Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro

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McDermott, Catherine; Allshire, Ashley; Pelt, Frank N.A.M. van; Heffron, James J.A.

2007-01-01

Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca 2+ , changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs)

Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

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Marcella L.B. Carneiro

2015-01-01

Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

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

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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.

Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

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Ryu HJ

2014-12-01

Full Text Available Hwa Jung Ryu,1,* Mu Yeb Seo,2,* Sung Kyu Jung,1 Eun Ho Maeng,2 Seung-Young Lee,2 Dong-Hyouk Jang,2 Taek-Jin Lee,2 Ki-Yeon Jo,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Meyoung-Kon Kim,3 Beom Jun Lee,5 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, 2Korea Testing and Research Institute, Gyunggido, 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, 5College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea *These authors contributed equally to this work and both should be considered first authors Abstract: Zinc oxide (ZnO works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there

Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

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Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

2018-03-01

Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

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Lakshmanan, Hariprasath; Raman, Jegadeesh; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

2016-12-24

Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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

2014-03-01

The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models

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Xing, Jiali; Wang, Gang; Zhao, Jichun; Wang, Eryin; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q.; Chen, Wei

2016-01-01

Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD_5_0 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS. - Highlights: • The acute and subchronic toxicity of PFOS was systematically investigated. • The acute oral LD_5_0 value for PFOS in C57BL/6J mice was 0.579 g/kg body weight. • PFOS disrupted the homeostasis of antioxidative systems. • PFOS induced hepatocellular apoptosis and triggered liver injury. - PFOS disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis, and triggered liver injury.

Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure

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Thophon, S.; Kruatrachue, M.; Upatham, E.S.; Pokethitiyook, P.; Sahaphong, S.; Jaritkhuan, S

2003-03-01

White seabass responded differently to cadmium at chronic and subchronic levels. - Histopathological alterations to white seabass, Lates calcarifer aged 3 months in acute and subchronic cadmium exposure were studied by light and scanning electron microscopy. The 96-h LC{sub 50} values of cadmium to L. calcarifer was found to be 20.12{+-}0.61 mg/l and the maximum acceptable toxicant concentration (MATC) was 7.79 mg/l. Fish were exposed to 10 and 0.8 mg/l of Cd (as CdCl{sub 2}H{sub 2}O) for 96 h and 90 days, respectively. The study showed that gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of cadmium while in the subchronic exposure, the toxic effect to gills was less than that of kidney and liver. Gill alterations included edema of the epithelial cells with the breakdown of pillar cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial and chloride cells. The liver showed blood congestion in sinusoids and hydropic swelling of hepatocytes, vacuolation and dark granule accumulation. Lipid droplets and glycogen content were observed in hepatocytes at the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cell vacuolation and numerous dark granule accumulation in many tubules. Tubular degeneration and necrosis were seen in some areas.

Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

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Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

2013-03-01

The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biochemical biomarker responses of green-lipped mussel, Perna canaliculus, to acute and subchronic waterborne cadmium toxicity

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Chandurvelan, Rathishri, E-mail: rch118@uclive.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Marsden, Islay D., E-mail: islay.marsden@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Gaw, Sally, E-mail: sally.gaw@canterbury.ac.nz [Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Glover, Chris N., E-mail: chris.glover@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand)

2013-09-15

Highlights: •Biochemical biomarkers were measured to assess effects of Cd on Perna canaliculus. •Biochemical responses varied between acute and subchronic exposure to Cd. •MTLP induction correlated strongly with Cd accumulation. •Alkaline phosphatase and glycogen levels decreased during subchronic Cd exposure. •Duration of Cd exposure influenced biochemical biomarker responses in mussels. -- Abstract: The biochemical responses of the green-lipped mussel, Perna canaliculus, to waterborne cadmium (Cd) were investigated in order to delineate toxic mechanisms, and the impacts of exposure dose and duration, of this important toxicant in a potential sentinel species. Mussels were exposed for either 96 h (acute: 0, 2000, 4000 μg L{sup −1} Cd) or for 28 d (subchronic: 0, 200, 2000 μg L{sup −1} Cd), and the digestive gland, gill and haemolymph were examined for impacts. Biochemical responses measured included those associated with metal detoxification (metallothionein-like protein; MTLP), oxidative stress (catalase, lipid peroxidation), cellular homeostasis (alkaline phosphatase, Na{sup +}, K{sup +}-ATPase; NKA), and energy utilisation (glycogen, haemolymph protein). Following acute exposure, digestive gland glycogen and gill NKA activity were significantly altered by Cd exposure relative to levels in mussels exposed to Cd-free seawater. Subchronic Cd exposure resulted in a significant increase in MTLP levels in both the gill and the digestive gland. This increase was correlated strongly with the levels of Cd accumulation measured in these tissues (R = 0.957 for gill, 0.964 for digestive gland). Catalase activity followed a similar pattern, although the correlation with tissue Cd accumulation was not as strong (R = 0.907 for gill, 0.708 for digestive gland) as that for MTLP. Lipid peroxidation increased in the digestive gland at Days 7 and 14 at both subchronic Cd levels tested, but this effect had largely dissipated by Days 21 and 28 (with the exception of

Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

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Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

2016-06-01

Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. Copyright © 2016 Elsevier Inc. All rights reserved.

A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

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Park HS

2014-12-01

Full Text Available Hark-Soo Park,1 Seon-Ju Kim,1 Taek-Jin Lee,1 Geon-Yong Kim,1 EunHo Meang,1 Jeong-Sup Hong,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Guk Hong,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park61General Toxicology Team, Korea Testing and Research Institute, Seoul, 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 4National Institute of Food and Drug Safety Evaluation, Seoul, 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, KoreaPurpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM,20(+ nanoparticles in Sprague Dawley rats for 90 days.Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM,20(+ NPs.Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with

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 ...

Safety assessment of the methanol extract of the stem bark of Amphimas pterocarpoides Harms: Acute and subchronic oral toxicity studies in Wistar rats

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Job Tchoumtchoua

2014-01-01

Full Text Available Amphimas pterocarpoides Harms (Leguminosae is widely used traditionally in Central and West Africa for the treatment of various ailments. However, no data regarding its safety have been published until now. Thus, the present study aimed to investigate the potential toxicity of the methanol extract of the stem bark of Amphimas pterocarpoides (AP in Wistar rats following the OECD guidelines. In acute oral toxicity, female rats received a single dose of 2000 mg/kg of AP and were observed for 14 days. In subchronic toxicity, doses of 150, 300, 600 mg/kg/day of AP were given per os to rats (males and females for 28 days. No death and abnormal behaviors were observed in acute toxicity and the LD50 was estimated higher than 5000 mg/kg. In the subchronic study, AP induced no significant variation in body weight and relative weight of organs, whereas a delayed decrease of white blood cell count and granulocytes was observed. Inconsistent increase of the total cholesterol/high density lipoprotein was observed at 600 mg/kg in males. Such variation (not dose dependent and without biological relevance indicate a wide margin of safety for the traditional use of AP.

Acute and Subchronic Toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from Chloroform Bay Leaf Extract (Eugenia Polyantha W.) with Palm Kernel Oil as A Carrier

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Prihapsara, F.; Mufidah; Artanti, A. N.; Harini, M.

2018-03-01

The present study was aimed to study the acute and subchronic toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with Palm Kernel Oil as carrier. In acute toxicity test, five groups of rat (n=5/groups) were orally treated with Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with doses at 48, 240, 1200 and 6000 mg/kg/day respectively, then the median lethal dose LD50, advers effect and mortality were recorded up to 14 days. Meanwhile, in subchronic toxicity study, 4 groups of rats (n=6/group) received by orally treatment of SNEDDS from chloroform bay leaf extract with doses at 91.75; 183.5; 367 mg/kg/day respectively for 28 days, and biochemical, hematological and histopatological change in tissue such as liver, kidney, and pancreatic were determined. The result show that LD50 is 1045.44 mg/kg. Although histopathological examination of most of the organs exhibited no structural changes, some moderate damage was observed in high‑ dose group animals (367 mg/kg/day). The high dose of SNEDDS extract has shown mild signs of toxicity on organ function test.

Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

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Basak Ozlem Perk

2013-01-01

Full Text Available The fruit of Physalis peruviana L. (PPL has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg−1 for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg−1 of lyophilized fruit juice and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

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Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

2013-01-01

The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg(-1) for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg(-1) of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

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Tesemma Sileshi

2014-03-01

Full Text Available Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract of Moringa stenopetala (M. stenopetala leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results: Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P<0.05 at 2 h (53.44% and 4.5 h (46.34% in diabetic mice and it was further fractionated chromatographically. This resulted in isolation of three chromatographic fractions (fraction 1, 2, and 3 which exhibited maximal blood glucose reduction (P<0.01 at 6 h (77.2%, at 4.5 h (69.1% and at 4.5 h (71.96% after administration. Furthermore, these fractions exhibited comparable antioxidant activity, and preliminary phytochemical screening indicated the presence of phenolic compounds which may be phenolic glycoside in all fractions. The subchronic toxicity study of the 70% ethanol extract of M. stenopetala leaves revealed that there were no significant differences in body weight, between controls and treated mice. Hematological analysis showed no differences in most parameters examined. Furthermore, it did not significantly affect plasma creatinine, urea, cholesterol, triglycerides and CA125 levels. It also did not significantly affect the plasma T3, T4 and THS level. It, however, caused a significant dose

Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints.

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Phillips, Blaine; Titz, Bjoern; Kogel, Ulrike; Sharma, Danilal; Leroy, Patrice; Xiang, Yang; Vuillaume, Grégory; Lebrun, Stefan; Sciuscio, Davide; Ho, Jenny; Nury, Catherine; Guedj, Emmanuel; Elamin, Ashraf; Esposito, Marco; Krishnan, Subash; Schlage, Walter K; Veljkovic, Emilija; Ivanov, Nikolai V; Martin, Florian; Peitsch, Manuel C; Hoeng, Julia; Vanscheeuwijck, Patrick

2017-11-01

While the toxicity of the main constituents of electronic cigarette (ECIG) liquids, nicotine, propylene glycol (PG), and vegetable glycerin (VG), has been assessed individually in separate studies, limited data on the inhalation toxicity of them is available when in mixtures. In this 90-day subchronic inhalation study, Sprague-Dawley rats were nose-only exposed to filtered air, nebulized vehicle (saline), or three concentrations of PG/VG mixtures, with and without nicotine. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared with vehicle exposure, the PG/VG aerosols showed only very limited biological effects with no signs of toxicity. Addition of nicotine to the PG/VG aerosols resulted in effects in line with nicotine effects observed in previous studies, including up-regulation of xenobiotic enzymes (Cyp1a1/Fmo3) in the lung and metabolic effects, such as reduced serum lipid concentrations and expression changes of hepatic metabolic enzymes. No toxicologically relevant effects of PG/VG aerosols (up to 1.520  mg PG/L + 1.890 mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6.6 mg/kg/day. This study demonstrates how complementary systems toxicology analyses can reveal, even in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Nutritional components and sub-chronic toxicity of genetically modified rice expressing human lactoferrin].

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Hu, Yichun; Piao, Jianhua; Yang, Xiaoguang

2012-01-01

To compare the nutritional components of genetically modified rice expressing human lactoferrin (hLf) with its parental rice, and to observe the sub-chronic toxicity of hLf rice. The nutritional components of hLf rice and its parental rice were determined by the National Standard Methods. Eighty weanling Wistar rats were randomly divided into 4 groups based on their gender and body weight: group A (hLf rice high-dose group with 71.45% rice), group B (hLf rice medium-dose group with 35. 725% rice), group C (parental rice group with 71.01% rice) and group D (AIN-93G diet group), and the latter two groups were used as the control. Body weight, dietary intake, blood routine test, blood biochemical examination, organ coefficient, bone density and the pathology of organs were investigated at the end of a 90-day feeding experiment. Except for human lactoferrin and Fe, there was no difference of main nutritional components, minerals and vitamins between groups. The differences of some indicators of blood routine (WBC, HGB, RBC and MCH), blood biochemistry (AST and GLU), organ coefficient and bone density between group A and B (hLf rice) with group C (parental rice) or group D (AIN-93G) were significant, while no difference of other indicators. Although some differences were observed, all indicators were still in the normal reference range. Therefore, there was no sign of toxic and adverse effects for hLf rice on rats.

Subchronic toxicity study in vivo and allergenicity study in vitro for genetically modified rice that expresses pharmaceutical protein (human serum albumin).

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Sheng, Yao; Qi, Xiaozhe; Liu, Yifei; Guo, Mingzhang; Chen, Siyuan; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

2014-10-01

Genetically modified (GM) crops that express pharmaceutical proteins have become an important focus of recent genetic engineering research. Food safety assessment is necessary for the commercial development of these crops. Subchronic toxicity study in vivo and allergenicity study in vitro were designed to evaluate the food safety of the rice variety expressing human serum albumin (HSA). Animals were fed rodent diets containing 12.5%, 25.0% and 50.0% GM or non-GM rice for 90 days. The composition analysis of the GM rice demonstrated several significant differences. However, most of the differences remained within the ranges reported in the literature. In the animal study, a range of indexes including clinical observation, feed efficiency, hematology, serum chemistry, organ weights and histopathology were examined. Random changes unrelated to the GM rice exposure, within the range of historical control values and not associated with any signs of illness were observed. The results of heat stability and in vitro digestion of HSA indicated no evidence of potential allergenicity of the protein. Overall, the results of these studies suggest that the GM rice appears to be safe as a dietary ingredient when it is used at up to 50% in the diet on a subchronic basis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Subchronic oral toxicity of silver nanoparticles

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Kim Yong

2010-08-01

Full Text Available Abstract Background The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. Results This study tested the oral toxicity of silver nanoparticles (56 nm over a period of 13 weeks (90 days in F344 rats following Organization for Economic Cooperation and Development (OECD test guideline 408 and Good Laboratory Practices (GLP. Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group: vehicle control, low-dose (30 mg/kg, middle-dose (125 mg/kg, and high-dose (500 mg/kg. After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P Conclusions The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level of 30 mg/kg and LOAEL (lowest observable adverse effect level of 125 mg/kg are suggested from the present study.

Acute and Sub-Chronic Toxicity Potential Effects of Alchornea ...

African Journals Online (AJOL)

The open field test showed that sub-chronic administration increased rearing behavior significantly at the dose of 250 mg/kg/28 days but had no effect on grooming. In conclusion, the ethanolic extract has no toxicological effect as observed on hematological, biochemical and histopathological parameters even at the ...

Subchronic and acute preclinical toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae)

International Nuclear Information System (INIS)

Garcia Gonzalez, Mildred; Coto Morales, Teresita; Ocampo, Rafael; Pazos, Liliana

2006-01-01

The effects of the aqueous extract of Petiveria alliacea, leaves were tested on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice, of 20 to 25 g mean weight. Treatments were in all cases doses of 1000 and 2000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed in both tests. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1000 mg/kg dose but not for the higher 2000 mg/kg doses. After administering the dose once after a starving period of six hours, no significant differences in intestinal motility could be found. (author) [es

Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae).

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García-González, Mildred; Morales, Teresita Coto; Ocampo, Rafael; Pazos, Liliana

2006-12-01

We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1,000 and 2,000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1,000 mg/kg dose but not for the higher 2,000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found.

Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

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Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

1999-12-01

The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary

Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

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Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2016-05-01

Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential. © 2016 Institute of Food Technologists®

Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

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Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

2016-07-01

Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Subchronic toxicity test of genetically modified rice with double antisense starch-branching enzyme gene].

Science.gov (United States)

Li, Min; Piao, Jianhua; Yang, Xiaoguang

2010-07-01

To observe the sub-chronic toxic effects of the genetically modified rice with double antisense SBE gene. Based on gender and weight, weanling Wistar rats were randomly sorted into five groups: non-genetically modified rice group (group A), genetically modified rice group (group B), half genetically modified rice group (group C), quarter genetically modified rice group (group D) and AIN-93G normal diet group (group E). Indicators were the followings: body weight, food consumption, blood routine, blood biochemical test, organ weight, bone density and pathological examination of organs. At the middle of the experiment, the percentage of monocyte of female group B was less than that of group E (P 0.05), and no notable abnormity in the pathological examination of main organs (P > 0.05). There were no enough evidence to confirm the sub-chronic toxicity of genetically modified rice on rats.

Toxicological evaluation of subchronic use of pioglitazone in mice

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Said Said Elshama

2016-07-01

Full Text Available Objective(s: Pioglitazone (Actos is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control received water, second (diabetic group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

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Ryu HJ

2014-12-01

Full Text Available Hwa Jung Ryu,1,* Nak-won Seong,2,* Byoung Joon So,1 Heung-sik Seo,2 Jun-ho Kim,2 Jeong-Sup Hong,2 Myeong-kyu Park,2 Min-Seok Kim,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Mu yeb Seo,2 Meyoung-Kon Kim,3 Eun Ho Maeng,2 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, South Korea; 2Korea Testing and Research Institute, Gyunggi-Do, South Korea; 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea; 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, South Korea *These authors contributed equally to this work Abstract: Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. Keywords: silica nanoparticles, toxicity, dermal route

Safety assessment of McB-E60 (extract of a Momordica sp.: Subchronic toxicity study in rats

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Narendra S. Deshmukh

Full Text Available Momordica charantia plant is consumed as a foodstuff in some south Asian curries while its extract preparations have been traditionally used for lowering blood glucose levels in patients with diabetes mellitus. Nutritional Health Institute Laboratories (NHIL, LLC, Florida informed that it patented a new plant McB, as an interhybrid of three plants of Momordica genus. The objective of the present study was to investigate potential adverse effects, if any, of McB-E60 (extract of a Momordica sp. in rats following subchronic administration. Sprague-Dawley rats (10/sex/group were administered via oral gavage 0 (control, 250, 500 and 1000 mg/kg body weight (bw/day of McB-E60 for 90 days. Additional 28-day recovery groups were maintained at control and high dose levels. No mortality or significant and adverse changes in clinical signs, neurological signs, body weight gain or feed intake were noted. No toxicologically significant changes in hematology, clinical chemistry, urinalysis and organ weights were noted. Gross and microscopic pathology examinations did not reveal treatment-related abnormalities. Any changes noted were incidental and within historical control ranges. Based on the results of this study, the No-Observed-Effect Level (NOEL for McB-E60 (extract of a Momordica sp. was determined as greater than 1000 mg/kg bw/day, the highest dose tested. Keywords: Dietary supplement, Safety, Toxicity

Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate.

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Normandin, Louise; Carrier, Gaétan; Gardiner, Phillip F; Kennedy, Greg; Hazell, Alan S; Mergler, Donna; Butterworth, Roger F; Philippe, Suzanne; Zayed, Joseph

2002-09-01

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.

Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

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Christapher, Parayil Varghese; Parasuraman, Subramani; Asmawi, Mohd Zaini; Murugaiyah, Vikneswaran

2017-06-01

Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg. Copyright © 2017 Elsevier Inc. All rights reserved.

Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

International Nuclear Information System (INIS)

Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

2014-01-01

Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems. (papers)

Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

Science.gov (United States)

Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

2014-06-01

Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems.

Subchronic toxicity, immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L.

Science.gov (United States)

Abu, Nadiah; Zamberi, Nur Rizi; Yeap, Swee Keong; Nordin, Noraini; Mohamad, Nurul Elyani; Romli, Muhammad Firdaus; Rasol, Nurulfazlina Edayah; Subramani, Tamilselvan; Ismail, Nor Hadiani; Alitheen, Noorjahan Banu

2018-01-27

Morinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated. In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice. Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays. Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.

COMPARATIVE STUDY FOR SUBCHRONIC TOXICITY OF VASELINE OIL AND GLYCELAX

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A. V. Voronkov

2016-01-01

Full Text Available Contemporary therapeutic approaches offer a wide range of laxative agents, which are often used without a control, exceeding the regime recommended. Therefore, the comparative study for subchronic toxicity of both drugs from this group (Vaseline oil and Glycelax appears interesting.The aim of the study was the comparison of a toxic influence of 14-days application of the drugs under study.Methods. The drugs were studied in two doses: higher therapeutic, and toxic, which 10 times exceeds therapeutic dose. We used “Polispektr-8/B” electrocardiograph, BC 2800vet (Mindray hematologic veterinary analyzer, BS-380 (Mindray biochemical analyzer, CL-50 urine analyzer. After the animals autopsy we determined organs’ coefficient (heart, lungs, spleen, liver, stomach, kidneys, adrenals.Results. While studying the ECG of female rats, amplitude of R wave increased after they got Glycelax in both doses. Female rats who got Vaseline oil this index decreased at minimum dose and increased at maximum dose. After Glycelax application, male rats had an increased activity of alanine aminotransferase. After Vaseline oil application at maximum dose, female rats had alkaline phosphatase activity lowered. Female rats, which got a maximum dose of Vaseline oil had a total protein lowered. Glycelax at maximum dose increased the content of bilirubin and its fractions in male and female rats, while Vaseline oil application at maximum dose increased the content of bilirubin in female rats. Male rats which got Glycelax had hemoglobin and hematocrit level increased.Conclusion. At long-term application of Vaseline oil, animals of both genders had heart disorders with possible development of arrhythmia, hepatotoxic effect, lipid exchange dysfunction. After excessive use of Glycelax the above mentioned is added with possible hemoglobin and rheological blood properties level decrease.

Nephroprotective effect of bee honey and royal jelly against subchronic cisplatin toxicity in rats

OpenAIRE

Ibrahim, Abdelazim; Eldaim, Mabrouk A. Abd; Abdel-Daim, Mohamed M.

2015-01-01

Cisplatin is one of the most potent and effective chemotherapeutic agents. However, its antineoplastic use is limited due to its cumulative nephrotoxic side effects. Therefore, the present study was undertaken to examine the nephroprotective potential of dietary bee honey and royal jelly against subchronic cisplatin toxicity in rats. Male Wistar rats were randomly divided into controls, cisplatin-treated, bee honey-pretreated cisplatin-treated and royal jelly-pretreated cisplatin-treated grou...

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.

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

Science.gov (United States)

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

90-Day oral toxicity study of D-tagatose in rats.

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Kruger, C L; Whittaker, M H; Frankos, V H; Trimmer, G W

1999-04-01

D-tagatose is a ketohexose, tastes like sugar and is useful as a low-calorie sweetener. To assess D-tagatose's safety, an oral 90-day toxicity study was conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15, and 20% D-tagatose. One control group (dietary control) received only lab chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At higher doses, treatment-related effects included transient soft stools in male and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained weight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose-group females at selected intervals compared to dietary control animals. No significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increased relative liver weights were noted in male and female animals from the 10, 15, and 20% dose groups compared to the dietary control. No gross pathological findings correlated with these increased liver weights. Minimal hepatocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded that histomorphologic changes associated with D-tagatose were restricted hepatocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the result of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet. Copyright 1999 Academic Press.

Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

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Segal, L; Penman, M G; Piriou, Y

2018-01-01

The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

Subchronic and Genetic Safety Assessment of a New Medicinal Dendrobium Species: Dendrobium Taiseed Tosnobile in Rats

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Li-Chan Yang

2018-01-01

Full Text Available Dendrobium Taiseed Tosnobile is a new species of herba dendrobii (Shi-Hu that was developed by crossbreeding D. tosaense and D. nobile. Its pharmacological activity and active component have been reported, but its subchronic toxicity and genetic safety have not yet been investigated. This study assessed the 90-day oral toxicity and genetic safety of the aqueous extracts of D. Taiseed Tosnobile (DTTE in male and female Sprague-Dawley (SD rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. DTTE was given orally to rats at 800, 1600, or 2400 mg/kg for 90 consecutive days, and distilled water was used for the control group. Genotoxicity studies were performed using a bacterial reverse mutation assay and in vivo mammalian cell micronucleus test in ICR mice and analyzed using flow cytometry. Throughout the study period, no abnormal changes were observed in clinical signs and body weight or on ophthalmological examinations. Additionally, no significant differences were found in urinalysis, hematology, and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. Based on results, the no-observed-adverse-effect level of DTTE is greater than 2400 mg/kg in SD rats.

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol.

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Toyoda, Takeshi; Cho, Young-Man; Akagi, Jun-Ichi; Mizuta, Yasuko; Matsushita, Kohei; Nishikawa, Akiyoshi; Imaida, Katsumi; Ogawa, Kumiko

2017-01-01

3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.

Subchronic inhalation toxicity of gold nanoparticles

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Chung Yong

2011-05-01

Full Text Available Abstract Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males and 145 g (females, were divided into 4 groups (10 rats in each group: fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3, middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3, and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3. The animals were exposed to gold nanoparticles (average diameter 4-5 nm for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH, and total protein were also monitored in a cellular bronchoalveolar lavage (BAL fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue

Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats

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Kjetil Berge

2015-01-01

Full Text Available The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w. There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL for the conditions of this study was considered to be 9.67% krill powder.

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

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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.

Safety evaluation of genetically modified DAS-40278-9 maize in a subchronic rodent feeding study.

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Zou, Shiying; Lang, Tianqi; Liu, Xu; Huang, Kunlun; He, Xiaoyun

2018-07-01

Genetically modified (GM) maize, DAS-40278-9, expresses the aryloxyalkanoate dioxygenase-1 (AAD-1) protein, which confers tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) and aryloxyphenoxypropionate (AOPP) herbicides. The aad-1 gene, which expresses the AAD-1 protein, was derived from Gram-negative soil bacterium, Sphingobium herbicidovorans. A 90-day sub-chronic toxicity study was conducted on rats as a component of the safety evaluation of DAS-40278-9 maize. Rats were given formulated diets containing maize grain from DAS-40278-9 or a non-GM near isogenic control comparator at an incorporation rate of 12.5%, 25%, or 50% (w/w), respectively for 90 days. In addition, another group of rats was fed a basic rodent diet. Animals were evaluated by cage-side and hand-held detailed clinical observations, ophthalmic examinations, body weights/body weight gains, feed consumption, hematology, serum chemistry, selected organ weights, and gross and histopathological examinations. Under the condition of this study, DAS-40278-9 maize did not cause any treatment-related effects in rats compared with rats fed diets containing non-GM maize. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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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

Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

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Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

2016-08-01

The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II.

Diuron exposure induces systemic and organ-specific toxicity following acute and sub-chronic exposure in male Wistar rats.

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Domingues, Alexandre; Barbisan, Luis Fernando; Martins, Priscila Raquel; Spinardi-Barbisan, Ana Lúcia Tozzi

2011-05-01

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substitute urea herbicide widely used on agricultural crops with potential mutagenic, teratogenic, reproductive and carcinogenic effects. Nonetheless, its toxic potential on the immune system needs a detailed assessment. Thus, in order to evaluate the adverse effect of this herbicide on lymphohematopoietic organs and macrophage activity, male Wistar rats were orally treated with Diuron at 125, 1250 and 2500 ppm for 14, 28 or 90 days. General signs of toxicity were observed in Diuron-treated groups (1250 and 2500 ppm), including reduced food intake and body weight gain, as well as higher relative weights for spleen, kidneys and liver (28 and 90-day toxicity studies) and elevated serum levels of ALT, albumin, total protein, creatinine and urea (28-day toxicity study). Diuron exposure caused a severe depletion of splenic white pulp compartments and cellularity, followed by a decreased number of CD4(+) T lymphocytes, increased extramedullary hematopoiesis and deposition of hemosiderin in red pulp. Despite alteration in macrophage spreading, the macrophagic activity was not significantly affected by the herbicide. Under these experimental conditions, the results suggest that Diuron exerts systemic and target-organ toxicity, mainly at higher concentration. Copyright © 2011 Elsevier B.V. All rights reserved.

Sub-Chronic Toxicity of the Hydroethanolic Leaf Extract of Telfairia occidentalis Hook. f. (Cucurbitaceae in Male Rats

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Abidemi J. Akindele

2018-01-01

Full Text Available Background: Due to its nutritional and medicinal values, the leaf of Telfairia occidentalis Hook f. (Cucurbitaceae is consumed in different parts of Nigeria. Acute and sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis were investigated in this study. Methods: Sixty-four male rats were randomized into four different groups of 16 animals each and were separately administered 80, 400 and 2000 mg/kg T. occidentalis orally (p.o. for 60 days. Animals were sacrificed and blood samples were collected for hematological and biochemical analyses. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: A significant (p < 0.05 reduction in weight of the testes, compared to the control group, was observed in the group treated with 2000 mg/kg extract. No significant change was observed in the weight of other vital organs relative to the control group. There were significant (p < 0.01 increases in sperm motility and count in the group administered 80 mg/kg extract and significant (p < 0.001 reductions in both parameters at 2000 mg/kg. There were significant increases in the levels of hemoglobin and packed cell volume at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, significant reductions in aspartate aminotransferase and alanine aminotransferase levels at doses of 400 and 2000 mg/kg relative to control were observed. Compared to control, the extract significantly reduced (p < 0.05 the level of total cholesterol (400 mg/kg and caused a significant increase in the level of high-density lipoprotein (80, 400 and 2000 mg/kg. Significant (p < 0.05 increase in the level of malondialdehyde, decrease in superoxide dismutase level and histopathological abnormalities were observed in the testes at 2000 mg/kg. Upon cessation of treatment with T. occidentalis for 30 days, the observed effects were reversed. Conclusions: The findings showed that the hydroethanolic

Toxicity study about a medicinal plant Casearia sylvestris: A contribution to the Brazilian Unified Health System (SUS).

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Ameni, A Z; Latorre, O A; Torres, L M B; Górniak, S L

2015-12-04

Casearia sylvestris S.w (Salicaceae) is catalogued by the Brazilian Unified Health System as a plant of interest for the Brazilian population with the purpose of treating inflammatory disorders, such as pain and gastrointestinal disorders based on the folk use and some literature about efficacy; however, no toxicological studies concerned the safety of extract fluid of this plant have been reported. The present study was carried out to evaluate the acute and subchronic toxicity of the hydroethanolic extract fluid (FE) obtained from leaves of C. sylvestris in Wistar rats. In the acute toxicity test three female Wistar rats were treated with a single dose of FE (2000 mg/kg) administered by oral gavage and observed for 14 days in order to identify signs of toxicity or death. In subchronic toxicity study animals received, by daily gavage three doses 60, 120 and 240 mg/kg of the FE of the plant for 28 and 90 days. The animals were observed daily for clinical signs and mortality. Body weight and food consumption were measured weekly and at the end of treatment were analysed hematological, biochemical and histopathological parameters. Also was analysed the cellularity of bone marrow and spleen. Moreover, phytochemical analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI was carried out to qualify the constituents of the extract. The results of acute study indicated that the LD50 is higher than 2000 mg/kg and at 28 and 90 day oral toxicity showed that there were no toxic effects detected in any of the parameters evaluated: body weight and relative organ weight, general behavioral changes, haematological and biochemical parameters and histopathological examination. The analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI identified the flavonoids rutin, quercetin and luteolin and also chlorogenic on the extract. Based on this study the hydroethanolic fluid extract of C. sylvestris could be safe even when used over a long period for therapeutic uses proposed by the Brazilian Unified Health

Assessment of the Toxicity of Sub-chronic Low and High Doses of the Bio-insecticide Spinosad on the Liver, Kidney and the Cerebellum in Male Albino Mice

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Sabry A El-Naggar

2017-06-01

Full Text Available ABSTRACT Spinosad (SPD is a highly selective insect control product. However, it was reported that SPD has toxicity toward other non-target organisms. This study was conducted to address the toxic effect of two sub-chronic low and high doses; 35 and 350 mg/kg SPD on some biochemical, histological and immunohistochemical parameters of the liver, kidney and cerebellum. Thirty-six male Swiss mice were divided into three groups of 12 mice each; first group (G1 served as a control, second group (G2 received a low sub-chronic dose of SPD that is equal to 35 mg/kg, and third group (G3 received a high sub-chronic dose of SPD that is equal to 350 mg/kg. The results showed that mice which were received 350 mg/kg SPD showed a significant decrease in the body weight and a significant increase in their relative kidney and spleen weights. They also showed a significant increase in alanine aminotransferase (ALT, triglycerides and urea levels. Histopathological examination showed cytoplasmic degeneration and cell necrosis in the liver and kidney. Immunohistochemical examination showed that cerebellum illustrated several neurodegenerative changes and a down-regulation of synaptophysin-Syp. In conclusion, exposure to a high dose of SPD that is equal to 350 mg/kg could cause a marked toxicity on the liver, kidney and cerebellum in male albino mice.

Acute and sub-chronic toxicity evaluations of aqueous extract from stem bark of Grewia mollis (Malvaceae in rats

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Pongri Adarki

2017-09-01

Full Text Available Introduction: Different parts of Grewia mollis Juss. (Malvaceae are commonly used in folk medicine to treat several ailments, including diarrhea, ulcers, rickets, cough and fever. Although several studies have proved its therapeutic effectiveness, there are very few toxicological studies on the plant. Objectives: This study was carried out to evaluate the acute and sub-chronic toxicity of the aqueous extract of G. mollis stem bark (GM in animals. Methods: In the acute study, rats were orally administrated with GM at doses of 150, 300, 600, 1200, 2400, 4800 and 9600 mg/kg to determine the oral medial lethal dose (LD50. In the chronic study, rats received three doses of GM (150, 300 and 600 mg/kg for 28 days. After the treatments, food intake, body weights, biochemical, hematological and histopathological parameters were analyzed. Results: The LD50 was estimated to be >9600 mg/kg. No significant alterations in the animal’s body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys, lungs, heart and spleen were observed. Conclusions: The results of this study provided evidence that oral administration of GM at dose of 600 mg/kg is relatively safe in rats and may not exert severe toxic effects.

Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

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Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

2003-01-01

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 μg/m 3 . At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 μg/m 3 , but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 μg/m 3 exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate

Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure.

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Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

2003-09-15

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.

Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures.

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Pauluhn, Jürgen

2010-01-01

Wistar rats were nose-only exposed to multiwalled carbon nanotubes (MWCNT, Baytubes) in a subchronic 13-week inhalation study. The focus of study was on respiratory tract and systemic toxicity, including analysis of MWCNT biokinetics in the lungs and lung-associated lymph nodes (LALNs). The time course and concentration dependence of pulmonary effects were examined by bronchoalveolar lavage (BAL) and histopathology up to 6 months postexposure. Particular emphasis was directed to the comparative characterization of MWCNT structures prior to and after micronization and dry powder dispersion into inhalation chambers. These determinations were complemented by additional analyses in digested BAL cells. Animals were exposed on 6 h/day, 5 days per week for 13 consecutive weeks to 0, 0.1, 0.4, 1.5, and 6 mg/m(3). The subchronic exposure to respirable solid aerosols of MWCNT was tolerated without effects suggestive of systemic toxicity. Kinetic analyses demonstrated a markedly delayed clearance of MWCNT from lungs at overload conditions. Translocation into LALNs occurred at 1.5 and 6 mg/m(3) and required at least 13 weeks of study to become detectable. At these exposure levels, the lung and LALN weights were significantly increased. Sustained elevations in BAL polymorphonuclear neutrophils and soluble collagen occurred at these concentrations with borderline effects at 0.4 mg/m(3). Histopathology revealed principal exposure-related lesions at 0.4 mg/m(3) and above in the upper respiratory tract (goblet cell hyper- and/or metaplasia, eosinophilic globules, and focal turbinate remodeling) and the lower respiratory tract (inflammatory changes in the bronchioloalveolar region and increased interstitial collagen staining). Granulomatous changes and a time-dependent increase of a bronchioloalveolar hyperplasia occurred at 6 mg/m(3). All end points examined were unremarkable at 0.1 mg/m(3) (no-observed-adverse-effect-level). In summary, this study demonstrates that the induced

A sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract of Paracoccus carotinifaciens in rats

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Toyohisa Katsumata

2014-01-01

Full Text Available Astaxanthin is believed to be beneficial to human health because it possesses strong antioxidant properties. A natural astaxanthin-rich carotenoid extract (ARE was produced by a well-controlled fermentation of a natural bacteria Paracoccus carotinifaciens, followed by the extraction and enrichment of the final product comprising mixture of carotenoids that is predominantly astaxanthin. The aim of this study was to evaluate the sub-chronic toxicity of the ARE using 6 week old Sprague-Dawley SPF rats [Crl:CD(SD]. The test article was suspended in olive oil and administered daily to the rats by oral gavage for 13 weeks at doses of 0 (olive oil, 250, 500 or 1000 mg/kg/day. Each group consisted of 10 animals of each sex. No deaths occurred and no treatment-related changes were observed in the detailed clinical observations, manipulative tests, grip strength, motor activity, body weights, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology. Dark-red feces were observed throughout the administration period in all treated groups due to excretion of the colored test article. Based on these results, it was concluded that the no observed adverse effect level (NOAEL for ARE was at least 1000 mg/kg/day for male and female rats, respectively.

Safety Assessment of Food and Feed from GM Crops in Europe: Evaluating EFSA's Alternative Framework for the Rat 90-day Feeding Study.

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Hong, Bonnie; Du, Yingzhou; Mukerji, Pushkor; Roper, Jason M; Appenzeller, Laura M

2017-07-12

Regulatory-compliant rodent subchronic feeding studies are compulsory regardless of a hypothesis to test, according to recent EU legislation for the safety assessment of whole food/feed produced from genetically modified (GM) crops containing a single genetic transformation event (European Union Commission Implementing Regulation No. 503/2013). The Implementing Regulation refers to guidelines set forth by the European Food Safety Authority (EFSA) for the design, conduct, and analysis of rodent subchronic feeding studies. The set of EFSA recommendations was rigorously applied to a 90-day feeding study in Sprague-Dawley rats. After study completion, the appropriateness and applicability of these recommendations were assessed using a battery of statistical analysis approaches including both retrospective and prospective statistical power analyses as well as variance-covariance decomposition. In the interest of animal welfare considerations, alternative experimental designs were investigated and evaluated in the context of informing the health risk assessment of food/feed from GM crops.

Effects of subchronic oral toxic metal exposure on the intestinal microbiota of mice

Institute of Scientific and Technical Information of China (English)

Qixiao Zhai; Tianqi Li; Leilei Yu; Yue Xiao; Saisai Feng; Jiangping Wu; Jianxin Zhao; Hao Zhang; Wei Chen

2017-01-01

Oral exposure to toxic metals such as cadmium （Cd),lead (Pb),copper (Cu) and aluminum （Al) can induce various adverse health effects in humans and animals.However,the effects of these metals on the gut microbiota have received limited attention.The present study demonstrated that long-term toxic metal exposure altered the intestinal microbiota of mice in a metal-specific and time-dependent manner.Subchronic oral Cu exposure for eight weeks caused a profound decline in gut microbial diversity in mice,whereas no significant changes were observed in groups treated with other metals.Cd exposure significantly increased the relative abundances of organisms from the genera Alistipes and Odoribacter and caused marked decreases in Mollicutes and unclassified Ruminococcaceae.Pb exposure significantly decreased the abundances of eight genera:unclassified and uncultured Ruminococcaceae,unclassified Lachnospiraceae,Ruminiclostridium_9,Rikenellaceae_RC9_gut_group,Oscillibacter,Anaerotruncus and Lachnoclostridium.Cu exposure affected abundances of the genera Alistipes,Bacteroides,Ruminococcaceae_UCG-014,Allobaculum,Mollicutes_RFg_norank,Rikenellaceae_RC9_gut_group,Ruminococcaceae_unclassified and Turicibacter.Al exposure increased the abundance of Odoribacter and decreased that of Anaerotruncus.Exposure to any metal for eight weeks significantly decreased the abundance of Akkermansia.These results provide a new understanding regarding the role of toxic metals in the pathogenesis of intestinal and systemic disorders in the host within the gut microbiota framework.

