased significantly with clinical progression, whereas it increased to within normal range during clinical improvements. The apparent diffusion coefficient of the other regions did not change. These results suggest that the clinical signs of patients with subacute sclerosing panencephalitis are attributable to frontal lobe dysfunction, and that apparent diffusion coefficient measurements may be useful in predicting the clinical course of subacute sclerosing panencephalitis.

  10. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Cuiping, E-mail: yangsophia76@hotmail.com; Zhang, Tianhong, E-mail: wdzth@sina.com; Li, Zheng, E-mail: lizh2524@126.com; Xu, Liang, E-mail: wj24998@163.com; Liu, Fei, E-mail: liufeipharm@163.com; Ruan, Jinxiu, E-mail: ruanjx1936@yahoo.com.cn; Liu, Keliang, E-mail: keliangliu55@126.com; Zhang, Zhenqing, E-mail: zhangzhenqingpharm@163.com

    2013-12-15

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max

  11. Clinical manifestations and arsenic methylation after a rare subacute arsenic poisoning accident.

    Science.gov (United States)

    Xu, Yuanyuan; Wang, Yi; Zheng, Quanmei; Li, Bing; Li, Xin; Jin, Yaping; Lv, Xiuqiang; Qu, Guang; Sun, Guifan

    2008-06-01

    One hundred and four workers ingested excessive levels of arsenic in an accident caused by leakage of pipeline in a copper-smelting factory. Clinical examinations were performed by physicians in a local hospital. Excreted urinary arsenic species were determined by cold trap hydride generation atomic absorption spectrometry. In the initial toxic phase, gastrointestinal symptoms were predominant (83 people, 79.8%). Most patients showed leucopenia (72 people, 69.2%), and increased serum alanine aminotransferase (84 people, 80.8%) and aspartate aminotransferase (58 people, 55.8%). Thirty-five patients (33.6%) had elevated red blood cells in urine. After 17 days of admission, many subjects (45 people, 43.3%) developed peripheral neuropathy and 25 of these 45 patients (24.0%) showed a decrease in motor and sensory nerve conduction velocity. In the comparison of urinary arsenic metabolites among subacute arsenic-poisoned, chronic high arsenic-exposed and control subjects, we found that subacute arsenic-poisoned patients had significantly elevated proportions of urinary inorganic arsenic (iAs) and methylarsonic acid (MMA) but reduced proportion of urinary dimethylarsinic acid (DMA) compared with chronic high arsenic-exposed and control subjects. Chronic exposed subjects excreted higher proportions of iAs and MMA but lower proportions of DMA in urine compared with control subjects. These results suggest that gastrointestinal symptoms, leucopenia, and hepatic and urinary injury are predominant in the initial phase of subacute arsenic poisoning. Peripheral neuropathy is the most frequent manifestation after the initial phase. The biomethylation of arsenic decreases in a dose rate-dependent manner.

  12. Toxicity of 4-vinyl-1-cyclohexene diepoxide after 13 weeks of dermal or oral exposure in rats and mice

    Energy Technology Data Exchange (ETDEWEB)

    Chhabra, R.S.; Elwell, M.R.; Peters, A. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA))

    1990-05-01

    4-Vinyl-1-cyclohexene diepoxide (VCHD) is used as a chemical intermediate and as a reactive diluent for diepoxides and epoxy resins. Toxicology studies were conducted by administering VCHD in acetone by dermal application or in corn oil by gavage to F344/N rats and B6C3F1 mice for 13 weeks. In the 13-week dermal studies, groups of 10 rats of each sex received 0.3 ml of VCHD in acetone at concentrations ranging from 6.25 to 200 mg/ml, and mice received 0.1 ml at concentrations ranging from 6.25 to 100 mg/ml. Skin lesions were observed at the site of application at the top two dose levels for both species and sexes, and consisted of acanthosis, parakeratosis, and hyperkeratosis of the epidermis and sebaceous gland hyperplasia. In mice, follicular atrophy of the ovary, characterized by decreased numbers of primary and secondary follicles, occurred at the 50- and 100-mg dose levels. In 13-week oral studies, groups of 10 rats and mice of each sex were administered VCHD at dose levels ranging from 62.5 to 1000 mg/kg in corn oil. In rats and mice, there were body weight decreases in the groups given the two highest doses. The major target organs in rats were forestomach (hyperplasia and hyperkeratosis) and kidney (tubular cell degeneration/necrosis and regeneration). In mice the target organs included forestomach (hyperplasia and hyperkeratosis), ovary (follicular atrophy), and testis (degeneration of germinal epithelium).

  13. Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats.

    Science.gov (United States)

    Abarikwu, S O; Benjamin, S; Ebah, S G; Obilor, G; Agbam, G

    2017-02-01

    This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl 2 ). After 15 days of oral administration of CO (2 ml kg -1 body weight) and MO (2 ml kg -1 body weight) along with intraperitoneal (i.p.) administration of HgCl 2 (5 mg kg -1 body weight) alone or in combination, we found that CO treatment did not protect against HgCl 2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl 2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl 2 (2 ml kg -1 body weight + 5 mg kg -1 body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl 2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl 2 -induced oxidative damage. © 2016 Blackwell Verlag GmbH.

  14. Safety assessment of the butyrate-producing Butyricicoccus pullicaecorum strain 25-3(T), a potential probiotic for patients with inflammatory bowel disease, based on oral toxicity tests and whole genome sequencing.

    Science.gov (United States)

    Steppe, Marjan; Van Nieuwerburgh, Filip; Vercauteren, Griet; Boyen, Filip; Eeckhaut, Venessa; Deforce, Dieter; Haesebrouck, Freddy; Ducatelle, Richard; Van Immerseel, Filip

    2014-10-01

    Inflammatory bowel disease (IBD) is a chronic inflammation of the digestive tract, characterized by dysbiosis of the intestinal microbiota. Probiotics have been suggested as a strategy to reduce active disease or extend remission. We isolated and characterized the butyrate-producing strain Butyricicoccus pullicaecorum 25-3(T) and identified it as a potential probiotic for patients with IBD. To evaluate the safety of 25-3(T) for use in humans, we conducted a standard acute oral toxicity test and a 28-day repeated oral dose toxicity test. The complete genome of B. pullicaecorum 25-3(T) was sequenced to search for virulence factors and antibiotic resistance determinants. The minimum inhibitory concentration (MIC) of 21 antimicrobials was determined. Results showed no adverse effects in the oral toxicity tests. B. pullicaecorum 25-3(T) is resistant against aminoglycosides and trimethoprim. The genome of 25-3(T) contains no virulence factors, one gene related to harmful metabolites and 52 sequences with high similarity to antimicrobial and toxic compound resistance genes, that did not correspond with a resistant phenotype. This first report of a safety assessment of a butyrate-producing strain from Clostridium cluster IV shows that B. pullicaecorum 25-3(T) is a non-pathogenic strain, but carries antibiotic resistance genes with the risk of transfer, that need further investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Oral (Gavage) Combined Developmental and Perinatal/Postnatal Reproduction Toxicity Study of Ammonium Salt of Perfluorinated Hexanoic Acid in Mice.

    Science.gov (United States)

    Iwai, Hiroyuki; Hoberman, Alan M

    2014-05-01

    The reproductive toxicity potential of Ammonium Salt of Perfluorinated Hexanoic Acid (PFHxA Ammonium Salt) in pregnant Crl: CD1(ICR) mice was investigated. Twenty females/group were administered the test substance or vehicle once daily from gestation day 6 through 18. Phase 1 doses: 0, 100, 350, and 500 mg/kg/d; phase 2: 0, 7, 35, and 175 mg/kg/d. Parameters evaluated include mortality, viability, body weights, clinical signs, abortions, premature deliveries, pregnancy and fertility, litter observations, maternal behavior, and sexual maturity in the F1 generation. The level of PFHxA Ammonium Salt was measured in the liver of F0 and F1 mice. At doses of 350 and 500 mg/kg/d maternal mortalities, excess salivation and changes in body weight gains occurred. Pup body weights were reduced on postpartum day (PPD) 0 in all the dosage groups, but persisted only in the 350 and 500 mg/kg/d groups. Additional effects at 300 and 500 mg/kg/d included stillbirths, reductions in viability indices, and delays in physical development. Levels of PFHxA Ammonium Salt in the livers of the 100 mg/kg/d dams were all below the lower limit of quantization (0.02 µg/mL); in the 350 mg/kg/d group, 3 of the 8 samples had quantifiable analytical results. In phase 2 no PFHxA Ammonium Salt was found in the liver. Adverse effects occurred only in the 175 mg/kg/d group and consisted of increased stillborn pups, pups dying on PPD 1, and reduced pup weights on PPD 1. Based on these data, the maternal and reproductive no observable adverse effect level of PFHxA Ammonium Salt is 100 mg/kg/d. © The Author(s) 2014.

  16. Single-dose oral toxicity study of a cross-linked sodium polyacrylate/polyvinyl alcohol copolymer in chickens (Gallus domesticus).

    Science.gov (United States)

    Haselbach, J; Berner, T; Wright, H; Dunlap, E

    2000-12-01

    A single-dose oral toxicity study of a grafted copolymer of cross-linked sodium polyacrylate with polyvinyl alcohol was conducted in chickens (Gallus domesticus) to demonstrate this copolymer's safety for use as a hydration medium in recently hatched poultry chicks. Three experimental groups, each composed of 25 male and 25 female 1-day-old chicks, were administered a one-time dose of 0, 3, or 6 g of the hydrated test article by gavage. All chicks were monitored daily for mortality and morbidity during their typical grow-out period of approximately 8 weeks. Interim sacrifices of one animal of each sex from each treatment group were made at 1, 2, 4, and 6 weeks. All surviving animals were necropsied at the end of the study. A single dose of up to 6 g of hydrated copolymer did not adversely affect these animals during their grow-out period. Mortality was comparable across all experimental groups, as no statistically significant survival differences were found. Body weights were also comparable across the three experimental groups at all time points during the study, and no statistically significant differences were detected in mean terminal body weights among the groups. Finally, lesion frequencies were similar across the three experimental groups, with none of the lesions deemed related to administration of the test article. Thus, the safety of this cross-linked sodium polyacrylate/polyvinyl alcohol copolymer has been demonstrated for its intended use. Copyright 2000 Academic Press.

  17. A 90-day oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, in F344 rats.

    Science.gov (United States)

    Nabae, K; Ichihara, T; Hagiwara, A; Hirota, T; Toda, Y; Tamano, S; Nishino, M; Ogasawara, T; Sasaki, Y; Nakamura, M; Shirai, T

    2005-07-01

    A subchronic oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.2%, 1.0% and 5.0% for 90 days. There were no treatment-related adverse effects with regard to body weight, food and water consumption, urinalysis, ophthalmology, hematology, serum biochemistry, and organ weight data. On clinical observation, red coloring of fur was noted in both sexes of the 1.0% and 5.0% group rats, with red feces observed in all treated group animals, and necropsy revealed all rats of the treated groups to have reddish coloration of the contents of the gastro-intestinal tract, due to the pigmentation and thus lacking toxicological significance. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 5.0% (3127 mg/kg body weight/day for males, 3362 mg/kg body weight/day for females) for beta-carotene derived from B. trispora under the present experimental conditions.

  18. EVALUATION OF DIPYRIDAMOLE ON ACUTE AND SUBACUTE MODELS OF INFLAMMATION IN MALE WISTAR RATS: AN EXPERIMENTAL STUDY

    Directory of Open Access Journals (Sweden)

    Angadi Netravathi B, Hiremath Shrishail V , Suranagi Vijayalakshmi V.

    2015-07-01

    Full Text Available Background: Atherosclerosis and its complications remains the major cause of death and premature disability. Atherogenesis involves elements of inflammation, a process that now provides a unifying theme in the pathogenesis of the disease. Anti-platelet drugs are currently used in the treatment of atherosclerosis and its complications. Our study evaluated the influence of dipyridamole on acute and sub-acute models of inflammation in male Wistar rats. Methods: Male Wistar rats (150-200g were divided into three groups i.e. control, Aspirin and dipyridamole (n=6 animals in each group. The effect of dipyridamole, administered orally, on inflammation was studied using acute (carrageenan induced rat paw edema and sub-acute (cotton pellet granuloma and histopathological examination of grass piths models. Experiment was conducted according to the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA guidelines. Analysis was done using one way ANOVA followed by Post Hoc Test of Dunnets. P<0.05 was considered as statistically significant. Results: Dipyridamole showed significant inhibition of rat paw edema in acute model (P<0.01 and granuloma dry weight, in sub acute model of inflammation when compared to control (P<0.01. Histopathological examination of grass pith revealed markedly reduced fibroblasts, granulation tissue, fibrous tissue and collagen in dipyridamole group when compared to control. Conclusion: Dipyridamole exhibited a significant anti inflammatory activity in acute and sub-acute models of inflammation.

  19. Subacute sclerosing panencephalitis: clinical and demographic characteristics.

    Science.gov (United States)

    Rafique, Arshad; Amjad, Nida; Chand, Prem; Zaidi, Syed Sohail Zahoor; Rana, Muhammad Suleman; Ahmed, Khalid; Ibrahim, Shahnaz

    2014-08-01

    To determine the clinical and demographic characteristics of children diagnosed with Subacute sclerosing panencephalitis (SSPE). Case series. The Aga Khan University Hospital, Karachi, from January 2000 to June 2012. A retrospective analysis was done, regarding medical charts of 43 children under the age of 16 years with a discharge diagnosis of SSPE. Demographic and clinical characteristics were recorded. RESULTS were expressed as percentages. Most of the 43 patients were male (72%). The average age at presentation was 8.7 years with average duration of symptoms being 100.6 days. History of measles was present in 17 patients (39.5%). All children had seizures at presentation and 65% had cognitive impairment. Most patients required poly therapy for control of seizures. Sodium valproate was the most commonly used anti-epileptic agent; Isoprinosine was tried in 22 (51%) patients. CSF for antimeasles antibodies was positive in approximately 86% of the 40 (93%) children. EEG showed burst suppression pattern in 36 (83.7%) cases. Forty-two patients (97.6%) were discharged home in a vegetative state. SSPE is progressive neurodegenerative disorder. It can be prevented by timely immunization against measles. Measles antibody in the CSF is diagnostic for SSPE and is helpful in early diagnosis. Most patients experience a gradual but progressive decline in motor and cognitive functions.

  20. Subacute posttraumatic ascending myelopathy: a literature review.

    Science.gov (United States)

    Zhang, J; Wang, G

    2017-07-01

    A literature review. Our aim was to summarise the history, epidemiology, aetiological mechanism, pathological study, clinical and radiological evaluation, treatment and prognosis of subacute posttraumatic ascending myelopathy (SPAM). Medical literature on SPAM were searched in the PubMed, Medline, Ovid and Embase databases. The cases of SPAM reported in literature were analysed, and the history, epidemiology, aetiological mechanism, pathological study, clinical and radiological evaluation, treatment and prognosis of SPAM were summarised. SPAM remains a relatively rare disorder occurring within the first few weeks after spinal cord injury (SCI). The incidence rate ranges from 0.42% to 1% among all SCI. SPAM is likely to occur in young and middle-aged male patients. Risk factors of SPAM include complete injury, low blood pressure, early postoperative mobilisation and nonsurgical treatment. SPAM is well recognised according to typical clinical manifestation and magnetic resonance imaging characteristics. There is no effective therapy for this neurological deterioration. The prognosis of SPAM is poor. There is usually a slight improvement of one or more level(s) below the maximal level of deterioration. The mortality rate is approximately 10%.

  1. Toxicity of cholecalciferol overdosage in white albino mice | Ogamba ...

    African Journals Online (AJOL)

    There is need to determine the effect of this vitamin overdosage in animals and possibly extrapolate the findings to human beings. Aim: To determine subacute and chronic toxicity of cholecalciferol overdosage in white albino mice. Methods: Increasing doses of cholecalciferol were given to three groups of white albino mice ...

  2. Toxicity And Immunomodulatory Activity Of Fractions Of Hibiscus ...

    African Journals Online (AJOL)

    This study evaluated immunomodulatory properties and the sub-acute toxicity profile of two fractions of the aqueous alcoholic extract of the dried calyx of Hibiscus sabdariffa in experimental animals. Immunomodulatory activity was evaluated using red blood cell-induced immunostimulation. The fractions were not found to ...