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

International Nuclear Information System (INIS)

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

1995-01-01

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

Dynamics of microcystins-LR and -RR in the phytoplanktivorous silver carp in a sub-chronic toxicity experiment

International Nuclear Information System (INIS)

Xie Liqiang; Xie Ping; Ozawa, Kazuhiko; Honma, Takamitsu; Yokoyama, Atsushi; Park, Ho-Dong

2004-01-01

A sub-chronic toxicity experiment was conducted to examine tissue distribution and depuration of two microcystins (microcystin-LR and microcystin -RR) in the phytoplanktivorous filter-feeding silver carp during a course of 80 days. Two large tanks (A, B) were used, and in Tank A, the fish were fed naturally with fresh Microcystis viridis cells (collected from a eutrophic pond) throughout the experiment, while in Tank B, the food of the fish were M. viridis cells for the first 40 days and then changed to artificial carp feed. High Performance Liquid Chromatography (HPLC) was used to measure MC-LR and MC-RR in the M. viridis cells, the seston, and the intestine, blood, liver and muscle tissue of silver carp at an interval of 20 days. MC-RR and MC-LR in the collected Microcystis cells varied between 268-580 and 110-292 μg g -1 DW, respectively. In Tank A, MC-RR and MC-LR varied between 41.5-99.5 and 6.9-15.8 μg g -1 DW in the seston, respectively. The maximum MC-RR in the blood, liver and muscle of the fish was 49.7, 17.8 and 1.77 μg g -1 DW, respectively. No MC-LR was detectable in the muscle and blood samples of the silver carp in spite of the abundant presence of this toxin in the intestines (for the liver, there was only one case when a relatively minor quantity was detected). These findings contrast with previous experimental results on rainbow trout. Perhaps silver carp has a mechanism to degrade MC-LR actively and to inhibit MC-LR transportation across the intestines. The depuration of MC-RR concentrations occurred slowly than uptakes in blood, liver and muscle, and the depuration rate was in the order of blood>liver>muscle. The grazing ability of silver carp on toxic cyanobacteria suggests an applicability of using phytoplanktivorous fish to counteract cyanotoxin contamination in eutrophic waters. - Silver carp are tolerant of cyanobacterial toxins, and might be used to control toxic algal blooms in highly eutrophic lakes

A 90-day subchronic feeding study of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

Science.gov (United States)

Song, Huan; He, Xiaoyun; Zou, Shiying; Zhang, Teng; Luo, Yunbo; Huang, Kunlun; Zhu, Zhen; Xu, Wentao

2015-04-01

Bacillus thuringiensis (Bt) transgenic rice line (mfb-MH86) expressing a synthetic cry1Ab gene can be protected against feeding damage from Lepidopteran insects, including Sesamia inferens, Chilo suppressalis, Tryporyza incertulas and Cnaphalocrocis medinalis. Rice flour from mfb-MH86 and its near-isogenic control MH86 was separately formulated into rodent diets at concentrations of 17.5, 35 and 70 % (w/w) for a 90-day feeding test with rats, and all of the diets were nutritionally balanced. In this study, the responses of rats fed diets containing mfb-MH86 were compared to those of rats fed flour from MH86. Overall health, body weight and food consumption were comparable between groups fed diets containing mfb-MH86 and MH86. Blood samples were collected prior to sacrifice and a few significant differences (p < 0.05) were observed in haematological and biochemical parameters between rats fed genetically modified (GM) and non-GM diets. However, the values of these parameters were within the normal ranges of values for rats of this age and sex, thus not considered treatment related. In addition, upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. In conclusion, these results demonstrated that no toxic effect was observed in the conditions of the experiment, based on the different parameters assessed. GM rice mfb-MH86 is as safe and nutritious as non-GM rice.

A 90-day repeated-dose toxicity study of dietary alpha linolenic acid-enriched diacylglycerol oil in rats.

Science.gov (United States)

Bushita, Hiroto; Ito, Yuichi; Saito, Tetsuji; Nukada, Yuko; Ikeda, Naohiro; Nakagiri, Hideaki; Saito, Kazutoshi; Morita, Osamu

2018-05-31

Diets supplemented with alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil-which mainly consists of oleic and linolenic, linoleic acids-have potential health benefits in terms of preventing or managing obesity. Although safety of DAG oil has been extensively investigated, toxicity of ALA-DAG oil has not been well understood. Hence, the present study was conducted to clarify the potential adverse effects, if any, of ALA-DAG oil in rats (10/sex/group) fed diets containing 1.375%, 2.75%, or 5.5% ALA-DAG oil for 90 days. Compared to control rats fed rapeseed oil or ALA-triacylglycerol oil (flaxseed oil), rats receiving ALA-DAG oil did not reveal any toxicologically significant treatment-related changes as evaluated by clinical signs, functional observational battery, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, organ weight, necropsy and histopathology. The no observed adverse effect levels for dietary exposure to ALA-DAG oil for male and female rats were 2916 and 3326 mg/kg body weight/day, respectively, the highest dose tested. The findings from this study suggest that consumption of ALA-DAG oil is unlikely to cause adverse effects. Copyright © 2018. Published by Elsevier Inc.

Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

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Wong Brian A

2005-10-01

Full Text Available Abstract Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is

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,

Acute and subchronic toxicity analysis of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles

Science.gov (United States)

Venkatasubbu, Gopinath Devanand; Ramasamy, S; Gaddam, Pramod Reddy; Kumar, J

2015-01-01

Nanoparticles are widely used for targeted drug delivery applications. Surface modification with appropriate polymer and ligands is carried out to target the drug to the affected area. Toxicity analysis is carried out to evaluate the safety of the surface modified nanoparticles. In this study, paclitaxel attached, folic acid functionalized, polyethylene glycol modified hydroxyapatite and titanium dioxide nanoparticles were used for targeted drug delivery system. The toxicological behavior of the system was studied in vivo in rats and mice. Acute and subchronic studies were carried out. Biochemical, hematological, and histopathological analysis was also done. There were no significant alterations in the biochemical parameters at a low dosage. There was a small change in alkaline phosphatase (ALP) level at a high dosage. The results indicate a safe toxicological profile. PMID:26491315

78 FR 11760 - 3-decen-2-one; Exemption from the Requirement of a Tolerance

Science.gov (United States)

2013-02-20

... in gelatins and puddings, 4.3 ppm in non-alcoholic beverages, and 4.0 ppm in alcoholic beverages..., 47942612, 47942613, and 47942614). The petitioner submitted acute toxicity studies conducted on the... Nos. 47942617 and 48422301). A subchronic 90-day oral toxicity study on the technical grade material...

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity.

Science.gov (United States)

Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

2013-10-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae

Directory of Open Access Journals (Sweden)

Mildred García-González

2006-12-01

Full Text Available We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1 000 and 2 000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week. Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1 000 mg/kg dose but not for the higher 2 000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found. Rev. Biol. Trop. 54 (4: 1323-1326. Epub 2006 Dec. 15Se evaluaron los efectos del estracto acuoso de las hojas de Petiveria alliacea, en la toxicidad aguda y toxicidad subcrónica, hematocritos, niveles de glucosa en la sangre y motilidad intestinal del ratón macho albino NGP, con un peso promedio de 20 a 25g. En todos los casos los tratamientos fueron dosis de 1 000 y 2 000 mg/kg de peso del animal y un tratamiento control con 0.5 ml de agua destilada, usando 10 animales por tratamiento y administrado oralmente cinco días por semana. Los períodos experimentales fueron de 18 y 70 días para toxicidad aguda y toxicidad subcrónica, respectivamente. No se observaron signos de mortalidad ni de toxidad en ambas pruebas. Con la dosis de 1 000 mg/kg hubo un leve pero significativo incremento en los niveles de glucosa durante las primeras tres semanas, pero no con la dosis más alta de 2 000 mg/kg. Después de administrar las dosis luego de un período de hambre de seis horas, no se encontraron diferencias significativas en la motilidad intestinal

A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

Directory of Open Access Journals (Sweden)

Xueming Tang

Full Text Available In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

Science.gov (United States)

Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

2012-01-01

In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

Use of hydra for chronic toxicity assessment of waters intended for human consumption

International Nuclear Information System (INIS)

Arkhipchuk, Victor V.; Blaise, Christian; Malinovskaya, Maria V.

2006-01-01

Methods developed with the cnidarian, Hydra attenuata (Pallas), have proven effective for screening acute toxicity in aqueous samples, whereas their use in revealing (sub)chronic toxic effects have had mitigated success. We therefore sought to explore manifestations of hydra mortality and abnormal morphological changes, as well as the reproductive capacity of hydras to further enhance the bioassay sensitivity and to assess (sub)chronic toxicity. These parameters were recorded following the onset of experiments after 8, 12 and 19-21 days of hydra exposure. Results obtained with potable waters (30 brands of bottled waters and artesian waters from 9 wells) showed chronic sublethal and lethal effects or reproduction rate inhibition for most samples. The effectiveness of the hydra toxicity test was demonstrated in comparison with other widely used bioassays. Our previous and present investigations suggest that hydra is a reliable and relevant test organism for the assessment of acute and chronic water toxicity. - Hydra is a reliable and relevant test organism for the assessment of acute and chronic toxicity of waters intended for human consumption

Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

OpenAIRE

Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

2013-01-01

Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora ...

Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

Science.gov (United States)

Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

2009-02-01

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

Energy Technology Data Exchange (ETDEWEB)

Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

2013-10-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

International Nuclear Information System (INIS)

Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

2013-01-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

Hematotoxicity and genotoxicity of mercuric chloride following subchronic exposure through drinking water in male rats.

Science.gov (United States)

Boujbiha, Mohamed Ali; Ben Salah, Ghada; Ben Feleh, Abdelraouf; Saoudi, Mongi; Kamoun, Hassen; Bousslema, Ali; Ommezzine, Asma; Said, Khaled; Fakhfakh, Faiza; El Feki, Abdelfattah

2012-07-01

Erythrocytes are a convenient model to understand the subsequent oxidative deterioration of biological macromolecules in metal toxicities. The present study examined the variation of hematoxic and genotoxic parameters following subchronic exposure of mercuric chloride via drinking water and their possible association with oxidative stress. Male rats were exposed to 50 ppm (HG1) and 100 ppm (HG2) of mercuric chloride daily for 90 days. A significant dose-dependent decrease was observed in red blood cell count, hemoglobin, hematocrit, and mean cell hemoglobin concentration in treated groups (HG1 and HG2) compared with controls. A significant dose-dependent increase was observed in lipid peroxidation; therefore, a significant variation was found in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase. Interestingly, mercuric chloride treatment showed a significant dose-dependent increase in frequency of total chromosomal aberration and in percentage of aberrant bone marrow metaphase of treated groups (p mercury treatment may be the major cause for chromosomal aberration as free radicals lead to DNA damage. These data will be useful in screening the antioxidant activities of natural products, which may be specific to the bone marrow tissue.

Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

Science.gov (United States)

Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

2013-01-01

Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

Comparative toxicity of low dose tributyltin chloride on serum, liver, lung and kidney following subchronic exposure.

Science.gov (United States)

Mitra, Sumonto; Gera, Ruchi; Singh, Vikas; Khandelwal, Shashi

2014-02-01

Tributyltin (TBT) pollution is rampant worldwide and is a growing threat due to its bio-accumulative property. Isolated studies of TBT toxicity on different organs are available but consolidated information is greatly lacking. We planned this study to delineate the effect of subchronic (1 month) exposure to low dose TBT-chloride (TBTC) (1 and 5 mg/kg) in male Wistar rats. Total tin concentration was found to be significantly increased in liver, kidney and blood, and marginally in lungs. Organo-somatic indices were seen to be altered with little effect on serum biochemical markers (liver and kidney function, and general parameters). Reactive oxygen species but not lipid peroxidation content was observed to be significantly elevated both in the tissues and serum. TBTC was found to act as a hyperlipidemic agent and it also affected heme biosynthetic pathway. Hematological analysis showed that TBTC exposure resulted in minor alterations in RBC parameters. Histological studies demonstrated marked tissue damage in all the 3 organs. Calcium inhibitors (BAPTA-AM, EGTA) and antioxidants (NAC, C-PC) significantly restored TBTC induced loss in cell viability, under ex-vivo conditions. Antioxidants were evidently more efficient in comparison to the calcium inhibitors, implying major role of oxidative stress pathways in TBTC toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of subchronic administration of nutmeg (Myristica fragrans Houtt) ethanolic extract to hematological parameters in rat

Science.gov (United States)

Bachri, M. S.; Yuliani, S.; Sari, A. K.

2017-11-01

Nutmeg is dried kernel of broadly ovoid seed of Myristica fragrans Houtt. It has been mentioned in ethnomedical literature as aphrodisiac, stomachic, carminative, tonic, and nervous stimulant. In order to establish the safety of nutmeg, the effect of the repeated administration of nutmeg is needed. The study was aimed to determine the toxic effect of subchronic administration of nutmeg ethanolic extract to hematological parameters in rat. A total of 28 male adult Wistar rats divided into 4 groups. Group I as control was given by 0.5% CMC-suspension, group II, III, and IV were given by 50, 100, and 200 mg/kg bw, respectively, of nutmeg ethanolic extract. The treatments were administered daily for 31 days. On day 31 bloods were taken from orbital sinus. The hematological parameter consisted of the numbers of erythrocyte and leukocyte as well as hemoglobin and total protein levels were measured. The data were statistically analyzed by one way Anova followed by LSD test. All of observed hematological parameters in rats showed that there were no significant difference between the nutmeg ethanolic extract treated groups and control group. The result indicated that the subchronic administration of 50, 100, and 200 mg/kg bw of nutmeg ethanolic extract did not cause the change of hematological parameters in rat.

90-Day Cycle Handbook

Science.gov (United States)

Park, Sandra; Takahashi, Sola

2013-01-01

90-Day Cycles are a disciplined and structured form of inquiry designed to produce and test knowledge syntheses, prototyped processes, or products in support of improvement work. With any type of activity, organizations inevitably encounter roadblocks to improving performance and outcomes. These barriers might include intractable problems at…

Evaluation of the safety of a genetically modified DAS-444Ø6-6 soybean meal and hulls in a 90-day dietary toxicity study in rats.

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Papineni, Sabitha; Murray, Jennifer A; Ricardo, Ekmay; Dunville, Christina M; Sura, Radha Krishna; Thomas, Johnson

2017-11-01

A 90-day sub chronic toxicity study was conducted in rats to evaluate the safety of genetically modified DAS-444Ø6-6 soybeans expressing herbicide tolerant proteins when compared with its conventional comparators (non-transgenic near isoline control soybean and three commercially available non-transgenic line control soybeans). Rats were given diets formulated with either 10% or 20% w/w of soybean meal and 1% or 2% hulls of DAS-444Ø6-6 soybean with an equivalent amount of hulls from an isoline non-transgenic control soybean for at least 90 days. In addition, three separate 20% w/w non-transgenic commercially available soybean varieties were also given to groups of rats to serve as reference controls. Animals were evaluated by cage-side and hand-held detailed clinical observations, ophthalmic examinations, body weights/body weight gains, feed consumption, hematology, prothrombin time, urinalysis, clinical chemistry, selected organ weights, and gross and histopathologic examinations. Under the conditions of this study, the genetically modified DAS-444Ø6-6 diets did not cause any treatment-related effects in rats following 90 days of dietary administration as compared with rats fed diets with soybean of isoline control or commercial reference controls and are considered equivalent to the diets prepared from conventional comparators. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

In vivo toxicity of the culturable marine cyanobacterium Geitlerinema pseudacutissimum CNP 1019 extract on male Swiss albino mice (Mus musculus).

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Maruthanayagam, Veerabadhran; Nagarajan, Manivel; Sundararaman, Muthuraman

2014-01-01

In this study, we investigated the in vivo toxicity of Geitlerinema pseudacutissimum CNP 1019 organic extract in a murine host. A single intraperitoneal injection of 1 g extract kg⁻¹ body weight (BW) did not exhibit mortality, whereas 3 g extract kg⁻¹ BW (approximate lethal dose) resulted in mortality within 5 days. To perform subchronic exposure toxicity analyses (i.e., daily exposure for a total of 14 days), a maximum concentration of ≤1 g extract kg⁻¹ BW was used. Subchronic toxicity studies in the treated mice, showed fluctuations of feed intake, loss of body weight, increase in specific activity of serum lactate dehydrogenase, alanine aminotransferase and decrease in whole serum protein concentration. LDH isoenzyme expression was found, and levels of the various isoforms were decreased as a result of the treatment. Histopathology studies in liver, kidney, and spleen isolated from the treated mice showed the presence of necrotic debris, hemorrhage, and micronuclei revealing the toxicity of the extract. The dose-dependent alterations in biochemical parameters in conjunction with the histological lesions noted in the animals treated with the prepared extract illustrate the likely potential toxicity to mammals from any encounters with the studied cyanobacterium.

Genotoxicity and subchronic toxicity evaluation of dried Euglena gracilis ATCC PTA-123017.

Science.gov (United States)

Simon, Ryan R; Vo, Trung D; Levine, Robert

2016-10-01

Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Spirulina in mitigating hemato-toxicity in Swiss albino mice exposed to aluminum and aluminum fluoride.

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Sharma, Shweta; Sharma, K P; Sharma, Subhasini

2016-12-01

Aluminum is ingested through foods, water, air, and even drugs. Its intake is potentiated further through foods and tea prepared in aluminum utensils and Al salt added in the drinking water for removal of suspended impurities and also fluoride in the affected areas. The ameliorating role of a blue green alga Spirulina is well documented to various pollutants in the animal models. We, therefore, examined its protective role (230 mg/kg body weight) on the hematology of male Swiss albino mice treated with aluminum (sub-acute = 78.4 mg/kg body weight for 7 days, sub-chronic = 7.8 mg/kg body weight for 90 days) and aluminum fluoride (sub-acute = 103 mg/kg body weight, sub-chronic = 21 mg/kg body weight), along with their recovery after 90 days of sub-chronic exposure. This study revealed significant reduction in the values of RBC (5-18 %), Hb (15-17 %), PCV (8-14 %), and platelets (26-36 %), and increase in WBC (54-124 %) in the treated mice, particularly after sub-acute exposure. Aluminum fluoride was comparatively more toxic than aluminum. Further, Spirulina supplement not only alleviated toxicity of test chemicals in Swiss albino mice but also led to their better recovery after withdrawal.

Toxicity assessment due to sub-chronic exposure to individual and mixtures of four toxic heavy metals

Energy Technology Data Exchange (ETDEWEB)

Cobbina, Samuel J.; Chen, Yao [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Zhou, Zhaoxiang; Wu, Xueshan; Zhao, Ting [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China); Zhang, Zhen [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Feng, Weiwei; Wang, Wei [School of Food and Biological Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Li, Qian [School of Pharmacy, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Wu, Xiangyang, E-mail: wuxy@ujs.edu.cn [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Yang, Liuqing, E-mail: yangliuqing@ujs.edu.cn [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China)

2015-08-30

Highlights: • Low dose single and mixtures of toxic metals had adverse effect on mice. • Metal mixtures exhibited higher toxicities compared to individual metals. • Mixtures of low dose Pb + Hg + Cd induced neuronal degeneration in brain of mice. • Exposure to Pb + Hg + As + Cd showed renal tubular necrosis in kidney. - Abstract: Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on toxicity of low dose mixtures. In this study, lead (Pb) (0.01 mg/L), mercury (Hg) (0.001 mg/L), cadmium (Cd) (0.005 mg/L) and arsenic (As) (0.01 mg/L) were administered individually and as mixtures to 10 groups of 40 three-week old mice (20 males and 20 females), for 120 days. The study established that low dose exposures induced toxicity to the brain, liver, and kidney of mice. Metal mixtures showed higher toxicities compared to individual metals, as exposure to low dose Pb + Hg + Cd reduced brain weight and induced structural lesions, such as neuronal degeneration in 30-days. Pb + Hg + Cd and Pb + Hg + As + Cd exposure induced hepatocellular injury to mice evidenced by decreased antioxidant activities with marginal increases in MDA. These were accentuated by increases in ALT, AST and ALP. Interactions in metal mixtures were basically synergistic in nature and exposure to Pb + Hg + As + Cd induced renal tubular necrosis in kidneys of mice. This study underlines the importance of elucidating the toxicity of low dose metal mixtures so as to protect public health.

Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats.

Science.gov (United States)

Whittaker, Margaret H; Wang, Gensheng; Chen, Xue-Qing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A

2011-07-15

Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures. Copyright © 2011. Published by Elsevier Inc.

Subchronic toxicity studies of t-butyl alcohol in rats and mice.

Science.gov (United States)

Lindamood, C; Farnell, D R; Giles, H D; Prejean, J D; Collins, J J; Takahashi, K; Maronpot, R R

1992-07-01

The purpose of this study was to evaluate the toxicity of t-butyl alcohol, an important commodity chemical, an additive to unleaded gasoline, and a contaminant of drinking water. Ninety-day toxicity studies were conducted in B6C3F1 mice and Fischer 344 (F344) rats of both sexes using dosed water. Dose levels of t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v). Lethality was observed at the 4% level of both sexes and species. Weight-gain depression was present in all dose levels of male rats; 4% female rats; 1, 2, and 4% male mice; and 2 and 4% female mice. Water consumption was increased at lower dose levels in male rats and decreased in the higher dose levels of both sexes of rats and female mice. Clinical signs in rats were ataxia in both sexes and hypoactivity in males. Clinical signs in mice were ataxia, abnormal posture, and hypoactivity. In rats, urine volumes were reduced, in association with crystalluria. Gross lesions at necropsy were urinary tract calculi, renal pelvic and ureteral dilatation, and thickening of the urinary bladder mucosa. Microscopic lesions were hyperplasia of transitional epithelia and inflammation of the urinary bladder. In male rats treated with t-butyl alcohol, microscopic renal changes were suggestive of alpha-2 mu-globulin nephropathy. No-effect levels for the urinary tract lesions were 1% in male rats and mice (803.7 mg/kg/day for the male rats and 1565.8 mg/kg/day for the male mice) and 2% in female rats and mice (1451.5 mg/kg/day for the female rats and 4362.9 mg/kg/day for the female mice). The results indicate that in rodents the urinary tract is the target organ for t-butyl alcohol toxicity, and males are more sensitive to t-butyl alcohol toxicity than females.

Crocin Restores Hypotensive Effect of Subchronic Administration of Diazinon in Rats

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Marjan Razavi

2013-01-01

Full Text Available Objective(s: In this study, the effects of crocin against subchronic toxicity of diazinon (DZN on systolic blood pressure (SBP and heart rate (HR were evaluated in rats. Materials and Methods: Rats were equally divided into 7 groups; control (corn oil, DZN (15 mg/kg, crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN, vitamin E (200 IU/kg plus DZN and crocin (50 mg/kg treated groups.  Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week and crocin (once a day were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method, malondealdehyde (MDA levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method; SBP and HR (tail cuff method were evaluated at the end of 4th week. Results: A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001. Crocin did not show any effects on cholinesterase activity. DZN increased MDA levels in aortic tissue (P< 0.001 in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01 and increased HR (P< 0.001 in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR. Conclusion: This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats.

A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats.

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Jeena, Kottarapat; Liju, Vijayastelter B; Kuttan, Ramadasan

2011-12-01

Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

Subacute and subchronic oral toxicity of p-chlorotoluene in the rat

Energy Technology Data Exchange (ETDEWEB)

Terrill, J.B.; Robinson, M.; Wolfe, G.W.; Billups, L.H.

1990-01-01

P-Chlorotoluene was administered by gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats at dose levels of 200, 600 and 1800 mg/kg/day and 50, 200 and 800 mg/kg/day, respectively. In the 14-day study 8 of 10 animals of each sex in the high-dose group died due to treatment. Other treatment-related signs for these animals included an adverse effect upon body weight, and clinical signs of salivation, tremors and prostration. In the 200 and 600 mg/kg/day groups there were no apparent treatment-related effects. In the 90-day study, 4 of 10 males and 2 of 10 females in the high-dose group died due to treatment. Other signs for this treatment group included an adverse effect upon body weight, and clinical signs of languid behavior, prostration, tremors, sensitive to touch, epistaxis and respiratory distress. Increases in alkaline phosphatase and creatinine (males only), and increases in adrenal (absolute and relative, females), kidney (relative, both sexes) and liver (relative, both sexes) weights were also noted.

Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities.

Science.gov (United States)

Goin, James E; Salem, Riad; Carr, Brian I; Dancey, Janet E; Soulen, Michael C; Geschwind, Jean Francois H; Goin, Kathleen; Van Buskirk, Mark; Thurston, Kenneth

2005-02-01

Intraarterial injection of yttrium 90 microspheres (TheraSpheres) is used in the treatment of hepatocellular carcinoma (HCC). This article presents an analysis of the incidence of liver toxicities (liver-related events) and pretreatment factors associated with liver toxicities after TheraSphere treatment. Eighty-eight TheraSphere-treated patients with low 90-day mortality risk were selected for analysis, with liver toxicities coded with use of standard oncology criteria. Descriptive and inferential statistical methods were applied to estimate the incidence of liver toxicities and to evaluate the influence of liver radiation dose and various pretreatment factors on the risk of their occurrence. Sixty-eight liver toxicities occurred in 37 of the 88 patients (42%). Thirty-two patients (36%) experienced 50 liver toxicities after the first treatment and nine of 23 patients (39%) who received a second treatment experienced 18 liver toxicities. Pretreatment total bilirubin and liver radiation dose were found to be associated with the risk of at least one liver toxicity and with the time to first occurrence of a liver toxicity after first treatment. Pretreatment total bilirubin also was associated with liver toxicities after the second treatment. Most of the toxicities resolved; however, those that did not resolve were attributed to tumor progression or advancing cirrhosis. The risk of liver toxicities in patients with unresectable HCC treated with TheraSpheres increases with increasing pretreatment total bilirubin level and liver radiation dose to a maximum of 150 Gy for a single administration. The toxicities attributed to treatment resolved over time, and none of the patients studied had confirmed radiation-induced liver disease. Consequently, doses as high as 150 Gy on a single administration and as high as 268 Gy on repeated administrations were well tolerated.

30-Day, 90-day and 1-year mortality after emergency colonic surgery

DEFF Research Database (Denmark)

Pedersen, T; Watt, S K; Tolstrup, M-B

2017-01-01

PURPOSE: Emergency surgery is an independent risk factor in colonic surgery resulting in high 30-day mortality. The primary aim of this study was to report 30-day, 90-day and 1-year mortality rates after emergency colonic surgery, and to report factors associated with 30-day, 90-day and 1-year...... mortality. Second, the aim was to report 30-day postoperative complications and their relation to in-hospital mortality. METHODS: All patients undergoing acute colonic surgery in the period from May 2009 to April 2013 at Copenhagen University Hospital Herlev, Denmark, were identified. Perioperative data...... postoperative deaths. CONCLUSION: Mortality and complication rates after emergency colonic surgery are high and associated with patient related risk factors that cannot be modified, but also treatment related outcomes that are modifiable. An increased focus on medical and other preventive measures should...

Past, present and emerging toxicity issues for jet fuel.

Science.gov (United States)

Mattie, David R; Sterner, Teresa R

2011-07-15

The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels. Copyright © 2011 Elsevier Inc. All rights reserved.

Past, present and emerging toxicity issues for jet fuel

International Nuclear Information System (INIS)

Mattie, David R.; Sterner, Teresa R.

2011-01-01

The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

Impact of repeated exposure on toxicity of perchloroethylene in Swiss Webster mice

International Nuclear Information System (INIS)

Philip, Binu K.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M.

2007-01-01

The aim was to study the subchronic toxicity of perchloroethylene (Perc) by measuring injury and repair in liver and kidney in relation to disposition of Perc and its major metabolites. Male SW mice (25-29 g) were given three dose levels of Perc (150, 500, and 1000 mg/kg day) via aqueous gavage for 30 days. Tissue injury was measured during the dosing regimen (0, 1, 7, 14, and 30 days) and over a time course of 24-96 h after the last dose (30 days). Perc produced significant liver injury (ALT) after single day exposure to all three doses. Liver injury was mild to moderate and regressed following repeated exposure for 30 days. Subchronic Perc exposure induced neither kidney injury nor dysfunction during the entire time course as evidenced by normal renal histology and BUN. TCA was the major metabolite detected in blood, liver, and kidney. Traces of DCA were also detected in blood at initial time points after single day exposure. With single day exposure, metabolism of Perc to TCA was saturated with all three doses. AUC/dose ratio for TCA was significantly decreased with a concomitant increase in AUC/dose of Perc levels in liver and kidney after 30 days as compared to 1 day exposures, indicating inhibition of metabolism upon repeated exposure to Perc. Hepatic CYP2E1 expression and activity were unchanged indicating that CYP2E1 is not the critical enzyme inhibited. Hepatic CYP4A expression, measured as a marker of peroxisome proliferation was increased transiently only on day 7 with the high dose, but was unchanged at later time points. Liver tissue repair peaked at 7 days, with all three doses and was sustained after medium and high dose exposure for 14 days. These data indicate that subchronic Perc exposure via aqueous gavage does not induce nephrotoxicity and sustained hepatotoxicity suggesting adaptive hepatic repair mechanisms. Enzymes other than CYP2E1, involved in the metabolism of Perc may play a critical role in the metabolism of Perc upon subchronic exposure

Unplanned readmission within 90 days after pediatric neurosurgery.

Science.gov (United States)

Chotai, Silky; Guidry, Bradley S; Chan, Emily W; Sborov, Katherine D; Gannon, Stephen; Shannon, Chevis; Bonfield, Christopher M; Wellons, John C; Naftel, Robert P

2017-12-01

OBJECTIVE Readmission and return to operating room after surgery are increasingly being used as a proxy for quality of care. Nearly 60% of these readmissions are unplanned, which translates into billions of dollars in health care costs. The authors set out to analyze the incidence of readmission at their center, to define causes of unplanned readmission, and to determine the preoperative and surgical variables associated with readmissions following pediatric neurosurgery. METHODS A total of 536 children who underwent operations for neurosurgical diagnoses between 2012 and 2015 and who were later readmitted were included in the final analysis. Unplanned readmissions were defined to have occurred as a result of complications within 90 days after index surgery. Patient records were retrospectively reviewed to determine the primary diagnosis, surgery indication, and cause of readmission and return to operating room. The cost for index hospitalization, readmission episode, and total cost were derived based on the charges obtained from administrative data. Bivariate and multivariable analyses were conducted. RESULTS Of 536 patients readmitted in total, 17.9% (n = 96) were readmitted within 90 days. Of the overall readmissions, 11.9% (n = 64) were readmitted within 30 days, and 5.97% (n = 32) were readmitted between 31 and 90 days. The median duration between discharge and readmission was 20 days (first quartile [Q1]: 9 days, third quartile [Q3]: 36 days). The most common reason for readmission was shunt related (8.2%, n = 44), followed by wound infection (4.7%, n = 25). In the risk-adjusted multivariable logistic regression model for total 90-day readmission, patients with the following characteristics: younger age (p = 0.001, OR 0.886, 95% CI 0.824-0.952); "other" (nonwhite, nonblack) race (p = 0.024, OR 5.49, 95% CI 1.246-24.2); and those born preterm (p = 0.032, OR 2.1, 95% CI 1.1-4.12) had higher odds of being readmitted within 90 days after discharge. The total

Subchronic toxicity of Nile tilapia with different exposure routes to Microcystis aeruginosa: Histopathology, liver functions, and oxidative stress biomarkers

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H. M. R. Abdel-Latif

2017-08-01

Full Text Available Background: Toxic cyanobacterial blooms (Microcystis aeruginosa contains microcystins [MCs] have been reported to induce clinicopathological alterations as well as different oxidative stress in aquatic biota. Aim: Three-week subchronic exposure experiment was carried out on Nile tilapia, to determine their effects on fish behavior, tissues, liver functions, antioxidant enzymes, and lipid peroxidation. Materials and Methods: Fish were exposed to four main treatments; orally fed diet plus toxic cells of M. aeruginosa (containing 3500 μg/g MC-LR, immersion in 500 μg MC-LR/L, intraperitoneal injection of M. aeruginosa MC-LR with a dose of 0.1 ml of extracted toxin at a dose of 200 μg/kg bwt, and the fourth one served as a control group, then the fish were sacrificed at the end of 3rd week of exposure. Results: The results revealed no recorded mortality with obvious behavioral changes and an enlarged liver with the congested gall bladder. Histopathology demonstrated fragmentation, hyalinization, and necrosis of the subcutaneous musculature marked fatty degeneration, and vacuolation of hepatopancreatic cells with adhesion of the secondary gill lamellae associated with severe leukocytic infiltration. Furthermore, liver functions enzymes (aspartate aminotransferase and alanine aminotransferase, and the activities of glutathione peroxidase, glutathione reductase, lipid peroxidase, and catalase enzymes were significantly increased in all treatments starting from the 2nd week as compared to the control levels. Conclusion: In this context, the study addresses the possible toxicological impacts of toxic M. aeruginosa contain MC-LR to Nile tilapia, and the results investigated that MC-LR is toxic to Nile tilapia in different routes of exposure as well as different doses.

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

Science.gov (United States)

2010-07-01

... displaying each type of lesion. (ii) When applicable, all observed results, qualitative and quantitative... be used throughout the duration of the study and the research sample should be stored under... method during the entire experimental period. (iii) For substances of low toxicity, it is important to...

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

Science.gov (United States)

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

2015-11-01

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

Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison.

Science.gov (United States)

Park, Eun-Jung; Choi, Je; Kim, Jae-Ho; Lee, Byoung-Seok; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun

2016-10-01

Impurity has been suggested as an important factor determining toxicity following exposure to single-walled carbon nanotubes (SWCNTs). In this study, we first compared immunotoxicity based on iron content on day 90 after a single intratracheal instillation of SWCNTs in male and female mice. The inflammatory responses were generally stronger in mice exposed to acid-purified (P)-SWCNTs compared to raw (R)-SWCNTs. In addition, both R- and P-SWCNTs induced Th1-polarized immune responses with apoptotic death of BAL cells and systemically impaired the function of antigen-presenting cells (APC). We also screened reproductive and developmental toxicity by cohabitating male and female mice on day 14 after instillation. Interestingly, the pregnancy rate rapidly decreased following exposure to both types of SWCNTs, especially R-SWCNTs. In addition, we investigated developmental immunotoxicity of the offspring on day 28 after exposure to both types of SWCNTs. Their hematological changes were clearer relative to those of the parents and a significant decrease in the alkaline phosphatase and potassium levels was observed in mice of both sexes exposed to the higher dose of R- and P-SWCNTs. In conclusion, we suggest that SWCNTs may induce Th1-polarized immune responses accompanied by suppression of APC function on day 90 after a single instillation without significant iron content dependance. In addition, the consecutive exposure of SWCNTs to the subsequent generation may exacerbate metabolic and hematological disturbance. Furthermore, our results underscore the need to clarify the reproductive and developmental health effects of SWCNTs.

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

SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

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The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

Mixtures of benzo(a)pyrene, dichlorodiphenyltrichloroethane and tributyltin are more toxic to neotropical fish Rhamdia quelen than isolated exposures.

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Oliveira, Heloísa H P; Liebel, Samuel; Rossi, Stéfani C; Azevedo, Ana C B; Barrera, Ellie A L; Garcia, Juan Ramon Esquivel; Grötzner, Sônia Regina; Neto, Francisco Filipak; Randi, Marco A F; Ribeiro, Ciro A O

2015-12-01

activation of cell defenses after the sub-chronic exposure. TBT increased melanomacrophages counting in the 5-day experiment and the mixtures increased it in the 5 and 15-day experiments. Overall, the majority of the biomarkers pointed to a more toxic effect when these contaminants were combined, leading to unexpected toxicities compared to individual exposure scenarios. These findings are relevant considering environmental exposure conditions, since organisms are often exposed to different combinations of contaminants. Copyright © 2015 Elsevier Inc. All rights reserved.

1997 Toxic Hazards Research Annual Report

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1998-05-01

evaluate the potential for CF 3I to produce reproductive toxicity and to provide additional information on the effect of CF 3I exposure on the...questions raised on the effects of CF 3I exposure following the recently completed acute and subchronic inhalation toxicity studies (Dodd et al., 1997a...individuals from potential toxic consequences resulting from exposure to combustion products of advanced composite materials (ACM), this laboratory has

Peritoneal dialysis technique success during the initial 90 days of therapy.

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Guest, Steven; Hayes, Andrew C; Story, Kenneth; Davis, Ira D

2012-01-01

Comparisons of technique success by peritoneal dialysis (PD) modality have typically excluded the initial 90 days of therapy. We analyzed a database of 51,469 new PD starts from 2004 to 2008 in the United States. The analysis concentrated on the initial 90 days of therapy to determine technique success and the impact of the continuous ambulatory PD (CAPD) and automated PD (APD) modalities. Overall, 13.3% of patients stopped PD within 90 days. Of patients starting directly on APD, 14.3% stopped PD within 90 days. Of patients starting on CAPD, 12.6% stopped PD within 90 days, and 63.4% changed to APD within 90 days. Only 3.3% of the latter patients failed to reach 90 days of therapy. By comparison, technique failure occurred in 28.8% of those initiating with and remaining on CAPD. We conclude that initial training to perform CAPD, with timely transfer to APD within the first 3 months, was associated with the greatest technique success at 90 days. The reasons for that success are unclear, and further research should be directed to determining factors responsible. It is possible that patients trained initially to CAPD but converted to APD have a greater understanding of the total therapy, which improves confidence. Those converted to APD may be more appreciative of the lifestyle benefits of APD, which translates into improved compliance; alternatively, technical factors associated with APD may be responsible. Those technical factors may include improved catheter function in the recumbent position during APD or the reduced infection risk associated with just 2 connect/disconnect procedures in APD compared with 8 in CAPD.

Acute and Subchronic Toxicity Study of Tud-Rak-Ka-Sai-Puu Recipe ...

African Journals Online (AJOL)

No defects of animal behavior were observed in the test groups. Both test and control groups (on the 90th day) as well as the satellite group (on the 118th day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry, and microanatomy.

Consequences of subchronic exposure to ethanolic extract from fruits and leaves of Schinus molle var. areira L. in mice.

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Bras, Cristina; Domínguez, Sergio; Codón, Stella; Minetti, Alejandra; Ferrero, Adriana

2010-10-28

Several extracts of Schinus molle var. areira L. plant proved to be useful for the treatment of different pathologies and for the control of insect pest. Due to these potential uses, it is necessary to study their safety. In this work, we evaluated the effects of subchronic exposure to ethanolic extracts from leaves and fruits of Schinus molle var. areira in mice. The plant extract was added to the diet at 1 g/kg body weight/day for 90 days. At the end of the exposure, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, several biochemical and histopathological studies were realized. The exposure to extract from leaves produced an increase in the number of rearings in the open field and of urine pools in the functional observational battery. On the other hand, the exposure to extract from fruits produced an increase in the neutrophil count and a decrease in the lymphocyte count and in the total cholesterol levels. None of the exposures affected the different organs evaluated. Our results suggest that subchronic exposure to ethanolic extracts from leaves and fruits of Schinus molle var. areira should be potentially useful in the treatment of lipid pathologies and safe to use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

In Vivo and In Vitro Toxicity Evaluation of Polyprenols Extracted from Ginkgo biloba L. Leaves

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Cheng-Zhang Wang

2015-12-01

Full Text Available Polyprenols of Ginkgo biloba L. leaves (GBP are a new type of lipid with 14–24 isoprenyl units, which in humans have strong bioactivity like the dolichols. A large amount of work showed that GBP had good antibacterial activity and powerful protective effects against acute hepatic injury induced by carbon tetrachloride and alcohol, as well as antitumor activity, but the safety of GBP was not considered. The current study was designed to evaluate the toxicity of these polyprenols. Acute toxicity in mice was observed for 14 days after GBP oral dosing with 5, 7.5, 10, 15 and 21.5 g/kg body weight (b. wt. Further, an Ames toxicity assessment was carried out by plate incorporation assay on spontaneous revertant colonies of TA97, TA98, TA100 and TA102, with GBP doses designed as 8, 40, 200, 1000 and 5000 μg/dish, and subchronic toxicity was evaluated in rats for 91 days at GBP doses of 500, 1000 and 2000 mg/kg b. wt./day. The weight, food intake, hematological and biochemical indexes, the ratio of viscera/body weight, and histopathological examinations of tissue slices of organs were all investigated. The results showed that no animal behavior and appearance changes and mortality were seen during the observation period with 21.5 g/kg GBP dose in the acute toxicity test. Also, no mutagenicity effects were produced by GBP (mutation rate < 2 on the four standard Salmonella strains (p > 0.05 in the Ames toxicity test. Furthermore, the no observed adverse effect level (NOAEL of GBP was 2000 mg/kg for 91 days feeding of rats in the subchronic toxicity tests. Results also showed the hematological and biochemical indexes as well as histopathological examination changed within a small range, and all clinical observation indexes were normal. No other distinct impacts on cumulative growth of body weight, food intake and food utilization rate were discovered with GBP. No significant difference was discovered for the rats’ organ weight and the ratio of viscera

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

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Miller, Desinia B.; Snow, Samantha J.; Henriquez, Andres; Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L.; Kodavanti, Urmila P.

2016-01-01

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

Energy Technology Data Exchange (ETDEWEB)

Miller, Desinia B. [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina (United States); Snow, Samantha J. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Henriquez, Andres [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina (United States); Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

2016-09-01

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These

Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.

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Lyoussi, Badiaa; Cherkaoui Tangi, Khadija; Morel, Nicole; Haddad, Mohamed; Quetin-Leclercq, Joelle

2018-01-01

The present investigation was carried out to evaluate the safety of an aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) by determining its cytotoxicity and potential toxicity after acute and sub-chronic administration in rodents. Cytotoxic activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and 3T3. Acute toxicity tests were carried out in mice by a single oral administration of Calycotome seed-extract (0 - 12 g/kg) as well as intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar rats by administration of oral daily doses for up to 90 days. Changes in body and vital organ weights, mortality, haematology, clinical biochemistry and histologic morphology were evaluated. The lyophilized aqueous extract of C. villosa exhibited a low cytotoxicity in all cell lines tested with an IC 50 > 100 µg/ml. In the acute study in mice, intra-peritoneal administration caused dose-dependent adverse effects and mortality with an LD 50 of 4.06 ± 0.01 g/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. Even AST and ALT were not affected while a significant decrease in serum glucose levels, at 300 and 600 mg/kg was detected. Histopathological examination of the kidney and liver did not show any alteration or inflammation at the end of treatment. In conclusion, the aqueous extract of C. villosa seed appeared to be non-toxic and did not produce mortality or clinically significant changes in the haematological and biochemical parameters in rats.

Subchronic administration of atomoxetine causes an enduring reduction in context-induced relapse to cocaine seeking without affecting impulsive decision making.

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Broos, Nienke; Loonstra, Rhianne; van Mourik, Yvar; Schetters, Dustin; Schoffelmeer, Anton N M; Pattij, Tommy; De Vries, Taco J

2015-07-01

Previous work has established a robust relationship between impulsivity and addiction, and revealed that impulsive decision making predisposes the vulnerability to cocaine-seeking behavior in rats. An important next step is to assess whether elevated relapse vulnerability can be treated via the reduction of impulsive decision making. Therefore, this study explored whether subchronic atomoxetine treatment can reduce relapse vulnerability by reducing impulsive decision making. Rats were trained in the delayed reward task and were subjected to 3 weeks of cocaine self-administration. Following drug self-administration, animals were divided to different experimental groups and received the noradrenaline transporter inhibitor and attention-deficit/hyperactivity disorder drug atomoxetine or vehicle subchronically for 20 days. On days 1 and 10 after treatment cessation, a context-induced reinstatement test was performed. Throughout the entire experiment, changes in impulsive decision making were continuously monitored. Subchronic treatment with atomoxetine reduced context-induced reinstatement both 1 and 10 days after treatment cessation, only in animals receiving no extinction training. Interestingly, neither subchronic nor acute atomoxetine treatments affected impulsive decision making. Our data indicate that the enduring reduction in relapse sensitivity by atomoxetine occurred independent of a reduction in impulsive decision making. Nonetheless, repeated atomoxetine administration seems a promising pharmacotherapeutical strategy to prevent relapse to cocaine seeking in abstinent drug-dependent subjects. © 2014 Society for the Study of Addiction.

The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

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Micovic Zarko

2016-09-01

Full Text Available Hyperhomocysteinemia (HHC, both basal and after methionine load, may occur due to genetic disorders or deficiencies of nutrients that affect the remethylation or trans-sulphuration pathways during methionine metabolism. HHC is involved in the pathogenesis of many illnesses as a result of its prooxidative effect and its impairment of antioxidative protection. The aim was to examine the effects of subchronic methionine overload on the body weight and standard biochemical parameters in rat serum and to examine whether simultaneous subchronic intraperotoneal administration of methionine alone or together with L-cysteine or N-acetyl-cysteine resulted in a change in the body weight and biochemical parameters in the rat serum. The research was conducted during a three-week period (male Wistar albino rats, n=36, body weight of approximately 160 g, age of 15-20 days, and the animals were divided into a control group and three experimental groups of 8-10 animals each: a control group (0.9% sodium chloride 0.1-0.2 ml/day; b methionine (0.8 mmol/kg/bw/day (MET group; c methionine (0.8 mmol/kg/bw/day + L-cysteine (7 mg/kg/bw/day (L-cys+MET group; and d methionine (0.8 mmol/kg/bw/day + N-acetyl-L-cysteine (50 mg/kg/bw/day (NAC+MET group. In addition to the body weight monitoring, the levels of total homocysteine and the standard biochemical parameters in blood samples (plasma or serum were determined. The results indicated that monitoring the homocysteine levels and standard biochemical parameters in blood could be used for analysis and could provide an excellent guideline for distinguishing between toxic and non-toxic doses of methionine intake, which may be meaningful for clinical applications.

Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto.

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Lampe, Bradley J; English, J Caroline

2016-02-01

Subtilisin NAT, commonly known as "nattokinase," is a fibrinolytic enzyme produced by the bacterial strain B. subtilis var. natto, which plays a central role in the fermentation of soybeans into the popular Japanese food natto. Recent studies have reported on the potential anticoagulatory and antihypertensive effects of nattokinase administration in humans, with no indication of adverse effects. To evaluate the safety of nattokinase in a more comprehensive manner, several GLP-compliant studies in rodents and human volunteers have been conducted with the enzyme product, NSK-SD (Japan Bio Science Laboratory Co., Ltd., Japan). Nattokinase was non-mutagenic and non-clastogenic in vitro, and no adverse effects were observed in 28-day and 90-day subchronic toxicity studies conducted in Sprague-Dawley rats at doses up to 167 mg/kg-day and 1000 mg/kg-day, respectively. Mice inoculated with 7.55 × 10(8) CFU of the enzyme-producing bacterial strain showed no signs of toxicity or residual tissue concentrations of viable bacteria. Additionally consumption of 10 mg/kg-day nattokinase for 4 weeks was well tolerated in healthy human volunteers. These findings suggest that the oral consumption of nattokinase is of low toxicological concern. The 90-day oral subchronic NOAEL for nattokinase in male and female Sprague-Dawley rats is 1000 mg/kg-day, the highest dose tested. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Subchronic exposure to low-doses of the nerve agent VX: Physiological, behavioral, histopathological and neurochemical studies

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Bloch-Shilderman, Eugenia; Rabinovitz, Ishai; Egoz, Inbal; Raveh, Lily; Allon, Nahum; Grauer, Ettie; Gilat, Eran; Weissman, Ben Avi

2008-01-01

The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult. As a consequence to these characteristics of VX, even the expected low levels should be examined for their potential to induce functional impairments including those associated with neuronal changes. In the present study, we developed an animal model for subchronic, low-dose VX exposure and evaluated its effects in rats. Animals were exposed to VX (2.25 μg/kg/day, 0.05 LD 50 ) for three months via implanted mini osmotic pumps. The rapidly attained continuous and marked whole-blood cholinesterase inhibition (∼ 60%), fully recovered 96 h post pump removal. Under these conditions, body weight, blood count and chemistry, water maze acquisition task, sensitivity to the muscarinic agonist oxotremorine, peripheral benzodiazepine receptors density and brain morphology as demonstrated by routine histopathology, remained unchanged. However, animals treated with VX showed abnormal initial response in an Open Field test and a reduction (∼ 30%) in the expression of the exocytotic synaptobrevin/vesicle associate membrane protein (VAMP) in hippocampal neurons. These changes could not be detected one month following termination of exposure. Our findings indicate that following a subchronic, low-level exposure to the chemical warfare agent VX some important processes might be considerably impaired. Further research should be addressed towards better understanding of its potential health ramifications and in search of optimal countermeasures

Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

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Gao, Yonglin; Wang, Yunzhi; Li, Yanshen; Han, Rui; Li, Chunmei; Xiao, Lin; Cho, Susan; Ma, Yukui; Fang, Chao; Lee, Albert W

2017-06-01

In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg. Copyright © 2017. Published by Elsevier Inc.

Effects of subchronic phencyclidine (PCP treatment on social behaviors, and operant discrimination and reversal learning in C57BL/6J mice

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Jonathan L Brigman

2009-02-01

Full Text Available Subchronic treatment with the psychotomimetic phencyclidine (PCP has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily x 7 days, followed by 7 days withdrawal in C57BL/6J mice on 1 social behaviors using a sociability/social novelty-preference paradigm, and 2 pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains that produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice.

Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

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Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

2008-03-01

The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

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

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Moon, Seol-Hee; Kim, Duyeol; Shimizu, Norihito; Okada, Tadashi; Hitoe, Shoketsu; Shimoda, Hiroshi

2017-01-01

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.

Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

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Taghizadeh, Mohsen; Ostad, Seyed Naser; Asemi, Zatollah; Mahboubi, Mohaddese; Hejazi, Sara; Sharafati-Chaleshtori, Reza; Rashidi, Aliakbar; Akbari, Hosein; Sharifi, Nasrin

2017-08-01

The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Infants 1-90 days old hospitalized with human rhinovirus infection.

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Bender, Jeffrey M; Taylor, Charla S; Cumpio, Joven; Novak, Susan M; She, Rosemary C; Steinberg, Evan A; Marlowe, Elizabeth M

2014-09-01

Human rhinovirus (HRV) is a common cause of respiratory illness in children. The impact of HRV infection on 1- to 90-day-old infants is unclear. We hypothesized that HRV infection would be clinically similar to respiratory syncytial virus (RSV) infection in the hospitalized infants. We conducted a retrospective study of hospitalized infants, who were 1-90 days old, with HRV or RSV within the Southern California Kaiser Permanente network over a 1-year period (August 2010 to October 2011). We identified 245 hospitalized infants who underwent respiratory virus testing. HRV was found in 52 infants (21%) compared to 79 infants (32%) with RSV (P = 0.008). Infants with HRV infection experienced longer hospital stays compared to those with RSV (median length of stay 4 days vs. 3 days, P = 0.009) and had fewer short hospital stays ≤3 days (P = 0.029). There was a trend in infants with HRV infection to be younger (P = 0.071) and have more fevers (P = 0.052). Recent advances in diagnostics allow for identification of a broad range of viral pathogens in infants. Compared to RSV, HRV was associated with longer hospital stays. Additional studies and improved, more specific testing, methods are needed to further define the effects of HRV infection in infants 1-90 days old. © 2014 Wiley Periodicals, Inc.

Effect of subchronic caffeine treatment on MK-801-induced changes in locomotion, cognition and ataxia in mice.

Science.gov (United States)

de Oliveira, R V; Dall'Igna, O P; Tort, A B L; Schuh, J F; Neto, P F; Santos Gomes, M W; Souza, D O; Lara, D R

2005-03-01

N-Methyl-D-aspartate (NMDA) receptor antagonists cause hyperlocomotion and cognitive deficits in rodents, and caffeine-tolerant mice show diminished locomotor response to NMDA receptor antagonists. The aim of this study was to evaluate the effect of subchronic caffeine treatment on MK-801-induced hyperlocomotion, ataxia and cognitive deficits, as well as amphetamine-induced hyperlocomotion in mice. Mice were treated subchronically with caffeine (0, 0.1, 0.3 and 1 mg/ml and 1, 3 and 7 days) and evaluated for locomotor activity, working memory (delayed alternation test), long-term memory (inhibitory avoidance task) and ataxia. Hyperlocomotion induced by MK-801 (0.25 mg/kg i.p.) was diminished after 3 days and almost abolished after 7 days of caffeine treatment at the 1 mg/ml dose, and this effect was also dose-dependent. Ataxia induced by 0.5 mg/kg MK-801 was not affected by caffeine treatment, but a short-lived hyperlocomotor effect was observed. Performance deficit in the inhibitory avoidance task induced by MK-801 (0.01 mg/kg) was prevented in mice treated with caffeine for 7 days at 1 mg/ml, and perseverative errors in the T-maze by MK-801 (0.4 mg/kg) were attenuated. The locomotor effect of amphetamine (5 mg/kg) was unaffected by subchronic caffeine treatment. The findings that hyperlocomotion and cognitive effects induced by MK-801 can be specifically influenced by reduced adenosinergic activity agree with a model of adenosine hypofunction in schizophrenia, since NMDA receptor antagonists are pharmacological models for this disorder.

190-C Facility <90 Day Storage Pad training plan

International Nuclear Information System (INIS)

Little, N.C.

1996-12-01

This is the Environmental Restoration Contractor (ERC) team training plan for the 190-C Facility <90 Day Storage Pad of Hazardous Waste. It is intended to meet the requirements of Washington Administrative Code (WAC) 173-303-330 and the Hanford Dangerous Waste Permit. Training unrelated to compliance with WAC 173-303-330 is not addressed in this training plan. WAC 173-303-330(1)(d)(ii, v, vi) requires that personnel be familiarized, where applicable, with waste feed cut-off systems, response to ground-water contamination incidents, and shutdown of operations. These are not applicable to 190-C Facility <90 Day Storage Pad, and are therefore not covered in this training plan

Reproduction and subchronic feeding study of carnauba wax in rats.

Science.gov (United States)

Parent, R A; Re, T A; Babish, J G; Cox, G E; Voss, K A; Becci, P J

1983-02-01

The reproductive performance of Wistar rats fed carnauba wax at levels of 0.1, 0.3 or 1% in the diet and the effects of subchronic administration of carnauba wax at these dose levels on the resultant progeny were studied. Reproductive indices, body-weight gain, food consumption, haematological and clinical chemical data, ophthalmic, gross and histopathological examinations were used to study the possible toxic or pathological effects. Serum free fatty acid levels were found to be decreased in male and female rats fed carnauba wax at dietary levels of 0.3 and 1.0%. No other effects of feeding carnauba wax at levels up to 1.0% of the diet were observed.

Intestinal lymphangiectasis and lipidosis in rats following subchronic exposure to indole-3-carbinol via oral gavage.

Science.gov (United States)

Boyle, Michael C; Crabbs, Torrie A; Wyde, Michael E; Painter, J Todd; Hill, Georgette D; Malarkey, David E; Lieuallen, Warren G; Nyska, Abraham

2012-06-01

To investigate the toxicity and carcinogenic potential of indole-3-carbinol (I3C), the National Toxicology Program has conducted 13-week subchronic studies in Fisher 344 rats and B6C3F1 mice, and chronic 2-year bioassays in Sprague-Dawley rats and B6C3F1 mice. While the chronic study results are not yet available, subchronic study results and short-term special evaluations of interim sacrifices in the 2-year rat bioassay are presented. F344 rats were orally gavaged ≤300 mg I3C/kg body weight 5 days a week for 13 weeks. Rats treated with ≥150 mg/kg demonstrated a dose-related dilation of lymphatics (lymphangiectasis) of the duodenum, jejunum, and mesenteric lymph nodes. Material within dilated lacteals stained positively for Oil Red O and Sudan Black, consistent with lipid. Electron microscopic evaluation confirmed extracellular lipid accumulation within the villar lamina propria, lacteals, and within villar macrophages. Analyses of hepatic and pulmonary CYP1A enzymes demonstrated dose-dependent I3C induction of CYP1A1 and 1A2. B6C3F1 mice orally gavaged ≤250 mg I3C/kg body weight did not demonstrate histopathological changes; however, hepatic CYP induction was similar to that in rats. The histopathologic changes of intestinal lymphangiectasis and lipidosis in this study share similarities with intestinal lymphangiectasia as observed in humans and dogs. However, the resultant clinical spectrum of protein-losing enteropathy was not present.

Precipitated withdrawal counters the adverse effects of subchronic cannabinoid administration on male rat sexual behavior.

Science.gov (United States)

Riebe, Caitlin J; Lee, Tiffany T; Hill, Matthew N; Gorzalka, Boris B

2010-03-26

In the present study, sexual behavior of male rats was assessed following prolonged treatment with the CB(1) receptor agonist, HU-210 (0.1mg/mg/day for 10 days) under conditions of drug maintenance, spontaneous withdrawal and precipitated withdrawal (induced via administration of the CB(1) receptor antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual activity in male rats was impaired under both the drug maintenance and spontaneous withdrawal conditions, as revealed by a reduction in frequency of both intromissions and ejaculations. Notably, the induction of precipitated drug withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual activity as seen by a reversal of the suppression of ejaculations. These data illustrate that, contrary to expectations, the impairments in male sexual activity following protracted cannabinoid administration are not due to drug withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by repeated drug exposure. 2010 Elsevier Ireland Ltd. All rights reserved.

Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania.

Science.gov (United States)

Fries, Gabriel R; Valvassori, Samira S; Bock, Hugo; Stertz, Laura; Magalhães, Pedro Vieira da Silva; Mariot, Edimilson; Varela, Roger B; Kauer-Sant'Anna, Marcia; Quevedo, João; Kapczinski, Flávio; Saraiva-Pereira, Maria Luiza

2015-09-01

Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. Copyright © 2015 Elsevier Ltd. All rights reserved.

Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

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Adamcakova-Dodd Andrea

2012-06-01

Full Text Available Abstract Background Aluminum oxide-based nanowhiskers (AO nanowhiskers have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Methods Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH3 and AlOOH]. Male mice (C57Bl/6 J were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines, blood (total and differential cell counts, lung histopathology and pulmonary mechanics. Results Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p p  Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

Acute, subacute and subchronic toxicological studies of carissa carandas leaves (ethanol extract): a plant active against cardiovascular diseases

International Nuclear Information System (INIS)

Shamim, S.

2014-01-01

The Purpose of this research study was to examine the toxicological effects of aqueous: ethanol (1:1) extract of Carissa carandas leaves extracts in rats. Methodolgy: Acute toxicity studies were conducted to check the LD50 values in experimental animals. Autopsy after acute toxicity revealed that no gross changes were observed in organs like liver, spleen, heart and kidney among the animals of group N (control) and S (treated). The appearance of organs of Group S animals was comparable with that of Group N animals. Results: No signs of toxicity and mortality were observed in treated group after sub acute toxicity as compared to the control group. The histopathological studies after subchronic toxicity in doses of 1750 mg/kg (p.o.) and 5000 mg/kg (p.o) showed no toxic effects on organs like liver, heart, kidney and spleen. While chronic toxicity in dose 5000 mg/kg (p.o.) showed some histological changes. (author)

A 90-day safety study of genetically modified rice expressing rhIGF-1 protein in C57BL/6J rats.

Science.gov (United States)

Tang, Maoxue; Xie, Tingting; Cheng, Wenke; Qian, Lili; Yang, Shulin; Yang, Daichang; Cui, Wentao; Li, Kui

2012-06-01

Genetically modified plants expressing disease resistance traits offer new treatment strategies for human diseases, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of transgenic rice expressing the recombinant human insulin-like growth factor-1 (rhIGF-1) compared to its parental wild rice. Male and female C57BL/6J rats were given a nutritionally balanced purified diet with 20% transgenic rhIGF-1 rice or 20% parental rice for 90 days. This corresponds to a mean daily rhIGF-1 protein intake of approximately 217.6 mg/kg body weight based on the average feed consumption. In the animal study a range of biological, biochemical, clinical, microbiological and pathological parameters were examined and several significant differences were observed between groups, but none of the effects were considered to be adverse. In conclusion, no adverse or toxic effects on C57BL/6J rats were observed in the design used in this 90-day study. These results will provide valuable information for the safety assessment of genetically modified food crops.

A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats

DEFF Research Database (Denmark)

Schrøder, Malene; Poulsen, Morten; Wilcks, Andrea

2007-01-01

An animal model for safety assessment of genetically modified foods was tested as part of the SAFOTEST project. In a 90-day feeding study on Wistar rats, the transgenic KMD1 rice expressing Cry1Ab protein was compared to its non-transgenic parental wild type, Xiushui 11. The KMD1 rice contained 15......, macroscopic and histopathological examinations were performed with only minor changes to report. The aim of the study was to use a known animal model in performance of safety assessment of a GM crop, in this case KMD1 rice. The results show no adverse or toxic effects of KMD1 rice when tested in the design...... used in this 90-day study. Nevertheless the experiences from this study lead to the overall conclusion that safety assessment for unintended effects of a GM crop cannot be done without additional test group(s)....

Toxicity of inhaled 90SrCl2 in Beagle dogs. XIII

International Nuclear Information System (INIS)

Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

1979-01-01

The metabolism, dosimetry and biological effects of inhaled 90 SrCl 2 in the Beagle dog are being studied to provide a basis for assessing the consequences of inhaling 90 Sr such as might be released in certain nuclear accidents. Seventy-two dogs were exposed to aerosols containing 90 Sr resulting in initial body burdens ranging from 2.5 to 250 μCi 90 Sr/kg body weight. To date, 60 90 Sr-exposed dogs have died or have been euthanized, six during the first 31 days after inhalation of 90 Sr with bone marrow aplasia and 54 between 585 and 5109 days after inhalation of 90 Sr. The latter group includes 32 dogs with bone-related neoplasms, two with upper respiratory tract carcinomas and five dogs with various diseases of the lower respiratory tract and heart. The other 15 dogs and diseases in organs that received little or no radiation dose, such as the gastrointestinal tract, urinary tract and the central nervous system. The skeletons of the dogs dying with bone-related neoplasms received initial radiation dose rates of 3.2 to 55 rads/day and cumulative doses to death of 2800 to 22 000 rads. Fourteen control dogs have died or been euthanized, two during the last year with mammary carcinoma and intestinal lymphosarcoma. Serial observations are continuing on the six surviving 90 Sr dogs and six controls

Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

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Olakunle James Onaolapo

2013-01-01

Full Text Available This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice.

Science.gov (United States)

Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

2013-01-01

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats

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Xiaofang Zhang

2016-11-01

Full Text Available Histone deacetylase inhibitors (HDACIs, such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

Evaluation of multiwalled carbon nanotubes toxicity in two fish species.

Science.gov (United States)

Cimbaluk, Giovani Valentin; Ramsdorf, Wanessa Algarte; Perussolo, Maiara Carolina; Santos, Hayanna Karla Felipe; Da Silva De Assis, Helena Cristina; Schnitzler, Mariane Cristina; Schnitzler, Danielle Caroline; Carneiro, Pedro Gontijo; Cestari, Marta Margarete

2018-04-15

Carbon Nanotubes are among the most promising materials for the technology industry. Their unique physical and chemical proprieties may reduce the production costs and improve the efficiency of a large range of products. However, the same characteristics that have made nanomaterials interesting for industry may be responsible for inducing toxic effects on the aquatic organisms. Since the carbon nanotubes toxicity is still a controversial issue, we performed tests of acute and subchronic exposure to a commercial sample of multiwalled carbon nanotubes in two fish species, an exotic model (Danio rerio) and a native one (Astyanax altiparanae). Using the alkaline version of the comet assay on erythrocytes and the piscine micronucleous, also performed on erythrocytes, it was verified that the tested carbon nanotubes sample did not generate apparent genotoxicity by means of single/double DNA strand break or clastogenic/aneugenic effects over any of the species, independently of the exposure period. Although, our findings indicate the possibility of the occurrence of CNTs-DNA crosslinks. Apparently, the sample tested induces oxidative stress after subchronic exposure as shown by activity of superoxide dismutase and catalase. The data obtained by the activity levels of acetylcholinesterase suggests acute neurotoxicity in Astyanax altiparanae and subchronic neurotoxicity in Danio rerio. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of lead toxicity by heat shock protein 90 (daf-21) is affected by temperature in Caenorhabditis elegans.

Science.gov (United States)

Wang, Yunbiao; Xu, Songbai; Liu, Jing; Zhang, Yanhui; Guo, Tai L

2014-06-01

In the nematode Caenorhabditis elegans, stress resistance can be regulated by dauer formation (daf) genes. In the present study, regulation of heavy metal lead (Pb) toxicity by the 90-kDa heat shock proteins (Hsp90; daf-21) was investigated in both wild-type C. elegans and daf-21/Hsp90 mutants by focusing on the effects of varied temperatures below (15°C) or above (25 and 30°C) the presumptive optimum growth temperature (20°C). More acute toxicity of Pb, indicated by the 24-h median lethal concentrations (LC50), was observed in wild-type adults than in the daf-21 mutant adults at 15, 20 and 25°C; however, the daf-21 mutant adults showed more sensitivity at 30°C. Enhanced Pb sensitivity (e.g., decrease LC50) in both types of C. elegans was observed with both increased and decreased temperatures when compared to that at 20°C. Additional examined endpoints included time course of toxicity at LC50s, pharyngeal pumping, reproduction, life span, and Hsp90 expression. Collective results showed that temperatures both above and below 20°C exacerbated Pb toxicity, and that the protein level of daf-21/Hsp90 was one of the most sensitive indicators of Pb toxicity in wild-type C. elegans, while pharyngeal pumping was more Pb sensitive in daf-21 mutants. Therefore, the expression of daf-21/Hsp90 has apparent utility for the prediction and assessment of Pb-induced toxicity in nematodes. Further, the stress responses related to Hsp90 expression in C. elegans may have considerable potential as sensitive biomarkers for the monitoring of environmental Pb contamination. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.

Science.gov (United States)

Zhang, Qiannan; Yang, Hui; Li, Yongning; Liu, Haibo; Jia, Xudong

2017-06-01

Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicological Assessment of β-(1à6-Glucan (Lasiodiplodan in Mice during a 28-Day Feeding Study by Gavage

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Janaína A. Túrmina

2012-12-01

Full Text Available Studies evaluating the toxicity caused by fungal exopolysaccharides of the β-(1®6-D-glucan type are rare. In this study, the toxicological effects of sub-chronic treatments with lasiodiplodan (β-(1®6-D-glucan from Lasiodiplodia theobromae MMPI were evaluated in mice through the assessment of biochemical, hematological, and histopathological alterations. Thirty-two mice (16 male, 16 female were used in this study divided in two groups; one group received lasiodiplodan (50 mg/kg body weight daily for 28 days via gavage, and another (control group received saline during the same period. Blood samples were collected via cardiac puncture for hematological and biochemical analyses. Liver, heart, kidney, and spleen were collected for histopathological analysis. Statistical analysis was performed through one-way analysis of variance and only p < 0.05 F-values were presented. Significant reduction in blood glucose in the male group (35%; p < 0.01, transaminases activity in both sexes (AST and ALT; ~35%; p < 0.05, and urea (20%; p < 0.01 in the female group was observed with the lasiodiplodan treatment. The results showed that sub-chronic treatments with lasiodiplodan did not generate hematological and histopathological alterations leading to signs of toxicity in healthy mice, independent of gender.

Toxicity of inhaled 90SrCl2 in beagle dogs. XI

International Nuclear Information System (INIS)

Muggenburg, B.A.; Rebar, A.H.; Benjamin, S.A.; Boecker, B.B.; Jones, R. K.; McClellan, R.O.; Pickrell, J.A.

1977-01-01

Studies on the metabolism, dosimetry, and effects of inhaled 90 SrCl 2 in the Beagle dog are continuing in an effort to provide a basis for assessing the consequences of inhaling 90 Sr such as might be released in certain nuclear accidents. Seventy-two dogs were exposed to aerosols containing 90 Sr resulting in initial body burdens ranging from 2.5 to 250 μCi 90 Sr/kg body weight. Forty-eight of these dogs are being maintained for lifetime observation. Twenty-five unexposed dogs serve as controls. The long-term retained burden (LTRB) in these dogs ranged from 1 to 120 μCi 90 Sr/kg. Twenty-four dogs with a mean LTRB of 38 μCi 90 Sr/kg have been assigned to a sacrifice study. Two of these dogs and one control dog were sacrificed at five days, one month and one year after inhalation of 90 Sr. To date, 51 90 Sr-exposed dogs have died or have been euthanized, six during the first 31 days after inhalation of 90 Sr with bone marrow aplasia and 45 between 585 and 4236 days after inhalation of 90 Sr. The latter group includes 12 dogs with bone-related hemangiosarcomas, 16 with osteosarcomas, three with fibrosarcomas, three with osteochondrosarcomas, one with osteochondrofibrosarcoma, two with leukemia, one with a baso-squamous carcinoma of the skull, one with a squamous cell carcinoma of the maxilla, one with a squamous cell carcinoma of the frontal sinus, one with a hemangiosarcoma of the heart, one with a myxosarcoma of the skull, one with transitional cell carcinoma, one with bronchioalveolar carcinoma, one with an epileptic seizure, one with pneumonia, one with cerebellar hemorrhage and three with a malabsorption syndrome

Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

Science.gov (United States)

Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

2014-01-01

A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system. PMID:25184300

Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

Directory of Open Access Journals (Sweden)

Shiying Zou

Full Text Available A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50 based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.

Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement.

Science.gov (United States)

Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

2013-01-01

Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health.

Sub-chronic toxicity study of a novel herbal-based formulation (Semelil on dogs

Directory of Open Access Journals (Sweden)

Farzamfar B

2008-04-01

Full Text Available Semelil (ANGIPARSTM, a novel herbal-based compound containing extract of Melilotus officinalis, was formulated for treatment of chronic wounds, especially diabetic foot ulcer. The purpose of this study was to investigate safety and toxicity effects of intramuscular administration of Semelil in dogs. "nPreliminary one-month study with Semelil was performed on 8 male and female dogs divided into 2 groups, test and control, four animals each. Semelil was administered intramuscularlyat a dose of 0.07 ml/kg body wt. once a day to the animals of the test group, while the control group received sterile saline. During experiments, general state of the animals including the dynamics of body weight changes, appetite, motor activity and behavior, hair condition, ECG parameters, rectal temperature of animals and data of hematological and biochemical tests were monitored for signs of toxicity and side-effects. Finally, morphology and histology analyses were performed using standard methods."nNo adverse health or toxicity effects were observed through the course of the study. No damaging consequences of Semelil injections on the functional state of main organs of the experimental animals were found. This observation gave a good evidence of a favorable safety profile compatible with potential therapeutic use of Semelil.

Distribution and Determinants of 90-Day Payments for Multilevel Posterior Lumbar Fusion: A Medicare Analysis.

Science.gov (United States)

Jain, Nikhil; Phillips, Frank M; Khan, Safdar N

2018-04-01

A retrospective, economic analysis. The objective of this article is to analyze the distribution of 90-day payments, sources of variation, and reimbursement for complications and readmissions for primary ≥3-level posterior lumbar fusion (PLF) from Medicare data. A secondary objective was to identify risk factors for complications. Bundled payments represent a single payment system to cover all costs associated with a single episode of care, typically over 90 days. The dollar amount spent on different health service providers and the variation in payments for ≥3-level PLF have not been analyzed from a bundled perspective. Administrative claims data were used to study 90-day Medicare (2005-2012) reimbursements for primary ≥3-level PLF for deformity and degenerative conditions of the lumbar spine. Distribution of payments, sources of variation, and reimbursements for managing complications were studied using linear regression models. Risk factors for complications were studied by stepwise multiple-variable logistic regression analysis. Hospital payments comprised 73.8% share of total 90-day payment. Adjusted analysis identified several factors for variation in index hospital payments. The average 90-day Medicare payment for all multilevel PLFs without complications was $35,878 per patient. The additional average cost of treating complications with/without revision surgery within 90 days period ranged from $17,284 to $68,963. A 90-day bundle for ≥3-level PLF with readmission ranges from $88,648 (3 levels) to $117,215 (8+ levels). Rates and risk factors for complications were also identified. The average 90-day payment per patient from Medicare was $35,878 with several factors such as levels of surgery, comorbidities, and development of complications influencing the cost. The study also identifies the risks and costs associated with complications and readmissions and emphasize the significant effect these would have on bundled payments (additional burden of up

Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

OpenAIRE

Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

2012-01-01

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after...

Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats

Directory of Open Access Journals (Sweden)

Qian-ying Guo

2015-12-01

Full Text Available BT799 is a genetically modified (GM maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt. The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58 at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control.

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

Science.gov (United States)

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver

International Nuclear Information System (INIS)

Lee, Min-Ho; Kim, Mingoo; Lee, Byung-Hoon; Kim, Ju-Han; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-Il; Chung, Heekyoung; Kong, Gu; Lee, Mi-Ock

2008-01-01

Valproic acid (VPA) is used clinically to treat epilepsy, however it induces hepatotoxicity such as microvesicular steatosis. Acute hepatotoxicity of VPA has been well documented by biochemical studies and microarray analysis, but little is known about the chronic effects of VPA in the liver. In the present investigation, we profiled gene expression patterns in the mouse liver after subchronic treatment with VPA. VPA was administered orally at a dose of 100 mg/kg/day or 500 mg/kg/day to ICR mice, and the livers were obtained after 1, 2, or 4 weeks. The activities of serum liver enzymes did not change, whereas triglyceride concentration increased significantly. Microarray analysis revealed that 1325 genes of a set of 32,996 individual genes were VPA responsive when examined by two-way ANOVA (P 1.5). Consistent with our previous results obtained using an acute VPA exposure model (Lee et al., Toxicol Appl Pharmacol. 220:45-59, 2007), the most significantly over-represented biological terms for these genes included lipid, fatty acid, and steroid metabolism. Biological pathway analysis suggests that the genes responsible for increased biosynthesis of cholesterol and triglyceride, and for decreased fatty acid β-oxidation contribute to the abnormalities in lipid metabolism induced by subchronic VPA treatment. A comparison of the VPA-responsive genes in the acute and subchronic models extracted 15 commonly altered genes, such as Cyp4a14 and Adpn, which may have predictive power to distinguish the mode of action of hepatotoxicants. Our data provide a better understanding of the molecular mechanisms of VPA-induced hepatotoxicity and useful information to predict steatogenic hepatotoxicity

PREDICE score as a predictor of 90 days mortality in patients with heart failure

Science.gov (United States)

Purba, D. P. S.; Hasan, R.

2018-03-01

Hospitalization in chronic heart failure patients associated with high mortality and morbidity rate. The 90 days post-discharge period following hospitalization in heart failure patients is known as the vulnerable phase, it carries the high risk of poor outcomes. Identification of high-risk individuals by using prognostic evaluation was intended to do a closer follow up and more intensive to decreasing the morbidity and mortality rate of heart failure.To determine whether PREDICE score could predict mortality within 90 days in patients with heart failure, an observational cohort study in patients with heart failure who were hospitalized due to worsening chronic heart failure. Patients were in following-up for up to 90 days after initial evaluation with the primary endpoint is death.We found a difference of the significantstatistical between PREDICE score in survival and mortality group (p=0.001) of 84% (95% CI: 60.9% - 97.4%).In conclusion, PREDICE score has a good ability to predict mortality within 90 days in patients with heart failure.

Biological responses of Neotropical freshwater fish Lophiosilurus alexandri exposed to ammonia and nitrite.

Science.gov (United States)

Dos Santos Silva, Márcio José; da Costa, Franklin Fernando Batista; Leme, Fabiola Paes; Takata, Rodrigo; Costa, Deliane Cristina; Mattioli, Cristiano Campos; Luz, Ronald Kennedy; Miranda-Filho, Kleber Campos

2018-03-01

This study aimed to elucidate the responses of the Neotropical fish Lophiosilurus alexandri exposed to ammonia and nitrite, following a period of recovering. Acute toxicity tests lasted 96h, subchronic toxicity tests lasted eight days and the detoxification trial lasted four days. Groups of 12 juveniles were maintained in 90-L tanks and treated with increasing concentrations of ammonia and nitrite, except during the recovery test. All treatments were performed with two replicates. The median lethal concentrations (LC 50 ) of 24, 48, 72 and 96h were estimated at 30.12; 24.35; 19.24 and 18.68mg·L -1 TA-N; 5.37; 4.57; 3.75 and 3.66mg·L -1 NH 3 -N and 20.37; 7.78; 7.09 and 5.86mg·L -1 NO 2 - -N, respectively. The NO 2 - caused significant decrease in hematocrit and increase in the urea levels during short-term exposure, with recovery of homeostasis after the subchronic and detox period. Acute exposure to ammonia increased the enzyme profile of transaminases, glucose and urea. Urea concentration remained high in the subchronic and detox tests. Histopathologies were observed in animals exposed to ammonia in both toxicity tests. It was highlighted detachment of epithelium, hyperemia and necrosis in the gills. Exposure to NO 2 - caused epithelium detachment and aneurysm. Vacuolization and swelling of hepatocytes were the most common injury for both nitrogenous compounds. We concluded that the L. alexandri has moderate tolerance to ammonia and nitrite. The recovery period revealed remedial response to ammonia and nitrite exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Prenatal Exposure to Carbon Black (Printex 90)

DEFF Research Database (Denmark)

Jackson, Petra; Vogel, Ulla; Wallin, Håkan

2011-01-01

Maternal pulmonary exposure to ultrafine particles during pregnancy may affect the health of the child. Developmental toxicity of carbon black (Printex 90) nanoparticles was evaluated in a mouse model. Time-mated mice were intratracheally instilled with Printex 90 dispersed in Millipore water on ...... on gestation days (GD) 7, 10, 15 and 18, with total doses of 11, 54 and 268 mu g Printex 90/animal. The female offspring prenatally exposed to 268 mu g Printex 90/animal displayed altered habituation pattern during the Open field test....

Same-day {sup 90}Y radioembolization: implementing a new treatment paradigm

Energy Technology Data Exchange (ETDEWEB)

Gabr, Ahmed; Kallini, Joseph Ralph; Gates, Vanessa L.; Hickey, Ryan; Desai, Kush; Thornburg, Bartley; Marshall, Karen; Salzig, Krystina; Williams, Melissa; Del Castillo, Carlene; Hohlastos, Elias; Lewandowski, Robert J. [Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Kulik, Laura; Ganger, Daniel [Northwestern University, Department of Medicine, Division of Hepatology, Chicago, IL (United States); Baker, Talia [Northwestern University, Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Chicago, IL (United States); Salem, Riad [Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Northwestern University, Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Chicago, IL (United States); Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Department of Medicine, Division of Hematology and Oncology, Chicago, IL (United States)

2016-12-15

To assess the feasibility of conducting pretreatment mesenteric angiography, coil embolization, {sup 99m}Tc macroaggregated albumin ({sup 99m}Tc-MAA) scintigraphy, and {sup 90}Y radioembolization treatment in a single, same-day, combined outpatient encounter. This was a retrospective study of 78 patients treated during the period 2008 - 2015 who were managed in a single outpatient encounter under the guidance of the Interventional Radiology Department and The Nuclear Medicine Department. Pretreatment planning was performed by reviewing baseline imaging and estimated perfused liver volume bearing the tumor. The region of interest was estimated using 3-D software; this value was used for dosimetry planning. Maximum lung shunting fractions of 10 % for hepatocellular carcinoma and 5 % for liver metastases were assumed. Subsequently, hepatic angiography and {sup 99m}Tc-MAA scintigraphy were performed followed by {sup 90}Y treatment in one outpatient encounter. Total in-room procedure time was recorded. All patients underwent same-day angiography, {sup 99m}Tc-MAA scintigraphy and {sup 90}Y radioembolization. Of the 78 patients, 16 received multiple segmental treatments to both lobes, 44 received treatment to the right lobe, and 18 received treatment to the left lobe. The median dose was 106 Gy. The median number of {sup 90}Y vials needed was two (range one to six). The median in-room time was 160 min (75 - 250 min). The residential status of the patients was as follows, 18 % (14/78) were local residents, 55 % (43/78) traveled from outside the city limits, 18 % (14/78) were from out-of-state, and 9 % (7/78) were resident abroad. Of the 78 patients, 61 (77 %) had hepatocellular carcinoma, and 17 (22 %) had liver metastases. The median lung dose was 3.5 Gy. This study demonstrated the feasibility of same-day {sup 90}Y evaluation and treatment while maintaining the principles of safe and effective {sup 90}Y infusion including tumoricidal dosimetry (lobar, segmentectomy

Comparison of in vivo toxicity, antioxidant and immunomodulatory activities of coconut, nipah and pineapple juice vinegars.