  3. Toxicity And Immunomodulatory Activity Of Fractions Of Hibiscus ...

    African Journals Online (AJOL)

    The two fractions caused a significant reduction in production of tissue necrosis factor – alpha and an increase in interleukin 10 (IL-10). Keywords: Hibiscus sabdariffa, plant extract and fractions, sub-acute toxicity, immuno-modulatory activity, cytokine production. African Journal of Trad, Comp and Alternative Medicine Vol.

  4. Subacute Sclerosing Panencephalitis in a Child with Human Immunodeficiency Virus Co-Infection

    OpenAIRE

    Maurya, Pradeep Kumar; Thakkar, Mayur Deepak; Kulshreshtha, Dinkar; Singh, Ajai Kumar; Thacker, Anup Kumar

    2016-01-01

    Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection.

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

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2015-09-15

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

  6. Subacute pain and function after fast-track hip and knee arthroplasty

    DEFF Research Database (Denmark)

    Andersen, Lasse Østergaard; Gaarn-Larsen, L; Kristensen, B B

    2009-01-01

    In a well-defined fast-track setup for total hip and knee arthroplasty, with a multimodal analgesic regimen consisting of intra-operative local anaesthetic infiltration and oral celecoxib, gabapentin and paracetamol for 6 days postoperatively, we conducted a prospective, consecutive, observational...... study. The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects, use of analgesics and functional ability 1-10 and 30 days postoperatively. Fast-track total hip and knee arthroplasty with early discharge (... levels of pain and postoperative nausea and vomiting with concomitant low use of opioids in > 95% of patients after discharge before day 10 after total hip arthroplasty. However, after total knee arthroplasty 52% patients reported moderate pain (VAS 30-59 mm), and 16% severe pain (VAS > or = 60 mm) when...

  7. Epilepsy in children with subacute sclerosing panencephalitis.

    Science.gov (United States)

    Jović, Nebojša J

    2013-01-01

    Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, fatal neurodegenerative disease of childhood and early adolescence caused by defective measles virus. The initial symptoms of SSPE usually involve regression in cognitive functioning and behavior or recurrent myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical course can occur. The aim of the study was to analyze clinical and EEG characteristics of both initially occurred seizures and epilepsy which developed in the course of the disease. Retrospective study was carried out on 19 children (14 boys, 5 girls) with SSPE diagnosed and treated at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged from 6.5 to 11.5 years (mean 8.6 years). SSPE onset ranged from 4.5 to 16.5 years (mean 10.05). Complete vaccination was performed in nine patients. Cognitive and behavioral decline was preceeded by 6-18 months in two children with intractable focal motor seizures with secondary generalization, one child with complex partial seizures and one with atypical absences. During the clinical course of the disease epilepsy developed in 10 (52.6%) cases, including four patients with seizures as the initial SSPE sign. It occurred mainly in the first year, while in three cases seizures appeared between 1 and 5 years of the disease evolution. Myoclonus was present independently from seizures. No significant inter-group differences were found relating to the type of SSPE progression and history of epilepsy. The only child with fulminant SSPE presented with initial seizures. Favorable seizure control was achieved in 60.0% patients. Intractable epilepsy developed in four patients. Atypical SSPE presentation can include mainly focal intractable seizures. Epilepsy developed during clinical course in 52.6% cases. No significant influence was found of the history of epilepsy on the type of SSPE progression.

  8. Subacute sclerosing panencephalitis: A clinical appraisal.

    Science.gov (United States)

    Jagtap, Sujit Abajirao; Nair, M D; Kambale, Harsha J

    2013-10-01

    Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis affecting primarily children and young adults, caused by a persistent infection of immune resistant measles virus. The aim of the present study is to describe the clinical profile and natural history of patients with SSPE. We collected data of patients with SSPE during 2004-2010 who fulfilled Dyken's criteria. We analyzed demographical, clinical, electrophysiological, and imaging features. Study included 34 patients, 26 (76.5%) males with age of onset from 3 to 31 years. Twenty one patients were below 15 years of age formed childhood SSPE and 13 above 15 years of age constituted adult onset group. 85.3% had low-socioeconomic status. Eleven received measles vaccination and seven were unvaccinated. 59.9% patients had measles history. Most common presenting symptom was scholastic backwardness (52.5%) followed by seizures (23.5%). Three patients each had cortical blindness, macular degeneration, decreased visual acuity, and optic atrophy. Electroencephalographic (EEG) showed long interval periodic complexes and cerebrospinal fluid anti-measles antibody was positive in all. Magnetic resonance imaging was done in 70.5% with was abnormal in 52.5%. Mean incubation period of SSPE after measles was 9.6 years. The follow-up duration was 1-10 years, (average of 2 years). Only one patient died from available data of follow-up, 9 were stable and 10 deteriorated in the form of progression of staging. SSPE is common in low-socioeconomic status. The profile of adult onset did not differ from childhood onset SSPE, except for a longer interval between measles infection and presence of the ophthalmic symptom as presenting feature in adult onset group.

  9. Epilepsy in children with subacute sclerosing panencephalitis

    Directory of Open Access Journals (Sweden)

    Jović Nebojša J.

    2013-01-01

    Full Text Available Introduction. Subacute sclerosing panencephalitis (SSPE is a rare, progressive, fatal neurodegenerative disease of childhood and early adolescence caused by defective measles virus. The initial symptoms of SSPE usually involve regression in cognitive functioning and behavior or recurrent myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical course can occur. Objective. The aim of the study was to analyze clinical and EEG characteristics of both initially occurred seizures and epilepsy which developed in the course of the disease. Methods. Retrospective study was carried out on 19 children (14 boys, 5 girls with SSPE diagnosed and treated at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged from 6.5 to 11.5 years (mean 8.6 years. Results. SSPE onset ranged from 4.5 to 16.5 years (mean 10.05. Complete vaccination was performed in nine patients. Cognitive and behavioral decline was preceeded by 6-18 months in two children with intractable focal motor seizures with secondary generalization, one child with complex partial seizures and one with atypical absences. During the clinical course of the disease epilepsy developed in 10 (52.6% cases, including four patients with seizures as the initial SSPE sign. It occurred mainly in the first year, while in three cases seizures appeared between 1 and 5 years of the disease evolution. Myoclonus was present independently from seizures. No significant inter-group differences were found relating to the type of SSPE progression and history of epilepsy. The only child with fulminant SSPE presented with initial seizures. Favorable seizure control was achieved in 60.0% patients. Intractable epilepsy developed in four patients. Conclusion. Atypical SSPE presentation can include mainly focal intractable seizures. Epilepsy developed during clinical course in 52.6% cases. No significant influence was found of the history of epilepsy on the type of SSPE progression.

  10. Subacute sclerosing panencephalitis: A clinical appraisal

    Directory of Open Access Journals (Sweden)

    Sujit Abajirao Abajirao

    2013-01-01

    Full Text Available Introduction: Subacute sclerosing panencephalitis (SSPE is a rare chronic, progressive encephalitis affecting primarily children and young adults, caused by a persistent infection of immune resistant measles virus. The aim of the present study is to describe the clinical profile and natural history of patients with SSPE. Methods: We collected data of patients with SSPE during 2004-2010 who fulfilled Dyken′s criteria. We analyzed demographical, clinical, electrophysiological, and imaging features. Results: Study included 34 patients, 26 (76.5% males with age of onset from 3 to 31 years. Twenty one patients were below 15 years of age formed childhood SSPE and 13 above 15 years of age constituted adult onset group. 85.3% had low-socioeconomic status. Eleven received measles vaccination and seven were unvaccinated. 59.9% patients had measles history. Most common presenting symptom was scholastic backwardness (52.5% followed by seizures (23.5%. Three patients each had cortical blindness, macular degeneration, decreased visual acuity, and optic atrophy. Electroencephalographic (EEG showed long interval periodic complexes and cerebrospinal fluid anti-measles antibody was positive in all. Magnetic resonance imaging was done in 70.5% with was abnormal in 52.5%. Mean incubation period of SSPE after measles was 9.6 years. The follow-up duration was 1-10 years, (average of 2 years. Only one patient died from available data of follow-up, 9 were stable and 10 deteriorated in the form of progression of staging. Conclusion: SSPE is common in low-socioeconomic status. The profile of adult onset did not differ from childhood onset SSPE, except for a longer interval between measles infection and presence of the ophthalmic symptom as presenting feature in adult onset group.

  11. Citrus aurantium (bitter orange) extract: Safety assessment by acute and 14-day oral toxicity studies in rats and the Ames Test for mutagenicity.

    Science.gov (United States)

    Deshmukh, N S; Stohs, S J; Magar, C C; Kadam, S B

    2017-11-01

    The primary active constituent in bitter orange extract (BOE) is p-synephrine. This study assessed the safety of a BOE standardized to 50% p-synephrine following short-term exposure to rats and by the Ames Test. Following 5000 mg/kg of the extract orally to female rats all animals survived. Administration at 2000 mg/kg to female rats for four days yielded no signs of toxicity. Five male and five female rats were administered the BOE at 0, 250, 500, 1000 and 2000 mg/kg/day for 14 days. No significant effects were observed at any dose with respect to body weights, food intake, absolute and relative organ weights, hematology, clinical chemistry, and pathology. Two male rats died after 2000 mg/kg with gastrointestinal impaction at necropsy. During week two of 1000 mg/kg and 2000 mg/kg/day, rats exhibited transient signs of repetitive burrowing of heads in the bedding material (hypoactivity) for about 15 and 45 min, respectively. The no-observed-effect-level (NOEL) was 500 mg/kg/day. The mutagenic potential was assessed at and up to the limit dose of 5000 μg/plate in a Salmonella typhimurium reverse mutation (Ames) test, performed in duplicate as a pre-incubation assay in the presence and absence of metabolic activation (S9). The BOE did not induce an increase in the frequency of revertant colonies at any dose in the five tester strains, and was therefore non-mutagenic. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks.

    Science.gov (United States)

    Boudreau, Mary D; Imam, Mohammed S; Paredes, Angel M; Bryant, Matthew S; Cunningham, Candice K; Felton, Robert P; Jones, Margie Y; Davis, Kelly J; Olson, Greg R

    2016-03-01

    There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US.

  13. wksl3, a New biocontrol agent for Salmonella enterica serovars enteritidis and typhimurium in foods: characterization, application, sequence analysis, and oral acute toxicity study.

    Science.gov (United States)

    Kang, Hyun-Wol; Kim, Jae-Won; Jung, Tae-Sung; Woo, Gun-Jo

    2013-03-01

    Of the Salmonella enterica serovars, S. Enteritidis and S. Typhimurium are responsible for most of the Salmonella outbreaks implicated in the consumption of contaminated foods in the Republic of Korea. Because of the widespread occurrence of antimicrobial-resistant Salmonella in foods and food processing environments, bacteriophages have recently surfaced as an alternative biocontrol tool. In this study, we isolated a virulent bacteriophage (wksl3) that could specifically infect S. Enteritidis, S. Typhimurium, and several additional serovars. Transmission electron microscopy revealed that phage wksl3 belongs to the family Siphoviridae. Complete genome sequence analysis and bioinformatic analysis revealed that the DNA of phage wksl3 is composed of 42,766 bp with 64 open reading frames. Since it does not encode any phage lysogeny factors, toxins, pathogen-related genes, or food-borne allergens, phage wksl3 may be considered a virulent phage with no side effects. Analysis of genetic similarities between phage wksl3 and four of its relatives (SS3e, vB_SenS-Ent1, SE2, and SETP3) allowed wksl3 to be categorized as a SETP3-like phage. A single-dose test of oral toxicity with BALB/c mice resulted in no abnormal clinical observations. Moreover, phage application to chicken skin at 8°C resulted in an about 2.5-log reduction in the number of Salmonella bacteria during the test period. The strong, stable lytic activity, the significant reduction of the number of S. Enteritidis bacteria after application to food, and the lack of clinical symptoms of this phage suggest that wksl3 may be a useful agent for the protection of foods against S. Enteritidis and S. Typhimurium contamination.

  14. Current therapies and future perspectives in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Tatli, Burak; Ekici, Bariş; Ozmen, Meral

    2012-04-01

    Subacute sclerosing panencephalitis is a progressive neurological disorder of children and young adults caused by a measles virus that became defective by persisting in the host. According to the results of clinical trials, antiviral and/or immunomodulatory therapy can slow the progression of the disease and improve life expectancy in patients. However, its long-term effects and eventual outcome remain debatable due to conflicting results and its lack of effect on the rapidly progressive form of the disease. Possible future therapies for subacute sclerosing panencephalitis are RNAi and antiapoptotic agents, which are currently in the hypothetical and experimental stages of research.

  15. Biological Parameters for Evaluating the Toxic Potency of Petroleum Ether Extract of Wattakaka volubilis in Wistar Female Rats

    Directory of Open Access Journals (Sweden)

    Velmani Gopal

    2014-09-01

    Full Text Available Objectives: The present study investigated the toxic properties of petroleum ether extract of Wattakaka (W. volubilis in Wistar female rats. Methods: An in vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the lethality concentrations were assessed for petroleum ether extract of W. volubilis. A water soluble portion of the test extract was used in different concentrations from 100-1000 μg/mL of 1 mg/mL stock solution. A 24-hours incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to calculate the percentage rate of dead nauplii with test extract administration against a potassium-dichromate positive control. The acute and the sub-acute toxicities of petroleum ether extract of W. volubilis were evaluated orally by using gavage in female Wistar rats. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Toxicity or death was evaluated following the administration of petroleum ether extract for 28 consecutive days in the female rats. Serum biochemical parameters, such as alanine aminotransferase (ALT, alkaline phosphatase (ALP, bilirubin, total cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium, potassium and α-amylase levels, were measured in the toxicity evaluations. Pathological changes in isolated organs, such as the liver, kidneys, and pancreas, were also examined using hematoxylin and eosin dye fixation after the end of the test extract’s administration. Results: The results of the brine-shrimp assay indicate that the evaluated concentrations of petroleum ether extract of W. volubilis were found to be non-toxic. In the acute and the sub-acute toxicity evaluations, no significant differences were observed between the control animals and the animals treated with extract of W. volubilis. No abnormal histological changes were observed in any of the animal groups treated with petroleum ether extract of W. volubilis

  16. Resolving MRI abnormalities with progression of subacute sclerosing panencephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Winer, J.B. (Saint Mary' s Hospital, Birmingham (UK)); Pires, M.; Kermode, A.; Ginsberg, L. (National Hospital for Nervous Diseases, Birmingham (UK)); Rossor, M. (Saint Mary' s Hospital, Birmingham (UK) National Hospital for Nervous Diseases, Birmingham (UK))

    1991-04-01

    Serial MRI was performed on a 15 year old girl with Subacute Sclerosing Pan-encephalitis (SSPE). After a period of remission she entered a phase of progressive deterioration. A repeat MRI showed significant resolution of the previous abnormalities. Her pathology and MRI scans are discussed.

  17. Epilepsia partialis continua in children with fulminant subacute sclerosing panencephalitis.

    Science.gov (United States)

    Kravljanac, Ruzica; Jovic, Nebojsa; Djuric, Milena; Nikolic, Ljubica

    2011-12-01

    Various inflammatory diseases of central nervous system, including subacute sclerosing panencephalitis, could cause epilepsia partialis continua. Two boys with epilepsia partialis continua with onset in terminal phase of atypical subacute sclerosing panencephalitis have been reported. Children were not vaccinated against measles, and the second case had history of measles at an early age. In both cases, the onset of subacute sclerosing panencephalitis was characterized by altered behavior and cognitive decline with very fast mental and neurological deterioration. One boy was suffering from complex partial seizures and myoclonic jerks synchronous with periodic electroencephalographic pattern. Diagnosis was proved by increased titers of antimeasles antibodies in both serum and cerebrospinal fluid. In terminal phase of the disease, epilepsia partialis continua of localized group of the muscles was diagnosed, with good response to intravenous infusion of midazolam. Surface electroencephalographic recordings during epilepsia partialis continua did not show the epileptic discharges. During the terminal phase of the disease, no other type of seizures and movement disorders were recognized, except epilepsia partialis continua. In spite of the treatment, period from the onset of disease to death lasted less than 3 months, suggesting very fulminant course of subacute sclerosing panencephalitis.