Science.gov (United States)

Mohamad, Nurul Elyani; Keong Yeap, Swee; Beh, Boon Keen; Romli, Muhammad Firdaus; Yusof, Hamidah Mohd; Kristeen-Teo, Ye Wen; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

2018-01-01

Vinegar is widely used as a food additive, in food preparation and as a food supplement. This study compared the phenolic acid profiles and in vivo toxicities, and antioxidant and immunomodulatory effects of coconut, nipah and pineapple juice vinegars, which were respectively prepared via a two-step fermentation using Saccharomyces cerevisiae 7013 INRA and Acetobacter aceti vat Europeans. Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4 + and CD8 + T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines. Overall, the data suggested that not all vinegar samples cause acute and sub-chronic toxicity in vivo. Moreover, the in vivo immunity and organ antioxidant levels were enhanced, to varying extents, by the phenolic acids present in the vinegars. The results obtained in this study provide appropriate guidelines for further in vivo bioactivity studies and pre-clinical assessments of vinegar consumption. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The sub-chronic toxicity of regular White Spirit in rats.

Science.gov (United States)

Carrillo, Juan-Carlos; Adenuga, M David; Mckee, Richard H

2014-10-01

Hydrocarbon solvents are mostly complex substances (UVCB) with carbon numbers in the range of approximately C5-C20. One of the most common types is a C9-C14 aliphatic solvent containing approximately 20% aromatics and commonly known as White Spirit in Europe and mineral spirits in the US. In previous repeated inhalation toxicity studies, White Spirit was reported to cause minimal systemic effects in most animal species with few effects other than male rat-specific kidney changes at levels up to approximately 2000mg/m(3). In the present study male and female rats were exposed to White Spirit vapors, 6h/day, 5days/week for 13weeks at levels of approximately 2000, 4000, or 8000mg/m(3) to assess the potential for effects at higher exposure levels. All of the rats survived the treatment period. In life observations were largely restricted to acute central nervous system (CNS) effects in the high exposure group. Terminal body weights of high exposure groups animals were significantly below control values. Statistically significant differences in the clinical and hematological observations were small and within normal physiological limits. Weights of some organs including liver, spleen and kidneys were elevated, but microscopic examination indicated that the only pathological effects were changes in the kidneys of the male rats, consistent with an α2u-globulin-mediated process, which is gender and species-specific and not relevant to humans. The overall no observed adverse effect level (NOAEC) was 4000mg/m(3). Copyright © 2014 Elsevier Inc. All rights reserved.

Compositional and toxicological analysis of a GM potato line with reduced α-solanine content – A 90-day feeding study in the Syrian Golden hamster

DEFF Research Database (Denmark)

Langkilde, Søren; Schrøder, Malene; Frank, Thomas

2012-01-01

Steroidal glycoalkaloids (GAs) are toxins, produced by plants of the Solanaceae family. The potato plant (Solanum tuberosum L.) and its tubers predominantly contain the two GAs α-chaconine and α-solanine. These compounds are believed to act in synergy, and the degree of toxicity may therefore...... for compositional similarity by analysing for a range of potato constituents, and (2) used in a 90-day feeding trial with the Syrian Golden hamster to study differential toxicity. The animal feeding study used diets with up to 60% freeze-dried potato powder from either line. Whilst data indicated some compositional...... concerns with regard to human (or animal) consumption....

A 90-day toxicity study of the effects of petroleum middle distillates on the skin of C3H mice.

Science.gov (United States)

Freeman, J J; McKee, R H; Phillips, R D; Plutnick, R T; Scala, R A; Ackerman, L J

1990-01-01

Petroleum middle distillates (PMDs) elicit skin tumors in mouse epidermal carcinogenesis studies. The response is characterized by a long latency with only a small percentage of animals developing tumors. Although the carcinogenic activity of certain other petroleum hydrocarbons largely depends upon the presence of polycyclic aromatic hydrocarbons (PAHs), many PMDs contain relatively low concentrations of PAHs. PMDs are also irritating to mouse skin, and chronic irritation may be involved in the development of skin tumors. This study was conducted to investigate the patterns of cutaneous irritation elicited by topical application of PMDs having compositional differences. The three PMDs selected for study were a steam cracked gas oil (SCGO), a lightly refined paraffinic oil (LRPO), and a jet fuel (JF). Male C3H/HeNCr1BR mice (25/group) were treated topically (37.5 microliters 2x/week for 13 weeks) with 10%, 50% or 100% (undiluted) concentrations of each PMD. Catalytically cracked clarified oil (CCCO, 10%), a potent carcinogen to mouse skin, was also tested. The vehicle was a noncarcinogenic mineral oil with a viscosity of 90 SUS. Cutaneous changes were evaluated by gross observations and light microscopy. Cutaneous irritation was the only significant toxic response in this study. Neither the vehicle nor any of the 10% PMD concentrations produced significant cutaneous irritation. The 10% CCCO and 50% PMD treatments all elicited slight to moderate proliferative and inflammatory changes in mouse skin. Ulcers were also observed microscopically in mice treated with 10% CCCO and 50% SCGO. The 100% SCGO treatment produced evidence of necrosis on Days 1-7 but not later in the study despite continued treatment. In contrast, the irritating effects of 100% LRPO were not evident until 2-3 weeks of study, and at study completion were characterized by moderately severe inflammatory and proliferative changes. The effects of 100% JF were qualitatively similar to 100% LRPO but less

The 5-day continuous infusion of cis-platinum: An update on toxicity pattern

International Nuclear Information System (INIS)

Salem, P.; Hashimi, L.; Jabboury, K.; Khalyl, M.

1986-01-01

In an attempt to further diminish the toxicity of Cis-Diamminodichloroplatinum (II) (DDP), clinical trials with the drug administered by 5-day continuous IV infusion were initiated in 1976. DDP cytotoxicity to asynchronous human lymphoma cells in culture was enhanced by prolonged exposure to the drug. Ninety-six patients patients with a varioty of histologically proven neoplastic diseases were intered in this study. All patients had a serum creatinine less than or equal to 1.5 mg/dl. Prior treatment was discontinued 3 to 4 weeks before initiation of cisplatin (DDP). Toxicity tables are presented of the general pattern of toxicity produced by 5-day DDP infustion and the gastrointestinal toxicity produced during the same period. A new dose schedule is presented which is apparently much less toxic than the bolus IV injection, in terms of immediate and delayed toxicities and allows the use of DDP for more prolonged periods of time in conjunction with radiation therapy

Plasma and blood volume in the calf from birth till 90 days of age

International Nuclear Information System (INIS)

Moellerberg, L.; Ekman, L.; Jacobsson, S.-O.

1975-01-01

Determinations of plasma volume were made of 9 clinically healthy Swedish Red and White calves from birth to 90 days of age by means of the isotop dilution technique. Commercially available 131 I labelled human serum albumin was used. Calculation of the total blood volume was based on the plasma volume and packed cell volume. The plasma and blood volumes increased per kg body weight in average 17 and 14 percent respectively from directly after birth to 24 hrs. old. From 1 to 90 days of age the plasma and blood volume fell steadily per kg body weight. Plasma volume expressed as a percentage of body weight was 5.3 percent at birth, 6.5 percent at 1 day old, and 4.9 percent at 90 days old. Corresponding values for blood were 8.4, 9.3 and 7.0 percent. (author)

Predictors of 30- and 90-day readmission following craniotomy for malignant brain tumors: analysis of nationwide data.

Science.gov (United States)

Donoho, Daniel A; Wen, Timothy; Babadjouni, Robin M; Schwartzman, William; Buchanan, Ian A; Cen, Steven Y; Zada, Gabriel; Mack, William J; Attenello, Frank J

2018-01-01

Hospital readmissions are a major contributor to increased health care costs and are associated with worse patient outcomes after neurosurgery. We used the newly released Nationwide Readmissions Database (NRD) to describe the association between patient, hospital and payer factors with 30- and 90-day readmission following craniotomy for malignant brain tumor. All adult inpatients undergoing craniotomy for primary and secondary malignant brain tumors in the NRD from 2013 to 2014 were included. We identified all cause readmissions within 30- and 90-days following craniotomy for tumor, excluding scheduled chemotherapeutic procedures. We used univariate and multivariate models to identify patient, hospital and administrative factors associated with readmission. We identified 27,717 admissions for brain tumor craniotomy in 2013-2014, with 3343 (13.2%) 30-day and 5271 (25.7%) 90-day readmissions. In multivariate analysis, patients with Medicaid and Medicare were more likely to be readmitted at 30- and 90-days compared to privately insured patients. Patients with two or more comorbidities were more likely to be readmitted at 30- and 90-days, and patients discharged to skilled nursing facilities or home health care were associated with increased 90-day readmission rates. Finally, hospital procedural volume above the 75th percentile was associated with decreased 90-day readmission rates. Patients treated at high volume hospitals are less likely to be readmitted at 90-days. Insurance type, non-routine discharge and patient comorbidities are predictors of postoperative non-scheduled readmission. Further studies may elucidate potentially modifiable risk factors when attempting to improve outcomes and reduce cost associated with brain tumor surgery.

Transcriptomic Analysis of Intestinal Tissues from Two 90-Day Feeding Studies in Rats Using Genetically Modified MON810 Maize Varieties.

Science.gov (United States)

Sharbati, Jutta; Bohmer, Marc; Bohmer, Nils; Keller, Andreas; Backes, Christina; Franke, Andre; Steinberg, Pablo; Zeljenková, Dagmar; Einspanier, Ralf

2017-01-01

Background: Global as well as specific expression profiles of selected rat tissues were characterized to assess the safety of genetically modified (GM) maize MON810 containing the insecticidal protein Cry1Ab. Gene expression was evaluated by use of Next Generation Sequencing (NGS) as well as RT-qPCR within rat intestinal tissues based on mandatory 90-day rodent feeding studies. In parallel to two 90-day feeding studies, the transcriptional response of rat tissues was assessed as another endpoint to enhance the mechanistic interpretation of GM feeding studies and/or to facilitate the generation of a targeted hypothesis. Rats received diets containing 33% GM maize (MON810) or near-isogenic control maize. As a site of massive exposure to ingested feed the transcriptomic response of ileal and colonic tissue was profiled via RT-qPCR arrays targeting apoptosis, DNA-damage/repair, unfolded protein response (UPR). For global RNA profiling of rat ileal tissue, we applied NGS. Results: No biological response to the GM-diet was observed in male and in female rat tissues. Transcriptome wide analysis of gene expression by RNA-seq confirmed these findings. Nevertheless, gene ontology (GO) analysis clearly associated a set of distinctly regulated transcripts with circadian rhythms. We confirmed differential expression of circadian clock genes using RT-qPCR and immunoassays for selected factors, thereby indicating physiological effects caused by the time point of sampling. Conclusion: Prediction of potential unintended effects of GM-food/feed by transcriptome based profiling of intestinal tissue presents a novel approach to complement classical toxicological testing procedures. Including the detection of alterations in signaling pathways in toxicity testing procedures may enhance the confidence in outcomes of toxicological trials. In this study, no significant GM-related changes in intestinal expression profiles were found in rats fed GM-maize MON810. Relevant alterations of

How subchronic and chronic health effects can be neglected for GMOs, pesticides or chemicals.

Science.gov (United States)

Séralini, Gilles-Eric; de Vendômois, Joël Spiroux; Cellier, Dominique; Sultan, Charles; Buiatti, Marcello; Gallagher, Lou; Antoniou, Michael; Dronamraju, Krishna R

2009-06-17

Chronic health effects are increasing in the world such as cancers, hormonal, reproductive, nervous, or immune diseases, even in young people. During regulatory toxicological subchronic tests to prevent these on mammalian health, prior commercialization of chemicals, including pesticides and drugs, or GMOs, some statistically significant findings may be revealed. This discussion is about the need to investigate the relevant criteria to consider those as biologically significant. The sex differences and the non linear dose or time related effects should be considered in contrast to the claims of a Monsanto-supported expert panel about a GMO, the MON 863 Bt maize, but also for pesticides or drugs, in particular to reveal hormone-dependent diseases and first signs of toxicities.

The First 90 Days of the New Middle School Principal in a Turnaround School: In-Depth Case Study of the Transition Period (First 90 Days)

Science.gov (United States)

Baeza, Marco A.

2010-01-01

This study analyzed skills, strategies, and theories that new middle school principals used to be successful during their transition period (the first 90 days) in turnaround schools. Based on research on transitions, three research questions guided the study: 1. Do middle school principals in a turnaround school situation find the transition…

Toxicity of strontium-90 depending on the way of its administration to animal organisms

International Nuclear Information System (INIS)

Shvedov, V.L.

1978-01-01

Toxicity of strontium-90 administered orally is almost thrice lower than that after parenteral administration. The values of the doses absorbed in the critical organ of rats, corresponding to LDsub(50/30), were 2400 to 2600 rad irrespective of the route of the radionuclide administration

Community pharmacy and mail order cost and utilization for 90-day maintenance medication prescriptions.

Science.gov (United States)

Khandelwal, Nikhil; Duncan, Ian; Rubinstein, Elan; Ahmed, Tamim; Pegus, Cheryl

2012-04-01

Pharmacy benefit management (PBM) companies promote mail order programs that typically dispense 90-day quantities of maintenance medications, marketing this feature as a key cost containment strategy to address plan sponsors' rising prescription drug expenditures. In recent years, community pharmacies have introduced 90-day programs that provide similar cost advantages, while allowing these prescriptions to be dispensed at the same pharmacies that patients frequent for 30-day quantities. To compare utilization rates and corresponding costs associated with obtaining 90-day prescriptions at community and mail order pharmacies for payers that offer equivalent benefits in different 90-day dispensing channels. We performed a retrospective, cross-sectional investigation using pharmacy claims and eligibility data from employer group clients of a large PBM between January 2008 and September 2010. We excluded the following client types: government, third-party administrators, schools, hospitals, 340B (federal drug pricing), employers in Puerto Rico, and miscellaneous clients for which the PBM provided billing services (e.g., the pharmacy's loyalty card program members). All employer groups in the sample offered 90-day community pharmacy and mail order dispensing and received benefits management services, such as formulary management and mail order pharmacy, from the PBM. We further limited the sample to employer groups that offered equivalent benefits for community pharmacy and mail order, defined as groups in which the mean and median copayments per claim for community and mail order pharmacy, by tier, differed by no more than 5%. Enrollees in the sample were required to have a minimum of 6 months of eligibility in each calendar year but were not required to have filled a prescription in any year. We evaluated pharmacy costs and utilization for a market basket of 14 frequently dispensed therapeutic classes of maintenance medications. The proportional share of claims for

Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

Science.gov (United States)

Clark, Charles R; Schreiner, Ceinwen A; Parker, Craig M; Gray, Thomas M; Hoffman, Gary M

2014-11-01

Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks. A portion of the animals were maintained for a four week recovery period to determine the reversibility of potential adverse effects. Increased kidney weight and light hydrocarbon nephropathy (LHN) were observed in treated male rats in all studies which were reversible or nearly reversible after 4weeks recovery. LHN is unique to male rats and is not relevant to human toxicity. The no observed effect level (NOAEL) in all studies was 10,000mg/m(3), except for G/MTBE (<2000) and G/TBA (2000). The results provide evidence that use of the studied oxygenates are unlikely to increase the hazard of evaporative emissions during refueling, compared to those from gasoline alone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Oral toxicity of Miglyol 812(®) in the Göttingen(®) minipig.

Science.gov (United States)

Le Bars, G; Dion, S; Gauthier, B; Mhedhbi, S; Pohlmeyer-Esch, G; Comby, P; Vivan, N; Ruty, B

2015-12-01

Miglyol 812(®), a mixture of medium-chain triglycerides, has been identified as an oral vehicle that could improve the solubility and possibly the bioavailability of orally administered drugs during the non-clinical safety assessment. The toxicity of Miglyol was assessed in Göttingen(®) minipigs upon daily oral administration (gavage) for six weeks, at dosing-volumes of 0.5 and 2 mL/kg/day, compared to controls receiving 0.5% CarboxyMethylCellulose/0.1% Tween(®) 80 in water at 2 mL/kg/day. The control vehicle did not induce any findings. Miglyol at 0.5 and 2 mL/kg/day induced transient tremors, abnormal color of feces and increase in triglycerides. Miglyol at 2 ml/kg/day also induced reduced motor activity, decreased food intake, respiratory signs (2/6 animals) and increased total and LDL-cholesterol. At necropsy, the lung of 3/6 animals treated at 2 mL/kg/day presented abnormal color and/or irregular surface correlated with a chronic bronchiolo-alveolar inflammation. This finding is probably due to aspiration pneumonia in relation to the administration method and the high viscosity of Miglyol. Overall, the oral administration of pure Miglyol 812(®) for six weeks up to 2 mL/kg was less tolerated than that of the control vehicle. Miglyol as vehicle for sub-chronic oral toxicity studies in minipigs should be used with a limited dosing-volume. Copyright © 2015 Elsevier Inc. All rights reserved.

Health effects of subchronic exposure to environmental levels of diesel exhaust.

Science.gov (United States)

Reed, M D; Gigliotti, A P; McDonald, J D; Seagrave, J C; Seilkop, S K; Mauderly, J L

2004-04-01

Diesel exhaust is a public health concern and contributor to both ambient and occupational air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center (NERC), a series of health assays was conducted on rats and mice exposed to environmentally relevant levels of diesel exhaust. This article summarizes the study design and exposures, and reports findings on several general indicators of toxicity and carcinogenic potential. Diesel exhaust was generated from a commonly used 2000 model 5.9-L, 6-cylinder turbo diesel engine operated on a variable-load heavy-duty test cycle burning national average certification fuel. Animals were exposed to clean air (control) or four dilutions of whole emissions based on particulate matter concentration (30, 100, 300, and 1000 microg/m(3)). Male and female F344 rats and A/J mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Exposures were characterized in detail. Effects of exposure on clinical observations, body and organ weights, serum chemistry, hematology, histopathology, bronchoalveolar lavage, and serum clotting factors were mild. Significant exposure-related effects occurring in both male and female rats included decreases in serum cholesterol and clotting Factor VII and slight increases in serum gamma-glutamyl transferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Carcinogenic potential as determined by micronucleated reticulocyte counts and proliferation of adenomas in A/J mice were unaffected by 6 mo of exposure. Parallel studies demonstrated effects on cardiac function and resistance to viral infection; however, the results reported here show few and only modest health hazards from subchronic or shorter exposures to realistic concentrations of

hepatorenal toxicity studies of sub-chronic administration of calyx

African Journals Online (AJOL)

DR. AMINU

significant (p>0.05) increase in concentrations of total protein and albumin were observed in ... suggest that high dose of calyx extracts of H.sabdariffa may be toxic to liver and kidney. .... monitoring liver damage (Wada and Snell, 1962).

Toxicological evaluation of a novel umami flavour compound: 2-(((3-(2,3-Dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

Full Text Available A toxicological evaluation of a umami flavour compound, 2-(((3-(2,3-dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine (S3643; CAS 902136-79-2, was completed for the purpose of assessing its safety for use in food and beverage applications. S3643 undergoes extensive oxidative metabolism in vitro with rat microsomes producing the S3643-sulfoxide and 4′-hydroxy-S3643 as the major metabolites. In incubations with human microsomes, the O-demethyl-S3643 and S3643-sulfoxide were produced as the major metabolites. In pharmacokinetic studies in rats, the S3643-sulfoxide represents the dominant biotransformation product. S3643 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in CHO-WBL cells. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S3643 was 100 mg/kg bw/day (highest dose tested when administered in the diet for 90 consecutive days. Keywords: Umami flavour, S3643, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis.

Science.gov (United States)

Daoust, Raoul; Emond, Marcel; Bergeron, Eric; LeSage, Natalie; Camden, Stéphanie; Guimont, Chantal; Vanier, Laurent; Chauny, Jean-Marc

2013-11-01

The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. © 2013 by the Society for Academic Emergency Medicine.

Toxicological evaluation of two novel bitter modifying flavour compounds: 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzylimidazolidine-2,4-dione and 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzyl-5,5-dimethylimidazolidine-2,4-dione

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

Full Text Available A toxicological evaluation of two novel bitter modifying flavour compounds, 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzylimidazolidine-2,4-dione (S6821, CAS 1119831-25-2 and 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzyl-5,5-dimethylimidazolidine-2,4-dione (S7958, CAS 1217341-48-4, were completed for the purpose of assessing their safety for use in food and beverage applications. S6821 undergoes oxidative metabolism in vitro, and in rat pharmacokinetic studies both S6821 and S7958 are rapidly converted to the corresponding O-sulfate and O-glucuronide conjugates. S6821 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in bone marrow polychromatic erythrocytes in vivo. S7958, a close structural analog of S6821, was also found to be non-mutagenic in vitro. In short term and subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for both S7958 and S6821 was 100 mg/kg bw/day (highest dose tested when administered as a food ad-mix for either 28 or 90 consecutive days, respectively. Furthermore, S6821 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: S6821, S7958, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

Science.gov (United States)

Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

2015-01-01

Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

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.

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

International Nuclear Information System (INIS)

McFarland, Craig A.; Quinn, Michael J.; Boyce, John; LaFiandra, Emily M.; Bazar, Matthew A.; Talent, Larry G.; Johnson, Mark S.

2011-01-01

The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD 50 values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at ≥15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: → Oral LD 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.

Clinical profile of bronchiolitis in infants younger than 90 days in Saudi Arabia

Directory of Open Access Journals (Sweden)

Syed Amir Ahmad

2014-01-01

Full Text Available Background: Bronchiolitis is a self-limiting disease of children caused by viral infections of the small airways with a wide spectrum of illness severity. Search of the literature reveals a need for refinement of criteria for testing for concomitant severe bacterial infections as well as appropriate therapeutic interventions for patients <90-day-old diagnosed with clinical bronchiolitis. We believe that a better understanding of the disease spectrum will help optimize health-care delivery to these patients. Aims: The aim of this study was to determine the clinical profile at presentation, disease course and outcome of bronchiolitis in <3-month-old infants who presented to our Pediatric Emergency Department (PED during one disease season. Settings: Retrospective chart review during one bronchiolitis season, from November 1, 2011 to April 20, 2012. Subjects: All <90-day-old infants presenting with clinical bronchiolitis presenting to Urban PED of a tertiary care university hospital during one bronchiolitis season. Materials and Methods: A retrospective chart review based on computer records of all emergency department visits of infants less than 90 days with a clinical diagnosis of bronchiolitis, covering the period between November 1, 2011 and April 30, 2012. Results: Out of the total of 1895 infants <90 days of age, 141 had a clinical diagnosis of bronchiolitis and 35 needed admission to hospital. Blood for culture was obtained from 47 infants, urine for culture was obtained from 46 infants and cerebrospinal fluid for culture was obtained from eight infants. One case of bacteremia was documented, but this was found to be a contaminant. No cases of meningitis occurred among these infants. However, one infant had a positive urine culture consistent with infection (Escherichia coli . Conclusion: Based on the results, it can be conclude that the risk of bacteremia or meningitis among infants <90 days of age with fever and bronchiolitis is low. The

Transcriptomic Analysis of Intestinal Tissues from Two 90-Day Feeding Studies in Rats Using Genetically Modified MON810 Maize Varieties

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Jutta Sharbati

2017-12-01

Full Text Available Background: Global as well as specific expression profiles of selected rat tissues were characterized to assess the safety of genetically modified (GM maize MON810 containing the insecticidal protein Cry1Ab. Gene expression was evaluated by use of Next Generation Sequencing (NGS as well as RT-qPCR within rat intestinal tissues based on mandatory 90-day rodent feeding studies. In parallel to two 90-day feeding studies, the transcriptional response of rat tissues was assessed as another endpoint to enhance the mechanistic interpretation of GM feeding studies and/or to facilitate the generation of a targeted hypothesis. Rats received diets containing 33% GM maize (MON810 or near-isogenic control maize. As a site of massive exposure to ingested feed the transcriptomic response of ileal and colonic tissue was profiled via RT-qPCR arrays targeting apoptosis, DNA-damage/repair, unfolded protein response (UPR. For global RNA profiling of rat ileal tissue, we applied NGS.Results: No biological response to the GM-diet was observed in male and in female rat tissues. Transcriptome wide analysis of gene expression by RNA-seq confirmed these findings. Nevertheless, gene ontology (GO analysis clearly associated a set of distinctly regulated transcripts with circadian rhythms. We confirmed differential expression of circadian clock genes using RT-qPCR and immunoassays for selected factors, thereby indicating physiological effects caused by the time point of sampling.Conclusion: Prediction of potential unintended effects of GM-food/feed by transcriptome based profiling of intestinal tissue presents a novel approach to complement classical toxicological testing procedures. Including the detection of alterations in signaling pathways in toxicity testing procedures may enhance the confidence in outcomes of toxicological trials. In this study, no significant GM-related changes in intestinal expression profiles were found in rats fed GM-maize MON810. Relevant

Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event.

Science.gov (United States)

Knudsen, Ib; Poulsen, Morten

2007-10-01

This article discusses the wider experiences regarding the usefulness of the 90-day rat feeding study for the testing of whole foods from genetically modified (GM) plant based on data from a recent EU-project [Poulsen, M., Schrøder, M., Wilcks, A., Kroghsbo, S., Lindecrona, R.H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Taylor, M., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007a. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design. Food Chem. Toxicol. 45, 364-377; Poulsen, M., Kroghsbo, S., Schrøder, M., Wilcks, A., Jacobsen, H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Sudhakar, D., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007b. A 90-day safety in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA). Food Chem. Toxicol. 45, 350-363; Schrøder, M., Poulsen, M., Wilcks, A., Kroghsbo, S., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Emami, K., Gatehouse, A., Shu, Q., Engel, K.-H., Knudsen, I., 2007. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats. Food Chem. Toxicol. 45, 339-349]. The overall objective of the project has been to develop and validate the scientific methodology necessary for assessing the safety of foods from genetically modified plants in accordance with the present EU regulation. The safety assessment in the project is combining the results of the 90-day rat feeding study on the GM food with and without spiking with the pure novel gene product, with the knowledge about the identity of the genetic change, the compositional data of the GM food, the results from in-vitro/ex-vivo studies as well as the results from the preceding 28-day toxicity study with the novel gene product, before the hazard characterisation is concluded. The results demonstrated the ability of the 90-day rat feeding study to detect the biological/toxicological effects of the

Subchronic Inhalation Toxicity Study of n-pentane in Rats

Directory of Open Access Journals (Sweden)

Jong-Kyu Kim

2012-09-01

Conclusion: The no-observable-adverse-effect level (NOAEL of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS.

FDA toxicity databases and real-time data entry

International Nuclear Information System (INIS)

Arvidson, Kirk B.

2008-01-01

Structure-searchable electronic databases are valuable new tools that are assisting the FDA in its mission to promptly and efficiently review incoming submissions for regulatory approval of new food additives and food contact substances. The Center for Food Safety and Applied Nutrition's Office of Food Additive Safety (CFSAN/OFAS), in collaboration with Leadscope, Inc., is consolidating genetic toxicity data submitted in food additive petitions from the 1960s to the present day. The Center for Drug Evaluation and Research, Office of Pharmaceutical Science's Informatics and Computational Safety Analysis Staff (CDER/OPS/ICSAS) is separately gathering similar information from their submissions. Presently, these data are distributed in various locations such as paper files, microfiche, and non-standardized toxicology memoranda. The organization of the data into a consistent, searchable format will reduce paperwork, expedite the toxicology review process, and provide valuable information to industry that is currently available only to the FDA. Furthermore, by combining chemical structures with genetic toxicity information, biologically active moieties can be identified and used to develop quantitative structure-activity relationship (QSAR) modeling and testing guidelines. Additionally, chemicals devoid of toxicity data can be compared to known structures, allowing for improved safety review through the identification and analysis of structural analogs. Four database frameworks have been created: bacterial mutagenesis, in vitro chromosome aberration, in vitro mammalian mutagenesis, and in vivo micronucleus. Controlled vocabularies for these databases have been established. The four separate genetic toxicity databases are compiled into a single, structurally-searchable database for easy accessibility of the toxicity information. Beyond the genetic toxicity databases described here, additional databases for subchronic, chronic, and teratogenicity studies have been prepared

Unplanned emergency department consultations and readmissions within 30 and 90 days of bariatric surgery.

Science.gov (United States)

Iskra, María P; Ramón, José M; Martínez-Serrano, Andrés; Serra, Carmen; Goday, Albert; Trillo, Lourdes; Lanzarini, Enrique; Pera, Manuel; Grande, Luis

2018-04-01

Hospital readmission is used as a measure of quality healthcare. The aim of this study was to determine the incidence, causes, and risk factors related to emergency consultations and readmissions within 30 and 90 days in patients undergoing laparoscopic gastric bypass and laparoscopic sleeve gastrectomy. Retrospective study of 429 patients operated on from January 2004 to July 2015 from a prospectively maintained database and electronic medical records. Demographic data, type of intervention, postoperative complications, length of hospital stay and records of emergency visits and readmissions were analyzed. Within the first 90 days postoperative, a total of 117 (27%) patients consulted the Emergency Department and 24 (6%) were readmitted. The most common reasons for emergency consultation were noninfectious problems related to the surgical wound (n=40, 34%) and abdominal pain (n=28, 24%), which was also the first cause of readmission (n=9, 37%). Postoperative complications, reintervention, associated surgery in the same operation and depression were risk factors for emergency consultation within the first 90 days of the postoperative period. Despite the high number of patients who visit the Emergency Department in the first 90 days of the postoperative period, few require readmission and none surgical reoperation. It is important to know the reasons for emergency consultation to establish preventive measures and improve the quality of care. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

High-sensitivity c-reactive protein (hs-CRP) value with 90 days mortality in patients with heart failure

Science.gov (United States)

Nursyamsiah; Hasan, R.

2018-03-01

Hospitalization in patients with chronic heart failure is associated with high rates of mortality and morbidity that during treatment and post-treatment. Despite the various therapies available today, mortality and re-hospitalization rates within 60 to 90 days post-hospitalization are still quite high. This period is known as the vulnerable phase. With the prognostic evaluation tools in patients with heart failure are expected to help identify high-risk individuals, then more rigorous monitoring and interventions can be undertaken. To determine whether hs-CRP have an impact on mortality within 90 days in hospitalized patients with heart failure, an observational cohort study was conducted in 39 patients with heart failure who were hospitalized due to worsening chronic heart failure. Patients were followed for up to 90 days after initial evaluation with the primary endpoint is death. Hs-CRP value >4.25 mg/L we found 70% was dead and hs-CRP value <4.25 mg/L only 6.9% was dead whereas the survival within 90 days. p:0.000.In conclusion, there were differences in hs-CRP values between in patients with heart failure who died and survival within 90 days.

Toxicity of 90Sr inhaled in a relatively insoluble form by Beagle dogs. IX

International Nuclear Information System (INIS)

Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1978-01-01

Studies on the biological effects of 90 Sr inhaled in a relatively insoluble form by Beagle dogs are being conducted to define the biological consequences of inhaling this radionuclide in a form which has a long retention time in the lung. One hundred and six dogs were exposed to a polydisperse aerosol (AMAD 1.4 to 2.8 μm and sigma/sub g/ 1.4 to 2.7) of fused aluminosilicate particles labeled with 90 Sr. Initial lung burdens ranged from 0.21 to 94 μCi 90 Sr per kilogram of body weight (μCi/kg). Eighteen control dogs were exposed to an aerosol of stable strontium in fused aluminosilicate particles. To date, 34 dogs having initial lung burdens of 8.9 to 94 μCi 90 Sr/kg and cumulative doses to lung of 33,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis between 159 and 2596 days after exposure. Twenty-nine dogs with initial lung burdens of 3.7 to 36 μCi 90 Sr/kg and cumulative doses to lung of 13,000 to 68,000 rads have died from hemangiosarcomas in the lung, heart or mediastinum between 644 and 2565 days after exposure. In addition, one dog developed a bronchioloalveolar carcinoma, another developed epidermoid carcinoma of the lung, another died of pneumonia while recovering from anesthesia, one dog died at 1821 days after exposure with an hemangiosarcoma of the spleen and two dogs developed squamous cell carcinomas in the nasal cavity. During the past year one dog was euthanized 2753 days after exposure (34,000 rads lung dose) as a result of an hemangiosarcoma which developed in a rib and spread widely. Another dog died 2830 days after exposure (35,000 rads lung dose) with a squamous cell carcinoma in the lung. An additional dog was euthanized 2636 days after exposure (12,000 rads lung dose) with widespread hemangiosarcoma of unknown origin. The remaining 36 exposed dogs and 18 controls are surviving at 1387 to 3168 days after exposure

Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

Energy Technology Data Exchange (ETDEWEB)

Steinbach, Christoph, E-mail: steinbach@frov.jcu.cz [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Fedorova, Ganna [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Prokes, Miroslav [Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, v.v.i., Kvetna 8, 603 65 Brno (Czech Republic); Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic)

2013-09-01

Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L{sup −1} to μg L{sup −1}. In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC{sub 50} values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L{sup −1} for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L{sup −1}. Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L{sup −1} of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of

Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

International Nuclear Information System (INIS)

Steinbach, Christoph; Fedorova, Ganna; Prokes, Miroslav; Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour

2013-01-01

Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L −1 to μg L −1 . In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC 50 values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L −1 for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L −1 . Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L −1 of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of common carp. • The

Risk factors for 90-day readmission in veterans with inflammatory bowel disease-Does post-discharge follow-up matter?

Science.gov (United States)

Malhotra, Ashish; Phatharacharukul, Parkpoom; Thongprayoon, Charat

2018-02-08

Repeat hospitalizations in veterans with inflammatory bowel disease (IBD) are understudied. The early readmission rate and potentially modifiable risk-factors for 90-day readmission in veterans with IBD were studied to avert avoidable readmissions. A retrospective cohort study was conducted using the data from veterans who were admitted to the Minneapolis VA Medical Center (MVMC) between January 1, 2007, and December 31, 2013, for an IBD-related problem. All-cause readmissions within 30 and 90 days were recorded to calculate early readmission rates. The multivariate logistic regression was used to identify the potential risk factors for 90-day readmission. There were 130 unique patients (56.9% with Crohn's disease and 43.1% with ulcerative colitis) with 202 IBD-related index admissions. The mean age at the time of index admission was 59.8 ± 15.2 years. The median time to re-hospitalization was 26 days (IQR 10-49), with 30- and 90-day readmission rates of 17.3% (35/202) and 29.2% (59/202), respectively. Reasons for all-cause readmission were IBD-related (71.2%), scheduled surgery (3.4%) and non-gastrointestinal causes (25.4%). The following reasons were independently associated with 90-day readmission: Crohn's disease (OR 3.90; 95% CI 1.82-8.90), use of antidepressants (OR 2.19; 95% CI 1.12-4.32), and lack of follow-up within 90 days with a primary care physician (PCP) (OR 2.63; 95% CI 1.32-5.26) or a gastroenterologist (GI) (OR 2.44; 95% CI 1.20-5.00). 51.0% and 49.0% of patients had documentation of a recommended outpatient follow-up with PCP and/or GI, respectively. Early readmission in IBD is common. Independent risk factors for 90-day readmission included Crohn's disease, use of antidepressants and lack of follow-up visit with PCP or GI. Further research is required to determine if the appropriate timing of post-discharge follow-up can reduce IBD readmissions.

Toxicity of inhaled 90Sr in fused aluminosilicate particles in beagle dogs. VIII

International Nuclear Information System (INIS)

Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1977-01-01

Studies on the metabolism, dosimetry and biological effects of 90 Sr inhaled in a relatively insoluble form by Beagle dogs have continued during the past year to define the biological consequences of inhaling this important radionuclide in a form which has a long retention time in the lung. One hundred and six dogs were exposed to a polydisperse aerosol of fused aluminosilicate particles labeled with 90 Sr. Initial lung burdens ranged from 0.21 to 94 μCi 90 Sr per kilogram of body weight (μCi/kg). Eighteen control dogs were exposed to an aerosol of stable strontium in fused aluminosilicate particles. These 124 dogs were assigned to the longevity study. An additional 26 dogs were exposed similarly to achieve lung burdens of approximately 1.5 to 12 μCi/kg and assigned for sacrifice at intervals after exposure to define metabolism and dosimetry of this aerosol in Beagle dogs. Of the longevity dogs, 33 dogs having initial lung burdens of 16 to 94 μCi 90 Sr/kg and cumulative doses to lung of 40,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis from 159 to 2373 days after exposure. Thirty-one dogs with initial lung burdens of 3.7 to 36 μCi 90 Sr/kg and cumulative doses to lung of 13,000 to 68,000 rads have died from hemangiosarcomas in the lung or heart between 644 and 2565 days after exposure. In addition, one dog developed a bronchioloalveolar carcinoma, another developed epidermoid carcinoma of the lung, another died of pneumonia while recovering from anesthesia, one dog died at 1821 days after exposure with a hemangiosarcoma of the spleen and two dogs developed squamous cell carcinomas in the nasal cavity. The remaining exposed dogs and controls of the longevity study are surviving at 1022 to 2803 days after exposure

PENGARUH PEMBERIAN SUBKRONIK EKSTRAK KELOPAK BUNGA ROSELLA (Hibiscus Sabdariffa L. TERHADAP KADAR SGPT SGOT DAN ALP

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Nurkhasanah Nurkhasanah

2016-11-01

Full Text Available Roselle (Hibiscus sabdariffa L. has been known as traditional medicinal plants. It needed to evaluate the safety of roselle extract on long-term oral administration. The research aimed to determine the savety of ethanolic extract of roselle calyx. Subchronic toxicity study of ethanolic extract of roselle calyx had been carried out on 60 Sprague Dawleys (SD rats for 28 days. The roselle extract was administered orally every day, with doses of 50,100 and 200 mg/kgBW. There are 2 satellite groups, kept for another 14 days after the treatment in order to detect a delayed occurrence of toxic effect. Satellite group was given extract 200 mg/kgBW for 28 days and followed aquadest treatment for 14 days. At the end of experiment the blood was collected for meansuring SGPT, SGOT and ALP activity. The result showed that treatment of roselle calyx extract had no significant changes in SGPT SGOT, ALP activity. The delayed effect was not also observed. The ethanolic extract of roselle calyx didn’t show toxic effects on the liver on subchronic administration.

Kinetics of introduction of micronucleated polychromatic erythrocytes in bone marrow and peripheral blood following subchronic microwave exposure

International Nuclear Information System (INIS)

Trosic, I.; Busljeta, I.; Pavicic, I.; Modlic, B.

2005-01-01

The aim of this study was to investigate the induction kinetics of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow (BM) and peripheral blood (PB) of rats during intermittent subchronic exposure to selected radiofrequency microwave (RF/MW) radiation. Rats were exposed to RF/MW 2.45 GHz, power density 5-10 mW/cm 2 2 hours a day, 7 days a week. The specific absorption rate (SAR) was 1.25±0.36 W/kg. The study included control groups. After the animals were killed, BM and PB smears were supravitally stained and MN frequency was recorded for both PB and BM by scoring 1000 PCEs/slides. The results were analysed using StatSoft 95 package. In comparison with controls, the MN frequency in BM significantly increased on experimental day 15. BM MN frequencies were elevated in each experimental phase. The incidence of MNPCEs in PB significantly increased after eight two-hour exposures. From that point on, MNPCEs declined to reach control values by the end of the experiment. These findings could indicate radiation effects on BM erythropoiesis and their reflection on PB. The kinetics MNPCE induction in BM and PB of irradiated rats revealed a complex chain of events, including temporary imbalance in erythrocyte maturation and/or proliferation processes, followed by a feedback mechanism of the homeostatic control system, and possible elimination of MNPCEs from PB by mononuclear phagocytes. This points to an adaptive mechanism in rats in response to experimental subchronic RF/MW exposure.(author)

Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats

International Nuclear Information System (INIS)

Seacat, Andrew M.; Thomford, Peter J.; Hansen, Kris J.; Clemen, Lisa A.; Eldridge, Sandra R.; Elcombe, Cliff R.; Butenhoff, John L.

2003-01-01

Perfluorooctanesulfonate (PFOS) is a widely disseminated persistent compound found at low (part-per-billion) concentrations in serum and liver samples from humans and fish-eating wildlife. This study investigated the hypotheses that early hepatocellular peroxisomal proliferation and hepatic cellular proliferation are factors in chronic liver response to dietary dosing, that lowering of serum total cholesterol is an early clinical measure of response to treatment, and that liver and serum PFOS concentrations are proportional to dose and cumulative dose after sub-chronic treatment. PFOS was administered in diet as the potassium salt at 0, 0.5, 2.0, 5.0, and 20 parts per million (ppm) to Sprague Dawley rats for 4 or 14 weeks. At 4 weeks, effects included decreased serum glucose and an equivocal (< twofold) increase in hepatic palmitoyl CoA oxidase (PCoAO) activity in 20 ppm dose-group males and elevation of alanine aminotransferase (ALT) in 20 ppm dose-group females. At 14 weeks, the 20 ppm males had increased liver weight, decreased serum cholesterol, increased non-segmented neutrophils, and increased ALT. Relative liver weights and urea nitrogen were increased in both sexes at 14 weeks. Hepatocytic hypertrophy and cytoplasmic vacuolation were observed in the 5 or 20 ppm male and the 20 ppm female dose groups. An increase in hepatic PCoAO activity was not observed at 14 weeks, and the average hepatocyte proliferation index was not increased, although, individual animals had mild increases. Serum and liver PFOS concentrations were proportional to dose and cumulative dose. Serum concentrations were generally higher in females than in males. The liver-to-serum PFOS ratios ranged from approximately 3:1 to 12:1. After 14 weeks, the no-observed-adverse effect level (NOAEL) in males and females was 5 ppm. The NOAEL corresponded to mean serum PFOS concentrations of 44 ppm (μg/ml) in males and 64 ppm in females and mean liver PFOS concentrations of 358 ppm in males and 370

Evaluation of platelet lymphocyte ratio and 90-day mortality in patients with acute exacerbation of chronic obstructive pulmonary disease.

Science.gov (United States)

Kumar, Praneel; Law, Stephanie; Sriram, Krishna B

2017-06-01

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have high mortality and health care costs. The platelet to lymphocyte ratio (PLR) is a marker of inflammation and has been reported to be elevated in patients with AECOPD compared to stable state. In this study, we sought to evaluate the association of the PLR in patients with AECOPD with 90-day mortality. We conducted a retrospective cohort study of patients admitted to our institution with a primary diagnosis of AECOPD between January 2014 and July 2014. Blood test results on admission were recorded. The primary outcomes were 90-day mortality. One hundred and eighty-one AECOPD patients were considered for the study. Death had occurred in 16 (9%) patients within 90 days of hospital discharge. Univariable analysis identified age, haemoglobin, neutrophil count, and urea level, neutrophil lymphocyte ratio (NLR) and PLR as being associated with increased 90-day mortality. Multivariable logistic regression analysis variables demonstrated that only PLR (P=0.03) was significantly associated with death at 90 days. Receiver operator characteristic analysis identified PLR ≥235 had a sensitivity of 63% and specificity of 74% in predicting 90-day mortality. PLR was ≥235 was also associated with worse survival (days) [mean ± standard deviation (SD): PLR ≥235 vs. PLR <235: 512±358 vs. 626±346, P=0.004]. A PLR ≥235 was significantly associated with 90-day mortality, which may provide prognostic guidance to clinicians.

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

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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.

Toxicity of inhaled 90Y in fused clay particles in beagle dogs. VI

International Nuclear Information System (INIS)

Hobbs, C.H.; Chiffelle, T.L.; Hahn, F.F.; Jones, R.K.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1974-01-01

Studies on the metabolism, dosimetry, and effects of inhaled 90 Y in fused clay in the Beagle dog are being continued to assess the consequences of inhalation of an energetic beta emitter that has a short effective half-life in the lung. A radiation dose pattern study in which 12 dogs were sacrificed in pairs at 0, 2, 4, 6, 8, and 12 days post-inhalation exposure has been completed. A longevity study in which 89 dogs have been exposed to 90 Y fused clay with initial lung burdens ranging from 80 to 5200 μCi/kg body weight and 12 control dogs were exposed to stable yttrium in fused clay is in progress. The 90 Y was retained in lung with a half-life similar to its physical half-life (64 hours) and with only small quantities translocated to tracheobronchial lymph nodes, skeleton, and liver. The infinite radiation doses to lung, tracheobronchial lymph nodes, skeleton, and liver for an initial lung burden of 100 μCi 90 Y/kg of body weight were estimated to be 1600, 170, 0.54, and 0.38 rads, respectively. Thirty-eight of 39 dogs with doses to lung from 9300 to 70,000 rads have died at 7.5 to 903 days post-exposure. The one surviving dog in this dose range has radiographic evidence of pulmonary fibrosis at 1316 days post-exposure. All the dogs that died had radiation pneumonitis. The dog that died at 903 days post-exposure with a dose to lung of 11,000 rads also had 2 small pulmonary adenomas. Fifty exposed dogs with doses to lung of 1300 to 7900 rads are surviving with no significant abnormalities at 1278 to 1834 days post-exposure and will be studied for the remainder of their lifespan. (U.S.)

Toxicological assessment of the hydroethanolic leaf extract of ...

African Journals Online (AJOL)

Introduction: Clerodendrum capitatum (Willd) Schumach. & Thonn (Lamiaceae) is used in African traditional medicine for the treatment of malaria, hypertension, obesity, jaundice and diabetes however there is lack of experimental data on its possible toxicity. This study investigated the acute and 28 days sub-chronic toxicity ...

E-submission Format for Sub-chronic and Chronic Studies

Science.gov (United States)

The purpose of this document is to suggest the format for final reports and to provide instructions for creation of Adobe PDF electronic submission documents for electronic submission of sub-chronic and chronic studies for pesticides.

Haematogical changes induced by subchronic glyphosate exposure ...

African Journals Online (AJOL)

The aim of this study was to determine the haematological changes induced by subchronic glyphosate exposure in Wistar rats and the ameliorative effect of zinc. Sixty adult male and female Wistar rats were used for the study. Twelve of them were used for the LD50 which was evaluated to be 3750 mg kg-1 with clinical ...

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

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Ramaswamy Ramaswamy

2012-10-01

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

Clinical Outcomes and 90-Day Costs Following Hemiarthroplasty or Total Hip Arthroplasty for Hip Fracture.

Science.gov (United States)

Nichols, Christine I; Vose, Joshua G; Nunley, Ryan M

2017-09-01

In the era of bundled payments, many hospitals are responsible for costs from admission through 90 days postdischarge. Although bundled episodes for hip fracture will have a separate target price for the bundle, little is known about the 90-day resource use burden for this patient population. Using Medicare 100% Standard Analytic Files (2010-2014), we identified patients undergoing hemiarthroplasty or total hip arthroplasty (THA). Patients were aged 65 and older with admitting diagnosis of closed hip fracture, no concurrent fractures of the lower limb, and no history of hip surgery in the prior 12 months baseline. Continuous Medicare-only enrollment was required. Complications, resource use, and mortality from admission through 90 days following discharge (follow-up) were summarized. Four cohorts met selection criteria for analysis: (1) hemiarthroplasty diagnosis-related group (DRG) 469 (N = 19,634), (2) hemiarthroplasty DRG 470 (N = 77,744), (3) THA DRG 469 (N = 1686), and (4) THA DRG 470 (N = 9314). All-cause mortality during the study period was 51.6%, 29.5%, 48.1%, and 24.9% with mean 90-day costs of $28,952, $19,243, $29,763, and $18,561, respectively. Most of the patients waited 1 day from admission to surgery (41%-51%). Incidence of an all-cause complication was approximately 70% in each DRG 469 cohort and 14%-16% in each DRG 470 cohort. This study confirms patients with hip fracture are a costly subpopulation. Tailored care pathways to minimize post-acute care resource use are warranted for these patients. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Long-term (30 days toxicity of NiO nanoparticles for adult zebrafish Danio rerio

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Kovrižnych Jevgenij A.

2014-03-01

Full Text Available Nickel oxide in the form of nanoparticles (NiO NPs is extensively used in different industrial branches. In a test on adult zebrafish, the acute toxicity of NiO NPs was shown to be low, however longlasting contact with this compound can lead to its accumulation in the tissues and to increased toxicity. In this work we determined the 30-day toxicity of NiO NPs using a static test for zebrafish Danio rerio. We found the 30-day LC50 value to be 45.0 mg/L, LC100 (minimum concentration causing 100% mortality was 100.0 mg/L, and LC0 (maximum concentration causing no mortality was 6.25 mg/L for adult individuals of zebrafish. Considering a broad use of Ni in the industry, NiO NPs chronic toxicity may have a negative impact on the population of aquatic organisms and on food web dynamics in aquatic systems.

<90 day storage training plan for the 103-B, 1701-BA, AND 1714-C buildings

International Nuclear Information System (INIS)

Snider, P.M.

1996-10-01

The 103-B, 1701-BA, and 1714C < 90 Day Storage Area stores characteristic wastes generated in the demolition of the 103-B, 1701-BA, and 1714-C Complex. Wastes (lead-based painted components) are packaged and stored in vendor shipment containers. This is the Environmental Restoration Contractor team training plan for the 103-B, 1701-BA, and 1714-C subgrade demolition < 90 Day Storage of Hazardous Waste. This document is intended to meet the requirements of Washington Administrative Code 173-303-330 and the Hanford Dangerous Waste Permit. Training unrelated to compliance with WAC 173-303-330 is not addressed in this training plan. WAC 173-303-330(1)(d)(2, 5, 6) requires that personnel be familiarized, where applicable, with waste feed cut-off systems, response to ground-water contamination incidents, and shutdown of operations. These are not applicable to 103-B, 1701-BA, and 1714-C Subgrade Demolition < 90 Day Storage, and therefore are not covered in this training plan

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Liver Effects

Science.gov (United States)

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Shymonyak, Svitlana; Uehara, Takeki; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of inter-individual variability in TCE metabolism and toxicity, especially in the liver. We tested a hypothesis that amounts of oxidative metabolites of TCE in mouse liver are associated with liver-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various liver toxicity phenotypes. In sub-acute study, inter-strain variability in TCE metabolite amounts was observed in serum and liver. No induction of Cyp2e1 protein levels in liver was detected. Serum and liver levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1, but not with degree of induction in hepatocellular proliferation. In sub-chronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Liver protein levels of Cyp2e1, Adh and Aldh2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE. PMID:25424544

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

International Nuclear Information System (INIS)

Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

2011-01-01

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents

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Marcelia Garcez Dória de Melo

2011-12-01

Full Text Available Atranorin (ATR is the main compound from the lichen Cladina kalbii Ahti, which grows in the arid regions of northeastern Brazil. This study was conducted to evaluate the anti-inflammatory and toxicological properties of ATR. To evaluate anti-inflammatory properties, paw edema was induced by injecting 0.1 mL of carrageenan into the subplantar region of the right hind paw of rats, and leukocyte migration was induced by injection of 500 µL of carrageenan into the peritoneal cavity of mice. In addition, we determined ATR cytotoxicity in L929 cells by MTT assay and acute (5 g/kg-single dose and subchronic (50 mg/kg-30 days toxicity tests in Wistar rats. The results showed that ATR (100 mg/kg and 200 mg/kg exhibited significant anti-inflammatory activity (paw edema and leukocyte migration. In the acute toxicity test, the animals showed hypoactivity and lethargy during the initial period (first 6 hours and increase in total protein, total and indirect bilirubin, and alkaline phosphatase after 14 days in ATR-treated male rats. The subchronic toxicity test revealed increases in total protein, globulin, gamma-glutamyl transferase, alkaline phosphatase, and total and direct bilirubin in ATR-treated female rats. Histological analysis revealed no changes in the architecture and morphology of the organs. These results suggest that ATR has significant anti-inflammatory activity, with no significant acute and subchronic toxicity or cytotoxicity.Atranorina (ATR é o principal composto do líquen Cladina kalbii Ahti, que cresce em terras áridas do nordeste brasileiro. Este estudo foi realizado para avaliar as propriedades antiinflamatórias e toxicológicas da ATR. Para avaliar as propriedades antiinflamatórias, o edema de pata foi induzido, administrando-se 0,1 mL de carragenina na região subplantar da pata traseira direita e a migração leucocitária foi induzida pela injeção de 500 µL de carragenina no peritônio. Além disso, determinou-se a

Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

DEFF Research Database (Denmark)

Eck, Lasse Karlsen; Jensen, Thomas Bo; Mastrogiannis, Dimitrios

2017-01-01

OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring. METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997...... group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers. CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available...

Digoxin Toxicity in a 14 Days Old Newborn: A Case Report

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İclal Sucaklı

2006-01-01

Full Text Available Digoxin is one of the most commonly used positive inotropic agent. Digitalis toxicity may occur easily because of digoxin has a narrow therapeutic window. Digitalis toxicity may result during treatment with digoxin or from accidental overdose of digoxin. An elevated serum level of digoxin (>2ng/ml is likely to be associated with toxicity, overdose of digoxin (>5ng/ml may lead to life-threatening arrhythmias. A 14-days old newborn with VSD, which had been prescribed the droplet form of digoxin but given the tablet form by the drugstore, was diagnosed as digitalis toxicity and hospitalized to our clinic. His mother expressed that she had given two tablets mashed with spoon and diluted. Bradycardia and grade 3/6 pansystolic murmur was determined in physical examination. Digoxin level in serum was >5 ng/ml and there was third degree atrioventricular block in ECG findings. The case has been presented to emphasize the importance of better evaluation of digoxin indications and making families of the patients conscious of the usage of digoxin.

Effects of lifetime ingestion of 90Sr in beagle dogs

International Nuclear Information System (INIS)

Book, S.A.; Spangler, W.L.; Swartz, L.A.

1982-01-01

To investigate the effects of lifetime 90 Sr ingestion, fifteen beagle dogs were fed the equivalent of 1.3, 4.0, and 12.0 μCi 90 Sr. Exposures prior to weaning were made by maternal administration of one of the same 90 Sr levels, begining at 21 days of gestation. Median survival was 12.5 years for the 1.3 μCi/day group, 6.5 years for the 4 μCi/day group, and 5.2 years of the 12 μCi/day group, compared to unirradiated control values of 14.5 to 15 years. The normal life span of more than half of the 1.3 μCi/day group is remarkable, considering they ingested 5900 to 7500 μCi 90 Sr during their lifetimes. One of seven 1.3 μCi/day dogs died of mycloproliferative syndrome (MPS), while one of four 4 μCi/day and one of four 12 μCi/day dogs died from MPS. In addition, another 12 μCi/day dog died of osteosarcoma and two others in the same group showed skeletal changes related to 90 Sr exposure. Other deaths were as could be expected in normal canine populations. Lifetime skeletal doses, determined by periodic whole-body counting, were 1990-3750, 1880-9230, and 6360-14,680 rad for the 1.3, 4, and 12 μCi/day groups, respectively. Comparison of these values with those from the large 90 Sr toxicity study at Davis in which 90 Sr feeding ended at 18 months of age indicates similar average skeletal doses from the two types of feeding regimens. The similarity of the skeletal doses may relate to the inability of 90 Sr to be incorporated to any great extent into a mature skeleton that no longer has the high calcium turnover associated with early life. As a result, deaths from lifetime 90 Sr ingestion appeared no earlier than when 90 Sr ingestion ended in early adulthood

Toxicity of inhaled 90Sr fused clay particles in beagle dogs. V

International Nuclear Information System (INIS)

Snipes, M.B.; Boecker, B.B.; Hahn, F.F.; Hobbs, C.H.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1974-01-01

Studies on the metabolism, dosimetry, and biological effects of 90 Sr in fused clay particles in Beagle dogs have continued with a view toward defining the biological consequences of inhaling this important radionuclide in a relatively insoluble form. Seventy-two dogs were exposed to a polydisperse aerosol (AMAD 1.4 to 2.8 μm and sigma/sub g/ 1.4 to 2.7) of fused montmorillonite clay particles labeled with 90 Sr to achieve graded initial lung burdens (ILB) of 3.7 to 94 μCi/kg body weight; 12 control dogs were exposed to an aerosol of stable strontium in fused clay particles. These 84 dogs were assigned to the 90 Sr fused clay longevity study. An additional 26 dogs were exposed similarly (AMAD 1.9 to 2.5 μm and sigma/sub g/ 1.6 to 2.0) and assigned for sacrifice (Series II) at intervals after exposure to define metabolism and dosimetry of this aerosol in Beagle dogs. Of the 72 longevity dogs, 32 dogs having ILBs of 29 to 94 μCi/kg and cumulative doses to lung to death of 40,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis from 159 to 477 days post-exposure. Fourteen dogs with ILBs of 15 to 36 μCi/kg and cumulative doses to lung to death of 34,000 to 68,000 rads have died from primary pulmonary hemangiosarcomas between 644 and 1214 days post-exposure. In addition, one dog developed a bronchiolo-alveolar carcinoma, another epidermoid carcinoma of the lung and a third, a squamous cell carcinoma in the nasal cavity. The remaining 26 exposed dogs and 12 controls of the longevity study are surviving at 1070 to 1707 days post-exposure. Dogs in the sacrifice series have been sacrificed to 1536 days post-exposure. (U.S.)

Time course and reasons for 90-day mortality in fast-track hip and knee arthroplasty

DEFF Research Database (Denmark)

Jørgensen, C C; Kehlet, H

2017-01-01

: Prospective observational study in 13,775 consecutive THA/TKAs with similar fast-track protocols and a median length of stay of 2 days. Complete 90-days follow-up through national registries, followed by review of medical records and death certificates. Relation between mortality and surgically induced organ...

Mercury accumulation and its distribution to metallothionein in mouse brain after sub-chronic pulse exposure to mercury vapor

Energy Technology Data Exchange (ETDEWEB)

Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Sawada, M.; Shimada, A. [Department of Veterinary Pathology, Tottori University, 4-101 Koyamacho, Minami, Tottori 680-0945 (Japan); Satoh, M. [Department of Hygienics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585 (Japan); Tohyama, C. [Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)

2004-09-01

Previously we found that exposure to mercury vapor effectively induced metallothionein (MT) biosynthesis in rat brain. Although the induction of not only MT-I/II but also MT-III was evident, the induction rate of the latter was much lower than that of the former. The brain of an MT-null mouse lacks MT-I/II, but has MT-III. Here we examined the effects of sub-chronic pulse exposure to mercury vapor on the brain MT in MT-null mice and their wild type controls. MT-null and wild type mice were preliminarily exposed to mercury vapor for 2 weeks at 0.1 mg Hg/m{sup 3} for 1 h/day for 3 days a week, and then exposed for 11 weeks at 4.1 mg Hg/m{sup 3} for 30 min/day for 3 days a week. This exposure caused no toxic signs such as abnormal behavior or loss of body weight gain in the mice of either strain throughout the experimental period. Twenty-four hours after the termination of the exposure, mice were sacrificed and brain samples were subjected to mercury analysis, MT assay, and pathological examination. The MT-null mice showed lower accumulation of mercury in the brain than the wild type mice. Mercury exposure resulted in a 70% increase of brain MT in the wild type mice, which was mostly accounted for by the increase in MT-I/II. On the other hand, the brain MT in the MT-null mice increased by 19%, suggesting less reactivity of the MT-III gene to mercury vapor. Although histochemical examination revealed silver-mercury grains in the cytoplasm of nerve cells and glial cells throughout the brains of both strains, no significant difference was observed between the two strains. (orig.)

Climate Prediction Center (CPC)Ensemble Canonical Correlation Analysis 90-Day Seasonal Forecast of Precipitation

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Ensemble Canonical Correlation Analysis (ECCA) precipitation forecast is a 90-day (seasonal) outlook of US surface precipitation anomalies. The ECCA uses...

Comparative toxicity of strontium-90 and radium-226 in beagle dogs

International Nuclear Information System (INIS)

Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

1990-01-01

The authors are completing a 30-year study of the biologic effects of 90 Sr and 226 Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of 90 Sr, (b) a single intravenous injection of 90 Sr, or (c) a series of eight intravenous injections of 226 Ra. Although administration of 90 Sr and 226 Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for 90 Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90 Sr. The last of the dogs died in 1986 at age 18.5, but the authors are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses

Comparative toxicity of strontium-90 and radium-226 in beagle dogs

International Nuclear Information System (INIS)

Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

1991-01-01

The authors are completing a 30-year study of the biological effects of 90 Sr and 226 Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of 90 Sr, (b) a single intravenous injection of 90 Sr, or (c) a series of eight intravenous injections of 226 Ra. Although administration of 90 Sr and 226 Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for 90 Sr and in exposures that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90 Sr. The last of the dogs died in 1986 at age 18.5 years, but the authors are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses

Effects of inorganic lead on Western fence lizards (Sceloporus occidentalis)

International Nuclear Information System (INIS)

Salice, Christopher J.; Suski, Jamie G.; Bazar, Matthew A.; Talent, Larry G.

2009-01-01

Although anthropogenic pollutants are thought to threaten reptilian species, there are few toxicity studies on reptiles. We evaluated the toxicity of Pb as lead acetate to the Western fence lizard (Sceloporus occidentalis). The acute lethal dose and sub-acute (14-day) toxicity studies were used to narrow exposure concentrations for a sub-chronic (60-day) study. In the sub-chronic study, adult and juvenile male lizards were dosed via gavage with 0, 1, 10 and 20 mg Pb/kg-bw/day. Mortality was limited and occurred only at the highest dose (20 mg Pb/kg-bw/d). There were statistically significant sub-lethal effects of 10 and 20 mg Pb/kg-bw/d on body weight, cricket consumption, organ weight, hematological parameters and post-dose behaviors. Of these, Pb-induced changes in body weight are most useful for ecological risk assessment because it is linked to fitness in wild lizard populations. The Western fence lizard is a useful model for reptilian toxicity studies. - The Western fence lizard, Sceloporus occidentalis, is sensitive to Pb and is a useful laboratory model for ecotoxicological testing of reptiles.

Effects of inorganic lead on Western fence lizards (Sceloporus occidentalis)

Energy Technology Data Exchange (ETDEWEB)

Salice, Christopher J., E-mail: chris.salice@ttu.ed [US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD 21010 (United States); Suski, Jamie G., E-mail: jamie.suski@ttu.ed [US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD 21010 (United States); Bazar, Matthew A., E-mail: matthew.bazar@us.army.mi [US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD 21010 (United States); Talent, Larry G., E-mail: larry.talent@okstate.ed [Oklahoma State University, Department of Natural Resource Ecology and Management, Stillwater, OK 74078 (United States)

2009-12-15

Although anthropogenic pollutants are thought to threaten reptilian species, there are few toxicity studies on reptiles. We evaluated the toxicity of Pb as lead acetate to the Western fence lizard (Sceloporus occidentalis). The acute lethal dose and sub-acute (14-day) toxicity studies were used to narrow exposure concentrations for a sub-chronic (60-day) study. In the sub-chronic study, adult and juvenile male lizards were dosed via gavage with 0, 1, 10 and 20 mg Pb/kg-bw/day. Mortality was limited and occurred only at the highest dose (20 mg Pb/kg-bw/d). There were statistically significant sub-lethal effects of 10 and 20 mg Pb/kg-bw/d on body weight, cricket consumption, organ weight, hematological parameters and post-dose behaviors. Of these, Pb-induced changes in body weight are most useful for ecological risk assessment because it is linked to fitness in wild lizard populations. The Western fence lizard is a useful model for reptilian toxicity studies. - The Western fence lizard, Sceloporus occidentalis, is sensitive to Pb and is a useful laboratory model for ecotoxicological testing of reptiles.

Factors Predictive of 90-Day Morbidity, Readmission, and Costs in Patients Undergoing Pelvic Exenteration.

Science.gov (United States)

Bogani, Giorgio; Signorelli, Mauro; Ditto, Antonino; Martinelli, Fabio; Casarin, Jvan; Mosca, Lavinia; Leone Roberti Maggiore, Umberto; Chiappa, Valentina; Lorusso, Domenica; Raspagliesi, Francesco

2018-06-01

Pelvic exenteration for recurrent gynecological malignancies is characterized by a high rate of severe complications. Factors predictive of morbidity, readmission, and cost were analyzed. Data of consecutive patients undergoing pelvic exenteration between January 2007 and December 2016 were prospectively evaluated. Fifty-eight patients were included in the analysis. Anterior, posterior, and total exenterations were executed in 39 (67%), 9 (16%), and 10 (17%) patients, respectively. Ten (15.5%) severe complications occurred: 8 (20.5%), 0 (0%), and 1 (10%) after anterior, posterior, and total exenterations, respectively. Radiotherapy dosage, time between radiotherapy and surgery, and previous administration of chemotherapy did not influence 90-day complications and readmission. At multivariable analysis, albumin levels less than 3.5 g/dL (odds ratio, 16.2 [95% confidence interval, 2.85-92.8]; P = 0.002) and history of deep vein thrombosis (odds ratio, 9.6 [95% confidence interval, 0.93-98.2]; P = 0.057) were associated with 90-day morbidity. Low albumin levels independently correlated with readmission (P = 0.011). The occurrence of 90-day postoperative complications and readmission increased costs of a median of +12,500 and +6000 euros, respectively (P < 0.05). Preoperative patient selection is a key point for the reduction of postoperative complications after pelvic exenteration. Further prospective studies are warranted to improve patient selection.

Recent trends in the dispensing of 90-day-supply prescriptions at retail pharmacies: implications for improved convenience and access.

Science.gov (United States)

Liberman, Joshua N; Girdish, Charmaine

2011-03-01

Mail-service pharmacies offer consumers the convenience of prescriptions filled with a 90-day supply of medication. Unlike mail-service pharmacies, retail pharmacies traditionally dispensed maintenance medication prescriptions with a 30-day supply. However, the retail landscape changed in May 2008 with Walmart's announcement of an extension of its $4 Prescription Program to include 90-day-supply prescriptions. To evaluate recent changes in access to and use of 90-day-supply maintenance medications dispensed via retail pharmacy. As of the first quarter of 2007, the proportion of retail-dispensed maintenance medications with a 90-day supply (compared with all maintenance prescriptions dispensed) among Medicare Part D plans, self-insured employers, and private health plans was 5.1%, 5.1%, and 5.0%, respectively. As of December 2009, this ratio had risen to 8.0% for Medicare plans and 8.1% for commercial health plans; the ratio among employers had risen more modestly to 6.1%. Of particular interest and importance, the proportion increased similarly for brand and for generic medications. There has been substantial growth in 90-day prescriptions dispensed via retail pharmacy, a trend that is likely to continue as more insurance providers adopt compatible benefit designs. It is important to continue monitoring these trends and to identify opportunities to rigorously evaluate their impact on medication adherence and healthcare costs.

Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

Science.gov (United States)

Mattila, M J; Koski, J; Strömberg, C

1987-02-01

Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar.

Toxicological evaluation of the flavour ingredient 4-amino-5-(3-(isopropylamino-2,2-dimethyl-3-oxopropoxy-2-methylquinoline-3-carboxylic acid

Directory of Open Access Journals (Sweden)

Amy J. Arthur

2015-01-01

Full Text Available A toxicological evaluation of 4-amino-5-(3-(isopropylamino-2,2-dimethyl-3-oxopropoxy-2-methylquinoline-3-carboxylic acid(S9632; CAS 1359963-68-0, a flavour with modifying properties,was completed for the purpose of assessing its safety for use in food and beverage applications. No Phase I biotransformations of S9632 were observed in rat or human microsomes in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S9632 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei or indicate interactions with the mitotic spindle in an in vivo mouse micronucleus assay at oral doses up to 2000 mg/kg. In subchronic oral toxicity studies in rats, the NOEL was 100 mg/kg/day (highest dose tested for S9632 when administered as a food ad-mix for 90 consecutive days. Furthermore, S9632 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

Toxicological evaluation of a novel cooling compound: 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethylacetamide

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

2015-01-01

Full Text Available A toxicological evaluation of a novel cooling agent, 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethyl acetamide (S2227; CAS 1374760-95-8, was completed for the purpose of assessing its safety for use in food and beverage applications. S2227 undergoes rapid oxidative metabolism in vitro, and in rat and dog pharmacokinetic studies is rapidly converted to its component carboxylic acid and secondary amine. S2227 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. The secondary amine hydrolysis product, N-(2-thienylmethyl-1H-pyrazol-3-amine (M179, was also evaluated for genotoxicity. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S2227 was 100 mg/kg/day (highest dose tested when administered by oral gavage for 90 consecutive days. Furthermore, S2227 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers.

Science.gov (United States)

Imhof, Anna; Brunner, Philippe; Marincek, Nicolas; Briel, Matthias; Schindler, Christian; Rasch, Helmut; Mäcke, Helmut R; Rochlitz, Christoph; Müller-Brand, Jan; Walter, Martin A

2011-06-10

To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers. In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Overall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.

The effect of subchronic fluoxetine treatment on learning and memory in adolescent rats

DEFF Research Database (Denmark)

Sass, Amdi; Wörtwein, Gitta

2012-01-01

Selective serotonin re-uptake inhibitors are increasingly used for the treatment of adolescents with behavioural disorders. However, the effect of this class of drugs during this sensitive period of brain development has not been extensively investigated. In this study we examine the effect of su...... in dorsal dentate gyrus and subgranular zone in young adulthood. This calls for further studies examining the long-term effects of this class of antidepressants on adolescent brain development and behaviour....... of subchronic treatment with the selective serotonin re-uptake inhibitor, fluoxetine (10mg/kg/day, i.p.) throughout adolescence (postnatal day 28-60) on learning and memory in the rat. Learning and memory were assessed at two time points: during adolescence, while the animals were being treated with fluoxetine...... and in young adulthood, 40 days after the termination of fluoxetine treatment. Fluoxetine treated rats were compared to a saline injected control group with respect to spatial navigation in the water maze, object recognition and object-in-place recognition memory. Additionally open field behaviour was examined...

The gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia

DEFF Research Database (Denmark)

Jørgensen, Bettina Merete Pyndt; Redrobe, Paul; Brønnum Pedersen, Tina

The gut microbiota has major impact on the individual. Here we show that the gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gut microbiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...... of memory performance in lister hooded rats. Furthermore the individual gut microbiota correlated to the individual behavior abserved in the tests conducted. In conclusion results show an influence of the gut microbiota on behavior in this model, and therefore it might be relavant to include the information...

Comparative toxicity of strontium-90 and radium-226 in beagle dogs

International Nuclear Information System (INIS)

Raabe, O.G.; Culbertson, M.R.; White, R.G.; Spangler, W.L.; Cain, G.R.; Parks, N.J.; Samuels, S.J.

1991-01-01

We are completing a 30-year study of the biological effects of 90 Sr and 226 Ra in the beagle in order to predict the possible long-term hazards to people from chronic exposure to low levels of irradiation. Animals received either radionuclide by several means of administration: (a) continual ingestion of 90 Sr, (b) a single intravenous injection of 90 Sr, or (c) a series of eight intravenous injections of 226 Ra. Although administration of 90 Sr and 226 Ra ended at 540 days of age, the animals continued to receive chronic, low-level radiation doses from these bone-seeking radionuclides throughout life. This project is the largest single cohort study in beagles of internally deposited radionuclides. It is unique in use of the ingestion route for 90 Sr and in exposure that began before birth and continued throughout development to adulthood with uniform labeling of the skeletons with 90 Sr. The last of the dogs died in 1986 at age 18.5 years, but we are continuing to investigate the significance of these long-term exposures given at low dose rates with regard to cancer production, physiologic well-being, and shortening of life through the detailed records that were kept and by study of preserved materials. All the data have been successfully accumulated and entered into a main-frame computer data base management system. Current work is exclusively directed at preparing research papers summarizing the results and the associated biostatistical and survival analyses. 15 refs., 1 fig., 4 tabs

Development of techniques for rapid analysis of 90Sr breakthrough and 90Y activity from a 90Sr-90Y generator

International Nuclear Information System (INIS)

Chism, S.E.; Goodwin, D.A.; Meares, C.F.

1986-01-01

Recently there has been interest in labelling monoclonal antibodies with therapeutic amounts of a pure beta emitting isotope. 90 Y offers many desirable features and may be conveniently and economically obtained from a 90 Sr- 90 Y generator. A potential hazard with this system is breakthrough of the parent 90 Sr which has a half life of 28 years and is an extremely toxic bone seeking isotope. Therefore it is essential that the daughter be completely separated from its parent. We have devised two simple techniques which allow us to monitor rapidly the amount of 90 Sr breakthrough and quantitate the 90 Y activity over a 5 log range. (author)

Is there value in retrospective 90-day bundle payment models for shoulder arthroplasty procedures?

Science.gov (United States)

Odum, Susan M; Hamid, Nady; Van Doren, Bryce A; Spector, Leo R

2018-05-01

The Centers for Medicare & Medicaid Services Bundled Payments for Care Improvement (BPCI) initiative was implemented as part of the Affordable Care Act. We implemented a retrospective payment model 2 for a 90-day total shoulder arthroplasty (TSA) episode to assess the value of TSA BPCI at our private practice. Expenditures and postacute event rates of 132 fee-for-service (FFS) patients who underwent a TSA operation between 2009 and 2012 were compared with 333 BPCI patients who had a TSA operation in 2015. The 90-day postacute events included an inpatient rehabilitation facility (IRF), skilled nursing facility (SNF), and home health (HH) admissions and readmissions. Expenditures were converted to 2016 dollars using the Consumer Price Index. Wilcoxon tests and multivariate generalized estimating equation were used to assess independent cost-drivers. The median FFS expenditure was $21,157 (interquartile range, $16,894-$30,748) compared with $17,894 (interquartile range, $15,796-$20,894) for BPCI (P model, we found BPCI had a 4% decrease in expenditures (P = .08). All postacute events were independently associated with higher expenditures. Our private practice implemented cost-containment practices, including clinical guidelines, patient navigators, and a BPCI management team. IRF and SNF utilization and the 90-day readmission rate significantly decreased. As a result, we were able to control the postacute spending, which resulted in decreased costs of performing TSA surgery. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

77 FR 45571 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To Delist the Green Turtle in...

Science.gov (United States)

2012-08-01

... [Docket No. 120425024-1024-01] RIN 0648-XB089 Endangered and Threatened Wildlife; 90-Day Finding on a Petition To Delist the Green Turtle in Hawaii and Notice of Status Review AGENCY: National Marine Fisheries... 90-day finding on a petition to identify the Hawaiian population of the green turtle (Chelonia mydas...

Spinal cord hemisection facilitates aromatic L-amino acid decarboxylase cells to produce serotonin in the subchronic but not the chronic phase

DEFF Research Database (Denmark)

Azam, Bushra; Wienecke, Jacob; Jensen, Dennis Bo

2015-01-01

12) were used with a postoperation interval at 5 days or 60 days. Using immunohistochemistry, first, we observed a significant reduction in the density of 5-HT-immunoreactive fibers in the spinal cord below the lesion on the injured side for both groups. Second, we found that the AADC cells were...... similarly expressed on both injured and uninjured sides in both groups. Third, increased production of 5-HT in AADC cells following 5-HTP was seen in 5-day but not in 60-day postinjury group. These results suggest that plastic changes of the 5-HT system might happen primarily in the subchronic phase...... and for longer period its function could be compensated by plastic changes of other intrinsic and/or supraspinal modulation systems....

Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

Science.gov (United States)

Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest

2013-10-01

There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.

What Factors are Associated With 90-day Episode-of-care Payments for Younger Patients With Total Joint Arthroplasty?

Science.gov (United States)

Pathak, Shweta; Ganduglia, Cecilia M; Awad, Samir S; Chan, Wenyaw; Swint, John M; Morgan, Robert O

2017-11-01

Total joint arthroplasty (TJA) has been identified as a procedure with substantial variations in inpatient and postacute care payments. Most studies in this area have focused primarily on the Medicare population and rarely have characterized the younger commercially insured populations. Understanding the inpatient and postdischarge care service-component differences across 90-day episodes of care and factors associated with payments for younger patients is crucial for successful implementation of bundled payments in TJA in non-Medicare populations. (1) To assess the mean total payment for a 90-day primary TJA episode, including the proportion attributable to postdischarge care, and (2) to evaluate the role of procedure, patient, and hospital-level factors associated with 90-day episode-of-care payments in a non-Medicare patient population younger than 65 years. Claims data for 2008 to 2013 from Blue Cross Blue Shield of Texas were obtained for primary TJAs. A total of 11,131 procedures were examined by aggregating payments for the index hospital stay and any postacute care including rehabilitation services and unplanned readmissions during the 90-day postdischarge followup period. A three-level hierarchical model was developed to determine procedure-, patient-, and hospital-level factors associated with 90-day episode-of-care payments. The mean total payment for a 90-day episode for TJA was USD 47,700 adjusted to 2013 USD. Only 14% of 90-day episode payments in our population was attributable to postdischarge-care services, which is substantially lower than the percentage estimated in the Medicare population. A prolonged length of stay (rate ratio [RR], 1.19; 95% CI, 1.15-1.23; p ≤ 0.001), any 90-day unplanned readmission (RR, 1.64; 95% CI, 1.57-1.71; p ≤ 0.001), computer-assisted surgery (RR, 1.031; 95% CI, 1.004-1.059; p ≤ 0.05), initial home discharge with home health component (RR, 1.029; 95% CI, 1.013-1.046; p ≤ 0.001), and very high patient morbidity

Hepatic Toxicity After Radioembolization of the Liver Using {sup 90}Y-Microspheres: Sequential Lobar Versus Whole Liver Approach

Energy Technology Data Exchange (ETDEWEB)

Seidensticker, Ricarda; Seidensticker, Max; Damm, Robert; Mohnike, Konrad [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany); Schuette, Kerstin; Malfertheiner, Peter [Universitaetsklinikum Magdeburg, Klinik fuer Gastroenterologie, Hepatologie und Infektiologie (Germany); Buskirk, Mark Van [Data Reduction (United States); Pech, Maciej; Amthauer, Holger; Ricke, Jens, E-mail: jens.ricke@med.ovgu.de [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany)

2012-10-15

Purpose: {sup 90}Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus 'whole liver' {sup 90}Y-radioembolization. Methods: Thirty-four patients with liver malignancy in noncirrhotic livers were included; {sup 90}Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed. Results: Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P < 0.05). Three patients treated with whole liver RE suffered from radioembolization-induced liver disease (REILD). Pathological increases in bilirubin at 3 months were observed for the whole liver group only (52.3 vs. 18.7 {mu}mol/l, P = 0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P < 0.05). Portal vein diameter increased significantly in whole liver-treated patients only (+17% vs. +6.6%, P = 0.043). Conclusions: Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy.

Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats.

Science.gov (United States)

Egerton, Alice; Reid, Lee; McGregor, Sandie; Cochran, Susan M; Morris, Brian J; Pratt, Judith A

2008-05-01

We have previously demonstrated that subchronic (five daily administrations of 2.6 mg/kg PCP) and chronic intermittent administration of 2.6 mg/kg PCP to rats produces hypofrontality and other neurochemical changes akin to schizophrenia pathology (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003). We sought to determine whether behavioral alterations related to discrete aspects of schizophrenia are also induced by these PCP treatment regimes. Following administration of vehicle or PCP according to the protocols described above, rats were assessed for attentional set shifting ability, prepulse inhibition (PPI), or social interaction and the locomotor response to a challenge dose of amphetamine. Ability to shift attentional set was impaired 72 h after the last PCP administration following the subchronic and chronic intermittent treatment regimes. PPI was disrupted after each acute administration of PCP in animals under the subchronic treatment regime. However, PPI deficits were not sustained 72 h after the last of five daily administrations. In subchronic and chronic PCP treated animals, no change was found in social interaction behavior, and there was little change in baseline or amphetamine-stimulated locomotor activity, employed as an indicator of dopaminergic hyperfunction. The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.

Hsp90 chaperone inhibitor 17-AAG attenuates Aβ-induced synaptic toxicity and memory impairment.