  18. High-Dose Intravenous Ribavirin Therapy for Subacute Sclerosing Panencephalitis

    Science.gov (United States)

    Hosoya, Mitsuaki; Shigeta, Shiro; Mori, Shuichi; Tomoda, Akemi; Shiraishi, Seiji; Miike, Teruhisa; Suzuki, Hitoshi

    2001-01-01

    Two patients with subacute sclerosing panencephalitis (SSPE) were treated safely and effectively with high doses of intravenous ribavirin combined with intraventricular alpha interferon. The ribavirin concentrations maintained in the serum and cerebrospinal fluid were higher than those which inhibit SSPE virus replication in vitro and in vivo. PMID:11181386

  19. A close look at EEG in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Demir, Nurhak; Cokar, Ozlem; Bolukbasi, Feray; Demirbilek, Veysi; Yapici, Zuhal; Yalcinkaya, Cengiz; Direskeneli, Guher Saruhan; Yentur, Sibel; Onal, Emel; Yilmaz, Gulden; Dervent, Aysin

    2013-08-01

    To define atypical clinical and EEG features of patients with subacute sclerosing panencephalitis that may require an overview of differential diagnosis. A total of 66 EEGs belonging to 53 (17 females and 36 males) consecutive patients with serologically confirmed subacute sclerosing panencephalitis were included in this study. Patient files and EEG data were evaluated retrospectively. EEGs included in the study were sleep-waking EEGs and/or sleep-waking video-EEG records with at least 2 hours duration. Cranial MRIs of the patients taken 2 months before or after the EEG records were included. Age range at the onset of the disease was 15 to 192 months (mean age: 80.02 months). Epilepsy was diagnosed in 21 (43%) patients. Among epileptic seizures excluding myoclonic jerks, generalized tonic-clonic type constituted the majority (58%). Tonic seizures were documented during the video-EEG recordings in four patients. Epileptogenic activities were found in 56 (83%) EEG recordings. They were localized mainly in frontal (58%), posterior temporal, parietal, occipital (26%), and centrotemporal (8%) regions. Multiple foci were detected in 26 recordings (39%). Epileptiform activities in the 39 (59%) EEGs appeared as unilateral or bilateral diffuse paroxysmal discharges. Recognition of uncommon clinical and EEG findings of subacute sclerosing panencephalitis, especially in countries where subacute sclerosing panencephalitis has not been eliminated yet, could be helpful in prevention of misdiagnosis and delay in the management of improvable conditions.

  20. Treatment of acute and subacute dorsal perilunate fracture dislocations

    Directory of Open Access Journals (Sweden)

    Levent Kucuk

    2014-04-01

    Outcomes: Results of the perilunate fracture dislocations treated in acute or subacute phase by open reduction and internal fixation via dorsal approach are satisfactory. There is a strong demand for prospective, randomized studies to compare the results of different treatment modalities. [Hand Microsurg 2014; 3(1.000: 1-7

  1. Speech and Language Therapy for Aphasia following Subacute Stroke

    NARCIS (Netherlands)

    Koyuncu, E.; Çam, P.; Altinok, N.; Çalli, D.E.; Yarbay Duman, T.; Özgirgin, N.

    2016-01-01

    The aim of this study was to investigate the time window, duration and intensity of optimal speech and language therapy applied to aphasic patients with subacute stroke in our hospital. The study consisted of 33 patients being hospitalized for stroke rehabilitation in our hospital with first stroke

  2. Virtual Reality Training for Upper Extremity in Subacute Stroke (VIRTUES)

    DEFF Research Database (Denmark)

    Brunner, Iris; Skouen, Jan Sture; Hofstad, Håkon

    2017-01-01

    Objective: To compare the effectiveness of upper extremity virtual reality rehabilitation training (VR) to time-matched conventional training (CT) in the subacute phase after stroke. Methods: In this randomized, controlled, single-blind phase III multicenter trial, 120 participants with upper...

  3. Autophagy regulated by prolyl isomerase Pin1 and phospho-Ser-GSK3αβ involved in protection of oral squamous cell carcinoma against cadmium toxicity

    Energy Technology Data Exchange (ETDEWEB)

    So, Keum-Young [Department of Anesthesiology and Pain Medicine College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of); Ahn, Sang-Gun [Department of Pathology, College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of); Oh, Seon-Hee, E-mail: seonh@chosun.ac.kr [Department of Premedicine, School of Medicine, College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of)

    2015-10-23

    Prolyl isomerase Pin1 plays an important role in cell proliferation and is overexpressed in many human tumors. However, its role in autophagy induction remains undefined. Here we show that Pin1 regulates cell survival via autophagy in cadmium (Cd)-exposed oral squamous cell carcinoma (OSCC). OSCC exposure to Cd induced autophagy, as demonstrated by the formation of green fluorescent punctae in transfected cells expressing GFP-conjugated microtubule-associated protein light chain 3 (LC3) and by LC3 flux in the presence of autophagy inhibitors. Suppression of Atg5 enhanced Cd-induced apoptosis, indicating that autophagy is involved in cell protection. In dose–response experiments, cleavage of procaspase-3, PARP-1, and LC3-II was induced by Cd with an IC{sub 50} of 45 μM. Expression of Pin1 was decreased at or above the Cd IC{sub 50} value and was inversely correlated with the level of phospho(p)-Ser-GSK3αβ. Genetic or pharmacologic inhibition of Pin1 suppressed Cd-induced autophagy, but increased p-Akt-mediated p-Ser-GSK3αβ; this was reversed by overexpression of Pin1. However, suppression of GSK3αβ inhibited Cd-induced autophagy and induced apoptosis, which could be reversed by overexpression of GSK3β. The PI3K inhibitor Ly294002 blocked p-Akt-mediated increases in p-Ser-GSK3αβ and autophagy and induced apoptosis. Therefore, p-Ser-GSK3αβ can directly regulate Cd-induced autophagy, although its function is suppressed by Pin1. Collectively, the present results indicate that targeting Pin1 and GSK3αβ at the same time could be an effective therapeutic tool for Cd-induced carcinogenesis. - Highlights: • Pin1 regulated autophagy to protect cells from cadmium toxicity. • Pin1 suppression inhibited cadmium-induced autophagy and induced apoptosis. • Pin1 inhibited the function of p-Ser-GSK3αβ in autophagy regulation. • p-Ser-GSK3αβ regulated autophagy independently of Pin1.

  4. Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

    National Research Council Canada - National Science Library

    Jesus, Douglas Rossi; Barbosa, Lorena Neris; Prando, Thiago Bruno Lima; Martins, Leonardo Franco; Gasparotto, Francielli; Guedes, Karla Moraes Rocha; Dragunski, Douglas Cardoso; Lourenço, Emerson Luiz Botelho; Dalsenter, Paulo Roberto; Gasparotto Junior, Arquimedes

    2015-01-01

    The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products...

  5. Psychiatric comorbidities in a young man with subacute myelopathy induced by abusive nitrous oxide consumption: a case report

    Directory of Open Access Journals (Sweden)

    Mancke F

    2016-09-01

    Full Text Available Falk Mancke,1,2,* Gintare Kaklauskaite,1,* Jennifer Kollmer,3 Markus Weiler1 1Department of Neurology, 2Department of General Psychiatry, Center for Psychosocial Medicine, 3Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Abstract: Nitrous oxide (N2O, a long-standing anesthetic, is known for its recreational use, and its consumption is on the rise. Several case studies have reported neurological and psychiatric complications of N2O use. To date, however, there has not been a study using standardized diagnostic procedures to assess psychiatric comorbidities in a patient consuming N2O. Here, we report about a 35-year-old male with magnetic resonance imaging confirmed subacute myelopathy induced by N2O consumption, who suffered from comorbid cannabinoid and nicotine dependence as well as abuse of amphetamines, cocaine, lysergic acid diethylamide, and ketamine. Additionally, there was evidence of a preceding transient psychotic and depressive episode induced by synthetic cannabinoid abuse. In summary, this case raises awareness of an important mechanism of neural toxicity, with which physicians working in the field of ­substance-related disorders should be familiar. In fact, excluding N2O toxicity in patients with recognized substance-related disorders and new neurological deficits is compulsory, as untreated for months the damage to the nervous system is at risk of becoming irreversible. Keywords: addictive disorders, laughing gas, subacute combined degeneration, substance use disorder, vitamin B12 deficiency

  6. Amiodarone Pulmonary Toxicity

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    Norman Wolkove

    2009-01-01

    Full Text Available Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects.

  7. Amiodarone pulmonary toxicity

    Science.gov (United States)

    Wolkove, Norman; Baltzan, Marc

    2009-01-01

    Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects. PMID:19399307

  8. Evidence of hair loss after subacute exposure to 2-chloroethyl ethyl sulfide, a mustard analog, and beneficial effects of N-acetyl cysteine.

    Science.gov (United States)

    Chatterjee, Diptendu; Mukherjee, Shyamali; Smith, Milton G; Das, Salil K

    2004-01-01

    Mustard gas has been used as a vesicant chemical warfare agent. However, a suitable biomarker for monitoring mustard gas exposure is not known. We observed that the hairs of the guinea pigs exposed intratracheally to subacute doses of 2-chloroethyl ethyl sulfide (CEES), a mustard analog, came out very easily though there was no sign of skin lesions or skin damage. Also the hairs looked rough and dry and lost the shiny glaze. There was no recovery from this hair loss, though the animals never became hairless, following CEES exposure. Hairs were observed in this study both visually and with light microscopy. Treatment with N-acetylcysteine (NAC) prior to CEES exposure could prevent the hair loss completely. Hence, sudden hair loss might be a good biomarker for subacute exposure of mustard gas to subjects at risks when the victims might have no other visible symptom of toxicity. Copyright 2004 Wiley Periodicals, Inc.

  9. Safety assessment of the aqueous extract of the flowers of Nymphaea lotus Linn (Nymphaeaceae): Acute, neuro- and subchronic oral toxicity studies in albinos Wistar rats.

    Science.gov (United States)

    Kameni Poumeni, Mireille; Bilanda, Danielle Claude; Dzeufiet Djomeni, Paul Désiré; Mengue Ngadena, Yolande Sandrine; Mballa, Marguerite Francine; Ngoungoure, Madeleine Chantal; Ouafo, Agnès Carolle; Dimo, Théophile; Kamtchouing, Pierre

    2017-03-24

    Background Nymphaea lotus Linn (N. lotus) is a medicinal plant widely used in Cameroon popular medicine, to treat neuropsychiatric conditions, male sexual disorders or as food supplement. However, scientific data on the pharmacotoxic profile of this plant are not available. The safety of N. lotus was assessed in acute, neuro- and subchronic toxicity studies by following the OECD guidelines. Effectively, no data have been published until now in regard to its safety on the nervous system. Methods Aqueous extract of N. lotus at doses of 200, 400 and 600 mg/kg body weight (BW) was evaluated for nitrites contents and orally administered to rats daily for 28 days (5 male, 5 female per group). The control group received distilled water (10 mL/kg) and a satellite group was used to observe reversal effects. Neurotoxicity of the plant was determined using open field test for motor coordination, ataxia and gait analysis. Clinical signs and state of livelihood were recorded during the 24 h, then for 28 days of treatments. At the end of 28-day period, animals were anesthetized and decapitated. The whole brain was homogenized for neurobiochemical analysis. Blood samples were collected with or without anticoagulant for hematological examinations and serum analysis. Specimens of liver, kidney, testis, ovaries, and brain were fixed in 10 % formalin and processed for histopathological examinations. Results Our findings indicate dose-dependent elevation of nitrites contents in the flowers aqueous extract of N. lotus. Acute toxicity study revealed no signs of toxicity neither at the dose 2,000 mg/kg nor at 5,000 mg/kg. Thus the LD50 value of aqueous extract of N. lotus flowers is superior to 5,000 mg/kg. The repeated administration of N. lotus during 28 days, induced no signs of neurobehavioral changes in male, but female rats exhibited dose-dependent response in the open field test, suggesting sex and dose-relative psychotropic effects of N. lotus. The evaluation of

  10. Hyperfixation of Tc-99m ECD in subacute cortical infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Seung; Kweon, Sun Uck; Ryu, Jin Sook; Moon, Dae Hyuk; Lee, Hee Kyung [College of Medicine, Ulsan Univ., Seoul (Korea, Republic of)

    2001-07-01

    It has been known that hyperfixation of Tc-99m ECD (HF) is not shown in subacute cerebral infarction because the brain distribution of Tc-99m ECD reflects not only perfusion but also the metabolic status of brain tissue. However, we observed several cases with HF in the subacute pure cortical infarction. To find out the cause of HF in subacute cortical infarction. We assessed the difference in associated cerebral hemodynamics and clinical findings between the subacute cortical infarctions with and without HF. We reviewed 16 patients (63.8{+-}8.6 yr, M/F: 15/1) with pure cortical infarction not involving adjacent subcortical white matter on MRI. All patients underwent acetazolamide stress brain perfusion SPECT using Tc-99m ECD and MRI at subacute period (7.3{+-}4.4 days from ictus). Uptake of Tc-99m ECD in infarcted cortex was assessed visually comparing the contralateral side. To assess the difference in associate clinical findings between the infarctions with and without HF, rCVR of the cerebral territory including infarcted cortex, extent of Gd-enhancement on MRI. Intervals between SPECT and ictus, and the presence of associated ICA stenosis were evaluated. Infarctions were focal (n=8) or multifocal (n=8) and located in frontoparietal cortices on MRI. Twelve patients were accompanied with ipsilateral ICA stenosis. Resting SPECT showed increased cortical uptake (=HF) in 7 patients and decreased in 9. rCVR of the MCA territory was preserved in all of the 7 patients with HF, compared with 4 of the 9 patients without HF (p=0.03). Gd-enhancement was minimal in all of the 7 patients with HF, compared with of the 0 patients without HF (p=0.03). Presence of ipsilateral ICA stenosis and intervals from ictus were not different (p>0.1) Subacute cerebral cortical infarction with HF was more frequently associated with preserved rCVR and minimal destruction of the blood-brain barrier than that without HF. Our findings suggest that HF may result from luxury perfusion of

  11. Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure

    Directory of Open Access Journals (Sweden)

    Mohammad Moshiri

    2017-03-01

    Full Text Available Objective(s: Pregabalin (PGB is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. Materials and Methods: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP. Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. Results: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. Conclusion: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations.

  12. Liver immunolocation of CYP P450 in an subacute toxicity experiment with Clorpirifos o,o-(3, 5, 6- trichloride -2-pyridyl phosphorotioato in young male tilapia (Oreochromis spp)/Inmunolocalización hepática de CYP P450 en un experimento de toxicidad subaguda por Clorpirifos 0,0-dietil 0-(3, 5, 6-tricloro-2-piridil fosforotioato) en machos juveniles de tilapia (Oreochromis spp)/Inmunolocalização hepática de CYP P450 num teste de toxicidade subaguda por Clorpirifos 0,0-dietil 0-(3, 5, 6-tricloro-2-piridil fosforotioato) em machos juvenis de tilápia (Oreochromis spp.)

    National Research Council Canada - National Science Library

    Jenny G Chaparro; Diego Alfonso Aranzazu Taborda; Laura Urrea; Berardo de J Rodríguez

    2013-01-01

    .... The objective of this study is to implement an immunohistochemical technique to immunolocate CYP 1A in the tissue of fish, performing a subacute exposition experiment of Clofopirifos in the liver of young male tilapia...

  13. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

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    Plengsuriyakarn Tullayakorn

    2012-03-01

    Full Text Available Abstract Background Chemotherapy of cholangiocarcinoma (CCA, a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR, the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL, fruits of Piper chaba Hunt. (De-Plee: PC, and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively. PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL, analgesic (CUR and

  14. Acute and Subchronic Toxicity Study of the Median Septum of Juglans regia in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Asma Ravanbakhsh

    2016-12-01

    Full Text Available Purpose: Median septum of Juglans regia L. (Juglandaceae with anti - diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities. Methods: In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600 , 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME, and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses. Results: The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morpholo gical and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a signific ant reduction of serum urea level (p<0.05, kidney’s xanthine dehydrogenase (XDH activity (p<0.001 and elevation of aldehyde oxidase (AO activity (p<0.05 in kidney. In the treated group, the mean diameter of glomerulus and proximal urine tube epitheliu m stature was slightly greater than control group. A significant increase in serum MDA level is subject for further studies. Conclusion: This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administratio n of JRSME may improve kidney structure and function and help in treatment of some chronic diseases.