Science.gov (United States)

Chen, Yaomin; Wang, Bin; Liu, Dan; Li, Jing Jing; Xue, Yueqiang; Sakata, Kazuko; Zhu, Ling-qiang; Heldt, Scott A; Xu, Huaxi; Liao, Francesca-Fang

2014-02-12

The excessive accumulation of soluble amyloid peptides (Aβ) plays a crucial role in the pathogenesis of Alzheimer's disease (AD), particularly in synaptic dysfunction. The role of the two major chaperone proteins, Hsp70 and Hsp90, in clearing misfolded protein aggregates has been established. Despite their abundant presence in synapses, the role of these chaperones in synapses remains elusive. Here, we report that Hsp90 inhibition by 17-AAG elicited not only a heat shock-like response but also upregulated presynaptic and postsynaptic proteins, such as synapsin I, synaptophysin, and PSD95 in neurons. 17-AAG treatment enhanced high-frequency stimulation-evoked LTP and protected neurons from synaptic damage induced by soluble Aβ. In AD transgenic mice, the daily administration of 17-AAG over 7 d resulted in a marked increase in PSD95 expression in hippocampi. 17-AAG treatments in wild-type C57BL/6 mice challenged by soluble Aβ significantly improved contextual fear memory. Further, we demonstrate that 17-AAG activated synaptic protein expression via transcriptional mechanisms through the heat shock transcription factor HSF1. Together, our findings identify a novel function of Hsp90 inhibition in regulating synaptic plasticity, in addition to the known neuroprotective effects of the chaperones against Aβ and tau toxicity, thus further supporting the potential of Hsp90 inhibitors in treating neurodegenerative diseases.

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.

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

Science.gov (United States)

Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

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 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.

Haloacetonitriles: metabolism and toxicity.

Science.gov (United States)

Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

2009-01-01

bioactivation process, depending on the particular HAN and the enzyme involved. HANs can inhibit CYP2E1-mediated metabolism, an effect which may be dependent on a covalent interaction with the enzyme. In addition, HAN compounds inhibit GST-mediated conjugation, but this effect is reversible upon dialysis, indicating that the interaction does not represent covalent binding. No subchronic studies of HAN toxicity are available in the literature. However, studies show that HANs produce developmental toxicity in experimental animals. The nature of developmental toxicity is affected by the type of administration vehicle, which renders interpretation of results more difficult. Skin tumors have been found following dermal application of HANs, but oral studies for carcinogenicity are negative. Pulmonary adenomas were increased following oral administration of HANs, but the A/J strain of mice employed has a characteristically high background rate of such tumors. HANs interact with DNA to produce unscheduled DNA repair, SCE and reverse mutations in Salmonella. HANs did not induce micronuclei or cause alterations in sperm head morphology in mice, but did induce micronuclei in newts. Thus, there is concern for the potential carcinogenicity of HANs. It would be valuable to delineate any relationship between the apparent threshold for micronuclei formation in newts and the potential mechanism of toxicity involving HAN-induced oxidative stress. Dose-response studies in rodents may provide useful information on toxicity mechanisms and dose selection for longer term toxicity studies. Additional studies are warranted before drawing firm conclusions on the hazards of HAN exposure. Moreover, additional studies on HAN-DNA and HAN-protein interaction mechanisms, are needed. Such studies can better characterize the role of metabolism in toxicity of individual HANs, and delineate the role of oxidative stress, both of which enhance the capacity to predict risk. Most needed, now, are new subchronic (and

Subchronic (13-week) oral toxicity study of α-cyclodextrin in dogs

NARCIS (Netherlands)

Lina, B.A.R.; Bär, A.

2004-01-01

The oral toxicity of α-cyclodextrin (α-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received α-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no

Subchronic (13-week) oral toxicity study of y-cyclodextrin in dogs

NARCIS (Netherlands)

Til, H.P.; Bär, A.

1998-01-01

The oral toxicity of γ-cyclodextrin (γ- CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received γ-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs

Evaluation of the toxic properties of naturally weathered Exxon Valdez crude oil to surrogate wildlife species

International Nuclear Information System (INIS)

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

1995-01-01

The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) to avian and mammalian wildlife species were evaluated using the surrogate species, mallard duck, Anas platyrhynchos, and European ferret, Mustela putorius. This study was conducted to evaluate the potential for toxic (rather than physical) injury to wildlife species that may have been exposed to WEVC, either through external contact or through dietary uptake. Previous studies have assessed the toxicity of unweathered crude oils, including Alaska North Slope Crude, but little information exists regarding the toxicity of a naturally weathered crude oil, typical of that encountered following a spill. A battery of laboratory toxicity tests was conducted, in compliance with standard and published test procedures, to evaluate acute and subchronic toxicity of WEVC. These included tests of food avoidance, reproductive effects, and direct eggshell application toxicity. Naturally weathered EVC, recovered postspill from Prince William Sound, was used as the test material. 36 refs., 7 figs., 4 tabs

Toxicological study of the butanol fractionated root extract of Asparagus africanus Lam., on some blood parameter and histopathology of liver and kidney in mice.

Science.gov (United States)

Kebede, Sintayehu; Afework, Mekbeb; Debella, Asfaw; Ergete, Wondwossen; Makonnen, Eyasu

2016-01-27

The butanol fractionated root extract of Asparagus africanus Lam., a traditional herb widely used to treat various ailments were analyzed for the presence of potential toxicity after single (acute) and repeated (subchronic) dose oral administration in adult swiss albino mice using gavages. For the acute study, butanol fractionated extract of the plant was administered in single doses of 1000, 3000 and 5000 mg/kg body weight. In the sub-chronic dose study, the extract was administered at doses of 300 and 600 mg/kg body weight/day for 42 days. Selected hematological and biochemical parameters of the blood followed by histopathological analysis were investigated after 42 days of daily administrations. The results were expressed as M ± SE, and differences at P fraction of the extract has high safety profile when given orally. After 42 days of daily dosing, in the sub-chronic study, no clinically significant changes were observed for hematological and biochemical parameters. Except an occasional small number of focal mononuclear lymphocytic cells infiltrations around the central and portal triad of the liver of a few mice, the histopathological parameters do not show significant change. It is concluded that, the butanol fractionated extract from A. africanus at the given dose does not show significant toxicity. The presence of focal inflammation on the liver of a few mice may be associated to the presence of flavonoid glycoside in the butanol fractionated extract.

Diagnostic testing for serious bacterial infections in infants aged 90 days or younger with bronchiolitis.

Science.gov (United States)

Liebelt, E L; Qi, K; Harvey, K

1999-05-01

To describe the different laboratory tests that are performed on young infants aged 90 days or younger with bronchiolitis and to identify historical and clinical predictors of infants on whom laboratory tests are performed. Cross-sectional study whereby information was obtained by retrospective review of medical records from November through March 1992 to 1995 of all infants with a clinical diagnosis of bronchiolitis. Urban pediatric emergency department. Two hundred eleven consecutive infants aged 90 days or younger (median age, 54 days) with 216 episodes of bronchiolitis. Historical and clinical data on each infant in addition to laboratory data that included a white blood cell count, urinalysis, and blood, urine, and cerebrospinal fluid cultures. Two or more laboratory tests (not including chest radiographs) were obtained in 48% of all infants and 78% of febrile infants. Of the 91 infants with a history of a temperature of 38.0 degrees C or more or temperature on presentation of 38.0 degrees C or more, white blood cell counts were obtained in 77%, blood cultures in 75%, urinalyses in 53%, urine cultures in 60%, and analyses-cultures of cerebrospinal fluid in 47%. Febrile infants were 10 times more likely to get at least 2 laboratory tests than afebrile infants (Ppredictors of whether laboratory studies were obtained. History of preterm gestation, aged younger than 28 days, previous antibiotic use, and presence of otitis media were not associated with obtainment of laboratory studies. No cases of bacteremia, urinary tract infection, or meningitis were found among all infants with bronchiolitis who had blood, urine, and/or cerebrospinal fluid cultures. There is wide variability in the diagnostic testing of infants aged 90 days or younger with bronchiolitis. The risks of bacteremia, urinary tract infection, and meningitis in infants with bronchiolitis seems to be low. History or a documented temperature of 38.0 degrees C or more; oxygen saturation of less than 92

90-day Readmission After Lumbar Spinal Fusion Surgery in New York State Between 2005 and 2014: A 10-year Analysis of a Statewide Cohort.

Science.gov (United States)

Baaj, Ali A; Lang, Gernot; Hsu, Wei-Chun; Avila, Mauricio J; Mao, Jialin; Sedrakyan, Art

2017-11-15

MINI: We assessed 90-day readmission and evaluated risk factors associated with readmission after lumbar spinal fusion surgery in New York State. The overall 90-day readmission rate was 24.8%. Age, sex, race, insurance, procedure, number of operated spinal levels, health service area, and comorbidities are major risk factors for 90-day readmission. Retrospective cohort study. The aim of this study was to assess 90-day readmission and evaluate risk factors associated with readmission after lumbar fusion in New York State. Readmission is becoming an important metric for quality and efficiency of health care. Readmission and its predictors following spine surgery are overall poorly understood and limited evidence is available specifically in lumbar fusion. The New York Statewide Planning and Research Cooperative System (SPARCS) was utilized to capture patients undergoing lumbar fusion from 2005 to 2014. Temporal trend of 90-day readmission was assessed using Cochran-Armitage test. Logistic regression was used to examine predictors associated with 90-day readmission. There were 86,869 patients included in this cohort study. The overall 90-day readmission rate was 24.8%. On a multivariable analysis model, age (odds ratio [OR] comparing ≥75 versus New York-Pennsylvania border: 0.67, 95% CI: 0.61-0.73), and comorbidity, i.e., coronary artery disease (OR: 1.26, 95% CI: 1.19-1.33) were significantly associated with 90-day readmission. Directions of the odds ratios for these factors were consistent after stratification by procedure type. Age, sex, race, insurance, procedure, number of operated spinal levels, HSA, and comorbidities are major risk factors for 90-day readmission. Our study allows risk calculation to determine high-risk patients before undergoing spinal fusion surgery to prevent early readmission, improve quality of care, and reduce health care expenditures. 3.

Toxicopathology and immunotoxicology of multiple exposures to diesel and crude oils in cattle

International Nuclear Information System (INIS)

Dziwenka, M.M.; Coppock, R.W.; Khan, A.A.; Hiltz, M.N.; Nation, P.N.; Field, C.J.

2002-01-01

The subchronic toxicology of crude and refined petroleum in cattle was examined during the course of a large study in which 40 cattle were gavaged with potable water, winter diesel fuel and crude oil for a period of up to 48 days. Blood samples for clinicopathologic parameters were collected weekly. The cattle were necropsied 22 days following the last dose. Representative tissues were taken from all organ systems for histopathology. It was shown that repeated oral exposure to petroleum products resulted in significant changes in the clinicopathologic and immunopathologic parameters of the cattle without producing significant macro- or microscopic tissue lesions. The liver was a target organ for subchronic crude and diesel toxicity. 5 refs., 1 tab., 10 figs

Preparation of 90Sr-90Y generator

International Nuclear Information System (INIS)

Jin Xiaohai; Yu Haibin; Zhang Jinming; Zhang Peixin; Lin Qiongfang

1990-01-01

In recent years, 90 Y has been considered as one of the best radionuclides for tumor radioimmunotherapy when chelated to tumor-associated antibodies. This evaluation is based on the superior properties of this radionuclide (suitable half-life, pure β-ray emitter of intermediate energy, stable daughters, and suitable chemical properties) and because it is available as a radionuclide generator product by decay of its 28a parent 90 Sr. The experimental conditions of 90 Sr- 90 Y generator are described. The elution efficiency of 90 Sr- 90 Y generator reaches 98%. One of the most important problems is the 90 Sr contamination breakthrough from the generator. The level of 90 Sr contamination must be controlled to the clinical standard. The cation exchange resin 732 (100-150 mesh) was successfully used for the separation of 90 Y from 90 Sr. The method used by the authors provides a 90 Y-HAc solution which is very simple and safe for administration to the patients. 90 Y was separated from 90 Sr almost completely, the level of the 90 Sr contamination per 740 MBq 90 Y product was only 0.74 kBq. However the toxicity of 90 Sr is extremely high, the human life-time permissible dose is 74 kBq, then 740 MBq of 90 Y is allowed to be administrated to a patient for 50-100 times

First Report of 90-Day Support of Two Calves with a Continuous-Flow Total Artificial Heart

Science.gov (United States)

Karimov, Jamshid H.; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A.; Fukamachi, Kiyotaka

2015-01-01

Objective The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. Methods CFTAH pumps have been implanted in 17 calves total. Hemodynamics, pump performance, and device-related adverse events were evaluated during studies and at necropsy. Results In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure [LAP], 16 ± 3 mm Hg; right atrial pressure [RAP], 17 ± 3 mm Hg; RAP-LAP difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three recent animals with the CFTAH recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last two were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. Conclusions The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. PMID:26173607

Prolonged Elevated Heart Rate and 90-Day Survival in Acutely Ill Patients: Data From the MIMIC-III Database.

Science.gov (United States)

Sandfort, Veit; Johnson, Alistair E W; Kunz, Lauren M; Vargas, Jose D; Rosing, Douglas R

2018-01-01

We sought to evaluate the association of prolonged elevated heart rate (peHR) with survival in acutely ill patients. We used a large observational intensive care unit (ICU) database (Multiparameter Intelligent Monitoring in Intensive Care III [MIMIC-III]), where frequent heart rate measurements were available. The peHR was defined as a heart rate >100 beats/min in 11 of 12 consecutive hours. The outcome was survival status at 90 days. We collected heart rates, disease severity (simplified acute physiology scores [SAPS II]), comorbidities (Charlson scores), and International Classification of Diseases (ICD) diagnosis information in 31 513 patients from the MIMIC-III ICU database. Propensity score (PS) methods followed by inverse probability weighting based on the PS was used to balance the 2 groups (the presence/absence of peHR). Multivariable weighted logistic regression was used to assess for association of peHR with the outcome survival at 90 days adjusting for additional covariates. The mean age was 64 years, and the most frequent main disease category was circulatory disease (41%). The mean SAPS II score was 35, and the mean Charlson comorbidity score was 2.3. Overall survival of the cohort at 90 days was 82%. Adjusted logistic regression showed a significantly increased risk of death within 90 days in patients with an episode of peHR ( P < .001; odds ratio for death 1.79; confidence interval, 1.69-1.88). This finding was independent of median heart rate. We found a significant association of peHR with decreased survival in a large and heterogenous cohort of ICU patients.

Effect of subchronic zinc toxicity on rat salivary glands and serum composition.

Science.gov (United States)

Mizari, Nazer; Hirbod-Mobarakeh, Armin; Shahinpour, Shervin; Ghalichi-Tabriz, Mostafa; Beigy, Maani; Yamini, Ali; Dehpour, Ahmad Reza

2012-11-01

Zinc plays an important role in a wide variety of metabolic processes in animal systems. The role of zinc in preservative treatment, fungicidal action and medicine, and addition of supplementary zinc have increased the probability of zinc toxicity, specially the chronic type. It is known that the composition and quantity of saliva influence the oral health. Regarding people's exposure to zinc in routine life and the importance of saliva, our purpose was to investigate the effects of oral zinc intoxication on secretory function in rat salivary glands and also on serum composition. In this study, there were five groups of female rats. Four groups received zinc acetate dehydrate through their drinking water. After 3 months of experiment, the chemical characteristics and flow rate of saliva and weight of salivary glands were determined. The effects of zinc on hematological and chemical factors of plasma were assessed too. Flow rate of submandibular glands was significantly lower in experimental groups and there were significant changes in Na(+), Ca(2+) and K(+) concentration both in saliva and in plasma. The serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, glucose levels in the plasma and urine creatinine levels were also altered in experimental groups in comparison with the control group. Our results show that zinc toxicity will affect the quantity and quality of saliva probably through changes in the various neurologic pathways to the salivary glands or effects on acinar cells of the salivary glands. Furthermore, our results showed that zinc toxicity will affect the liver and renal function.

Heat shock protein 90 in neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Rodina Anna

2010-06-01

Full Text Available Abstract Hsp90 is a molecular chaperone with important roles in regulating pathogenic transformation. In addition to its well-characterized functions in malignancy, recent evidence from several laboratories suggests a role for Hsp90 in maintaining the functional stability of neuronal proteins of aberrant capacity, whether mutated or over-activated, allowing and sustaining the accumulation of toxic aggregates. In addition, Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1, the master regulator of the heat shock response, mechanism that cells use for protection when exposed to conditions of stress. These biological functions therefore propose Hsp90 inhibition as a dual therapeutic modality in neurodegenerative diseases. First, by suppressing aberrant neuronal activity, Hsp90 inhibitors may ameliorate protein aggregation and its associated toxicity. Second, by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity. This mini-review will summarize our current knowledge on Hsp90 in neurodegeneration and will focus on the potential beneficial application of Hsp90 inhibitors in neurodegenerative diseases.

A 90-day Bundled Payment for Primary Single-level Lumbar Discectomy/Decompression: What Does "Big Data" Say?

Science.gov (United States)

Jain, Nikhil; Virk, Sohrab S; Phillips, Frank M; Yu, Elizabeth; Khan, Safdar N

2018-04-01

Episode-based bundling may become the major form of reimbursement for many elective spine procedures. As the amount for a 90-day episode of care is not known for a lumbar discectomy, we analyzed the previous reimbursements from Commercial payers (2007-Q2 2015), Medicare Advantage (2007-Q2 2015), and Medicare (2005-2012) for a primary single-level lumbar discectomy/decompression. Distribution of payments among various service providers was studied and a 90-day bundle was simulated. Depending on the payer type, the average facility costs constituted 59.7% to 73.6% of total payments, followed by surgeon's fees, which accounted for 13.7% to 18.5%. Postacute services made up 8.8% to 15.8% of the total reimbursement. Surgeries performed in the inpatient setting were significantly more expensive as compared with surgeries performed in the outpatient setting (P<0.01). The average 90-day bundle amount was estimated at $11,091, $6571, and $6239 for Commercial payers, Medicare Advantage, and Medicare, respectively. Overall, service providers in the Southern region were reimbursed the lowest from Commercial payers and Medicare, compared with other regions. Postacute services are not as major cost drivers after discectomy as after total joint arthroplasty or hip fracture repair.

40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

Science.gov (United States)

2010-07-01

... of animals displaying each type of lesion. (ii) All observed results (quantitative and qualitative... exposure apparatus including design, type, volume, source of air, system for generating aerosols, method of... substance should be used, if possible throughout the duration of the study, and the research sample should...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Science.gov (United States)

2010-07-01

... test, the number of animals showing lesions, the types of lesions and the percentage of animals displaying each type of lesion. (ii) When applicable, all observed results, qualitative and quantitative... possible, throughout the duration of the study, and the research sample should be stored under conditions...

90 days bioassay in sprague-dawley rats exposed to 20KHz magnetic field

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung-Ho [College of Veterinary Medicine, Chonnam National Univ. Kwangju (Korea, Republic of); Song, Ji-Eun; Lee, Yun-Sil [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Pack, Jeong-Ki [ETRI, Daejon (Korea, Republic of); Yoo, Done-SIk [College of Engineering, Daejon (Korea, Republic of)

2002-07-01

Sprague Dawley rats (20 rats/group [10 males, 10 females] in sham and magnetic field exposed groups) were exposed in carrousel irradiator to an 20 KHz magnetic field for 8 hrs/day, 5 days/week, for 90 days. Urine analysis (pH, SG, protein, ketone body, RBC, WBC, glucose, bilirubin, and urobilinogen), blood analysis (WBC, RBC, HGB; henoglubin concentration, HCT; hematocrit, MCV; mean corpuscular volume, MCH; mean corpuscular hemoglobin, MCHC; mean corpuscular hemoglobin concentration, and PLT; platelet or thrombocyte count), blood biochemistry (total protein, blood urea nitrogen, creatinine, glucose, total bilirubin, total cholesterol, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), histopathological analysis for organs such as liver, kidney, testis, ovary, spleen, brain, heart, and lung were performed. When compared to the sham control rats, there were no significant differences in above analysis of magnetic field exposed rats. From the results, there were no significant differences between control and exposed fetus.

First report of 90-day support of 2 calves with a continuous-flow total artificial heart.

Science.gov (United States)

Karimov, Jamshid H; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A R; Fukamachi, Kiyotaka

2015-09-01

The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. CFTAH pumps have been implanted in 17 calves total. Hemodynamic parameters, pump performance, and device-related adverse events were evaluated during studies and at necropsy. In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure, 16 ± 3 mm Hg; right atrial pressure, 17 ± 3 mm Hg; right atrial pressure-left atrial pressure difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; and pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three animals with recent CFTAH implantation recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last 2 were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to human surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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

African Journals Online (AJOL)

AJL

2012-06-14

Jun 14, 2012 ... Thailand registered PN in the list of herbal medical ... Pharmacy, Silpakorn University, Nakorn Pathom, Thailand. The ... automated blood analyzer (Hitachi Science Systems Ltd., Ibaraki, ..... toxic effects of the extracts in both concurrent control and ..... uric acid levels might be necessary when patients are.

Effect of head-only sub-chronic GSM exposure on spatial memory of rats

International Nuclear Information System (INIS)

Ammari, Mohamed; Brillaud, Elsa; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; Seze, Rene de; Faculte des Sciences de Bizerte, Jarzouna

2008-01-01

Full text: Introduction: Low power electromagnetic fields (EMF) are suspected to produce deficit memory in rats. The study of Dubreuil et al (2003) showed that a short-term (10-15 days) exposure 'head-only' to GSM 900 MHz radio frequencies does not produce a deficit memory in adult rats. The aim of our experiment was to determine if head-only sub-chronic exposure (2 months) of rats to GSM signal for 45 min at a SAR = 1.5 W/Kg and for 15 min at 6 W/Kg induce deficit in spatial memory of rats in radial maze test. Materials and methods: Exposure system: Animals were placed in Plexiglas rockets with an individual loop antenna placed above the rat's head. Four animals were exposed at the time. Loop antennas were connected to a generator and emitted a GSM signal (900 MHz, pulsed at 217 Hz, 1/8 duty factor) 5 days / week for 8 weeks. Experimental group: 30 Sprague-Dawley male rats were randomly assigned to 5 different groups: a) 6 rats exposed 15 min at SAR = 6 W/Kg; b) 6 rats exposed 45 min at SAR = 1.5 W/g; c) 6 rats sham controls (3 for 5 min and 3 for 45 min, SAR = 0 W/Kg); d) 6 rats without any treatment and manipulation (cage control); e) 6 rats were injected (i.p) S.B.H 0.1 mg/Kg (Sigma Aldrich) as positive control group. Behavioural procedure: The radial maze protocol consists of two consecutive phases: the training task (10 days) and the test task (8 days). In the first phase, rats were trained to visit the 8 arms of the maze without returning to an arm already visited. In the second phase (8 days), a 45-min intra-trial delay was introduced after four visited arms. After the intra-delay, the rat was placed in the maze to finish the test task, which is visiting four other arms he had not visited. During the training task, exposure took place before the behavioural task. During the test task, exposure or sham-exposure took place during the intra-delay. Results and discussion: In all experiments, performance of exposed rats (1.5 and 6 W/Kg) was compared with that of

Ninety-Day Subchronic Oral Toxicity Study of Pyridostigmine Bromide in Rats. Volume 1

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1990-05-01

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Safety Profile of Meswak Root Extract on Liver, Kidney, Sexual Hormones and Hematological Parameters of Rats

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Abeer Y. IBRAHIM

2012-02-01

Full Text Available This study was conducted to investigate the safety profile of Salvadora persica (Salvadoraceae aqueous alcoholic root extract by carrying out acute and sub-chronic toxicity assessment in order to find out any side effect of the traditionally using of these root sticks. Regarding to acute toxicity test, mice were administered the extract up to 5 g kg-1, intraperitoneally. Animals were then observed for behavioural changes; signs of toxicity, and mortality within 24 h. Surviving mice were monitored for 7 days for signs of delayed toxicity. In the sub-chronic toxicity test, rats were daily treated with the extract at a dose of 400 mg kg-1 intraperitoneally, for 30 days. At the end of the test period, hematological and biochemical parameters were determined in blood and serum samples with determination of vital organs weights. In the acute toxicity test, the extract was practically non-toxic showing no mortality and visible signs of delayed toxicity. The LD50, given intraperitoneally, was estimated to be 4 g kg-1. Administration of extract (at a dose of 400 mg Kg-1 b.wt. to male and female rats for 30 days did not produce any significant (P < 0.05 effect on hematological and most biochemical parameters also vital organs weights. The root extract showed adverse effects on sexual hormones, by increasing estrogen secretion and reducing testosterone level in male rats. At the same time, the extract reduces progesterone level in female satellite group. Overall, Meswak aqueous extract is safe concerning liver and kidney functions and hematological assessments; however, it induces reversal effect on sexual hormones levels determined in sera.

Leukoaraiosis predicts poor 90-day outcome after acute large cerebral artery occlusion.

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Henninger, Nils; Lin, Eugene; Baker, Stephen P; Wakhloo, Ajay K; Takhtani, Deepak; Moonis, Majaz

2012-01-01

To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007-2010) at a single academic institution. The final study cohort included 87 patients with acute ILAO subjected to multimodal CT imaging within 24 h of symptom onset. LA severity was assessed using the van Swieten scale on non-contrast CT. Leptomeningeal collaterals were graded using CT angiogram source images. Hemorrhagic transformation (HT) was determined on follow-up CT. Multivariate logistic regression controlling for HT, treatment modality, demographic, as well as baseline clinical and imaging characteristics was used to identify independent predictors of a poor outcome (90-day mRS >2). The median National Institutes of Health Stroke Scale (NIHSS) at baseline was 15 (interquartile range 9-21). Twenty-four percent of the studied patients had severe LA. They were more likely to have hypertension (p = 0.028), coronary artery disease (p = 0.015), poor collaterals (p Coexisting LA may predict poor functional outcome in patients with acute anterior circulation ILAO independent of other known important outcome predictors such as comorbid state, admission functional deficit, collateral status, hemorrhagic conversion, and treatment modality. Copyright © 2012 S. Karger AG, Basel.

Genetic and rat toxicity studies of cyclodextrin glucanotransferase

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Robert R. Maronpot

Full Text Available Introduction: Microbiologically derived cyclodextrin glucanotransferase (CGTase is used commercially as a processing agent in manufacture of food, pharmaceuticals, and cosmetics. Its toxic potential was evaluated in anticipation of use in the production of alpha-glycosyl isoquercitrin, a water-soluble form of quercetin. Methods: Following OECD guidelines, CGTase, produced by Bacillus pseudalcaliphilus DK-1139, was evaluated in a genotoxicity battery consisting of a bacterial reverse mutation assay, an in vitro micronucleus (MN assay and MN and comet assays using B6C3F1 male and female mice. These same genotoxicity assays were also conducted for sodium sulfate, a contaminant of CGTase preparation. In a 90-day Sprague Dawley rat toxicity study, CGTase was administered by gavage in water at daily doses of 0, 250, 500, and 1000 mg/kg/day. Results: CGTase did not induce mutations with or without metabolic activation in the bacterial reverse mutation assay. Formation of micronuclei was not induced in either in vitro or in vivo MN assays with or without metabolic activation. No induction of DNA damage was detected in male or female mouse liver, stomach, or duodenum in the comet assay. Sodium sulfate also tested negative in these same genotoxicity assays. In the 90-day repeated dose rat study there were no treatment-related adverse clinical or pathological findings. Conclusion: The genotoxicity assays and repeated dose toxicity study support the safe use of CGTase in production of alpha-glycosyl isoquercitrin. Keywords: Micronucleus assay, Comet assay, Enzymatically modified isoquercitrin (EMIQ, Food additive, Flavonol, Sodium sulfate

Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene and tetryl in rats. Final report

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Reddy, T.V.; Daniel, F.B.

1994-09-01

Toxic effects of 1,3-Dinitrobenzene (1,3-DNB) in male and female F344 rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of 1,3-DNB (0, 2.5, 10, 25, 75 and 150 mg/kg diet) for fourteen days. The average daily 1 ,3-DNB doses consumed were 0.21, 0.87, 2.02, 6.28 and 11.82 mg/kg b.w. for females and 0.21, 0.80, 1.98, 5.77 and 10.56 for males. Food consumption was significantly decreased in high dose animals of both sexes. Final body weights were not altered but relative organ weights were significantly changed in the 150 and 75 mg dose groups involving the spleen (males and females) and testes (males). Hematology and clinical chemistry studies indicated significantly increased values in both sexes relating to reticulocytes and methemoglobin in the 150 and 75 mg/kg dose groups while the red blood cell count, hemoglobin level and % hematocrit were decreased in these same groups. In addition, the levels of bilirubin, protein and albumin were increased in high dose males, Histopathological evaluations suggested that the susceptible organs for 1,3-DNB toxicity were kidneys (hyaline droplets), spleen (erythroid cell hyperplasia), brain (malacia and microgliosis), testes (seminiferous tubular degeneration). These changes were noted mainly in the 150 and 75 mg/kg dose groups except those changes involving the brain (150 mg/kg group only).

Relative toxicity of bifenthrin to Hyalella azteca in 10 day versus 28 day exposures.

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Anderson, Brian S; Phillips, Bryn M; Voorhees, Jennifer P; Petersen, Megan A; Jennings, Lydia L; Fojut, Tessa L; Vasquez, Martice E; Siegler, Catherine; Tjeerdema, Ronald S

2015-04-01

Many watersheds in the Central Valley region of California are listed as impaired due to pyrethroid-associated sediment toxicity. The Central Valley Regional Water Quality Control Board is developing numeric sediment quality criteria for pyrethroids, beginning with bifenthrin. Criteria are being developed using existing data, along with data from 10 d and 28 d toxicity tests with Hyalella azteca conducted as part of the current study. A single range-finder and 2 definitive tests were conducted for each test duration. Median lethal concentrations (LC50s), as well as LC20s and inhibition concentrations (IC20s) were calculated based on measured whole sediment bifenthrin concentrations and interstitial water concentrations. Sediment LC50s were also corrected for organic C content. Average LC50s were not significantly different in 10 d versus 28 d tests with H. azteca: 9.1 and 9.6 ng/g bifenthrin for 10 d and 28 d tests, respectively. Average LC20 values were also similar with concentrations at 7.1 and 7.0 for 10 d and 28 d tests, respectively. Bifenthrin inhibition concentrations (IC20s) based on amphipod growth were variable, particularly in the 28 d tests, where a clear dose-response relationship was observed in only 1 of the definitive experiments. Average amphipod growth IC20s were 3.9 and 9.0 ng/g for 10 d and 28 d tests, respectively. Amphipod growth calculated as biomass resulted in IC20s of 4.1 and 6.3 ng/g for the 10 d and 28 d tests, respectively. Lack of a clear growth effect in the longer term test may be related to the lack of food adjustment to account for amphipod mortality in whole sediment exposures. The average C-corrected LC50s were 1.03 and 1.09 μg/g OC for the 10 d and 28 d tests, respectively. Interstitial water LC50s were determined as the measured dissolved concentration of bifenthrin relative to interstitial water dissolved organic carbon. The average LC50s for dissolved interstitial water bifenthrin were

New modalities (setting, fractionation) of radioimmunotherapy by 90Y-ibritumomab tiuxetan (90Y zevalin) in first line treatment of follicular type non Hodgkin malignant lymphomas: efficiency, toxicity and personalized dosimetry approach

International Nuclear Information System (INIS)

Morschhauser, F.

2008-12-01

Rationale: radioimmunotherapy (R.I.T.) with 90 Y-ibritumomab tiuxetan ([ 90 Y] Zevalin ) is a new treatment option for patients with relapsed/refractory non Hodgkin follicular lymphoma (F.L.). Efficacy increases when Zevalin is used earlier in the disease course. Currently, Zevalin dosage is based on weight and not dosimetry. This most likely results in a wide range of absorbed dose to critical organs and tumor, which in turn translates in unpredictable efficacy and toxicity. Optimizing R.I.T. with [ 90 Y] Zevalin will require its use as part of first-line therapy and implementation of patient-specific dosimetry methods in clinical trials. Objectives and methods: we have consecutively studied 2 new modalities of using Zevalin in first line therapy of F.L.. First, we conducted an international, randomized, phase 3 trial to evaluate the efficacy and safety of consolidation with Zevalin(15 MBq/Kg) in patients with advanced-stage F.L. achieving at least a partial response after induction immuno chemotherapy. A second approach consisted of evaluating a fractionated schedule with 2 doses of Zevalin (11.1 MBq/kg each), 9 to 13 weeks apart, as front line therapy in F.L. patients with high tumor burden. As part of this second approach, we designed a refined imaging-based (planar and 3-dimensional) dosimetry protocol to improve prediction of dose efficacy and toxicity after each dose of zevalin. Data acquisition was performed in 3 centers (Lille, Nantes and Manchester) while data treatment and specific dose calculations for major organ, tumor masses and bone marrow were centralized. Conclusion: Consolidation of first remission with 90 Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging P.F.S. by 2 years and resulting in high P.R.-to-C.R. conversion rates regardless of type of first-line induction treatment. Preliminary data show the feasibility of front line fractionated R.I.T. with Zevalin in patient

Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

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Chia-Yu Chang

2015-01-01

Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

Hepatorenal toxicity studies of sub-chronic administration of calyx ...

African Journals Online (AJOL)

Group A, was fed with growers mesh and distilled water as control. Groups B to F were administered orally with the aqueous extract at 1, 2, 3, 4 and 5g /kg body weight respectively and the treatment period was 28 days. A decreased in weights of the animals were observed at all dose levels. The activities of liver maker ...

A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

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Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

2012-01-01

Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right p...

Chronic liver disease and 90-day mortality in 21,359 patients following peptic ulcer bleeding--a Nationwide Cohort Study.

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Holland-Bill, L; Christiansen, C F; Gammelager, H; Mortensen, R N; Pedersen, L; Sørensen, H T

2015-03-01

Bleeding is a serious and frequent complication of peptic ulcer disease. Hepatic dysfunction can cause coagulopathy and increases the risk of peptic ulcer bleeding. However, whether chronic liver disease increases mortality after peptic ulcer bleeding remains unclear. To examine the prognostic impact of chronic liver disease on mortality after peptic ulcer bleeding. We used population-based medical registries to conduct a cohort study of all Danish residents hospitalised with incident peptic ulcer bleeding from 2004 through 2011. We identified patients diagnosed with liver cirrhosis or non-cirrhotic chronic liver disease before their admission for peptic ulcer bleeding. We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan-Meier method (1 - survival function) and used a Cox regression model to estimate mortality rate ratios (MRRs), controlling for potential confounders. We identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these, 653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3% and 20.7%, respectively, compared to 18.3% among patients without chronic liver disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95% CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non-cirrhotic chronic liver disease. Patients with chronic liver disease, particularly liver cirrhosis, are at increased risk of death within 90 days after hospitalisation for peptic ulcer bleeding compared to patients without chronic liver disease. © 2015 John Wiley & Sons Ltd.

Sub-chronic lead exposure produces β1-adrenoceptor downregulation decreasing arterial pressure reactivity in rats.

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Toscano, Cindy Medici; Simões, Maylla Ronacher; Alonso, Maria Jesus; Salaices, Mercedes; Vassallo, Dalton Valentim; Fioresi, Mirian

2017-07-01

Lead is considered a causative factor for hypertension and other cardiovascular diseases. To investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β 1 -adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo. Male Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days. Blood pressure in the Pb rats increased starting from the first week of treatment until the end of the study [systolic blood pressure, Ct: 122±4 vs. Pb: 143±3mmHg; diastolic blood pressure, Ct: 63±4 vs. Pb: 84±4mmHg]. The heart rate was also increased (Ct: 299±11 vs. Pb: 365±11bpm), but the pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats. Isoproterenol increased the left ventricular systolic and end-diastolic pressure, and heart rate only in Ct rats, suggesting that lead induced β 1 -adrenoceptor downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb rats, suggesting the involvement of cyclooxygenase-derived products (which are associated with reduced nitric oxide bioavailability) in this process. These findings offer further evidence that the effects of sub-chronic lead exposure in vitro can be reproduced in vivo-even at low concentrations-thus triggering mechanisms for the development of hypertension. Therefore, lead should be considered an environmental risk factor for cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

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Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

2014-11-01

Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of General Practitioner Transient Ischemic Attack Training on 90-Day Stroke Outcomes: Secondary Analysis of a Cluster Randomized Controlled Trial.

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Ranta, Annemarei; Dovey, Susan; Gommans, John; Tilyard, Murray; Weatherall, Mark

2018-07-01

Many patients with transient ischemic attack (TIA) receive initial assessments by general practitioners (GPs) who may lack TIA management experience. In a randomized controlled trial (RCT), we showed that electronic decision support for GPs improves patient outcomes and guideline adherence. Some stroke services prefer to improve referrer expertise through TIA/stroke education sessions instead of promoting TIA decision aids or triaging tools. This is a secondary analysis of whether a GP education session influenced TIA management and outcomes. Post hoc analysis of a multicenter, single blind, parallel group, cluster RCT comparing TIA/stroke electronic decision support guided GP management with usual care to assess whether a pretrial TIA/stroke education session also affected RCT outcomes. Of 181 participating GPs, 79 (43.7%) attended an education session and 140 of 291 (48.1%) trial patients were managed by these GPs. There were fewer 90-day stroke events and 90-day vascular events or deaths in patients treated by GPs who attended education; 2 of 140 (1.4%) and 10 of 140 (7.1%) respectively, compared with those who did not; 5 of 151 (3.3%), and 14 of 151 (9.3%), respectively. Logistic regression for association between 90-day stroke and 90-day vascular events or death and education, however, was nonsignificant (odds ratio [OR] .42 (.08 to 2.22), P = .29 and .59 (95% confidence interval [CI] .27 to 1.29), P = .18 respectively. Guideline adherence was not improved by the education session: OR .84 (95% CI .49 to 1.45), P = .54. In the described setting, a GP TIA/stroke education session did not significantly enhance guideline adherence or reduce 90-day stroke or vascular events following TIA. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Molecular mechanisms mediating the neuroproyective effects of quinacrine and minocycline on cell death induced by the prion protein fragment 90-231 (hPrP90-231

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V. Villa

2011-01-01

Full Text Available The effects of quinacrine and minocycline on the toxicity induced by hPrP90-231 were studied. By mild thermal denaturation, hPrP90-231 can be converted in a toxic PrPSc-like structure affecting the survival of SH-SY5Y cells. Quinacrine and minocycline prevented hPrP90-231-induced toxicity interfering with different mechanisms: protective effects of quinacrine are mediated by the binding to the fragment that abolished hPrP90-231 structural changes and cell internalization, whereas, minocycline reverted MAP kinase neurotoxic signaling exerted by the prion fragment.

GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs

International Nuclear Information System (INIS)

Guerrouahen, Bella S.; Hahn, Tobias; Alderman, Zefora; Curti, Brendan; Urba, Walter; Akporiaye, Emmanuel T.

2016-01-01

Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer

Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

Science.gov (United States)

Esteves, Julie; Taylor, Laura C.; Vanya, Robert D.; Dean, S. Lance; Wood, Scott J.

2011-01-01

INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and

In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae) Leaves.

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Fonseca, Aldilane Gonçalves; Ribeiro Dantas, Luzia Leiros Sena Fernandes; Fernandes, Júlia Morais; Zucolotto, Silvana Maria; Lima, Adley Antoninni Neves; Soares, Luiz Alberto Lira; Rocha, Hugo Alexandre Oliveira; Lemos, Telma Maria Araújo Moura

2018-01-01

The species Kalanchoe brasiliensis , known as "Saião , " has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis . The action of the extract (concentrations from 0.1 to 1000 uL/100 uL) in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal) and 786-0 (kidney carcinoma), showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo , the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats Final Report

Energy Technology Data Exchange (ETDEWEB)

Sasser, L. B.; Miller, R. A.; Kalkwarf, D, R.; Buschbom, R. L.; Cushing, J. A.