  15. Subacute thyroiditis (de Quervain) presenting as a painless cold nodule

    Energy Technology Data Exchange (ETDEWEB)

    Bartels, P.C.; Boer, R.O.

    1987-09-01

    A 49-yr-old woman presented with a solid, painless, nontender nodule in the left thyroid lobe. Thyroid scintigraphy revealed a solitary cold area in the left lobe and a slightly decreased 24-hr radioactive iodine thyroid uptake (9%). Although there were no specific clinical or biochemical signs suggesting thyroiditis needle aspiration cytology showed the presence of a subacute thyroiditis. Approximately 1 mo later the entire thyroid gland was affected leading to a completely suppressed thyroid radioiodine uptake and elevated serum thyroid hormone concentrations. This case illustrates that in the early phase of the disease, subacute thyroiditis may present as a solitary, painless, cold nodule and should be considered in the differential diagnosis of such lesions.

  16. Measles-vaccinated Israeli boy with subacute sclerosing panencephalitis.

    Science.gov (United States)

    Har-Even, Ronly; Aichenbaum, Sergio; Rabey, Jose M; Livne, Amir; Bistritzer, Tzvy

    2011-06-01

    Subacute sclerosing panencephalitis is a rare neurologic disorder of childhood and adolescence. We describe a 16-year-old boy who manifested the disease despite proper vaccinations. He was hospitalized because of bedwetting, involuntary limb movements, abnormal speech, and balance disturbances. Immunoglobulin G antibodies against measles were strongly positive, with a high relative cerebrospinal fluid/serum ratio. Polymerase chain reaction for measles produced negative results. Electroencephalography registered slow activity with high voltage discharges every few seconds, and with triphasic complex morphology. Magnetic resonance imaging revealed diffuse white matter changes, mostly around the posterior regions and lateral ventricles. Treatment with valproic acid, levetiracetam, carbamazepine, and intravenous immunoglobulin G was ineffective. Inosiplex and interferon-β-1a were also administrated. The patient became comatose, with generalized myoclonic jerks, and died 1 year later. An autopsy was not performed. This patient illustrates that subacute sclerosing panencephalitis should be suspected among young vaccinated subjects. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Synthesis, Characterization, and Acute Oral Toxicity Evaluation of pH-Sensitive Hydrogel Based on MPEG, Poly(ε-caprolactone), and Itaconic Acid

    National Research Council Canada - National Science Library

    Tan, Liwei; Xu, Xu; Song, Jia; Luo, Feng; Qian, Zhiyong

    2013-01-01

    .... The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10000 mg/kg body weight...

  18. Subacute Sclerosing Panencephalitis in a Child with Human Immunodeficiency Virus Co-Infection.

    Science.gov (United States)

    Maurya, Pradeep Kumar; Thakkar, Mayur Deepak; Kulshreshtha, Dinkar; Singh, Ajai Kumar; Thacker, Anup Kumar

    2016-12-01

    Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection. © 2016 Marshfield Clinic.

  19. ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

    Directory of Open Access Journals (Sweden)

    Daniel Komnig

    Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

  20. ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

    Science.gov (United States)

    Komnig, Daniel; Imgrund, Silke; Reich, Arno; Gründer, Stefan; Falkenburger, Björn H

    2016-01-01

    Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC). Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

  1. Paracoccidioidomycosis: acute-subacute clinical form, juvenile type*

    Science.gov (United States)

    Marques, Silvio Alencar; Lastória, Joel Carlos; de Camargo, Rosangela Maria Pires; Marques, Mariangela Esther Alencar

    2016-01-01

    The authors report aspects of paracoccidioidomycosis, acute-subacute clinical form, juvenile type, in a 19-year-old female patient. Paracoccidioidomycosis, juvenile type, classically occurs in young patients, both sexes, with lymphoma-like aspects as initial presentation. However, following the natural history of the disease the lymph nodes assume patterns of infectious disease, as an abscess and fistulae. Systemic dissemination of the disease can occur and lethality and morbidity are significant in this clinical presentation. PMID:27438214

  2. Herbal hepatitis: subacute hepatic necrosis secondary to chaparral leaf.

    Science.gov (United States)

    Katz, M; Saibil, F

    1990-04-01

    A 33-year-old woman developed subacute hepatic necrosis after several months of ingestion of Chaparral Leaf, an herbal product. Symptoms first appeared 3 months after she began taking the tablets. The patient unwittingly carried out a clinical challenge by reducing, then increasing, the dose of pills. The public and the medical profession must be wary of all "harmless" nonprescription medications, whether purchased in pharmacies or elsewhere.

  3. Visual deterioration as presentation of subacute sclerosing panencephalitis.

    Science.gov (United States)

    Johnston, H M; Wise, G A; Henry, J G

    1980-01-01

    A 7-year-old boy presented with deteriorating vision and macular degenerative changes. A month later he had developed unusual behaviour and increasing forgetfulness. An electroencephalogram showing periodic complexes, and high measles complement-fixation titres in the cerebrospinal fluid and blood, confirmed the diagnosis of subacute sclerosing panencephalitis. Four months after the onset of visual symptoms he started having myoclonic jerks. Images Fig. 1 Fig. 2 PMID:7436466

  4. Subacute sclerosing panencephalitis. Changes on CT scan during acute relapse

    Energy Technology Data Exchange (ETDEWEB)

    Modi, G.; Bill, P. (Wentworth Hospital, Durban (South Africa). Dept. of Medicine); Campbell, H. (Wentworth Hospital, Durban (South Africa). Dept. of Radiology)

    1989-11-01

    A 19-year-old female patient presented in an acute state of akinetic mutism. Serological analysis of serum and cerebrospinal fluid demonstrated the presence of antibodies to measles virus. CT scan carried out during this acute phase of relapse demonstrated white matter enhancement affecting the cortical white matter of the frontal lobes and corpus callosum. These features indicate that active demyelination occurs during acute relapse in subacute sclerosing panencephalitis (SSPE) and suggest that immunotherapy should be considered during this acute phase. (orig.).

  5. Antibodies to borna disease virus in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Güngör, Serdal; Anlar, Banu; Turan, Nuri; Yilmaz, Hüseyin; Helps, Chris R; Harbour, Dave A

    2005-09-01

    Mechanisms causing persistence and reactivation of measles virus in subacute sclerosing panencephalitis (SSPE) are unknown. Borna disease virus (BDV) frequently causes latent or persistent infection in the nervous system. We investigated a possible association of these viruses in SSPE. Although BDV seropositivity was similar in SSPE and control groups, SSPE patients with high antibodies to BDV had earlier and more rapid disease. The findings suggest that BDV might be involved in the course, but not in the etiopathogenesis, of SSPE.

  6. Subacute osteoporotic compression fracture: Misleading magnetic resonance appearance

    Energy Technology Data Exchange (ETDEWEB)

    Frager, D.; Elkin, C.; Swerdlow, M.; Bloch, S.

    1988-03-01

    Three patients with benign subacute osteoporotic vertebral compression fractures are presented. T/sub 1/ weighted magnetic resonance (MR) images (SE 500/30) showed decreased vertebral signal. Because the results of the MR examination were thought to indicate malignant disease, extensive medical workups, including one biopsy, were pursued in all three patients. Routine (SE 500/30) spin-echo pulse sequences cannot definitively distinguish between benign and malignant vertebral compression fractures.

  7. Protease production by Streptococcus sanguis associated with subacute bacterial endocarditis.

    OpenAIRE

    Straus, D. C.

    1982-01-01

    A viridans streptococcus (Streptococcus sanguis biotype II) isolated from the blood of a patient with subacute bacterial endocarditis was examined for protease production. In broth culture, extracellular proteolytic enzymes were not produced by this organism until after the early exponential phase of growth, with maximal protease production occurring during the stationary phase. Four distinct proteases were isolated and purified from the supernatant fluids of stationary-phase cultures, employ...

  8. Mealtime interruptions, assistance and nutritional intake in subacute care.

    Science.gov (United States)

    Porter, Judi; Wilton, Anita; Collins, Jorja

    2016-09-01

    Protected mealtimes is an initiative to support increased nutritional intake for all hospitalised patients, particularly those who are malnourished. The increased focus on maximising independence of patients in the subacute setting may provide a supportive environment for implementing these strategies. The aim of the present study was to gain insight into subacute ward practices at mealtimes under usual conditions (i.e. at baseline) where no protected mealtimes policy was implemented. Participants were patients aged ≥65 years recruited from subacute care facilities at a large healthcare network in Victoria, Australia. Participants were observed at mealtimes and mid meals (i.e. morning tea, afternoon tea and supper) to determine daily energy and protein intake, provision of mealtime assistance and mealtime interruptions. Almost all participants received assistance when it was needed, with positive and negative interruptions experienced by 56.2% and 76.2% of participants, respectively. There was an energy deficit of approximately 2 MJ per day between average intake and estimated requirements. In conclusion, mealtime practices were suboptimal, with particularly high rates of negative interruptions. Protected mealtimes is one strategy that may improve the mealtime environment to support patients' dietary intake. Prospective studies are needed to evaluate its implementation and effects.

  9. EFFECT OF POSITIONAL RELEASE TECHNIQUE IN SUBJECTS WITH SUBACUTE TRAPEZITIS

    Directory of Open Access Journals (Sweden)

    Sweety Charles Carvalho

    2014-06-01

    Full Text Available Background: Trapezius stretching combined with positional release technique (PRT have found effective in trapezitis, studies are limited to find which technique has shown effective over the other due to lack of control group. The purpose of the study is to find the effect of PRT on pain intensity, functional disability and range of motion in subjects with subacute trapezitis. Method: An experimental study design, selected subjects with subacute trapezitis was randomized into Study and Control group. Total 40 subjects, 20 subjects in each group; data was collected who completed the study. Control group received passive trapezius muscle stretching while Study group received positional release technique with passive trapezius muscle stretching for 8 sessions in 2 weeks. Outcome measurements such as Visual Analogue scale, Neck disability index and cervical Range of motion were measured. Results: There is statistically significant difference (p<0.05 showing improvement in means of VAS, NDI and Range of motion before and after intervention within the groups and there is statistically significant difference when the post-intervention means after 2 weeks of treatment were compared between Study and Control group. Conclusion: It is concluded that the Positional Release Technique with trapezius stretching found to be significantly more added effect than trapezius stretching alone in improving pain, functional disability and cervical movements for subjects with subacute trapezitis.

  10. Cerebrospinal fluid nitric oxide levels in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Yilmaz, Deniz; Yüksel, Deniz; Senbil, Nesrin; Eminzade, Sude; Kilinç, Kamer; Anlar, Banu; Gürer, Yavuz

    2009-09-01

    Oxidative damage plays a role in neurodegenerative diseases. Levels of cerebrospinal fluid nitrite and nitrate levels (oxidation products that provide an indirect estimation of nitric oxide) were investigated in relation to clinical and laboratory features in subacute sclerosing panencephalitis (n = 47) and age-matched control (n = 43) groups. Significantly decreased levels of nitrite (median, 4.91 micromol/L) and nitrate (median, 6.14 micromol/L) were found in the patients. Nitrite and nitrate levels did not correlate with clinical or laboratory findings, except for presence of myoclonus. Cerebrospinal fluid nitrite levels of subacute sclerosing panencephalitis patients without myoclonic jerks were significantly higher than in those with myoclonus (median, 15.63 vs 4.34 micromol/L, respectively). The higher levels of nitrite in these patients can be explained by short disease duration and early stages of disease. Nitrate levels in subacute sclerosing panencephalitis patients with myoclonus (median, 9.26 micromol/L) were higher than in those without myoclonus (median, 4.25 micromol/L). Microbleeding resulting in conversion of nitrite to nitrate and increased production of superoxide can be suggested as possible mechanisms underlying these findings.

  11. Subacute and acute fasciolosis in sheep in southern Brazil.

    Science.gov (United States)

    Fiss, Leticia; de Lourdes Adrien, Maria; Marcolongo-Pereira, Clairton; Assis-Brasil, Nathalia D; Sallis, Eliza S V; Riet-Correa, Franklin; Ruas, Jerônimo L; Schild, Ana Lucia

    2013-02-01

    Eight outbreaks of acute and subacute fasciolosis are reported in sheep in the municipality of Santa Vitória do Palmar, southern Brazil, in areas used for irrigated rice cultivation, which are subject to frequent flooding. Two outbreaks occurred mid-winter during July and August, and six occurred during spring and early summer. Morbidity ranged from 3 to 66.7 %, and mortality ranged from 3 to 50 %. Clinical signs included weight loss, mucosal pallor, apathy, depression, muscle tremors, and drooling; these were followed by death within approximately 24 h. Some sheep were found dead. Gross lesions were characterized by an irregular liver capsule with fibrin deposition and hemorrhages. The liver parenchyma contained hemorrhagic tracts or irregular clear areas alternated with dark hemorrhagic areas. Histologically, hemorrhagic dark red tracts of necrotic liver parenchyma and an inflammatory infiltrate were noted; these lesions coincided with the presence of immature flukes. Langhans-type giant cells, fibrous tissue, and bile duct cell proliferation were observed in subacute cases. Chronic fasciolosis is a well-known disease to farmers in southern Brazil; nevertheless, acute and subacute fasciolosis, which are more difficult to diagnose and treat, may cause important economic losses. Efficient control of fasciolosis requires integration of measures to treat infections in the definitive host, to reduce the population of snails of the genus Lymnaea, and to avoid contact between the parasite and host by appropriate pasture management.

  12. MR findings of subacute necrotizing myelopathy: case report

    Energy Technology Data Exchange (ETDEWEB)

    Na, Dong Gyu; Chang, Kee Hyun; Han, Moon Hee; Kim, Hyun Jip; Kim, Chong Jai; Chi, Je G. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1994-04-15

    Subacute necrotizing myelopathy(SNM) is a rare non-tumorous disease of spinal cord characterized by subacute clinical course of progressive neurological deterioration. We report MR findings of a patient with pathologically proved SNM. 1 case of pathologically proved subacute necrotizing myelopathy. The patients was a 56-year-old man with progressive motor weakness and sensory loss of the lower extremities, and urinary and fecal incontinence for 11 months. Spine MRI revealed diffuse enlargement of the thoracic spinal cord from T2 to T7 level. Signal intensity of the expanded spinal cord was isointense relative to normal cord on T1-weighted image and hyperintense on proton-density and T2-weighted images. On contrast enhanced T1-weighted image, there was diffuse homogeneous enhancement in the expanded cord lesion. MR demonstration of stable persistence of spinal cord lesion or atrophy over months or years with clinical findings of gradual progressive neurologic deterioration may be helpful in the diagnosis of SNM.

  13. Assessment of acute and subchronic oral toxicity of ethanolic extract of Pothomorphe umbellata L. Miq (Pariparoba Avaliação da toxidade oral aguda e subcrônica de extrato etanólico de Pothomorphe umbellata L. Miq. (Parapiroba

    Directory of Open Access Journals (Sweden)

    Sonia Barros

    2005-03-01

    Full Text Available There is a high degree of concern regarding the secure use of plant extracts and, for this very reason, preclinical and clinic toxicological evaluation of these extracts are needed. With the aim to assure the quality and the safety of the extract and due to the scarcity of literature information about Pariparoba extract toxicity, our purpose was to investigate the acute and subchronic toxicity of the standardized ethanolic dried root extract of Pothomorphe umbellata L. Miq. This extract was administered orally to adult swiss mice and wistar rats and the mutagenic potencial of the extract was also evaluated. The extract showed to be non toxic.Existe uma grande preocupação quanto ao uso seguro de extratos vegetais e, por esta razão, a necessidade de estudos toxicológicos pré-clínicos e clínicos destes extratos. O objetivo deste trabalho foi o de avaliar a toxicidade aguda e subcrônica do extrato hidroalcoólico liofilizado de Pothomorphe umbellata L. Miq., administrado por via oral para animais de laboratório. O potencial mutagênico do extrato foi também avaliado pelo teste do micronúcleo. Os resultados dos estudos a curto e médio prazo demonstraram que o extrato não apresenta propriedades tóxicas.

  14. Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico-in-vitro-in-vivo approach.

    Science.gov (United States)

    Magotra, Asmita; Sharma, Anjna; Singh, Samsher; Ojha, Probir Kumar; Kumar, Sunil; Bokolia, Naveen; Wazir, Priya; Sharma, Shweta; Khan, Inshad Ali; Singh, Parvinder Pal; Vishwakarma, Ram A; Singh, Gurdarshan; Nandi, Utpal

    2017-11-21

    Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for new chemical entity (NCE) which can be not only effective against both susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also safe and faster acting with the target, thereby shortening the prolonged TB treatments. We have identified a potential nitrofuranyl methyl piperazine derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory concentration (MIC) value of 0.0072 μM against H37Rv strain. Objective of the present study is to investigate physicochemical, pharmacokinetic, efficacy and toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive manner to assess the likelihood of developing IIIM-MCD-211 as a clinical candidate. Results of computational prediction reveal that compound does not violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays evidence of P-glycoprotein (P-gp) induction but no inhibition ability in rhodamine cell exclusion assay. IIIM-MCD-211 shows high permeability and plasma protein binding based on parallel artificial membrane permeability assay (PAMPA) and rapid equilibrium dialysis (RED) model, respectively. IIIM-MCD-211 has adequate metabolic stability in rat liver microsomes (RLM) and favourable pharmacokinetics with admirable correlation during dose escalation study in Swiss mice. IIIM-MCD-211 has capability to appear into highly perfusable tissues. IIIM-MCD-211 is able to actively prevent progression of TB infection in chronic infection mice model. IIIM-MCD-211 shows no substantial cytotoxicity in HepG2 cell line. In acute toxicity study, significant increase of total white blood cell (WBC) count in treatment group as compared to control group is observed. Overall, amenable preclinical data make IIIM-MCD-211 ideal

  15. Characteristics of Staphylococcus aureus isolated from acute, sub-acute and sub-clinical staphylococcosis in rabbits

    Directory of Open Access Journals (Sweden)

    Rajeshkumar J. Tirpude

    2012-12-01

    Full Text Available Staphylococcus aureus bacteria isolated from different clinical presentations of staphylococcosis in rabbits were examined for the production of various virulence factors using biochemical and immunological tests. In the total of 106 S. aureus isolates; toxic shock syndrome toxin-1, staphylococcal enterotoxin-C, DNase, α-haemolysin, β-haemolysin, δ-haemolysin, protein A and clumping factor were observed with a frequency of 33.2, 16.98, 83.96, 69.81, 36.79, 100, 78.30 and 54.72 percent, respectively. No SE-A, SE-B and SE-D producing isolates were recovered in this study. All the S. aureus isolates from acute staphylococcosis produced TSST-1, SE-C and protein A. While δ–haemolysin and clumping factor were not detected in any acute isolates, these factors were observed at a relatively higher frequency in isolates from sub-acute and sub-clinical staphylococcosis. Coagulase type III was observed more predominantly with a frequency of 45.28%, while coagulase types V and VII were not observed in any isolate. Most of the virulence factors belonged to coagulase type III followed by type VI. TSST-1 and SE-C along with coagulase types III and VI could be correlated with the acute and sub-acute staphylococcal infections in rabbits in this study.

  16. Acute and subacute toxicological evaluation of the aerial extract of Monsonia angustifolia E. Mey. ex. A. Rich in Wistar rats

    CSIR Research Space (South Africa)

    Afolayan, AJ

    2016-01-01

    Full Text Available single oral dose of 5000mg/kg (b.w.). For the 28-day daily oral dosing, the extract was administered at 75, 150, and 300mg/kg b.w.; 1% ethanol in sterile distilled water was used as control. Clinical toxicity signs were subsequently evaluated. At a single...

  17. Comparison of activated charcoal and sodium polystyrene sulfonate resin efficiency on reduction of amitriptyline oral absorption in rat as treatments for overdose and toxicities

    Directory of Open Access Journals (Sweden)

    Gholamhossein Yousefi

    2017-01-01

    Full Text Available Objective(s: Comparative in vivo studies were carried out to determine the adsorption characteristics of amitriptyline (AMT on activated charcoal (AC and sodium polystyrene sulfonate (SPS. AC has been long used as gastric decontamination agent for tricyclic antidepressants and SPS has showed to be highly effective on in-vitro drugs adsorption. Materials and Methods: Sprague-Dawley male rats were divided into six groups. Group I: control, group II: AMT 200 mg/kg as single dose orally, group III and IV: AC 1g/kg as single dose orally 5 and 30 min after AMT administration respectively, and group 5 and 6: SPS 1 g/kg as single dose orally 5 and 30 min after AMT administration, respectively. 60 min after oral administration of AMT (Tmax of AMT determined in rats, Cmax plasma levels were determined by a validated GC-Mass method. Results: The Cmax values for groups II to IV were determined as 1.1, 0.5, 0.6, 0.1 and 0.3 µg/ml, respectively. Conclusion: AC and SPS could significantly reduce Cmax of AMT when administrated either 5 or 30 min after AMT overdose (P

  18. Erratum : Thesaurus for histopathological findings in publically available reports of repeated-dose oral toxicity studies in rats for 156 chemicals.

    Science.gov (United States)

    Nishikawa, Satoshi; Yamashita, Tatsuhiro; Imai, Toshio; Yoshida, Midori; Sakuratani, Yuki; Yamada, Jun; Maekawa, Akihiko; Hayashi, Makoto

    2010-08-01

    Because histopathological findings are often conclusive indicators of the toxicities of chemicals, standardization of nomenclature and construction of a thesaurus for histopathological findings are important for the comparative evaluation of histopathological data from repeated-dose toxicity studies (RTS). however, terms for histopathological findings have not been standardized and different technical terms are used to indicate almost the same things in RTS. The present study was conducted to construct and easy-to-use thesaurus for histopathological findings in order to facilitate hazard assessments of untested chemicals by the category approach using knowledge of the toxicity of analogue chemicals. We used reports of 28-day RTS, conducted on rats by gavage, which were posted on the websites of the National Institute of health Sciences (NIHS) and the National Institute of Technology and Evaluation (NITE). The histopathological data were from 156 reports on RTS conducted by 13 institutions in Japan. As a result of this study, major parts of the thesaurus were devoted to the findings in the liver, kidney, stomach, adrenal, thyroid and testis; the first three organs are known to be the main targets of chemicals. We also decided that findings such as swelling and enlargement of hepatocytes should be categorized as synonyms for terms meaning hypertrophy. Our thesaurus will be helpful in assessing or screening new untested chemical by the category approach using knowledge of the toxicities of analogues of the new chemical. The RTS database with this thesaurus will be made publically available in 2010.

  19. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement

    NARCIS (Netherlands)

    Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Bossi, Paolo; Majorana, Alessandra; Gastaldi, Giorgio; Berruti, Alfredo; Trippa, Fabio; Nicolai, Pietro; Barasch, Andrei; Russi, Elvio G.; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M.

    2016-01-01

    Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis,

  20. Subacute haematotoxicity after PRRT with {sup 177}Lu-DOTA-octreotate: prognostic factors, incidence and course

    Energy Technology Data Exchange (ETDEWEB)

    Bergsma, Hendrik; Konijnenberg, Mark W.; Kam, Boen L.R.; Teunissen, Jaap J.M.; Kooij, Peter P.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Franssen, Gaston J.H.; Eijck, Casper H.J. van [Erasmus Medical Center, Department of Surgery, Rotterdam (Netherlands)

    2016-03-15

    In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from {sup 131}I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with {sup 177}Lu-DOTA{sup 0}-Tyr{sup 3}-octreotate ({sup 177}Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit. The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined. Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 x 10{sup 9}/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq {sup 177}Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients. The incidence of subacute haematological toxicity after PRRT with {sup 177}Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from {sup 131}I, seems not to be valid for PRRT with {sup 177}Lu-DOTATATE. (orig.)

  1. Subacute combined degeneration of the spinal cord in a Nigerian child

    African Journals Online (AJOL)

    2015-12-19

    Dec 19, 2015 ... Abstract: Background: Vitamin. B12 deficiency has been reported to be associated with a spectrum of neurological disorders among which is subacute combined de- generation of the spinal cord. Method: We report a case of subacute combined degeneration of the spinal cord secondary to vitamin B12 ...

  2. Subacute combined degeneration of the spinal cord in a Nigerian child

    African Journals Online (AJOL)

    Background: Vitamin B12 deficiency has been reported to be associated with a spectrum of neurological disorders among which is subacute combined degeneration of the spinal cord. Method: We report a case of subacute combined degeneration of the spinal cord secondary to vitamin B12 deficiency and discussed the ...

  3. Prognostic factors for disability and sick leave in patients with subacute non-malignant pain

    DEFF Research Database (Denmark)

    Valentin, Gitte H; Pilegaard, Marc S; Vaegter, Henrik B

    2016-01-01

    OBJECTIVE: This systematic review aims to identify generic prognostic factors for disability and sick leave in subacute pain patients. SETTING: General practice and other primary care facilities. PARTICIPANTS: Adults (>18 years) with a subacute (≤3-month) non-malignant pain condition. Eligibility...... reporting of all factors examined. TRIAL REGISTRATION NUMBER: CRD42014008914.......OBJECTIVE: This systematic review aims to identify generic prognostic factors for disability and sick leave in subacute pain patients. SETTING: General practice and other primary care facilities. PARTICIPANTS: Adults (>18 years) with a subacute (≤3-month) non-malignant pain condition. Eligibility...... criteria were cohort studies investigating the prediction of disability or long-term sick leave in adults with a subacute pain condition in a primary care setting. 19 studies were included, referring to a total of 6266 patients suffering from pain in the head, neck, back and shoulders. PRIMARY...

  4. Midazolam or diazepam administration during electroencephalography helps to diagnose subacute sclerosing panencephalitis (SSPE).

    Science.gov (United States)

    Yilmaz, Kutluhan; Sahin, Derya Aydin

    2010-08-01

    Although diagnostic contribution of intravenous diazepam administration during electroencephalography (EEG) recording in subacute sclerosing panencephalitis has been known, no another drug with less potential side effects has been studied in this procedure. In this study, diazepam is compared with midazolam in 25 subacute sclerosing panencephalitis-diagnosed children and 10 children with subacute sclerosing panencephalitis-suggesting symptoms, normal EEG findings and no certain diagnosis. Neither midazolam nor diazepam affected typical periodic slow-wave complexes. However, in the patients with atypical EEG abnormalities, midazolam, like diazepam, attenuated sharp or sharp-and-slow waves, and therefore made the identification of periodic slow-wave paroxysms easier. In the patients with normal EEGs, both midazolam and diazepam revealed typical periodic complexes on EEG recording in the same 3 patients. Cerebrospinal fluid examination verified the diagnosis of subacute sclerosing panencephalitis. The findings suggest that midazolam or diazepam administration increases the contribution of EEG recording in atypical cases with subacute sclerosing panencephalitis.

  5. Subacute cutaneous lupus erythematosus inducing unilateral sensorimotor neuropathy.

    Science.gov (United States)

    Psarelis, Savvas; Georgiades, Fanourios; Ioannou, Antreas; Xenophontos, Eleni; Georgiou, Georgios; Papanicolaou, Eleni

    2017-05-01

    We describe the case of a 32-year-old male with previous history of subacute cutaneous lupus erythematosus (SCLE) who presented with arthritis followed by a unilateral lower-limb sensorimotor impairment, without biochemical or immunological marker abnormalities. Our patient currently satisfies only three of the systemic lupus international collaborating clinics criteria. Management of such patients is challenging due to lack of examples in the literature, with this case being the first described where a seronegative patient with SCLE demonstrated neurological involvement. A brief review of the available literature is included.

  6. Atypical clinical course subacute sclerosing panencephalitis presenting as acute Encephalitis

    Science.gov (United States)

    Komur, Mustafa; Arslankoylu, Ali E; Okuyaz, Cetin; Kuyucu, Necdet

    2012-01-01

    We report a 14-year-old boy who presented with loss of consciousness and gait instability. The electroencephalogram (EEG) showed generalized slowing with irregular activity and cerebral magnetic imaging revealed asymmetrical nonspecific signals on basal ganglia. His second electroencephalogram revealed periodical generalized high-voltage slow wave complexes which did not disappear with diazepam induction. Subacute sclerosing panencephalitis (SSPE) was considered and the diagnosis was confirmed with the identification of measles antibodies in cerebrospinal fluid. Our findings show that SSPE should be in mind in the differential diagnosis of meningoencephalitis and acute disseminated encephalomyelitis and highlight the significance of EEG in the diagnosis of unidentified cases. PMID:23248691

  7. Catatonia as presenting clinical feature of subacute sclerosing panencephalitis.

    Science.gov (United States)

    Dayal, Prabhoo; Balhara, Yatan Pal Singh

    2014-01-01

    Catatonia is not a usual clinical presentation of subacute sclerosing panencephalitis (SSPE), especially in the initial stages of illness. However, there is only one reported case of SSPE presenting as catatonia among children. In this report, however, there were SSPE-specific changes on EEG and the catatonia failed to respond to lorazepam. We describe a case of SSPE in a child presenting as catatonia that presented with clinical features of catatonia and did not have typical EEG findings when assessed at first contact. He responded to lorazepam and EEG changes emerged during the course of follow-up.

  8. Computed tomographic findings of early subacute sclerosing panencephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, H.; Wulff, C.H.

    1982-03-01

    Computed tomography of the brain (CT) was carried out at the early stages of subacute sclerosing panencephalitis (SSPE) in three children. The lateral ventricles were very small and the hemispheric sulci and interhemispheric fissures were not visible in all three patients in contrast to severe atrophy found at a later stage in one patient. The early CT abnormalities were revealed at the same time as the titres of measles antibodies in blood and cerebrospinal fluid were elevated, and the characteristic periodic complexes in the electroencephalogram established the diagnosis of SSPE. The CT changes indicating brain swelling reflect the reactive changes of this slow virus infection.

  9. Oxidant and antioxidant status in children with subacute sclerosing panencephalitis.

    Science.gov (United States)

    Caksen, Hüseyin; Ozkan, Mustafa; Cemek, Mustafa; Cemek, Fatma

    2014-11-01

    We analyzed serum alpha-tocopherol, beta-carotene, retinol, and ascorbic acid levels and malondialdehyde and reduced glutathione concentrations on erythrocyte and cerebrospinal fluid in 30 patients with subacute sclerosing panencephalitis to evaluate oxidant and antioxidant status. Serum alpha-tocopherol, beta-carotene, retinol, ascorbic acid levels, and erythrocyte and cerebrospinal fluid reduced glutathione concentrations were decreased; however, erythrocyte and cerebrospinal fluid malondialdehyde levels were increased in the patients. Cerebrospinal fluid malondialdehyde levels were different between clinical stages of the disease (P panencephalitis and that antioxidants were increased as defense mechanisms of the organism against oxidative damage. © The Author(s) 2013.

  10. The pharmacokinetic study on the mechanism of toxicity attenuation of rhubarb total free anthraquinone oral colon-specific drug delivery system.

    Science.gov (United States)

    Zhang, Lin; Chang, Jin-hua; Zhang, Bao-qi; Liu, Xi-gang; Liu, Pei; Xue, He-fei; Liu, Li-yan; Fu, Qiang; Zhu, Meng; Liu, Cui-zhe

    2015-07-01

    Rhubarb is commonly used as laxatives in Asian countries, of which anthraquinones are the major active ingredients, but there are an increased number of concerns regarding the nephrotoxicity of anthraquinones. In this study, we compared the pharmacokinetic characteristics of rhubarb anthraquinones in rats after orally administered with rhubarb and rhubarb total free anthraquinone oral colon-specific drug delivery granules (RTFA-OCDD-GN), and then explained why these granules could reduce the nephrotoxicity of anthraquinones when they produced purgative efficacy. A sensitive and reliable high performance liquid chromatography (HPLC) method has been fully validated for simultaneous determination of the five active components of rhubarb, and successfully applied to investigate and compare the remarkable differences in pharmacokinetic study of rhubarb anthraquinones after orally administered with rhubarb and RTFA-OCDD-GN. The results showed that, compared with rhubarb group, the AUC, Cmax, t1/2z and Vz/F of aloe-emodin, rhein, emodin and chrysophanol in rats receiving the RTFA-OCDD-GN were significantly decreased, and the Tmax of the four analytes was prolonged. Moreover, the Tmax of rhein, the Cmax of chrysophanol and emodin all have significant differences (Pattenuated research. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Absence of hematological side effects in acute and subacute nasal dosing of erythropoietin with a low content of sialic acid.