1989-06-30

Occupational health standards have not been established for sulfur mustard [bis(2- chlorethyl)-sulfide], a strong alkylating agent with known mutagenic properties. Seventytwo Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12/group/ sex) and gavaged with either 0, 0.003 , 0.01 , 0.03 , 0.1 or 0.3 mg/kg of sulfur mustard in sesame oil 5 days/week for 13 weeks. No dose-related mortality was observed. A significant decrease (P ( 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg/kg group. Hematological evaluations and clinical chemistry measurements found no consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathologic evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg/kg and males at 0.1 mg/kg. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, an apparent increase in mitotic activity of the basilar epithelial cells, and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated NOEL for HD in this 90-day study is 0.1 mg/kg/day when administered orally.

UJI TOKSISITAS SUBKRONIS INFUSA DAUN SIRIH MERAH (Piper crocatum Ruiz & Pav PADA TIKUS: STUDI TERHADAP GAMBARAN MIKROSKOPIS JANTUNG DAN KADAR SGOT DARAH

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Ignasius Kuncarli

2016-04-01

Full Text Available Abstract: Red betel (Piper crocatum Ruiz & Pav is one of the plants used as traditional medicine community. To determine the level of safety of long-term consumption, then tested subchronic toxicity. The study aimed to determine the relationship spectrum of toxic effects of infusion with changes in levels of serum glutamic oxaloacetic transaminase (SGOT and cardiac histopathology. The study was purely experimental, randomized study design complete unidirectional pattern. A total of 40 Wistar rats (20 males and 20 females, 2-3 months were divided randomly into 4 groups: control group distilled water and 1.38; 2.07; 3.105 g/KgBW of red betel leaf infusion with administration once daily for 28 days. Observations were made before treatment and on day 28 by orbital sinus sampling through to measurement of blood levels of SGOT be analyzed by one way ANOVA and partially dissected mouse to see the damage to the heart. The results showed there was no significant change (p <0.05 in SGOT levels compared the control group. Histology showed no specific changes were observed after administrating 28 days of red betel leaf infusion. The red betel leaf infusion did not cause significant change in SGOT level and histology of heart. Keywords : red betel, subchronic toxicity tests, SGOT, cardiac histology.

Scientific opinion on the appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms

DEFF Research Database (Denmark)

Petersen, Annette

The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for T2 and HT2 of 0.02 μg/kg body weight (bw) per day based on a new in vivo subchronic toxicity study in rats that confirmed that immune- and haematotoxicity are the critical effects of T2...

Stressing Out Hsp90 in Neurotoxic Proteinopathies.

Science.gov (United States)

Inda, Carmen; Bolaender, Alexander; Wang, Tai; Gandu, Srinivasa R; Koren, John

2016-01-01

A toxic accumulation of proteins is the hallmark pathology of several neurodegenerative disorders. Protein accumulation is regularly prevented by the network of molecular chaperone proteins, including and especially Hsp90. For reasons not yet elucidated, Hsp90 and the molecular chaperones interact with, but do not degrade, these toxic proteins resulting in the pathogenic accumulation of proteins such as tau, in Alzheimer's Disease, and α-synuclein, in Parkinson's Disease. In this review, we describe the associations between Hsp90 and the pathogenic and driver proteins of several neurodegenerative disorders. We additionally describe how the inhibition of Hsp90 promotes the degradation of both mutant and pathogenic protein species in models of neurodegenerative diseases. We also examine the current state of Hsp90 inhibitors capable of crossing the blood-brain barrier; compounds which may be capable of slowing, preventing, and possible reversing neurodegenerative diseases.

Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

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Johnnie J Orozco

Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

Short-term toxicity studies with triphenyltin compounds in rats and guinea-pigs

NARCIS (Netherlands)

Verschuuren, H.G.; Kroes, R.; Vink, H.H.; Esch, G.J. van

1966-01-01

Short-term toxicity studies have been carried out in rats and guinea-pigs fed diets containing triphenyltin acetate (TPTA), triphenyltin hydroxide (TPTH) or triethyltin hydroxide (TETH) for 90 days at levels ranging from 0 to 50 ppm. The lowest dietary levels found to retard growth in rats and

Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro.

Science.gov (United States)

Bijlsma, P B; van Raaij, M T; Dobbe, C J; Timmerman, A; Kiliaan, A J; Taminiau, J A; Groot, J A

2001-05-01

Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to male rats. At 8 days before the noise experiments, 50% of the animals were cannulated in the vena cava for blood sampling during the experimental period. The other 50% of the animals were sacrificed at Day 9, segments of ileum were mounted in Ussing chambers and perfused at 37 degrees C. Horseradish peroxidase (HRP) was added mucosally, serosal appearance was detected enzymatically and tissues were fixed for electron microscopy. In the animals exposed to 95-dB noise, plasma corticosterone levels were enhanced twofold compared to controls, and ileal HRP flux was enhanced twofold. Electron micrographs of tissue from stressed or control animals showed no detectable paracellular staining of HRP. Quantification of HRP-containing endosomes in enterocytes revealed a twofold increase in endosome number in the animals exposed to 95-db noise indicating that the increased HRP permeability was primarily due to increased endocytosis. In contrast to the animals exposed to 95-dB noise, rats exposed to 105-dB noise showed no increase in corticosterone levels and ileal HRP fluxes were not significantly different from controls. We conclude that mild subchronic noise stress may cause a decrease in intestinal barrier function by increased transcytosis of luminal antigens.

Effects of nickel chloride and oxygen depletion on behaviour and vitality of zebrafish (Danio rerio, Hamilton, 1822) (Pisces, Cypriniformes) embryos and larvae

International Nuclear Information System (INIS)

Kienle, Cornelia; Koehler, H.-R.; Filser, Juliane; Gerhardt, Almut

2008-01-01

We examined acute (2 h exposure of 5-day-old larvae) and subchronic (exposure from fertilization up to an age of 11 days) effects of NiCl 2 .6H 2 O on embryos and larvae of zebrafish (Danio rerio), both alone and in combination with oxygen depletion. The following endpoints were recorded: acute exposure: locomotory activity and survival; subchronic exposure: hatching rate, deformations, locomotory activity (at 5, 8 and 11 days) and mortality. In acute exposures nickel chloride (7.5-15 mg Ni/L) caused decreasing locomotory activity. Oxygen depletion (≤2.45 ± 0.16 mg O 2 /L) also resulted in significantly reduced locomotory activity. In the subchronic test, exposure to ≥10 mg Ni/L resulted in delayed hatching at an age of 96 h, in decreased locomotory activity at an age of 5 days, and increased mortality at an age of 11 days (LC 20 = 9.5 mg Ni/L). The observed LOEC for locomotory activity (7.5 mg Ni/L) is in the range of environmentally relevant concentrations. Since locomotory activity was already affected by acute exposure, this parameter is recommended to supplement commonly recorded endpoints of toxicity. - Increasing concentrations of nickel chloride and decreasing concentrations of oxygen lead to reduced vitality and locomotory activity in Danio rerio embryos and larvae

Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218

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Donald S. Karanewsky

Full Text Available A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7, a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested for S2218 sulfate salt (S8069 when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: Flavours with modifying properties, S2218, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation, Developmental toxicity evaluation

Skilled Nursing Facility Partnerships May Decrease 90-Day Costs in a Total Joint Arthroplasty Episode Under the Bundled Payments for Care Improvement Initiative.

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Behery, Omar A; Kouk, Shalen; Chen, Kevin K; Mullaly, Kathleen A; Bosco, Joseph A; Slover, James D; Iorio, Richard; Schwarzkopf, Ran

2018-03-01

The Bundled Payments for Care Improvement initiative was developed to reduce costs associated with total joint arthroplasty through a single payment for all patient care from index admission through a 90-day post-discharge period, including care at skilled nursing facilities (SNFs). The aim of this study is to investigate whether forming partnerships between hospitals and SNFs could lower the post-discharge costs. We hypothesize that institutionally aligned SNFs have lower post-discharge costs than non-aligned SNFs. A cohort of 615 elective, primary total hip and knee arthroplasty subjects discharged to an SNF under the Bundled Payments for Care Improvement from 2014 to 2016 were included in our analysis. Patients were grouped into one of the 3 categories of SNF alignment: group 1: non-partners; group 2: agreement-based partners; group 3: institution-owned partners. Demographics, comorbidities, length of stay (LOS) at SNF, and associated costs during the 90-day post-operative period were compared between the 3 groups. Mean index hospital LOS was statistically shortest in group 3 (mean 2.7 days vs 3.5 for groups 1 and 2, P = .001). SNF LOS was also shortest in group 3 (mean 11 days vs 19 and 21 days in groups 2 and 1 respectively, P Total SNF costs and total 90-day costs were both significantly lower in group 3 compared with groups 1 and 2 (P total 90-day costs, without increased risk of readmissions, compared with other SNFs. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicity of iron oxide nanoparticles to grass litter decomposition in a sandy soil

Science.gov (United States)

Rashid, Muhammad Imtiaz; Shahzad, Tanvir; Shahid, Muhammad; Imran, Muhammad; Dhavamani, Jeyakumar; Ismail, Iqbal M. I.; Basahi, Jalal M.; Almeelbi, Talal

2017-02-01

We examined time-dependent effect of iron oxide nanoparticles (IONPs) at a rate of 2000 mg kg-1 soil on Cynodon dactylon litter (3 g kg-1) decomposition in an arid sandy soil. Overall, heterotrophic cultivable bacterial and fungal colonies, and microbial biomass carbon were significantly decreased in litter-amended soil by the application of nanoparticles after 90 and 180 days of incubation. Time dependent effect of nanoparticles was significant for microbial biomass in litter-amended soil where nanoparticles decreased this variable from 27% after 90 days to 49% after 180 days. IONPs decreased CO2 emission by 28 and 30% from litter-amended soil after 90 and 180 days, respectively. These observations indicated that time-dependent effect was not significant on grass-litter carbon mineralization efficiency. Alternatively, nanoparticles application significantly reduced mineral nitrogen content in litter-amended soil in both time intervals. Therefore, nitrogen mineralization efficiency was decreased to 60% after 180 days compared to that after 90 days in nanoparticles grass-litter amended soil. These effects can be explained by the presence of labile Fe in microbial biomass after 180 days in nanoparticles amendment. Hence, our results suggest that toxicity of IONPs to soil functioning should consider before recommending their use in agro-ecosystems.

Role of uptake of [14C]valine into protein in the development of tolerance to diisopropylphosphorofluoridate (DFP) toxicity

International Nuclear Information System (INIS)

Gupta, R.C.; Dettbarn, W.D.

1986-01-01

In a subchronic toxicity study male Sprague-Dawley rats were daily treated with diisopropylphosphorofluoridate (DFP) (0.5 mg/kg, sc) for 14 days. Maximum signs of anticholinesterase toxicity were observed during Days 4 and 5 comparable to those seen 10-15 min following a single sublethal dosage (1.5 mg DFP/kg, sc). Signs disappeared after Days 6-7 of exposure and rats became apparently normal during the remainder of the treatment period. Significant hypothermia was seen following the second to fifth doses with maximum effect after the fifth injection. Subsequent injections of DFP did not cause any reduction in temperature. Incorporation of [ 14 C]valine was measured 24 hr after the 5th and 14th injections of DFP, at a time when body temperature had recovered to control values. The rate of in vivo incorporation of [ 14 C]valine was measured 0.5, 1.0, and 2.0 hr after a subcutaneous injection of L-[1- 14 C]valine at a dose of 5 microCi/mmol/100 g body wt. After five injections the rate of L-[1- 14 C]valine uptake into the free amino acid pool and the incorporation into the protein bound pool was significantly (p less than 0.01) reduced in discrete brain regions, liver, kidney, and skeletal muscles. At the end of the 14-day treatment, protein synthesis in all the skeletal muscles tested had recovered completely (p greater than 0.01) to the values of nontreated control animals. In brain, liver, and kidney, however, no recovery was seen during this period. The recovery of protein synthesis in skeletal muscle may be one of the mechanisms that lead to tolerance development during prolonged administration of subacute concentrations of DFP

Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry

DEFF Research Database (Denmark)

Nielsen, Brian S.; Larsen, Erik Huusfeldt; Ladefoged, Ole

2017-01-01

Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example......Cl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter...... with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected....

Subacute Toxicity Study of 40 kGy Irradiated Ready-to-Eat Bulgogi

International Nuclear Information System (INIS)

Park, J.G.; Kim, J.H.; Lee, J.W.; Byun, M.W.; Jeon, Y.E.; Kang, I.J.; Hwang, H.J.

2011-01-01

The wholesomeness of 40 kGy irradiated ready-to-eat (RTE) bulgogi was evaluated by subacute toxicity studies (body weight, food consumption, organ weight, hematology, serum biochemistry, and histopathological examination) with groups of 40 male and female ICR mice fed the agent at dietary levels of 5% for 90 days. There were no treatment-related adverse effects with regard to body weight, food consumption, organ weight, hematology, serum biochemistry, and histopathology. The no-observed-adverse-effect-level (NOAEL) was also determined to be greater than dietary level of at least 5% (3900 mg/kg body weight/day for males, 3500 mg/kg body weight/day for females) for samples under the present experimental conditions. These results suggest that, under these experimental conditions, RTE bulgogi irradiated at 40 kGy did not show any toxic effects

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels

Science.gov (United States)

Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

2017-01-01

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism. PMID:28394286

New magnetostratigraphy for the Olduvai Subchron in the Koobi Fora Formation, northwest Kenya, with implications for early Homo

Science.gov (United States)

Lepre, Christopher J.; Kent, Dennis V.

2010-02-01

A problematic magnetostratigraphy for the Koobi Fora Formation has contributed to debates on the evolutionary implications for early hominin fossils. To address this, 50 independent samples distributed over a nearly 63-m-thick interval were collected from the lower-middle KBS Member type section in fossil collection Area 102, northeast Turkana Basin. Characteristic directions obtained by thermal demagnetization define a coherent magnetostratigraphy that is supported by alternating-field studies on 28 sister specimens and the prior tephrochronological framework. Two long polarity intervals were recognized, each 30-40 m in thickness, and interpreted as the upper part of the normal polarity Olduvai Subchron and the overlying reverse polarity Matuyama Chron. The end Olduvai consists of a normal-reverse-normal polarity sequence occurring over a thickness of at least 1 m but perhaps up to 5 m, suggesting that this subchron has a short reverse interval in its uppermost part. Such a fine-scale structure also has been reported from several other sites, like the Pliocene-Pleistocene boundary and point stratotype section at Vrica, Italy, which serves as a basis for formally delimiting three temporally discrete polarity subintervals for the Olduvai Subchron. These paleomagnetic results that place the upper boundary of the Olduvai at ˜ 48 m above the base of the KBS Member, coupled with published radioisotopic dates, firmly secure the age of partial cranium KNM-ER 3733 in the interval 1.78-1.48 Ma, with an interpolated age of ˜ 1.7 Ma, giving this fossil the most unambiguous numerical-age constraints, as compared to the oldest Homo cranial remains from Europe and Asia. Nonetheless, assured placement of the top of the Olduvai Subchron in the KBS Member is not sufficient in the face of other uncertainties to influence conventional interpretations of the timing and direction for the global dispersal of early Homo erectus.

Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival after Unmanipulated Haploidentical Blood and Marrow Transplantation.

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Deng-Mei Tian

Full Text Available Rapid immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT is significantly associated with lower infection, relapse and possibly secondary malignancy rates. The aim of this study was to investigate the role of peripheral lymphocyte subsets, especially CD3+CD8+ cytotoxic T cell recovery, in predicting transplant outcomes, including the overall survival (OS and non-relapse mortality (NRM rates after unmanipulated haploidentical blood and marrow transplantation (HBMT.Peripheral blood samples were obtained from 214 HBMT recipients with hematological malignancies. The peripheral lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, and CD19+ B cells were analyzed by flow cytometry at days 30, 60, 90, 180, 270 and 360 after HBMT.The CD3+CD8+ cytotoxic T cell recovery at day 90 (CD3+CD8+-90 was correlated with bacterial infection (P = 0.001, NRM (P = 0.001, leukemia-free survival (LFS, P = 0.005, and OS (P = 0.001 at a cutoff value of 375 cells/μL CD3+CD8+ T cells. The incidence of bacterial infection in patients with the CD3+CD8+-90 at ≥375 cells/μL was significantly lower than that of cases with the CD3+CD8+-90 at <375 cells/μL after HBMT (14.6% versus 41.6%, P<0.001. Multivariate analysis showed the rapid recovery of CD3+CD8+ T cells at day 90 after HBMT was strongly associated with a lower incidence of NRM (HR = 0.30; 95% CI: 0.15-0.60; P = 0.000 and superior LFS (HR = 0.51; 95% CI: 0.32-0.82; P = 0.005 and OS (HR = 0.38; 95% CI: 0.23-0.63; P = 0.000.The results suggest that the rapid recovery of CD3+CD8+ cytotoxic T cells at day 90 following HBMT could predict superior transplant outcomes.

Potential Occupational Risks Associated with Pulmonary Toxicity of Carbon Nanotubes.

Science.gov (United States)

Manke, Amruta; Luanpitpong, Sudjit; Rojanasakul, Yon

Given their remarkable properties, carbon nanotubes (CNTs) have made their way through various industrial and medicinal applications and the overall production of CNTs is expected to grow rapidly in the next few years, thus requiring an additional recruitment of workers. However, their unique applications and desirable properties are fraught with concerns regarding occupational exposure. The concern about worker exposure to CNTs arises from the results of recent animal studies. Short-term and sub-chronic exposure studies in rodents have shown consistent adverse health effects such as pulmonary inflammation, granulomas, fibrosis, genotoxicity and mesothelioma after inhalation or instillation of several types of CNTs. Furthermore, physicochemical properties of CNTs such as dispersion, functionalization and particle size can significantly affect their pulmonary toxicity. Risk estimates from animal studies necessitate implementation of protective measures to limit worker exposure to CNTs. Information on workplace exposure is very limited, however, studies have reported that CNTs can be aerosolized and attain respirable airborne levels during synthesis and processing activities in the workplace. Quantitative risk assessments from sub-chronic animal studies recommend the health-based need to reduce exposures below the recommended exposure limit of 1 µg/m 3 . Practice of prevention measures including the use of engineering controls, personal protective equipment, health surveillance program, safe handling and use, as well as worker training can significantly minimize worker exposure and improve worker health and safety.

Prediction of 90 Day and Overall Survival after Chemoradiotherapy for Lung Cancer: Role of Performance Status and Body Composition.

Science.gov (United States)

Bowden, J C S; Williams, L J; Simms, A; Price, A; Campbell, S; Fallon, M T; Fearon, K C H

2017-09-01

If appropriate patients are to be selected for lung cancer treatment, an understanding of who is most at risk of adverse outcomes after treatment is needed. The aim of the present study was to identify predictive factors for 30 and 90 day mortality after chemoradiotherapy (CRT), and factors that were prognostic for overall survival. A retrospective cohort study of 194 patients with lung cancer who had undergone CRT in South East Scotland from 2008 to 2010 was undertaken. Gender, age, cancer characteristics, weight loss, body mass index (BMI), performance status (Eastern Cooperative Oncology Group; ECOG) and computed tomography-derived body composition variables were examined for prognostic significance using Cox's proportional hazards model and logistic regression. The median overall survival was 19 months (95% confidence interval 16.3, 21.7). Four of 194 patients died within 30 days of treatment completion, for which there were no independent predictive variables; 22/194 (11%) died within 90 days of treatment completion. BMI < 20 and ECOG performance status ≥2 were independent predictors of death within 90 days of treatment completion (P = 0.001 and P = 0.004, respectively). Patients with either BMI < 20 or ECOG performance status ≥ 2 had an odds ratio of death within 90 days of 5.97 (95% confidence interval 2.20, 16.19), rising to an odds ratio of 13.27 (1.70, 103.47) for patients with both BMI < 20 and ECOG performance status ≥ 2. Patients with low muscle attenuation had significantly reduced overall survival (P = 0.004); individuals with low muscle attenuation had a median survival of 15.2 months (95% confidence interval 12.7, 17.7) compared with 23.0 months (95% confidence interval 18.3, 27.8) for those with high muscle attenuation, equating to a hazard ratio of death of 1.62 (95% confidence interval 1.17, 2.23, P = 0.003). Poor performance status, low BMI and low muscle attenuation identify patients at increased risk of premature death after

Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP: effects of modafinil and relevance to cognitive deficits in schizophrenia?

Directory of Open Access Journals (Sweden)

John P Redrobe

2010-11-01

Full Text Available Phencyclidine (PCP induces a behavioural syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p. or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP-treatment. Acute treatment with modafinil (64 mg/kg, p.o. ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c., risperidone (0.2 mg/kg, i.p. and donepezil (3 mg/kg, p.o. were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP-NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS.

Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.

Science.gov (United States)

Gulec, Seza A; Cohen, Steven J; Pennington, Kenneth L; Zuckier, Lionel S; Hauke, Ralph J; Horne, Heather; Wegener, William A; Teoh, Nick; Gold, David V; Sharkey, Robert M; Goldenberg, David M

2011-06-15

Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer. ©2011 AACR.

Preclinical evaluations of norcantharidin-loaded intravenous lipid microspheres with low toxicity.

Science.gov (United States)

Lin, Xia; Zhang, Bo; Zhang, Keru; Zhang, Yu; Wang, Juan; Qi, Na; Yang, Shenshen; He, Haibing; Tang, Xing

2012-12-01

The aim of this study was to perform a systematic preclinical evaluation of norcantharidin (NCTD)-loaded intravenous lipid microspheres (NLM). Pharmacokinetics, biodistribution, antitumor efficacy and drug safety assessment (including acute toxicity, subchronic toxicity, hemolysis testing, intravenous stimulation and injection anaphylaxis) of NLM were carried out in comparison with the commercial product disodium norcantharidate injection (NI). The pharmacokinetics of NLM in rats was similar to that of NI, and a non-linear correlation was observed between AUC and dose. A comparable antitumor efficacy of NLM and NI was observed in mice inoculated with A549, BEL7402 and BCAP-37 cell lines. It was worth noting that the NLM produced a lower drug concentration in heart compared with NI, and significantly reduced the cardiac and renal toxicity. The LD(50) of NLM was twice higher than that of NI. In NLM, over 80% of NCTD was loaded in the lipid phase or bound with phospholipids. Thus, NCTD was sequestered by direct contacting with body fluids and largely avoided distribution into tissues, consequently leading to significantly reduced cardiac and renal toxicity. These preclinical results suggested that NLM could be a useful potential carrier for parenteral administration of NCTD, while providing a superior safety profile.

Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Wiseman, G.A.; Dunn, W.L.; White, C.A.; Berlfein, J.R.; Ding, E.; Grillo-Lopez, A.J.; Stabin, M.; Erwin, W.; Spies, S.; Dahlbom, M.; Silverman, D.H.S.; Raubitschek, A.; Karvelis, K.; Schultheiss, T.; Witzig, T.E.; Belanger, R.

2000-01-01

Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90 Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90 Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received 111 In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8) on day 0 followed by a therapeutic dose of 90 Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of 111 In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T 1/2 , blood AUC

Safety of a novel botanical extract formula for ameliorating allergic rhinitis.

Science.gov (United States)

Amit, A; Saxena, V S; Pratibha, N; Bagchi, M; Bagchi, D; Stohs, S J

2003-01-01

Allergic rhinitis (also known as hay fever) is the most commonly occurring immunological disorder, and it affects 40 million men, women, and children in the United States. Symptomatically, it is an inflammation and irritation of the mucous membranes that line the nose. Allergy is defined as a state of hypersensitivity or hyperimmunity caused by exposure to a particular antigen (allergen) that results in increased reactivity upon subsequent exposure. A novel botanical formulation, Aller-7/NR-A2, was developed for the treatment of allergic rhinitis; it is a combination of medicinal plant extracts from Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum. This novel formulation has demonstrated potent antihistaminic, anti-inflammatory, antispasmodic, antioxidant, and mast-cell-stabilization activities. All of the doses for these toxicity studies were selected according to the guidelines of the Organization for Economic Cooperation and Development, the World Health Organization, and the Environmental Protection Agency. Acute toxicity of Aller-7 was evaluated in Swiss Albino mice at doses of 125, 250, 500, 1000, and 1500 mg/kg. After 15 days of treatment, the animals were sacrificed. No histopathological changes were observed in major vital organs. A similar study was conducted in Albino Wistar rats, which were sacrificed at the end of 15 days. No histopathological changes or toxicity was observed at up to 2 g/kg body weight. Subacute toxicity was conducted in Albino Wistar rats at a dose of 90 mg/kg body weight for 3 days, then at 180 mg/kg for the next 3 days, and then at 270 mg/kg for 3 weeks. After 28 days, the animals were sacrificed and tested; no toxicity was observed. In a subchronic toxicity study, there was no observed adverse effect level at 1 g/kg body weight in rats. In a teratological assay, at doses of 3.0 g/kg (20 times the recommended dose) and 1.8 g/kg, respectively, no

Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers.

Science.gov (United States)

Villard, Linda; Romer, Anna; Marincek, Nicolas; Brunner, Philippe; Koller, Michael T; Schindler, Christian; Ng, Quinn K T; Mäcke, Helmut R; Müller-Brand, Jan; Rochlitz, Christoph; Briel, Matthias; Walter, Martin A

2012-04-01

Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes. In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) or with cycles alternating between [(90)Y-DOTA]-TOC and (177)lutetium-labeled DOTA-TOC ([(177)Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles. A total of 486 patients completed three or more treatment cycles; 237 patients received [(90)Y-DOTA]-TOC and 249 patients received [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC. Patients receiving [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC had a significantly longer survival than patients receiving [(90)Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups. [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC was associated with improved overall survival compared with [(90)Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.

Intravitreal bevacizumab in pigmented rabbit eyes: histological analysis 90 days after injection Bevacizumabe intravítreo em olhos de coelhos não albinos: análise histológica 90 dias após a injeção

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João Carlos Diniz Arraes

2009-10-01

Full Text Available PURPOSE: To evaluate bevacizumab toxicity in neurosensorial retina and retinal pigment epithelium in pigmented rabbit eyes by means of histological studies. METHODS: Thirty eyes of fifteen rabbits were distributed into three groups: sham group (S, that received a 0.1 ml balanced saline solution (BSS intravitreal injection (10 eyes; group 1, that received a 1.25 mg (0.1 ml bevacizumab intravitreal injection (10 eyes; and group 2, that received a 2.5 mg (0.1 ml bevacizumab intravitreal injection (10 eyes. Rabbits were sacrificed 90 days after the procedure and both eyes of each rabbit were enucleated. A histological examination of neurosensorial retina and retinal pigmented epithelium (RPE was performed. Its morphological features and layer thickness were also analyzed. RESULTS: No histological differences in neurosensorial retina or in retinal pigmented epithelium were found and layer thickness did not differ significantly between balanced saline solution-injected eyes and bevacizumab-injected eyes. CONCLUSION: After a 90-day follow-up period, a single 1.25 or 2.5 mg bevacizumab intravitreal injection did not lead to toxic damage in the neurosensorial retina and retinal pigment epithelium of pigmented rabbit eyes, and it appears to be a safe procedure for retinal neovascular diseases.OBJETIVOS: Avaliar a toxicidade do bevacizumabe na retina neurossensorial e epitélio pigmentado da retina (EPR em olhos de coelhos não albinos pelos estudos histológicos. MÉTODOS: Trinta olhos de 15 coelhos foram distribuídos em três grupos: 10 olhos no grupo placebo (P, que recebeu uma injeção intravítrea de 0,1 ml de solução salina balanceada (SSB; 10 olhos no grupo 1, que recebeu uma injeção intravítrea de 1,25 mg (0,1 ml de bevacizumabe; e 10 olhos no grupo 2, que recebeu uma injeção intravítrea de 2,5 mg (0,1 ml de bevacizumabe. Os coelhos tiveram seus dois olhos enucleados sob anestesia geral e submetidos à eutanásia 90 dias após a inje

Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study.

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McConville, Thomas Howe; Sullivan, Sean Berger; Gomez-Simmonds, Angela; Whittier, Susan; Uhlemann, Anne-Catrin

2017-01-01

Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent public health threat. Intestinal colonization with CRE has been identified as a risk factor for the development of systemic CRE infection, but has not been compared to colonization with third and/or fourth generation cephalosporin-resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by colonization on adverse outcomes is less clear, particularly in critically ill patients admitted to the intensive care unit (ICU). We carried out a cohort study of consecutive adult patients screened for rectal colonization with CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical variables and assessed the relationship between CRE or Ceph-R colonization and subsequent systemic CRE infection within 30 days (primary outcome) and all-cause mortality within 90 days (secondary outcome). Among 338 ICU patients, 94 (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and 3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and 15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE colonization independently predicted development of a systemic CRE infection at 30 days (aOR 10.8, 95% CI2.8-41.9, p = 0.0006); Ceph-R colonization did not (aOR 0.5, 95% CI0.1-3.3, p = 0.5). CRE colonization was associated with increased 90-day mortality in a univariable analysis (p-value 0.001), in a multivariable model, previous hospitalization and medical ICU admission were independent predictors of 90-day mortality whereas CRE colonization approached significance (aOR 2.3, 95% CI1.0-5.3, p = 0.056). Our study highlights the increased risk of CRE infection and mortality in patients with CRE colonization at the time of ICU admission. Future studies are needed to assess how CRE

76 FR 62375 - Endangered and Threatened Species; 90-Day Finding on Petitions To Delist Coho Salmon Under the...

Science.gov (United States)

2011-10-07

... Salmon Under the Endangered Species Act AGENCY: National Marine Fisheries Service (NMFS), National.... SUMMARY: We, NMFS, announce a 90-day finding on three petitions to delist coho salmon (Oncorhynchus... delist coho salmon under the ESA. We also received two similar petitions from the Siskiyou County Water...

In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae Leaves

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Aldilane Gonçalves Fonseca

2018-01-01

Full Text Available The species Kalanchoe brasiliensis, known as “Saião,” has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis. The action of the extract (concentrations from 0.1 to 1000 uL/100 uL in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal and 786-0 (kidney carcinoma, showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo, the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

Sources and pathways of 90Sr in the North Atlantic-Arctic region: present day and global warming

International Nuclear Information System (INIS)

Gao Yongqi; Drange, Helge; Johannessen, Ola M.; Pettersson, Lasse H.

2009-01-01

The spatial and temporal distributions of the anthropogenic radionuclides 137 Cs and 90 Sr, originating from nuclear bomb testing, the Sellafield reprocessing plant in the Irish Sea (UK), and from the Ob and Yenisey river discharges to the Arctic Ocean, have been simulated using the global version of the Miami Isopycnic Coordinate Ocean Model (MICOM). The physical model is forced with daily atmospheric re-analysis fields for the period of 1948-1999. Comparison of the temporal evolution of the observed and the simulated concentrations of 90 Sr has been performed in the Kara Sea. The relative contributions of the different sources on the temporal and spatial distributions of the surface 90 Sr are quantified over the simulated period. It follows that the Ob river discharge dominated the surface 90 Sr over most of the Arctic Ocean and along the eastern and western coasts of Greenland before 1960. During the period of 1980-1990, the atmospheric fallout and the Ob river discharge were equally important for the 90 Sr distribution in the Arctic Ocean. Furthermore, an attempt has been made to explore the possible dispersion of accidental released 90 Sr from the Ob and Yenisey rivers under a global warming scenario (2 x CO 2 ). The difference between the present-day and the global warming scenario runs indicates that more of the released 90 Sr from the Ob and Yenisey rivers is confined to the Arctic Ocean in the global warming run, particularly in the near coastal, non-European part of the Arctic Ocean.

Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

International Nuclear Information System (INIS)

Liu Jing; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

2007-01-01

Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation

A 90 day safety assessment of genetically modified rice expressing Cry1Ab/1Ac protein using an aquatic animal model.

Science.gov (United States)

Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Wang, Jia-Mei; Ding, Jia-Tong; Chen, Xiu-Ping; Peng, Yu-Fa

2015-04-15

In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein.

78 FR 13614 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List the Humphead Wrasse as...

Science.gov (United States)

2013-02-28

... Petition To List the Humphead Wrasse as Threatened or Endangered Under the Endangered Species Act AGENCY... endangered and designate critical habitat under the Endangered Species Act (ESA). We find that the petition... within 90 days of [[Page 13615

Does a concomitant exposure to lead influence unfavorably the naphthalene subchronic toxicity and toxicokinetics?

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Katsnelson, Boris A; Minigaliyeva, Ilzira A; Degtyareva, Tamara D; Privalova, Larisa I; Beresneva, Tatyana A

2014-01-01

Rats were given 20 times during 40 d either naphthalene per gavage or the same and lead acetate intraperitoneally in single doses corresponding to 5% of the respective 50% lethal doses. The concomitant exposure to lead not only added some typical indicators of lead toxicity to the moderate naphthalene intoxication picture but also exaggerated some less specific indices for intoxication. However, a number of such indices testified to attenuation of naphthalene's adverse effects under the impact of lead. Lead also lowered urinary excretion of both total and conjugated naphthalene, while the free- to total naphthalene ratio in urine sharply increased. These results corroborate implicitly the initial hypothesis that lead, being an inhibitor of cytochrome P450, hinders phase I of the naphthalene biotransformation and, thus, the formation of derivates which can be more toxic but are capable of entering into reactions of conjugation with resulting detoxication and elimination of naphthalene from the body. © 2013 SETAC.

Chronic toxicity and hazard assessment of an inorganic mixture simulating irrigation drainwater to razorback sucker and bonytail

Science.gov (United States)

Hamilton, Steven J.; Buhl, Kevin J.; Bullard, Fern A.; Little, Edward E.

2000-01-01

We conducted two 90 day chronic toxicity studies with two endangered fish, razorback sucker and bonytail. Swim-up larvae were exposed in a reconstituted water simulating the middle Green River. The toxicant mixture simulated the environmental ratio and concentrations of inorganics reported in a Department of the Interior study for the mouth of Ashley Creek on the Green River, and was composed of nine elements. The mixture was tested at 1X, 2X, 4X, 8X, and 16X where X was the measured environmental concentration (2 μg/L arsenic, 630 μg/L boron, 10 μg/L copper, 5 μg/L molybdenum, 51 μg/L selenate, 8 μg/L selenite, 33 μg/L uranium, 2 μg/L vanadium, and 20 μg/L zinc). Razorback sucker had reduced survival after 60 days exposure to the inorganic mixture at 8X, whereas growth was reduced after 30 and 60 days at 2X and after 90 days at 4X. Bonytail had reduced survival after 30 days exposure at 16X, whereas growth was reduced after 30, 60, and 90 days at 8X. Swimming performance of razorback sucker and bonytail were reduced after 60 and 90 days of exposure at 8X. Whole-body residues of copper, selenium, and zinc increased in a concentration-response manner and seemed to be regulated at 90 days of exposure at 4X and lower treatments for razorback sucker, and at 8X and lower for bonytail. Adverse effects occurred in fish with whole-body residues of copper, selenium, and zinc similar to those causing similar effects in other fish species. Comparison of adverse effect concentrations with measured environmental concentrations showed a high hazard to the two endangered fish. Irrigation activities may be a contributing factor to the decline of these endangered fishes in the middle Green River. 

Bioaccumulation, morphological changes, and induction of metallothionein gene expression in the digestive system of the freshwater crab Sinopotamon henanense after exposure to cadmium.

Science.gov (United States)

Wu, Hao; Li, Yingjun; Lang, Xingping; Wang, Lan

2015-08-01

To study the responses of digestive system of the freshwater crab Sinopotamon henanense to the exposure with cadmium (Cd), crabs were acutely exposed to 7.25, 14.50, and 29.00 mg/l Cd for 96 h and subchronically exposed to 0.725, 1.450, and 2.900 mg/l for 21 days. Cd bioaccumulation in the hepatopancreas and digestive tract (esophagus and intestine) was examined. Furthermore, histopathological alterations of the esophagus, midgut, hindgut, and hepatopancreas were assessed in animals from the 29.0 and 2.90 mg/l Cd treatment groups, and expression of metallothionein messenger RNA (MT mRNA) in the hepatopancreas and intestine was measured in all treatment groups. The results showed difference in the middle and high concentrations between acute and subchronic treatment groups. Cd content in digestive tract after acute 14.5 and 29.0 mg/l Cd exposure was significantly higher than that at subchronic 1.45 and 2.90 mg/l exposure, but Cd levels in hepatopancreas were not significantly different under the same condition. Acute exposure to Cd induced greater morphological damage than subchronic exposure: large areas of epithelial cells were necrotic in hepatopancreas and midgut, which detached from the basal lamina. Vacuolated muscle cells were observed in the hindgut of animals from the acute exposure group, but the changes of esophageal morphology were not obvious after acute or subchronic treatments. The expression of MT mRNA increased with increasing Cd concentration, and MT mRNA level in acute exposure groups was significantly lower when compared to the subchronic exposure groups. Higher Cd content and lower MT mRNA expression in the acutely exposed groups may be responsible for more severe damage of digestive system in these exposure groups.

Subchronic toxicity evaluation of γ-aminobutyric acid (GABA) in rats.

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Takeshima, Kazuhito; Yamatsu, Atsushi; Yamashita, Yusuke; Watabe, Kazuya; Horie, Noriko; Masuda, Kazuyuki; Kim, Mujo

2014-06-01

γ-Aminobutyric acid (GABA) is an amino acid compound contained in vegetables such as tomatoes and also widely distributed in mammals. GABA acts as an inhibitory neurotransmitter and promotes parasympathetic activity to provide several beneficial effects, for instance, relaxation, anti-stress, and insomnia. GABA, produced via a fermentation process, has been available as a functional food ingredient. As part of a program to assess its safety, GABA was administered by oral gavage at doses of 500, 1250, and 2500mg/kg body weight to groups of 10 male and 10 female Sprague-Dawley rats for 13weeks. Treatment was not associated with the test substance-related mortality and appeared to be well tolerated. There were no toxicologically and statistically significant changes in urinalysis, hematology, clinical chemistry parameters, and in necropsy findings. A few statistically significant changes in food consumption and body weights were noted in the male groups while any significant changes were not noted in female groups. There was no effect of treatment on organ weights or on the results of the histopathological examinations. The results of toxicity evaluation support the safety use of GABA and the potential use as a functional food ingredient. Copyright © 2014 Elsevier Ltd. All rights reserved.

75 FR 41436 - Endangered and Threatened Wildlife; Notice of 90-Day Finding on a Petition to Revise Critical...

Science.gov (United States)

2010-07-16

...-02] RIN 0648-XW94 Endangered and Threatened Wildlife; Notice of 90-Day Finding on a Petition to Revise Critical Habitat for the Endangered Leatherback Sea Turtle Under the Endangered Species Act (ESA... finding on a petition to revise critical habitat for the endangered leatherback sea turtle under the...

Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.

Science.gov (United States)

Geschwind, Jean Francois H; Salem, Riad; Carr, Brian I; Soulen, Michael C; Thurston, Kenneth G; Goin, Kathleen A; Van Buskirk, Mark; Roberts, Carol A; Goin, James E

2004-11-01

Unresectable hepatocellular carcinoma is extremely difficult to treat. TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are injected into the hepatic arteries. This article reviews the safety and survival of patients with hepatocellular carcinoma who were treated with yttrium-90 microspheres. Eighty patients were selected from a database of 108 yttrium-90 microsphere-treated patients and were staged by using Child-Pugh, Okuda, and Cancer of the Liver Italian Program scoring systems. Patients were treated with local, regional, and whole-liver approaches. Survival from first treatment was analyzed with Kaplan-Meier and Cox regression methods. Adverse events and complications of treatment were coded by using the Southwest Oncology Group toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy. Thirty-two patients (40%) received more than 1 treatment. Survival correlated with pretreatment Cancer of the Liver Italian Program scores ( P = .002), as well as with the individual Cancer of the Liver Italian Program components, Child-Pugh class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients classified as Okuda stage I (n = 54) and II (n = 26) had median survival durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%, respectively ( P = .02). One patient died of liver failure judged as possibly related to treatment. Thus, in selected patients with hepatocellular carcinoma, yttrium-90 microsphere treatment is safe and well tolerated. On the basis of these results, a randomized controlled trial is warranted comparing yttrium-90 microsphere treatment with transarterial chemoembolization by using the Cancer of the Liver Italian Program system for prospective stratified randomization.