    Science.gov (United States)

    Lagarto, Alicia; Bueno, Viviana; Guerra, Isbel; Valdés, Odalys; Couret, Micaela; López, Raisel; Vega, Yamile

    2011-09-01

    The use of human recombinant erythropoietin (EPO) as a neuroprotective agent is limited due to its hematological side effects. An erythropoietin along with a low content of sialic acid (rhEPOb), similar to that produced in the brain during hypoxia, may be used as a neuroprotective agent without risk of thrombotic events. The objective of this investigation was to assess the toxicological potential of a nasal formulation with rhEPOb in acute, subacute and nasal irritation assays in rats. Healthy Wistar rats (Cenp:Wistar) were used for the assays. In an irritation test, animals received 15 μl of rhEPOb into the right nostril. Rats were sacrificed after 24 h and slides of the nasal mucosa tissues were examined. Control and treated groups showed signs of a minimal irritation consisting of week edema and vascular congestion in all animals. In the acute toxicity test, the dose of 47,143 UI/kg was administered by nasal route. Hematological patterns, body weight, relative organ weight, and organ integrity were not affected by single dosing with rhEPOb. In the subacute toxicity test, Wistar rats of both sexes received 6,600 UI/kg/day for 14 days. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, selected tissue weights, and histopathological examinations. An increase of lymphocytes was observed in males that was considered to reflect an immune response to treatment. Histopathological examination of organs and tissues did not reveal treatment-induced changes. The administration of rhEPOb at daily doses of 6,600 UI/kg during 14 days did not produce hematological side effects. These results suggest that rhEPOb could offer the same neuroprotection as EPO, without hematological side effects. Copyright © 2010 Elsevier GmbH. All rights reserved.

  12. Oral Herpes

    Science.gov (United States)

    ... Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities ... care. NIDCR > Image Gallery > Oral Health > Oral Herpes Oral Herpes Main Content Title: Oral Herpes Description: Herpes ( ...

  13. Oral Warts

    Science.gov (United States)

    ... Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities ... care. NIDCR > Image Gallery > Oral Health > Oral Warts Oral Warts Main Content Title: Oral Warts Description: Warts ...

  14. Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Lin

    2009-03-01

    Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

  15. Toxicidad oral a 60 días del aceite de sacha inchi (Plukenetia volubilis L. y linaza (Linum usitatissimum L. y determinación de la dosis letal 50 en roedores Oral toxicity at 60-days of sacha inchi oil (Plukenetia volubilis L. and linseed (Linum usitatissimum L., and determination of lethal dose 50 in rodents

    Directory of Open Access Journals (Sweden)

    Arilmi Gorriti

    2010-09-01

    Full Text Available Objetivos. Evaluar la toxicidad oral a 60 días y determinar la dosis letal 50 (DL 50 de los aceites crudos de sacha inchi (Plukenetia volubilis L. y linaza (Linum ussitatisimum en ratas Holtzman y en ratones cepa Balb C57, respectivamente. Materiales y métodos. Para la evaluación de la toxicidad oral a dosis repetida por 60 días se utilizó 24 ratas macho Holtzman divididos en tres grupos de ocho cada uno, los grupos fueron: solución salina fisiológica 4 mL/kg (SSF, aceite de sacha inchi 0,5 mL/kg (SI05 y aceite de linaza 0,5 mL/kg (L05, durante el experimento se controló semanalmente el peso corporal y signos de toxicidad en los grupos investigados, así como colesterol total, HDL, triglicéridos, glucosa, urea, TGP y fosfatasa alcalina a los 30 y 60 días de iniciado el experimento. Para la evaluación de la DL50 se usó ratones macho cepa Balb C57 en grupos de diez animales, se administró por vía oral dosis crecientes de aceites crudos hasta alcanzar 1 mL/kg (37 g/kg; Resultados. Los parámetros séricos en las ratas indican que no existe toxicidad alguna a los 60 días y que la administración de los aceites disminuyeron los niveles de colesterol, triglicéridos e incrementaron el HDL con respecto al grupo control. La DL50 muestra que los aceites crudos de sacha inchi y linaza presentan dosis por encima de los 37 g/kg de masa corporal. Conclusiones. Los aceites de sacha inchi y linaza son inocuos a 60 días y presentan una DL50 por encima de los 37 g/kg de animal.Objectives. To evaluate the oral toxicity at 60 days and to determine the lethal dose 50 (LD 50 of raw sacha inchi (Plukenetia volubilis L. and linseed (Linum ussitatisimum oils in Holtzman rats and mice of the strain Balb C57 respectively. Materials and methods. For the evaluation of the oral toxicity of repeated doses for 60 days, 24 male Holtzman rats were used, divided in three groups of 8 each, the groups were: physiologic saline solution 4 mL/kg (FSS, sacha inchi oil

  16. 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.

    Science.gov (United States)

    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.

  17. Subacute cannabinoid treatment: anticonvulsant activity and withdrawal excitability in mice.

    Science.gov (United States)

    Karler, R; Turkanis, S A

    1980-03-01

    1 The effects of subacute treatment with cannabidiol, delta 9-tetrahydrocannabinol (delta 9-THC), phenytoin and phenobarbitone on anticonvulsant activity and on withdrawal excitability in mice were compared in three electrically induced seizure-threshold tests. 2 In the maximal electroshock-threshold test, subacute treatment did not alter the anticonvulsant activity of cannabidiol, phenytoin or phenobarbitone, but tolerance developed to delta 9-THC. 3 In the 60 Hz electroshock-threshold test, the activity of delta 9-THC and cannabidiol did not change, but tolerance developed to phenobarbitone, and there was an increase in sensitivity to phenytoin. 4 In the 6 Hz electroshock-threshold test, there was an increase in sensitivity to both delta 9-THC and cannabidiol, there was tolerance to phenobarbitone, while the activity of phenytoin did not change. 5 Although tolerance developed in some of the seizure-threshold tests to delta 9-THC and phenobarbitone, tolerance to cannabidiol and phenytoin did not develop in any of the tests. 6 Hyperexcitability followed withdrawal from only delta 9-THC (6 Hz and 60 Hz electroshock-threshold tests) and phenobarbitone (maximal electroshock-threshold and 60 Hz electroshock-threshold tests). 7 The delta 9-THC withdrawal hyperexcitability suggests that the use of marihuana may jeopardize the control of seizures in epileptics.

  18. Changes of resting cerebral activities in subacute ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2015-01-01

    Full Text Available This study aimed to detect the difference in resting cerebral activities between ischemic stroke patients and healthy participants, define the abnormal site, and provide new evidence for pathological mechanisms, clinical diagnosis, prognosis prediction and efficacy evaluation of ischemic stroke. At present, the majority of functional magnetic resonance imaging studies focus on the motor dysfunction and the acute stage of ischemic stroke. This study recruited 15 right-handed ischemic stroke patients at subacute stage (15 days to 11.5 weeks and 15 age-matched healthy participants. A resting-state functional magnetic resonance imaging scan was performed on each subject to detect cerebral activity. Regional homogeneity analysis was used to investigate the difference in cerebral activities between ischemic stroke patients and healthy participants. The results showed that the ischemic stroke patients had lower regional homogeneity in anterior cingulate and left cerebrum and higher regional homogeneity in cerebellum, left precuneus and left frontal lobe, compared with healthy participants. The experimental findings demonstrate that the areas in which regional homogeneity was different between ischemic stroke patients and healthy participants are in the cerebellum, left precuneus, left triangle inferior frontal gyrus, left inferior temporal gyrus and anterior cingulate. These locations, related to the motor, sensory and emotion areas, are likely potential targets for the neural regeneration of subacute ischemic stroke patients.

  19. Neuronal loss is an early component of subacute sclerosing panencephalitis.

    Science.gov (United States)

    Yüksel, Deniz; Diren, Barış; Ulubay, Hakan; Altunbaşak, Sakir; Anlar, Banu

    2014-09-02

    We performed diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) studies in a group of patients with subacute sclerosing panencephalitis (SSPE) in order to estimate the pathologic process underlying the phenotypic variability. Patients with SSPE who had MRI including DTI and MRS examinations were evaluated according to their clinical status as determined by the SSPE Scoring System and their mental age as determined by tests appropriate for age and developmental level. Comparisons of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and metabolite ratios of frontal periventricular white matter, parieto-occipital periventricular white matter, and globus pallidus in both hemispheres were made between control and SSPE groups, and between SSPE subgroups. Control (n = 18) and SSPE (n = 39) groups differed in all DTI and MRS parameters except FA, choline (Cho), and Cho/creatine (Cr). SSPE cases had higher ADC and lower N-acetylaspartate (NAA), NAA/Cho, and NAA/Cr in all regions of interest, suggesting cell loss. Disease progression rate and neurologic deficit appeared to be associated with the degree of ADC elevation and NAA reduction: the group with severe global deterioration had the lowest NAA (230.75 ± 197.97 in forceps minor), and rapid progression was associated with acute reduction in NAA. The combination of MRS and diffusion MRI findings suggests neuronal loss can be a primary target in rapidly or subacutely progressing SSPE, and preservation or regeneration of axonal structure may be beneficial in chronic cases. © 2014 American Academy of Neurology.

  20. Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity.

    Science.gov (United States)

    Upadhyayula, Pavan S; Yang, Jason; Yue, John K; Ciacci, Joseph D

    2017-11-07

    Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

  1. Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

    Directory of Open Access Journals (Sweden)

    Pavan S. Upadhyayula

    2017-11-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017. Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV. However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

  2. Fever of unknown origin: subacute thyroiditis versus typhoid fever.

    Science.gov (United States)

    Cunha, Burke A; Thermidor, Marjorie; Mohan, Sowjanya; Valsamis, Ageliki S; Johnson, Diane H

    2005-01-01

    Fever of unknown origin (FUO) is not infrequently a diagnostic dilemma for clinicians. Common infectious causes include endocarditis and abscesses in adults, and noninfectious causes include neoplasms and certain collagen vascular diseases, for example, polymyalgia rheumatica, various vasculitides, and juvenile rheumatoid arthritis (adult Still's disease). Subacute thyroiditis is a rare cause of FUO. Among the infectious causes of FUO, typhoid fever is relatively uncommon. We present a case of FUO in a traveler returning from India whose initial complaints were that of left-sided neck pain and angle of the jaw pain, which initially suggested the diagnosis of subacute thyroiditis. After an extensive FUO workup, when typhoid fever is a likely diagnostic possibility, an empiric trial of anti- Salmonella therapy has diagnostic and therapeutic significance. The presence of relative bradycardia, and response to quinolone therapy, was the basis of the clinical diagnosis of typhoid fever as the explanation for this patients FUO. This case illustrates the diagnostic difficulties in assessing patients with FUO with few diagnostic findings.

  3. Protease production by Streptococcus sanguis associated with subacute bacterial endocarditis.

    Science.gov (United States)

    Straus, D C

    1982-01-01

    A viridans streptococcus (Streptococcus sanguis biotype II) isolated from the blood of a patient with subacute bacterial endocarditis was examined for protease production. In broth culture, extracellular proteolytic enzymes were not produced by this organism until after the early exponential phase of growth, with maximal protease production occurring during the stationary phase. Four distinct proteases were isolated and purified from the supernatant fluids of stationary-phase cultures, employing a combination of ion-exchange column chromatography, gel filtration column chromatography, and polyacrylamide gel electrophoresis. All four proteases could be eluted from a diethylaminoethyl cellulose column at a sodium chloride gradient concentration of 0.25 M but were separable by gel filtration chromatography on a Sephadex G-100 column. They varied in molecular weights as determined by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis from approximately 13,000 to 230,000. All four proteases had pH optima of between 8.0 and 9.0, and two of the proteases were active against casein, human serum albumin, and gelatin but were not active against elastin and collagen. The remaining two proteases were able to degrade only casein and gelatin. These results show that S. sanguis is able to excrete maximal levels of potentially destructive enzymes when the organisms are not actively multiplying. This finding may explain some of the damage caused in heart tissue by these organisms during subacute bacterial endocarditis. Images PMID:6759404

  4. Sub-chronic oral toxicity study in Sprague-Dawley rats with hypoxia mimetic cobalt chloride towards the development of promising neutraceutical for oxygen deprivation

    OpenAIRE

    Shrivastava, Kalpana; Bansal, Anju; Singh, Bhagwat; Sairam, Mustoori; Ilavazhagan, Govindaswamy

    2010-01-01

    Abstract The present study evaluates the toxicity from sub-chronic administration of CoCl2 (12.5 mg cobalt kg-1 BW for seven days) to male Sprague-Dawley rats in view of the beneficial effects of CoCl2 in animals and for developing efficacious therapeutic regimen in humans. 32 rats weighing 200?25g were used for all experiments. Blood was collected for hematological and biochemical analysis and various organs were dissected after perfusion of animals under anesthesia for other anal...

  5. [Toxicity of hydroxyquinoline derivatives].

    Science.gov (United States)

    Pashov, D; Simeonov, S P; Drumev, D; Peĭnikova, Ts; Dzhurov, A

    1980-01-01

    We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.

  6. TOXICITY OF SOME PLANTS IMPLICATED AS POISONS IN ...

    African Journals Online (AJOL)

    Different parts of eight plants implicated in Akwa Ibom ethnomedicinal literature as toxic were examined for toxicity in rats after oral and intraperitoneal administration. Only the ethanolic extract of S. indica leaves was toxic by both oral and intraperitoneal routes. The extract of C. edulis roots, E. kamerunica leaves, ...

  7. Expression patterns of micro-RNAs 146a, 181a, and 155 in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Yiş, Uluç; Tüfekçi, Uğur Kemal; Genç, Şermin; Çarman, Kürşat Bora; Bayram, Erhan; Topçu, Yasemin; Kurul, Semra Hız

    2015-01-01

    Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated virus, showing inflammation, neurodegeneration, and demyelination. Although many factors are emphasized in the pathogenesis of subacute sclerosing panencephalitis, the exact mechanism of neurodegeneration remains unknown. Micro-RNAs are small, noncoding RNAs that regulate gene expression at the posttranscriptional levels. Micro-RNAs are essential for normal immune system development; besides they are also implicated in the pathogenesis of many chronic inflammatory disorders. The aim of this study is to investigate the expression patterns of micro-RNAs 146a, 181a, and 155 in peripheral blood mononuclear cells of patients with subacute sclerosing panencephalitis. We enrolled 39 patients with subacute sclerosing panencephalitis and 41 healthy controls. Quantitative analysis of micro-RNAs 146a, 181a, and 155 were performed using specific stem-loop primers followed by real-time polymerase chain reaction. All of 3 micro-RNAs were upregulated in subacute sclerosing panencephalitis patients. In addition, the level of micro-RNA 155 expression was higher in stage 3 patients. But, micro-RNA 146a and 181a expression levels showed no association or correlation with clinically relevant data. Alteration of peripheral blood mononuclear cell micro-RNAs in subacute sclerosing panencephalitis may shed new light on the pathogenesis of disease and may contribute to the aberrant systemic rise in mRNA levels in subacute sclerosing panencephalitis. © The Author(s) 2014.

  8. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement.

    Science.gov (United States)

    Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Bossi, Paolo; Majorana, Alessandra; Gastaldi, Giorgio; Berruti, Alfredo; Trippa, Fabio; Nicolai, Pietro; Barasch, Andrei; Russi, Elvio G; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M

    2016-06-01

    Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements). Copyright © 2016. Published by Elsevier Ireland Ltd.

  9. Acute Oral Mammalian Toxicity and Effect of Solvents on Efficacy of Maerua edulis (Gilg. & Ben. De Wolf against Rhipicephalus (Boophilus decoloratus Koch, 1844 (Acarina: Ixodidae, Tick Larvae

    Directory of Open Access Journals (Sweden)

    Emmanuel T. Nyahangare

    2016-01-01

    Full Text Available Efficacy and toxicity of aqueous and organic solvents extracts of Maerua edulis against ticks and mice, respectively, were determined. Ground leaves were extracted separately using cold water, cold water plus surfactant (1% v/v liquid soap, hot water plus surfactant, hexane, or methanol to make 25% w/v stock solutions from which serial dilutions of 5, 10, 20, and 25% were made. For each concentration, 20 Rhipicephalus decoloratus tick larvae were put in filter papers impregnated with extracts and incubated for 48 h at 27°C and 85–90% RH for mortality observation after 24 h and 48 h. In the toxicity experiment, hot water plus surfactant treatments of 5, 10, 20, and 25% (w/v M. edulis were administered in suspension per os to sexually mature Balb/C mice and observed for clinical signs and mortality for 72 h. Larvae mortality was highest (>98% in methanol-extracted M. edulis treatments (20 and 25%, which was not different from the amitraz-based control (Tickbuster®. Mortality was also higher in the hot water than in cold water plus surfactant treatments (P<0.05. No postadministration adverse health effects were observed in the mice. These results suggest that M. edulis is an effective tick remedy best extracted using methanol or hot water plus surfactant.

  10. Ninety-day oral toxicity study of rhamsan gum, a natural food thickener produced from Sphingomonas ATCC 31961, in Crl:CD(SD)IGS rats.

    Science.gov (United States)

    Hagiwara, Akihiro; Imai, Norio; Doi, Yuko; Sano, Masashi; Tamano, Seiko; Omoto, Toshio; Asai, Iwao; Yasuhara, Kazuo; Hayashi, Shim-mo

    2010-08-01

    This study was designed to evaluate and characterize any subchronic toxicity of rhamsan gum, a polysaccharide produced from Sphingomonas strain ATCC 31961, when administered to both sexes of Crl:CD(SD)IGS rats at dietary levels of 0 (control), 0.5, 1.5, and 5.0% (10 rats/sex/group). During the study, the treatment had no adverse effects on clinical signs, survival, body weights and food and water consumption, or on findings of urinalysis, ophthalmology, hematology, or blood biochemistry. Examination of gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Increased relative cecum (filled) and cecum (empty) weights, evident in males of 1.5% group and both sexes of the 5.0% group, were considered to be a physiological adaptation. Thus, the results indicated the toxic level of rhamsan gum to be more than 5.0%, and the no-observed-adverse-effect level (NOAEL) was concluded to be 5.0% (3,362 mg/kg body weights/day for males, and 4,304 mg/kg body weights/day for males) from the present study.

  11. A ninety-day oral toxicity study of a new type of processed gum arabic, from Acacia tree (Acacia senegal) exudates, in F344 rats.

    Science.gov (United States)

    Doi, Y; Ichihara, T; Hagiwara, A; Imai, N; Tamano, S; Orikoshi, H; Ogasawara, K; Sasaki, Y; Nakamura, M; Shirai, T

    2006-04-01

    This study was designed to evaluate and characterize any subchronic toxicity of a new type of gum arabic (SUPER GUM [Acacia(sen)SUPER GUM]), a naturally processed polysaccharide exudate from gum acacia trees (Acacia senegal), when administered to both sexes of F344 rats at dietary levels of 0 (control), 1.25%, 2.5%, and 5.0% (10 rats/sex/group). During the study, the treatment had no effects on clinical signs, survival, body weights, and food and water consumption, or on findings of urinalysis, ophthalmology, hematology, or blood biochemistry. Gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Increased relative cecum (filled) weights, evident in both sexes of 5.0% group and females of 1.25% and 2.5% groups, were considered to be a physiological adaptation. Thus, the results indicated the toxic level of SUPER GUM to be more than 5.0%, and the no observed adverse effect level (NOAEL) was concluded to be 5.0% (3,117 mg/kg body weights/day for males, and 3,296 mg/kg body weights/day for males) from the present study.

  12. An evaluation of neuropeptide Y status in subacute sclerosing panencephalitis patients.

    Science.gov (United States)

    Abuhandan, M; Calik, M; Almaz, V; Taskın, A; Cakmak, A; Selek, S

    2013-01-01

    This study aimed to evaluate the neuropeptide Y values of patients with subacute sclerosing panencephalitis. The study comprised 38 patients diagnosed with subacute sclerosing panencephalitis at our clinic, who were being routinely followed-up, together with a control group of 36. Using the Risk and Haddad classification for clinical staging, 16 patients were determined as Stage II and 22 patients as Stage III. Neuropeptide Y values were measured by Enzyme Immunoassay methods. The neuropeptide Y values of the all patients with subacute sclerosing panencephalitis were found to be significantly high compared to the control group (ppanencephalitis.

  13. Subacute thyroiditis following influenza vaccine: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Munther S. Momani

    2015-06-01

    Full Text Available Subacute thyroiditis following influenza vaccination is a rarely reported condition. Here, we review this condition and report the case of a 40-year-old male who developed subacute thyroiditis following the administration of an influenza vaccine containing the (H1N1 pandemic 2009 strain. Interestingly, the patient had history of pericarditis and his HLA typing showed HLA B35. Physicians should be aware of this complication for influenza vaccine and of the relationship of HLA B35 haplotype with the susceptibility to subacute thyroiditis and other autoimmune disorders.

  14. Acute and sub-chronic toxicity studies of three plants used in Cameroonian ethnoveterinary medicine: Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) leaves, Carica papaya L. (Caricaceae) seeds or leaves, and Mimosa pudica L. (Fabaceae) leaves in Kabir chicks.

    Science.gov (United States)

    Nghonjuyi, Ndaleh Wozerou; Tiambo, Christian Keambou; Taïwe, Germain Sotoing; Toukala, Jean Paul; Lisita, Frederico; Juliano, Raquel Soares; Kimbi, Helen Kuokuo

    2016-02-03

    Aloe vera (L.) Burm. f. (Xanthorrhoeaceae), Carica papaya L. (Caricaceae) and Mimosa pudica L. (Fabaceae) are widely used in the Cameroonian ethnoveterinary medicine as a panacea, and specifically for gastrointestinal disorders as well as an anthelmintic and antibacterial. The present study evaluated the potential toxicity of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds, and Mimosa pudica leaves after acute and sub-chronic administration in chicks. For the acute toxicity test a single administration of each of the four hydroalcoholic extracts was given orally at doses ranging from 40 to 5120 mg/kg (n=5/group/sex). In the sub-chronic study, these extracts were given orally as a single administration to chicks at doses of 80, 160, 320 and 640 mg/kg/day for 42 days. The anti-angiogenic properties of these extracts (5-320 µg/mg) were investigated in the chick chorioallantoic membrane in vivo. In the acute toxicity test, none of the four studied hydroalcoholic extracts induced mortality or significant behavioural changes. The sub-acute treatment with the four plant extracts did not alter either the body weight gain or the food and water consumption. However, the results indicated that Aloe vera leaf extract acute treatment by oral route at doses up to 2560 mg/kg did not produce death in 50% (5/10) of chicks during 24h or 14 days of observation, but 20% (2/10) chicks died. The haematological and biochemical analyses did not show significant differences in any of the parameters examined in female or male groups, with the exception of a transient rise in white blood cell counts at high doses (640 mg/kg). Additionally, these extracts did not have the potential for anti-angiogenic effects through the inhibition of neo-angiogenesis in the chick chorioallantoic membrane in vivo. The results showed that the therapeutic use of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds and Mimosa pudica leaves had very low

  15. Effects of a toxic cyanobacterial bloom (Planktothrix agardhii) on fish: insights from histopathological and quantitative proteomic assessments following the oral exposure of medaka fish (Oryzias latipes).

    Science.gov (United States)

    Marie, Benjamin; Huet, Hélène; Marie, Arul; Djediat, Chakib; Puiseux-Dao, Simone; Catherine, Arnaud; Trinchet, Isabelle; Edery, Marc

    2012-06-15

    Cyanobacterial toxic blooms often occur in freshwater lakes and constitute a potential health risk to human populations, as well as to fish and other aquatic organisms. Microcystin-LR (the cyanotoxin most commonly detected in the freshwater environment) is a potent hepatotoxin, deregulating the kinase pathway by inhibiting phosphatases 1 and 2A. Although toxicological effects have been clearly linked to the in vitro exposure of fish to purified microcystins, cyanotoxins are produced by the cyanobacteria together with numerous other potentially toxic molecules, and their overall and specific implications for the health of fish have still not been clearly established and remain puzzlingly difficult to assess. The medaka fish (Oryzias latipes) was chosen as an in vitro model for studying the effects of a cyanobacterial bloom on liver protein contents using a gel free quantitative approach, iTRAQ, in addition to pathology examinations on histological preparations. Fish were gavaged with 5 μL cyanobacterial extracts (Planktothrix agardhii) from a natural bloom (La Grande Paroisse, France) containing 2.5 μg equiv. MC-LR. 2h after exposure, the fish were sacrificed and livers were collected for analysis. Histological observations indicate that hepatocytes present glycogen storage loss, and cellular damages, together with immunological localization of MCs. Using a proteomic approach, 304 proteins were identified in the fish livers, 147 of them with a high degree of identification confidence. Fifteen of these proteins were statistically significantly different from those of controls (gavaged with water only). Overall, these protein regulation discrepancies clearly indicate that oxidative stress and lipid regulation had occurred in the livers of the exposed medaka fish. In contrast to previous pure microcystin-LR gavage experiments, marked induction of vitellogenin 1 protein was observed for the first time with a cyanobacterial extract. This finding was confirmed by ELISA

  16. Evaluación de la toxicidad aguda oral y de la actividad antimicrobiana de una mezcla de aceite de hígado de tiburones de Cuba Assessment of the oral acute toxicity and the antimicrobial activity of an oily mixture from shark's liver of Cuba

    Directory of Open Access Journals (Sweden)

    Caridad Margarita García Peña

    2010-09-01

    Full Text Available Se evaluó la toxicidad aguda oral y la actividad antimicrobiana de una mezcla de aceites de hígado de tiburón, de las especies Rhincodon typu (tiburón ballena y Galeocerdo cuvier (tiburón tigre, que habitan en zonas aledañas a las costas del litoral norte occidental de Cuba, para su posterior uso farmacéutico, debido a que presenta un alto contenido de vitaminas y de ácidos grasos, que le confieren actividad antioxidante y antiinflamatoria. El estudio de la toxicidad aguda oral demostró que la mezcla de aceites de hígado de tiburones, no provocó alteraciones macroscópicas en los órganos extraídos, ni síntomas tóxicos severos, ni mortalidad de ninguno de los animales empleados en el estudio a la dosis de 20 mL/kg. Los resultados del estudio de la actividad antimicrobiana demostraron una ligera actividad bacteriostática frente a K. pneumoniae; además una actividad antifúngica frente a Microsporum canis; y resistencia frente a C. albicans y T. mentagrophytes a las concentraciones evaluadas.The total acute toxicity and the antimicrobial activity of an oil mixtures from shark liver of Rhicodon typu (whale-shark and Galeocerdo cuvier (tigger-shark was assessed in species leaving in the adjacent costs of Cuban northern coastal for its subsequent pharmaceutical use due to its high content of vitamins and fatty acids and its antioxidant and anti-inflammatory activity. Study of oral acute toxicity demonstrated that oil mixture of shark liver hasn't macroscopic alterations in removed organs, severe toxic symptoms and on mortality of any animals used in study at 20 mL/kg dose. Study results of antimicrobial activity showed a slight bacteriostatic activity against K. pneumoniae and an antifungal activity against Microsporum canis, and a resistance against C. albicans and T. mentagrophytes at assessed concentrations.

  17. In vivo assessment of the toxic potential of Dissotis rotundifolia whole plant extract in Sprague–Dawley rats

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    Charles Ansah

    2016-07-01

    Conclusions: The results obtained from the sub-acute toxicological assessment of D. rotundifolia extract suggest that the extract is non-toxic at doses up to 1000 mg/kg/day administered for a period of 14 days.

  18. The Toxicity and Anti-cancer Activity of the Hexane Layer of Melia azedarach L. var. japonica Makino's Bark Extract.

    Science.gov (United States)

    Kim, Hyun Woo; Kang, Se Chan

    2012-03-01

    In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28- day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

  19. Case report: subacute tetraplegia in an immunocompromised patient.

    Science.gov (United States)

    Zeller, Daniel; Heidemeier, Anke; Grigoleit, Götz Ulrich; Müllges, Wolfgang

    2017-02-10

    Clinical reasoning in Neurology is based on general associations which help to deduce the site of the lesion. However, even "golden principles" may occasionally be deceptive. Here, we describe the case of subacute flaccid tetraparesis due to motor cortical lesions. To our knowledge, this is the first report to include an impressive illustration of nearly symmetric motor cortical involvement of encephalitis on brain MRI. A 51 year old immunocompromized man developed a high-grade pure motor flaccid tetraparesis over few days. Based on clinical presentation, critical illness polyneuromyopathy was suspected. However, brain MRI revealed symmetrical hyperintensities strictly limited to the subcortical precentral gyrus. An encephalitis, possibly due to CMV infection, turned out to be the most likely cause. While recognition of basic clinical patterns is indispensable in neurological reasoning, awareness of central conditions mimicking peripheral nervous disease may be crucial to detect unsuspected, potentially treatable conditions.

  20. Subacute brachial diplegia associated with West Nile virus myelitis.

    Science.gov (United States)

    Zafar, Sahar F; Ubogu, Eroboghene E

    2012-06-01

    Brachial diplegia is a clinical term used to describe weakness restricted to the upper extremities. We report a case of brachial diplegia associated with West Nile virus infection. A 48-year-old man developed severe painless bilateral upper extremity weakness within a few weeks of a flu-like illness. Clinical examination revealed marked periscapular, shoulder girdle, and humeral muscle atrophy and bilateral scapular winging, with near symmetrical bilateral hypotonic upper extremity weakness. This was associated with clinical signs of an encephalomyelopathy without cognitive or sensory deficits. Electrophysiological studies demonstrated a subacute disorder of motor neurons, their axons or both, involving the cervical and thoracic myotomes, with ongoing denervation. Serological studies confirmed recent West Nile virus (WNV) infection. Gradual improvement occurred following conservative supportive therapies. Progressive brachial diplegia is a rare neuromuscular presentation of WNV neuroinvasive disease. This case report adds to the clinical spectrum of WNV-induced neurologic sequelae. Copyright © 2012 Wiley Periodicals, Inc.

  1. Spectrophotometry of cerebrospinal fluid in subacute and chronic subdural haematomas

    Science.gov (United States)

    Kjellin, K. G.; Steiner, L.

    1974-01-01

    Spectrophotometric examinations were performed on cerebrospinal and subdural fluids in subacute (five patients) and chronic (20 patients) subdural haematomas, with special reference to the diagnostic aid of CSF spectrophotometry. Spectrophotometric xanthochromia of haemorrhagic origin was found in all CSFs examined, while definite visible xanthochromia was observed in only 28% and the CSF was judged as colourless in 52% of those cases. Characteristic bleeding patterns were found spectrophotometrically in all the 20 CSFs examined within 24 hours after lumbar puncture, haematoma patterns being detected in 90-95% of the cases. In many cases the electrophoretically separated protein fractions of CSF and subdural fluids were spectrophotometrically examined. In conclusion, CSF spectrophotometry is a simple, fast, and extremely sensitive method, which in our opinion should be used routinely in the diagnosis of suspected subdural haematomas, if lumbar puncture is not contraindicated. PMID:4140892

  2. Subacute Sclerosing Panencephalitis in a Toddler: Changing Epidemiological Trends

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    Roosy Aulakh

    2013-01-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is a devastating “slow virus” brain disease resulting from persistent measles virus infection of neurons. The age at presentation is usually 8 to 11 years with onset usually occurring 2–10 years after measles infection. We report a 2-and-half-year-old boy who presented with progressively increasing myoclonic jerks and subtle cognitive decline. He was diagnosed as a case of SSPE based on clinical features, typical electroencephalographic finding, and elevated cerebrospinal fluid/serum measles antibody titers. He had measles 4 months prior to onset of symptoms. This case along with review of recently published reports suggests progressively decreasing latency period between measles infection and onset of symptoms observed in cases with SSPE. Clinical implication would mean investigating for SSPE even in infants or toddlers with compatible clinical features and recent history of measles infection.

  3. Subacute sclerosing panencephalitis resembling Rasmussen's encephalitis on magnetic resonance imaging.

    Science.gov (United States)

    Jakkani, Ravi Kanth; Sureka, Jyoti; Panwar, Sanuj

    2015-09-01

    Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressing but invariably fatal disease that is related to a prior measles virus infection and most commonly affects paediatric patients. Magnetic resonance (MR) imaging is the modality of choice for determining such changes in white matter. SSPE typically demonstrates bilateral but asymmetric periventricular and subcortical white matter involvement. We herein report a rare case of unilateral white matter involvement in a 13-year-old boy with SSPE that closely simulated Rasmussen's encephalitis. To the best of our knowledge, this is the first report of an atypical presentation on MR imaging in which SSPE was a rare cause of unilateral brain parenchymal involvement in a patient with intractable seizures.

  4. Notes from the Field: Subacute Sclerosing Panencephalitis Death - Oregon, 2015.

    Science.gov (United States)

    Liko, Juventila; Guzman-Cottrill, Judith A; Cieslak, Paul R

    2016-01-15

    In 2015, the Oregon Health Authority was notified of the death of a boy with subacute sclerosing panencephalitis (SSPE), a rare and fatal complication of measles. The patient, aged 14 years, had reportedly been vaccinated against measles in the Philippines at age 8 months. However, the patient contracted measles at age 1 year while still in the Philippines. He had been well until 2012, when his neurodegenerative symptoms began. After the diagnosis of SSPE was made, the patient remained in home hospice care until his death. Investigators from the Oregon Health Authority and the Oregon Health and Science University reviewed the patient's medical records and interviewed the parents. Vaccination against measles can prevent not only acute measles and its complications, but also SSPE.

  5. Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis

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    Huber, M.; Herholz, K.; Pawlik, G.; Szelies, B.; Juergens, R.H.; Heiss, W.D.

    1989-01-01

    Regional cerebral glucose metabolism was studied in a 15-year-old boy with subacute sclerosing panencephalitis before and after therapy with human interferon beta, using positron emission tomography of fluorine 18-2-fluoro-2-deoxyglucose. At first examination, metabolism was symmetrically decreased in the thalamus, cerebellum, and all cortical areas except prerolandic motor cortex, but increased in lentiform nucleus. A computed tomographic scan was normal. Six months later, bilateral focal necrosis centered in the previously hypermetabolic putamen was demonstrated by computed tomography and magnetic resonance imaging. The caudate nucleus and the superoposterior part of the putamen were spared, still showing increased metabolism. Corresponding with some clinical improvement, cortical glucose consumption rates had returned to a normal level.

  6. Subacute sclerosing panencephalitis (SSPE) the story of a vanishing disease.

    Science.gov (United States)

    Gadoth, Natan

    2012-10-01

    Subacute sclerosing panencephalitis (SSPE), is a devastating "slow virus" brain disease which affects young children who had measles some 6-7 years earlier. Although, the pandemic of SSPE during 1960-1980's was almost eradicated due to mass immunization, the disease is still taking the life of young children in countries where measles immunization is incomplete and in world regions where genetic polymorphism to this particular infection is present. The present review was written for the fortunate young generation of pediatricians and pediatric neurologists who probably have not seen a case of SSPE during their career, and for those who work in counties where the disease has not been eradicated. It is also a reminder that with full coverage of measles immunization this devastating disease can be fully eradicated. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  7. Subacute Sclerosing Panencephalitis with Atypical Clinical and MRI Findings

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    Buse Rahime Hasırcı

    2016-04-01

    Full Text Available Subacute sclerosing panencephalitis (SSPE is a progressive inflammatory disorder of the central nervous system and a slow virus infection caused by aberrant measles virüs. Typical neurological manifestations include psychomotor impairment, progressive intellectual deterioration, myoclonic jerks and behavioral changes, with or without pyramidal symptoms. It usually affecting people aged 10 to 14 year. We report the case of an 17-year-old girl presenting with initial symptom of visual loss, seizures, a lack of SSPE specific EEG pattern, late onset and atypical fast progression of disease. The case highlights the importance of atypical clinical findings of SSPE at onset and also firstly disappearing, then appearing MRI findings at sequential images which can complicate the accurate diagnosis. High suspicion is needed because of its rareness.

  8. Atypical magnetic resonance imaging features in subacute sclerosing panencephalitis

    Directory of Open Access Journals (Sweden)

    Biplab Das

    2016-01-01

    Full Text Available Objectives: Subacute sclerosing panencephalitis (SSPE is rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection with measles virus. No cure for SSPE exists, but the condition can be managed by medication if treatment is started at an early stage. Methods and Results: Heterogeneity of imaging findings in SSPE is not very uncommon. But pial and gyral enhancements are very rarely noticed. Significant asymmetric onset as well as pial-gyral enhancements is not reported. Herein we present a case of 16 years adolescent of SSPE having remarkable asymmetric pial-gyral enhancements, which were misinterpreted as tubercular infection. Conclusion: Early diagnosis and treatment is encouraging in SSPE, although it is not curable with current therapy. Clinico-radiological and electrophysiological correlation is very important in diagnosis of SSPE, more gravely in patients having atypical image findings as in our index case.

  9. Fulminant adult-onset subacute sclerosing panencephalitis: a case report

    Science.gov (United States)

    Faivre, Anthony; Souraud, Jean-Baptiste; McGonigal, Aileen; Alla, Philippe; Grapperon, Jacques; Valance, Jacques

    2009-01-01

    We present the case of a young adult who developed acute encephalopathy with severe status epilepticus and rapid deterioration to vegetative state and death within 6 weeks. Although the clinical picture, MRI and EEG findings were atypical, the hypothesis of subacute sclerosing panencephalitis (SSPE) was suggested by markedly increased intrathecal IgG synthesis in the cerebrospinal fluid, and diagnosis was confirmed by the presence of high antimeasles antibodies in cerebrospinal fluid and brain biopsy findings. Acute SSPE is an exceptionally rare and little-known form of SSPE with protean symptomatology, and this case is to our knowledge the first observation of SSPE presenting with status epilepticus in adults. Our case reinforces the need to include, even in developed countries, SSPE as a diagnostic possibility in unexplained acute encephalopathies. PMID:21686559

  10. Mesenchymal stem cell application in children with subacute sclerosing panencephalitis.

    Science.gov (United States)

    Kuşkonmaz, Bariş; Uçkan, Duygu; Yalnizoğlu, Dilek; Günel, Mintaze; Karli Oğuz, Kader; Konuşkan, Bahadir; Anlar, Banu

    2015-09-01

    Subacute sclerosing panencephalitis (SSPE) is a serious, often fatal disease that responds poorly to current treatment modalities. Recently, the ability of mesenchymal stem cells (MSCs) to produce neurotrophic factors and inflammatory molecules has placed them among potential treatment agents for neurological conditions. We report the results of four patients treated with MSC for SSPE. The patients were followed up clinically, and by periodical laboratory evaluations, magnetic resonance imaging (MRI), and electroencephalography. One patient deteriorated to stage III of the disease, two patients remained in the same stage, and one died from disease progression and respiratory problems. Neurological findings and electroencephalography scores were consistent with the clinical course of the patient whereas MRI showed new inflammatory lesions in two patients. This is the first report of the application of MSC in SSPE. No benefit is demonstrated. © 2015 Mac Keith Press.

  11. Atypical magnetic resonance imaging features in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Das, Biplab; Goyal, Manoj Kumar; Modi, Manish; Mehta, Sahil; Chakravarthi, Sudheer; Lal, Vivek; Vyas, Sameer

    2016-01-01

    Subacute sclerosing panencephalitis (SSPE) is rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection with measles virus. No cure for SSPE exists, but the condition can be managed by medication if treatment is started at an early stage. Heterogeneity of imaging findings in SSPE is not very uncommon. But pial and gyral enhancements are very rarely noticed. Significant asymmetric onset as well as pial-gyral enhancements is not reported. Herein we present a case of 16 years adolescent of SSPE having remarkable asymmetric pial-gyral enhancements, which were misinterpreted as tubercular infection. Early diagnosis and treatment is encouraging in SSPE, although it is not curable with current therapy. Clinico-radiological and electrophysiological correlation is very important in diagnosis of SSPE, more gravely in patients having atypical image findings as in our index case.

  12. Subacute Sclerosing Panencephalitis in a Toddler: Changing Epidemiological Trends

    Science.gov (United States)

    Aulakh, Roosy; Tiwari, Abhimanyu

    2013-01-01

    Subacute sclerosing panencephalitis (SSPE) is a devastating “slow virus” brain disease resulting from persistent measles virus infection of neurons. The age at presentation is usually 8 to 11 years with onset usually occurring 2–10 years after measles infection. We report a 2-and-half-year-old boy who presented with progressively increasing myoclonic jerks and subtle cognitive decline. He was diagnosed as a case of SSPE based on clinical features, typical electroencephalographic finding, and elevated cerebrospinal fluid/serum measles antibody titers. He had measles 4 months prior to onset of symptoms. This case along with review of recently published reports suggests progressively decreasing latency period between measles infection and onset of symptoms observed in cases with SSPE. Clinical implication would mean investigating for SSPE even in infants or toddlers with compatible clinical features and recent history of measles infection. PMID:24416610

  13. Progressive subacute Miller-Fisher syndrome successfully treated with plasmapheresis.

    Science.gov (United States)

    Ejma, Maria; Waliszewska-Prosół, Marta; Hofman, Anna; Budrewicz, Sławomir; Podemski, Ryszard; Bilińska, Małgorzata; Koszewicz, Magdalena

    2015-01-01

    Miller-Fisher Syndrome (MFS) is a rare acute polyneuropathy composed of the clinical triad of ataxia, areflexia and ophthalmoplegia, with a monophasic, self-limited course and spontaneous improvement. The authors present a 65-year-old man with Miller-Fisher syndrome consisting of bilateral ophthalmoplegia, trigeminal and facial nerve palsy, mild ataxia and peripheral neuropathy. The disease had a progressive, subacute course within 3 months. A high titer of anti-GQ1b antibodies was detected. As a result of plasmapheresis, complete recovery was achieved. The presented case was atypical in its clinical course and treatment. It could support the theory of the continuity between MFS, Bickerstaff brainstem encephalitis (BBE), and Guillain-Barré syndrome (GBS). Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Subacute bacterial endocarditis presenting as left upper quadrant abdominal pain

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    Yung-Ta Kao

    2013-09-01

    Full Text Available Infective endocarditis is a microbial infection of the endocardial surface of the heart. Its symptoms and signs are varied, and include fever, heart murmur, peripheral embolism, and heart failure. The diagnosis of subacute bacterial endocarditis (SBE is suggested by a history of an indolent process characterized by fever, fatigue, anorexia, and unexplained weight loss. These patients may have had an invasive procedure, such as dental work, or abused intravenous drugs prior to the diagnosis of SBE. Although uncommon, the patients may present with nonspecific symptoms caused by peripheral embolic events. Herein, we report a 25-year-old male diagnosed with SBE, who presented with the unusual symptom of sudden onset of left upper quadrant abdominal pain for 2 days. His clinical history is also discussed.

  15. Subacute liver failure by pseudocirrhotic metastatic breast cancer infiltration.

    Science.gov (United States)

    Jüngst, Christoph; Krämer, Jens; Schneider, Günther; Lammert, Frank; Zimmer, Vincent

    2013-01-01

    Hepatic metastases are common in the clinical course of breast cancer and typically appear as mass lesions. This report describes the case of a 70-year-old woman with a history of breast cancer and no previously known liver disease presenting with the first episode of variceal bleeding and subacute hepatic failure. Imaging studies indicated liver cirrhosis without signs of malignant focal lesions. Comprehensive diagnostic work-up was negative for specific causes of liver disease and provided no evidence for tumor recurrence. Finally transjugular liver biopsy revealed a marked diffuse desmoplastic infiltration by breast cancer cells. Malignant pseudocirrhosis is an unusual pattern of metastatic, tumor spread representing a rare but important differential diagnosis of progressive liver failure. Liver biopsy is the key procedure to establish the diagnosis as imaging studies may mimic cirrhosis.

  16. A rare pathogen for subacute osteomyelitis in adolescent: Serratia marcescens.

    Science.gov (United States)

    Turgut, Necmettin; Akgul, Turgut; Arzu, Ufuk; Batıbay, Sefa Giray; Ekinci, Mehmet; Şen, Cengiz; Korkmaz, Murat

    2015-01-01

    There are various pathogens reported for osteomyelitis. Osteomyelitis is bone infection which produces pain and fever, also threatens bone instability. It can lead to nonunion. The purpose of this report was to describe a case with union delay of the tibia due to serratia marcescens osteomyelitis. Serratia marcescens is an unexpected pathogen for subacute osteomyelitis in adolescence. Because of difficulty of diagnosis, treatment can be delayed or the situation can cause complications like nonunion or loss of function. Serratia marcescens is an unexpected pathogen for subacute osteomyelitis in adolescence. Because of difficulty of diagnosis, treatment can be delayed or cause complications like nonunion or loss of function. We present a meningomyelocele female adolescent operated with distal tibia varus osteotomy for correcting ankle valgus deformity. Insufficient healing was determined at osteotomy side on radiographs. The patient's erythrocyte sedimentation rate and CRP level was slightly higher with minimal clinical inflammation. MRI examination showed abscess formation at T2 imaging. Debridement, grafting and circular external fixation was performed. Sulperazon was started for drug therapy. Union was achieved after compression and distraction osteogenesis by circular external fixator. Orthopedic surgeons should be aware of opportunistic infections like serratia and keep in mind as a probable cause of disease. Osteomyelitis is one of our main problems in orthopedics. Serratia does not come to mind as a causative factor when we learn the patient has osteomyelitis. We give treatment for the most expected pathogens like staphylococcus species firstly. This shows us the importance of bone biopsies and wound culture tests. Presented case is diagnosed as serratia osteomyelitis after culture results and given treatment with antibiotics and debridement. Orthopedic surgeons should be aware of opportunistic infections like serratia and keep in mind when diagnosing the

  17. Mammalian Toxicological Evaluations of TNT Wastewaters. Volume III. Acute and Subacute Mammalian Toxicity of Condensate Water.

    Science.gov (United States)

    1979-04-01

    produced a mild, compensatory anemia (transitory; not I observed at 24 weeks), hemosiderosis of the spleen accompanied in some cases by congestion...reticulocytosis; testicular atrophy; uterine hyperplasia; hemosiderosis ; neuropathy; head trauma; cardiac arrhythmia; LDH; mutagens.I I 20 ABSTRACT... hemosiderosis of the spleen; testicular atrophy with atrophy and aspermia of the epididymis and moderate focal interstitial cell hyperplasia; hyperplasia of

  18. Acute and subacute toxicity study of ethanolic extract of the stem ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-02-22

    Feb 22, 2010 ... tilis and Salmonella typhii. Ethanolic extract of the stem bark was shown by Tijani et al. .... mainly the brain, heart, lungs, kidneys, liver, intestine, stomach, spleen and testes were removed and weighed. ..... than AST because it is more sensitive to hepatic damage. (Herfindal and Gourley, 2000) and there is a ...

  19. Acute and sub-acute toxicity study of Clerodendrum inerme, Jasminum mesnyi Hance and Callistemon citrinus

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    Bharat Bhushan

    2014-01-01

    Conclusions: The results demonstrated that there is a wide margin of safety for the therapeutic use of each of the four extracts of three plants. The findings also corroborated the traditional use of these extracts.

  20. Acute and Sub-acute Toxicity Profile of Aqueous Leaf Extract of ...

    African Journals Online (AJOL)

    (AST), alanine aminotransferase (ALT), alkaline phosphate (ALP) and gamma glutaryltransferase. (GGT), total bilirubin, total protein and albumin were determined using Piccolo express automatic chemistry analyzer (Abaxis Inc. Union. City, CA 94587, USA). The serum levels of creatinine, magnesium, calcium, chloride, ...