Dietary and Food Processing for a 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

Science.gov (United States)

Zhao, Zhiruo; Fu, Yuming; Dong, Chen; Liu, Guanghui

A 4-day cycle dietary menu was developed to meet the requirements of balanced diet of the crew within the 90-day closed experiment of bioregenerative life support in the Lunar Palace 1. The menu consisted of items prepared from crops and insect grown inside the system, as well as prestored food. Dairy recipe was composed of breads, vegetables, meats and soups, which provided about 2900 kcal per crew member per day. During food processing, to maximize nutrient recovery and minimize waste production, the whole wheat grains and chufa nuts were milled. Further, the carrot leaves and yellow mealworms were used as salad materials and bread ingredients, respectively. The sensory acceptability of the dishes in the menu was evaluated by flavor, texture, and appearance. Our results show that all dishes in the 4-day cycle menu were highly acceptable, which satisfies nutritional requirement of the crew members in the closed habitation.

Latent Toxicity of Endothall to Anadromous Salmonids During Seawater Challenge.

Science.gov (United States)

Courter, Lauren A; Garrison, Thomas M; Courter, Ian I

2016-05-01

Limited evidence exists on the latent effects of toxicant exposure on the seawater adaptability of anadromous salmon and steelhead. It is unclear whether such an effect exists for the widely used and relatively non-toxic herbicide endothall. Coho salmon, Oncorhynchus kisutch (coho), Chinook salmon, O. tshawytscha (Chinook), and anadromous rainbow trout, O. mykiss (steelhead) were subjected to a 10-day seawater challenge following freshwater treatments [0-12 mg acid equivalent (a.e)./L at 96 h]. Mean survival resulted in 82 % (n = 225), 84 % (n = 133), 90 % (n = 73) and 59 % (n = 147) survival for 0, 3-5, 6-8, and 9-12 mg a.e./L, respectively. Our results indicate a lower toxicity threshold compared with previously reported acute toxicity results, but higher compared with previous seawater challenge studies. We demonstrate the utility of the seawater challenge assay to accurately define toxic effects of pesticides on salmonids with complex life-histories.

Toxicity Induced after Subchronic Administration of the Synthetic Food Dye Tartrazine in Adult Rats, Role of Oxidative Stress

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Narges El Golli

2016-04-01

Full Text Available The present study was conducted to evaluate the toxic potential of tartrazine, a food color, in different tissues in adult rat: blood, liver, kidneys, and spleen. Tartrazine was administered orally at a dose of 300 mg/kg of body weight to adult male Wistar rats during a period of 30 days. Tartrazine treatment led to an increase in platelets count, a reduction in peripheral lymphocytes and in spleen T CD8-lymphocytes. Furthermore, tartrazine increased the activities of hepatocellular enzymes and promoted changes in kidney biomarkers. In order to explore the possible mechanism involved, oxidative-stress assessment was performed. Results identified critical oxidative alterations in all tested organs, as shown by the promotion of lipid peroxidation and the modification of endogenous antioxidant-defense enzymes. Thus, tartrazine is able to induce in adult rats’ hematotoxicity, immunotoxicity, and liver and kidney injuries by changing the whole balance between oxidants and antioxidants.

Chronic liver disease and subchronic nephritis in a male warty chameleon (Furcifer verrucosus with transient hyperglycaemia – case report

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Zdeněk Knotek

2011-01-01

Full Text Available A two-year old male warty chameleon (Furcifer verrucosus weighing 160 g was presented for veterinary examination following 4 weeks of decreased ability to catch insects with the tongue and difficulty in swallowing the prey. Non-invasive endoscopy did not reveal any macroscopic changes of the oral cavity mucosa or the cranial part of the esophagus. Dorsoventral and laterolateral plain and contrast radiographs revealed enlargement of the medial part of the liver without any visible abnormalities in the regions of the esophagus, stomach or small intestine. Abnormalities in the plasma chemistry profile included transient hyperglycaemia (52.68–57.18 mmol/l and hyperuricaemia (452.70–622.20 μmol/l. The chameleon was examined at 7, 20 and 22 weeks after initial examination. Its body weight decreased to 120 g. A blood profile revealed normoglycaemia (16.37–10.22 mmol/l and hyperphosphataemia (2.92–3.06 mmol/l at the last three examinations. The chameleon died suddenly 33 days after the final examination. Necropsy revealed the presence of a large liver cyst, filled with fluid. The liver had lost all of its normal structure. The kidneys showed a large area with fibrosis and multiple uric acid tophi. The post mortem findings were defined as liver with fatty degeneration and moderate fibrotic changes with large cyst, subchronic nephritis with uric acid tophi, and mineralization in the myocardium. This paper describes the first documented case of transient hyperglycaemia in a warty chameleon (Furcifer verrucosus associated with chronic liver disease and subchronic nephritis.

Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

Science.gov (United States)

Zhao, Kai; Ren, Fangfang; Han, Fangting; Liu, Qiwen; Wu, Guogan; Xu, Yan; Zhang, Jian; Wu, Xiao; Wang, Jinbin; Li, Peng; Shi, Wei; Zhu, Hong; Lv, Jianjun; Zhao, Xiao; Tang, Xueming

2016-01-01

In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3) studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

Directory of Open Access Journals (Sweden)

Kai Zhao

Full Text Available In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1 studying horizontal gene transfer (HGT in Sprague Dawley rats fed transgenic rice for 90 d; (2 examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3 studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

Endogenous thiols enhance thallium toxicity

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Montes, Sergio; Rios, Camilo [Instituto Nacional de Neurologia y Neurocirugia, ' ' Manuel Velasco Suarez' ' , Departamento de Neuroquimica, Mexico, D.F (Mexico); Soriano, Luz; Monroy-Noyola, Antonio [Universidad Autonoma del Estado de Morelos, Laboratorio de Neuroproteccion, Facultad de Farmacia, Cuernavaca, Morelos (Mexico)

2007-10-15

Either L-methionine (L-met) or L-cysteine (L-cys), given alone and in combination with Prussian blue (PB) was characterized as treatment against acute thallium (Tl) toxicity in rats. Animals were intoxicated with 32 mg/kg Tl acetate corresponding to rat LD{sub 50}. Antidotal treatments were administered during 4 days, as follows: (1) vehicle, (2) L-met 100 mg/kg i.p. twice a day, (3) L-cys 100 mg/kg i.p. twice a day, (4) PB 50 mg/kg oral, twice a day, (5) L-met + PB and (6) L-cys + PB. Mortality was as follows: control 50%; L-met 80%; L-cys 80%; PB 20%; L-met + PB 90% and L-cys + PB 100%. In a different experiment, using 16 mg/kg of Tl, tissue levels of this metal were analyzed. PB treatment statistically diminished Tl content in body organs and brain regions (P < 0.01). Whereas, separate treatments of L-met and L-cys failed to decrease Tl content in organs and brain regions; while its administration in combination with PB (L-met + PB and L-cys + PB groups) lowered Tl levels in body organs in the same extent as PB group. Results indicate that L-met and L-cys administered alone or in combination with PB should not be considered suitable treatments against acute Tl toxic effects because this strategy failed to prevent mortality and Tl accumulation in brain. (orig.)

Pubertal dependent effects of cadmium on episodic prolactin secretion in male rats

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Lafuente, A.; Alvarez-Demanuel, E.; Marquez, N. [Fac. de Cienicas, Orense (Spain). Lab. de Toxicologia; Esquifino, A.I. [Dept. Bioquimica, Facultad de Medicina, Universidad Complutense, 28040-Madrid (Spain)

1999-02-01

This work was undertaken to assess if exposure to cadmium related to puberty may affect the episodic pattern of prolactin. Male rats were submitted to cadmium exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose of 50 ppm in the drinking water. Control age-matched rats received cadmium-free water. Prepubertal cadmium administration decreased mean serum prolactin levels and the absolute amplitude of the prolactin pulses. Subchronic exposure to cadmium of adult rats decreased mean serum prolactin levels, the absolute amplitude of the prolactin pulses and their duration, and the mean half-life of the hormone. These results suggest that subchronic cadmium exposure changes the secretory pattern of prolactin in adult male rats in a puberty-dependent way. (orig.) With 1 fig., 1 tab., 37 refs.

Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice

Czech Academy of Sciences Publication Activity Database

Lebedová, J.; Nováková, Z.; Večeřa, Zbyněk; Buchtová, Marcela; Dumková, J.; Dočekal, Bohumil; Bláhová, L.; Mikuška, Pavel; Míšek, Ivan; Hampl, A.; Hilscherová, K.

(2018), s. 1-17 ISSN 1743-5390 R&D Projects: GA ČR(CZ) GBP503/12/G147; GA ČR(CZ) GAP503/11/2315 Institutional support: RVO:68081715 ; RVO:67985904 Keywords : nanoparticles * oxidative stress * subchronic * tissue damage Subject RIV: CB - Analytical Chemistry, Separation; DN - Health Impact of the Environment Quality (UZFG-Y) OBOR OECD: Analytical chemistry Impact factor: 6.428, year: 2016

Relationship between Activities of Daily Living and Readmission within 90 Days in Hospitalized Elderly Patients with Heart Failure

Directory of Open Access Journals (Sweden)

Masahiro Kitamura

2017-01-01

Full Text Available Aims. To examine the relationship between activities of daily living (ADL and readmission within 90 days and assess the cutoff value of ADL to predict readmission in hospitalized elderly patients with heart failure (HF. Methods. This cohort study comprised 589 consecutive patients with HF aged ≥65 years, who underwent cardiac rehabilitation from May 2012 to May 2016 and were discharged home. We investigated patients’ characteristics, basic attributes, and ADL (motor and cognitive Functional Independence Measure [FIM]. We analyzed the data using the unpaired t-test, χ2 test, Cox proportional hazard model, receiver operating characteristic (ROC curve, and Kaplan-Meier method. Results. Of 589 patients, 113 met the criteria, and they were divided into the nonreadmission (n=90 and readmission groups (n=23. Age, body mass index, New York Heart Association class, hemoglobin level, and motor FIM score were significantly different between the two groups (p<0.05. The body mass index (hazard ratio [HR]: 0.87; p<0.05 and motor FIM score (HR: 0.94; p<0.01 remained statistically significant. The cutoff value for the motor FIM score determined by ROC curve analysis was 74.5 points (area under the curve = 0.78; p<0.001. Conclusion. The motor FIM score in elderly patients with HF was an independent predictor of rehospitalization within 90 days.

Acute and subchronic airway inflammation after intratracheal instillation of quartz and titanium dioxide agglomerates in mice

DEFF Research Database (Denmark)

Roursgaard, Martin; Jensen, Keld A; Poulsen, Steen Seier

2011-01-01

This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compo...

High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data.

Science.gov (United States)

Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye, Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

2012-07-01

To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

Energy Technology Data Exchange (ETDEWEB)

Ghilezan, Michel, E-mail: mghilezan@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States); Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States)

2012-07-01

Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

International Nuclear Information System (INIS)

Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

2012-01-01

Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6–40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable-risk prostate cancer patients treated with

Hematological toxicity of Zevalin1-{sup 90}Y used in mono-therapy or in consolidation among 39 patients suffering of B non Hodgkin lymphomas (B-N.H.L.); Toxicite hematologique du Zevalin1-90Y utilise en monotherapie ou en consolidation chez 39 patients atteints de LNH B

Energy Technology Data Exchange (ETDEWEB)

Boin, C.; Barre, E.; Gaillard, I.; Faure, P.; Moretti, J.L. [Hopital Saint-Louis, Service de pharmacie/medecine nucleaire, 75 - Paris (France); Sibon, D.; Brice, P.; Thieblemont, C. [Hopital Saint-Louis, Service d' hemato-oncologie, 75 - Paris (France); Bonnot-Lours, S.; Meignan, M. [Hopital Henri-Mondor, service de pharmacie/medecine nucleaire, 94 - Creteil (France)

2010-07-01

Purpose: an important heterogeneity of hematological toxicity of Zevalin -{sup 90}Y was observed in patients treated in mono-therapy or consolidation. In a context of ambulatory follow-up, it seems interesting to look for predicting this toxicity according to the clinico biological characteristics of patients. This would allow to select and follow in an optimum way the candidates to this treatment. A bi-centric retrospective study was lead for which objective was to enlighten the factors associated to this toxicity. Conclusions: a comprehensive study of clinico biological history and compliance with warnings of product characteristics summary will allow to select at the best the candidates to radioimmunotherapy by Zevalin-{sup 90}Y. this treatment represents an interesting option in some patients (particularly aged patients), stays efficient and well tolerated. (N.C.)

Predictive modelling of 2-year potency outcomes using a novel 90-day erection fullness scale after robot-assisted radical prostatectomy.

Science.gov (United States)

Huynh, Linda M; Osann, Kathryn; Skarecky, Douglas; Ahlering, Thomas E

2018-03-09

To introduce a patient-reported erection fullness scale (%fullness) after robot-assisted radical prostatectomy (RARP) as a qualitative adjunct to the five-item version of the International Index of Erectile Function (IIEF-5) and as a 90-day predictor of 2-year potency outcomes. Prospective data were collected from 540 men with preoperative IIEF-5 scores of 22-25 who underwent RARP by a single surgeon, and of whom 299 had complete data at all time points up to 2 years. In addition to standard assessment tools (IIEF-5 and erections sufficient for intercourse [ESI]), the men were asked to 'indicate the fullness you are able to achieve in erections compared to before surgery?' (range: 0-100%). The primary outcome was prediction of potency (defined as ESI) at 24 months, based on 90-day %fullness tertile (0-24%, 25-74% and 75-100%). A total of 299 men with complete follow-up were included in the study. Significant predictors of 24-month potency included age, body mass index, pathological stage, nerve-sparing status and %fullness tertiles. When the men (preoperative IIEF-5 score 22-25) were assessed at 90 days after RARP, 181/299 (61%) had erections inadequate for intercourse. If IIEF-5 scores of 1-6 were used, 142/181 men (78%) would be targeted for early intervention. By contrast, if 0-24% fullness was used, 88/181 men (49%) would be targeted. If both the IIEF-5 score and %fullness were used, this would be reduced to 77/181 men (43%). We introduce %fullness as a qualitative adjunct to the IIEF-5 score, and separately as a 90-day predictor of 2-year potency recovery. This initial report is hypothesis-generating, such that the use of %fullness enables the identification of men who are most likely to benefit from early, secondary intervention. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, β-catenin and antidepressant-like effects.

Science.gov (United States)

Pilar-Cuéllar, F; Vidal, R; Pazos, A

2012-02-01

5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically. Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyuridine (BrdU) incorporation, and β-catenin protein expression in different cellular fractions, as well as 5-HT(1A) receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy. mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of β-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT(1A) receptor function in any of the groups studied. The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT(2A) receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated β-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT(1A) receptor desensitization in the dorsal raphe nucleus. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Characterisation of immune responses in healthy foals when a multivalent vaccine protocol was initiated at age 90 or 180 days.

Science.gov (United States)

Davis, E G; Bello, N M; Bryan, A J; Hankins, K; Wilkerson, M

2015-11-01

Protection from infectious disease requires antigen-specific immunity. In foals, most vaccine protocols are delayed until 6 months to avoid maternal antibody interference. Susceptibility to disease may exist prior to administration of vaccination at age 4-6 months. The aim of this investigation was to characterise immune activation among healthy foals in response to a multivalent vaccine protocol and compare immune responses when foals were vaccinated at age either 90 or 180 days. Randomised block design. Twelve healthy foals with colostral transfer were blocked for age and randomly assigned to vaccination at age 90 days (treatment) or at age 180 days (control). Vaccination protocols included a 3-dose series and booster vaccine administered at age 11 months. Immune response following vaccination at age 90 or 180 days was comparable for several measures of cellular immunity. Antigen specific CD4+ and CD8+ expression of interleukin-4, interferon-γ and granzyme B to eastern equine encephalomyelitis, western equine encephalomyelitis, West Nile virus, tetanus toxoid, equine influenza and equine herpesvirus-1/4 antigens were evident for both groups 30 days after initial vaccine and at age 344 days. Both groups showed a significant increase in antigen-specific immunoglobulin G expression following booster vaccine at age 11 months, thereby indicating memory immune responses. The data presented in this report demonstrate that young foals are capable of immune activation following a 3-dose series with a multivalent vaccine, despite presence of maternal antibodies. Although immune activation does not automatically confer protection, several of the immune indicators measured showed comparable expression in foals vaccinated at 3 months relative to control foals vaccinated at age 6 months. In high-risk situations where immunity may be required earlier than following a conventional vaccine series, our data provide evidence that foals respond to immunisation initiated at 3 months

40 CFR 799.5055 - Hazardous waste constituents subject to testing.

Science.gov (United States)

2010-07-01

...) Health effects testing—(1) Subchronic toxicity—(i) Required test. (A) An oral gavage subchronic toxicity... substance. Suggested determinations are: Calcium, phosphorus, chloride, sodium, potassium, fasting glucose (with the period of fasting appropriate to the species), serum glutamic oxaloacetic transaminase (now...

Cadmium accumulation and elimination in tissues of juvenile olive flounder, Paralichthys olivaceus after sub-chronic cadmium exposure

International Nuclear Information System (INIS)

Kim, Seong-Gil; Jee, Jung-Hoon; Kang, Ju-Chan

2004-01-01

Cd accumulation and elimination in tissue of olive flounder. - Experiments were carried out to investigate the accumulation and elimination of cadmium (Cd) in tissues (gill, intestine, kidney, liver and muscle) of juvenile olive flounder, Paralichthys olivaceus, exposed to sub-chronic concentrations (0, 10, 50, 100 μg l -1 ) of Cd. Cd exposure resulted in an increased Cd accumulation in tissues of flounder with exposure periods and concentration, and Cd accumulation in gill and liver increased linearly with the exposure time. At 20 days of Cd exposure, the order of Cd accumulation in organs was gill > intestine > liver > kidney > muscle and after 30 days of exposure, those were intestine > gill > liver > kidney > muscle. An inverse relationship was observed between the accumulation factor (AF) and the exposure level, but AF showed an increase with exposure time. During the depuration periods, Cd concentration in the gill, intestine and liver decreased immediately following the end of the exposure periods. No significant difference was found Cd in concentration in the kidney and muscle during depuration periods. The order of Cd elimination rate in organs were decreased intestine > liver > gill during depuration periods

Blueberry (Vaccinium ashei Reade) extract ameliorates ovarian damage induced by subchronic cadmium exposure in mice: Potential δ-ALA-D involvement.

Science.gov (United States)

Izaguirry, Aryele Pinto; Soares, Melina Bucco; Vargas, Laura Musacchio; Spiazzi, Cristiano Chiapinotto; Dos Santos Brum, Daniela; Noremberg, Simone; Mendez, Andreas Sebastian Loureiro; Santos, Francielli Weber

2017-01-01

Females are born with a finite number of oocyte-containing follicles and ovary damage results in reduced fertility. Cadmium accumulates in the reproductive system, damaging it, and the cigarette smoke is a potential exposure route. Natural therapies are relevant to health benefits and disease prevention. This study verified the effect of cadmium exposure on the ovaries of mice and the blueberry extract as a potential therapy. Blueberry therapy was effective in restoring reactive species levels and δ-aminolevulinate dehydratase activity, and partially improved the viability of cadmium-disrupted follicles. This therapy was not able to restore the 17 β-hydroxysteroid dehydrogenase activity. Extract HPLC evaluation indicated the presence of quercetin, quercitrin, isoquercetin, and ascorbic acid. Ascorbic acid was the major substance and its concentration was 620.24 µg/mL. Thus, cadmium accumulates in the ovaries of mice after subchronic exposure, inducing cellular damage, and the blueberry extract possesses antioxidant properties that could protect, at least in part, the ovarian tissue from cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 188-196, 2017. © 2015 Wiley Periodicals, Inc.

76 FR 12683 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Texas...

Science.gov (United States)

2011-03-08

...-0011; MO 92210-0-0008] Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To... are to base this finding on information submitted with the petition, supporting information submitted... diet (Chapman 1972, pp. 878-879). Although they do not tend to construct their burrows in croplands...

The safety of PolyGlycopleX® (PGX® as shown in a 90-day rodent feeding study

Directory of Open Access Journals (Sweden)

Ann Marone Palma

2009-01-01

Full Text Available Abstract Background This study was designed to evaluate the safety of PolyGlycopleX® (PGX®, a novel viscous dietary polysaccharide (fiber, when administered to Sprague Dawley® rats in the diet for 90 days. Methods Groups of ten male and ten female rats each consumed PGX mixed in the diet at levels of 0, 1.25, 2.5 or 5.0% for 90 days, then evaluated for toxicological effects on parameters that included neuromotor activity, body weight, clinical chemistry, urinalysis, hematology, and histopathology. Results Mean body weight, mean feed consumption and food efficiency in the treated groups were generally comparable to controls for both male and female rats. No changes were noted in neuromotor behavior, and histopathological analysis revealed no significant changes between treated and control animals. There were no differences in mean organ weight, organ-to-body weight or organ-to-brain weight values between controls and treated animals. Decreased red blood cell count occurred in the high dose males and increases in aspartate and alanine aminotransferase enzyme levels and triglycerides, while significant decreases in serum sodium, potassium and chloride concentrations were observed in the females fed 5.0% PGX. However, the decreased mineral concentrations may be the result of significantly increased urinary volume in both males and females at the high dose, with a concomitant decrease in urinary specific gravity (males and females and protein concentration (females. These results were within historical control values, did not correlate with any histopathological changes, and were not considered adverse. Conclusion The results indicate a no observed adverse effect level (NOAEL for PGX at 5.0% of the diet, corresponding to an average daily intake of 3219 and 3799 mg/kg bw/day in male and female rats, respectively.

Early Results of Medicare's Bundled Payment Initiative for a 90-Day Total Joint Arthroplasty Episode of Care.

Science.gov (United States)

Iorio, Richard; Clair, Andrew J; Inneh, Ifeoma A; Slover, James D; Bosco, Joseph A; Zuckerman, Joseph D

2016-02-01

In 2011 Medicare initiated a Bundled Payment for Care Improvement (BPCI) program with the goal of introducing a payment model that would "lead to higher quality, more coordinated care at a lower cost to Medicare." A Model 2 bundled payment initiative for Total Joint Replacement (TJR) was implemented at a large, tertiary, urban academic medical center. The episode of care includes all costs through 90 days following discharge. After one year, data on 721 Medicare primary TJR patients were available for analysis. Average length of stay (LOS) was decreased from 4.27 days to 3.58 days (Median LOS 3 days). Discharges to inpatient facilities decreased from 71% to 44%. Readmissions occurred in 80 patients (11%), which is slightly lower than before implementation. The hospital has seen cost reduction in the inpatient component over baseline. Early results from the implementation of a Medicare BPCI Model 2 primary TJR program at this medical center demonstrate cost-savings. IV economic and decision analyses-developing an economic or decision model. Copyright © 2016 Elsevier Inc. All rights reserved.

40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

Science.gov (United States)

2010-07-01

..., but not produce an incidence of fatalities which would prevent a meaningful evaluation. The lowest... termination. (iii) The day of observation of each abnormal sign and its subsequent course. (iv) Body weight... the findings of preceding studies and considered in terms of the incidence and severity of observed...

Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

Science.gov (United States)

Benzidane, Yassine; Goven, Delphine; Abd-Ella, Aly Ahmed; Deshayes, Caroline; Lapied, Bruno; Raymond, Valérie

2017-09-01

Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and β1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and β1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is

Hydroethanolic extract of the inner stem bark of Cedrela odorata has low toxicity and reduces hyperglycemia induced by an overload of sucrose and glucose.

Science.gov (United States)

Giordani, Morenna Alana; Collicchio, Thiago Carvalho Mamede; Ascêncio, Sergio Donizeti; Martins, Domingos Tabajara de Oliveira; Balogun, Sikiru Olaitan; Bieski, Isanete Geraldini Costa; da Silva, Leilane Aparecida; Colodel, Edson Moleta; de Souza, Roberto Lopes; de Souza, Damiana Luiza Pereira; de França, Suélem Aparecida; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda

2015-03-13

Cedrela odorata L. (Meliaceae) is a native plant of the Amazon region and its inner stem bark is used in the treatment of diabetes in the form of maceration in Brazilian popular medicine. Until now, there is no scientific study on this activity. The present study was aimed at evaluating the anti-hyperglycemic activity, anti-diabetic, toxicity, antioxidant and potential mechanism of action of hydroethanolic extract of the inner stem bark of Cedrela odorata. The inner stem bark extract of Cedrela odorata was prepared by maceration in 70% ethanol for 7 days to obtain hydroethanolic extract of Cedrela odorata (HeECo). The preliminary phytochemical analysis was performed according to procedures described in the literature. Selected secondary metabolites detected were quantified by high performance liquid chromatography (HPLC). Acute toxicity of HeECo was investigated in male and female mice with oral administration of graded doses of HeECo from 10 to 5000 mg/kg. Subchronic oral toxicity study was done by oral administration of HeECo (500 mg/kg) and vehicle for 30 days to both sexes of Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Anti-hiperglycemic and antidiabetic effects were evaluated in streptozotocin-induced diabetic rats. In acute evaluation, the animals received pretreatment with 250 and 500 mg/kg of HeECo, before carbohydrate overload. For subchronic effect, the antidiabetic activity of HeECo was evaluated using the same doses for 21 days. At the end of the treatments, the levels of triacylglycerols, malondialdehyde, total antioxidant status, superoxide dismutase and glutathione peroxidase activities were evaluated in the plasma. The extract showed low acute toxicity. HeECo exhibited inhibitory activity against α-glucosidase and caused a lowering in the peak levels of blood glucose in

76 FR 56381 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Franklin...

Science.gov (United States)

2011-09-13

... distributions of any bumble bee in the world (Williams 1998, as cited in the petition (p. 6)). The original... To List the Franklin's Bumble Bee as Endangered AGENCY: Fish and Wildlife Service, Interior. ACTION... Service (Service), announce a 90-day finding on a petition to list the Franklin's bumble bee (Bombus...

Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats

International Nuclear Information System (INIS)

Theumer, M.G.; Lopez, A.G.; Masih, D.T.; Chulze, S.N.; Rubinstein, H.R.

2003-01-01

Maize co-contamination with aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequently found in several countries. Although the alterations on nutritional and immunologic parameters induced by these mycotoxins, when administered individually, are partially characterised, little is known about the effects induced in animals by a subchronic administration of both toxins mixtures. We have studied the nutritional and immunological alterations induced in rats fed during 90 days with a diet without mycotoxins, containing 40 ppb AFB1, and with a diet containing a mixture of 40 ppb AFB1 and 100 ppm FB1. Animals fed with the mixture of toxins obtained lower body weight than the control ones. The mitogenic response of spleen mononuclear cells (SMC) in vivo was higher in animals fed with AFB1. In in vitro studies, lower proliferations of SMC pre-exposed to AFB1 and to the mixture of toxins were detected. The SMC of animals fed with AFB1 produced lower levels of IL-2, higher of IL-4 and equal levels of IL-10. The SMC of animals fed with both toxins produced higher levels of IL-4, lower of IL-10 and equal levels of IL-2. The SMC preincubated with an AFB1-FB1 mixture produced higher concentrations of IL-4, lower of IL-10 and equal levels of IL-2. The peritoneal macrophages of animals that consumed AFB1 released less H 2 O 2 , while animals fed with the mixture of toxins produced higher levels. In in vitro studies, macrophages pre-exposed to the mixture of toxins released less H 2 O 2 . These results show different immunobiological effects produced by a mixture of mycotoxins in comparison to the individual action of the same toxins

Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats

Energy Technology Data Exchange (ETDEWEB)

Theumer, M G; Lopez, A G; Masih, D T; Chulze, S N; Rubinstein, H R

2003-04-15

Maize co-contamination with aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequently found in several countries. Although the alterations on nutritional and immunologic parameters induced by these mycotoxins, when administered individually, are partially characterised, little is known about the effects induced in animals by a subchronic administration of both toxins mixtures. We have studied the nutritional and immunological alterations induced in rats fed during 90 days with a diet without mycotoxins, containing 40 ppb AFB1, and with a diet containing a mixture of 40 ppb AFB1 and 100 ppm FB1. Animals fed with the mixture of toxins obtained lower body weight than the control ones. The mitogenic response of spleen mononuclear cells (SMC) in vivo was higher in animals fed with AFB1. In in vitro studies, lower proliferations of SMC pre-exposed to AFB1 and to the mixture of toxins were detected. The SMC of animals fed with AFB1 produced lower levels of IL-2, higher of IL-4 and equal levels of IL-10. The SMC of animals fed with both toxins produced higher levels of IL-4, lower of IL-10 and equal levels of IL-2. The SMC preincubated with an AFB1-FB1 mixture produced higher concentrations of IL-4, lower of IL-10 and equal levels of IL-2. The peritoneal macrophages of animals that consumed AFB1 released less H{sub 2}O{sub 2}, while animals fed with the mixture of toxins produced higher levels. In in vitro studies, macrophages pre-exposed to the mixture of toxins released less H{sub 2}O{sub 2}. These results show different immunobiological effects produced by a mixture of mycotoxins in comparison to the individual action of the same toxins.

Toxicity assessment of Erythrophleum ivorense and Parquetina nigrescens

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Louis Adu-Amoah

2014-01-01

Full Text Available Erythrophleum ivorense and Parquetina nigrescens are found growing in tropical regions and they are used in African traditional medicine to treat various ailments including wounds, boils and anaemic conditions. Some species of plant in the Erythrophleum genus are also known to be poisonous and toxic to several livestock. However, there is no information on the toxicity of E. ivorense and P. nigrescens. This study is to determine the cytotoxicity and subchronic toxicity properties of methanol leaf extract (EIML and methanol stem barks extract (EIMB of E. ivorense and methanol leaf and aerial part extract of P. nigrescens (PNML. Concentrations from 0.1 to 100 μg/mL of the extracts were used to determine the influence of the extracts on the release of lactate dehydrogenase (LDH from HaCaT keratinocytes. The EIML and EIMB extracts showed increase in LDH released from HaCaT keratinocytes at 0.1–10 μg/mL and 1–100 μg/mL for the PNML extracts (p > 0.05. Wistar rats were orally administered with 100, 300 and 1000 mg/kg body weight of the extracts (EIML, EIMB and PNML, respectively for 35 days. Tissues from the kidney and liver of the rats treated with lower doses (100–300 mg/kg body weight of EIML extract showed highly vascularized kidneys with numerous glomerular tufts, healthy hepatocytes and sinusoids in liver. However, there were persistent renal tissue inflammation and glomerular degeneration in kidney, and increased inflammatory infiltrates with few vacuolations and scarrings in liver in rats treated with higher extract dose of 1000 mg/kg body weight of rat. The rats treated with EIMB extract showed persistent renal and hepatocyte inflammations with glomerular and hepatocyte necrosis at all administered doses (100, 300 and 1000 mg/kg body weight which are indications of renal and hepatic toxicities. Though rats administered with 100 and 300 mg/kg of PNML extract showed renal haemorrhage and inflammation and hepatic inflammation, the rats

76 FR 56607 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List 42 Great...

Science.gov (United States)

2011-09-13

... global climate models and hydrological models (Bates et al. 2008, p. 3). Thus, while the information in... initiation of status reviews. SUMMARY: We, the U.S. Fish and Wildlife Service (Service), announce a 90-day... reviews of these 32 species to determine if listing is warranted. To ensure that the status reviews are...

Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

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Barfod Kenneth K

2010-09-01

Full Text Available Abstract Background The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF, clearance of bacteria from the lung lumen and histological alterations of the lungs. Hazard identifications of the biopesticides were carried out using intratracheal (i.t. instillation, followed by an inhalation study. The two commercial biopesticides used were based on the Bt. subspecies kurstaki and israelensis, respectively. Groups of BALB/c mice were i.t instilled with one bolus (3.5 × 105 or 3.4 × 106 colony forming units (CFU per mouse of either biopesticide. Control mice were instilled with sterile water. BALFs were collected and the inflammatory cells were counted and differentiated. The BALFs were also subjected to CFU counts. Results BALF cytology showed an acute inflammatory response dominated by neutrophils 24 hours after instillation of biopesticide. Four days after instillation, the neutrophil number was normalised and inflammation was dominated by lymphocytes and eosinophils, whereas 70 days after instillation, the inflammation was interstitially located with few inflammatory cells present in the lung lumen. Half of the instilled mice had remaining CFU recovered from BALF 70 days after exposure. To gain further knowledge with relevance for risk assessment, mice were exposed to aerosols of biopesticide one hour per day for 2 × 5 days. Each mouse received 1.9 × 104 CFU Bt israelensis or 2.3 × 103 CFU Bt kurstaki per exposure. Seventy days after end of the aerosol exposures, 3 out of 17 mice had interstitial lung inflammation. CFU could be recovered from 1 out of 10 mice 70 days after exposure to aerosolised Bt kurstaki. Plethysmography showed that inhalation of Bt aerosol did not induce airway irritation. Conclusions Repeated low dose aerosol

190-C Facility <90 Day Storage Pad supplemental information to the Hanford facility contingency plan

International Nuclear Information System (INIS)

Little, N.C.

1996-12-01

The 190-C Facility <90 Day Storage Pad stores waste oils primarily contaminated with lead generated while draining equipment within the building of residual lubricating oils. Waste oils are packaged and stored in fifty-five gallon drums, or other containers permitted by the Site Specific Waste Management Instruction. Bechtel Hanford, Inc. (BHI) manual BHI-EE-02, Environmental Requirements Procedures, references this document. This document is to be used to demonstrate compliance with the contingency plan requirements in Washington Administrative Code, Chapter 173-303, Dangerous Waste Regulations, for certain Resource Conservation and Recovery Act of 1976 (RCRA) waste management units (units). Refer to BHI-EE-02, for additional information

75 FR 19925 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List a Distinct...

Science.gov (United States)

2010-04-16

... List a Distinct Population Segment of the Fisher in Its United States Northern Rocky Mountain Range as...), announce a 90-day finding on a petition to list a distinct population segment (DPS) of the fisher (Martes...). Taxonomy We accept the characterization of the fisher as a species, Martes pennanti, based on the review of...

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.

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.

Pharmacokinetic and Genomic Effects of Arsenite in Drinking Water on Mouse Lung in a 30-Day Exposure

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Jaya Chilakapati

2015-06-01

Full Text Available The 2 objectives of this subchronic study were to determine the arsenite drinking water exposure dependent increases in female C3H mouse liver and lung tissue arsenicals and to characterize the dose response (to 0, 0.05, 0.25, 1, 10, and 85 ppm arsenite in drinking water for 30 days and a purified AIN-93M diet for genomic mouse lung expression patterns. Mouse lungs were analyzed for inorganic arsenic, monomethylated, and dimethylated arsenicals by hydride generation atomic absorption spectroscopy. The total lung mean arsenical levels were 1.4, 22.5, 30.1, 50.9, 105.3, and 316.4 ng/g lung tissue after 0, 0.05, 0.25, 1, 10, and 85 ppm, respectively. At 85 ppm, the total mean lung arsenical levels increased 14-fold and 131-fold when compared to either the lowest noncontrol dose (0.05 ppm or the control dose, respectively. We found that arsenic exposure elicited minimal numbers of differentially expressed genes (DEGs; 77, 38, 90, 87, and 87 DEGs after 0.05, 0.25, 1, 10, and 85 ppm, respectively, which were associated with cardiovascular disease, development, differentiation, apoptosis, proliferation, and stress response. After 30 days of arsenite exposure, this study showed monotonic increases in mouse lung arsenical (total arsenic and dimethylarsinic acid concentrations but no clear dose-related increases in DEG numbers.

Strontium-90 in the US diet, 1982

International Nuclear Information System (INIS)

Klusek, C.S.

1984-07-01

Estimates of 90 Sr intake via the total diet in New York City and San Francisco have been made since 1960 from quarterly food samplings and average consumption statistics. The dietary intake of 90 Sr has decreased from the maximum levels attained during 1963 to 1964, but the decline has become more gradual in recent years due to the continuing small amounts of 90 Sr deposition and the little-changing cumulative deposit of 90 Sr in soil. The annual intake in 1982 averaged 5.4 pCi/day (0.20 Bq/day) in New York, and 2.6 pCi/day (0.096 Bq/day) in San Francisco, little changed from the previous year. Further gradual reductions in 90 Sr intake are anticipated during 1983. 11 references, 7 figures, 4 tables

Strontium-90 in the US diet, 1982

International Nuclear Information System (INIS)

Klusek, C.S.

1984-07-01

Estimates of 90 Sr intake via the total diet in New York City and San Francisco have been made since 1960 from quarterly food samplings and average consumption statistics. The dietary intake of 90 Sr has decreased from the maximum levels attained during 1963-1964, but the decline has become more gradual in recent years due to the continuing small amounts of 90 Sr deposition and the little-changing cumulative deposit of 90 Sr in soil. The annual intake in 1982 averaged 5.4 pCi/day (0.20 Bq/day) in New York, and 2.6 pCi/day (0.096 Bq/day) in San Francisco, little changed from the previous year. Further gradual reductions in 90 Sr intake are anticipated during 1983. 1 reference, 7 figures, 4 tables

Safety evaluation of an açai-fortified fruit and berry functional juice beverage (MonaVie Active(®)).

Science.gov (United States)

Schauss, Alexander G; Clewell, Amy; Balogh, Lajos; Szakonyi, Ilona Pasics; Financsek, Istvan; Horváth, János; Thuroczy, Julianna; Béres, Erzsébet; Vértesi, Adél; Hirka, Gabor

2010-11-28

The safety of an açai (Euterpe oleracea Mart.) pulp enriched fruit and berry juice, MonaVie Active®, fortified with the functional ingredient, glucosamine, was studied. The beverage was found not to be mutagenic, clastogenic, cytotoxic, or genotoxic, as determined by the bacterial reverse mutation assay, chromosomal aberration assay, mouse micronucleus assay, and mammalian cell gene mutation (L5178Y) assay. The single dose LD50 based on a 14-day acute oral toxicity study is greater than 20,000 mg/kg bw, the highest dose tested. In a repeat dose 90-day oral subchronic toxicity study by gavage, 220 animals were randomly assigned to a control group, an untreated group, or one of three experimental groups (10, 20 and 40 g/kg bw). No treatment-related significant changes in body weight, food and water consumption, ophthalmology, organ weights, urinanalysis, hematological and clinical chemistry, or gross pathology, were observed in surviving animals compared to the control groups. Three animals died midway through the observation period (male, 20 g/kg bw/day; male 40 g/kg bw/day; and, female, 10 g/kg bw/day). These animals died without preceding clinical symptoms, histopathological lesions, or evidence of injury to tissue or organs except for signs of suffocation/aspiration congestion, which was concluded to be due to problems with the gavage administration of the fluid test article, and not due to the test article itself. The NOEAL was determined to be 40 g/kg bw/day for male and female rats, which was the highest dose tested. Phylloquinone (vitamin K1) content averaged 21.7 μg/100 g, comparable to amounts found in iceberg lettuce. In conclusion, the results provide additional experimental evidence that MonaVie Active® juice is non-toxic. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Safety evaluation of an acai-fortified fruit and berry functional juice beverage (MonaVie Active®)

International Nuclear Information System (INIS)

Schauss, Alexander G.; Clewell, Amy; Balogh, Lajos; Szakonyi, Ilona Pasics; Financsek, Istvan; Horvath, Janos; Thuroczy, Julianna; Beres, Erzsebet; Vertesi, Adel; Hirka, Gabor

2010-01-01

The safety of an acai (Euterpe oleracea Mart.) pulp enriched fruit and berry juice, MonaVie Active ® , fortified with the functional ingredient, glucosamine, was studied. The beverage was found not to be mutagenic, clastogenic, cytotoxic, or genotoxic, as determined by the bacterial reverse mutation assay, chromosomal aberration assay, mouse micronucleus assay, and mammalian cell gene mutation (L5178Y) assay. The single dose LD50 based on a 14-day acute oral toxicity study is greater than 20,000 mg/kg bw, the highest dose tested. In a repeat dose 90-day oral subchronic toxicity study by gavage, 220 animals were randomly assigned to a control group, an untreated group, or one of three experimental groups (10, 20 and 40 g/kg bw). No treatment-related significant changes in body weight, food and water consumption, ophthalmology, organ weights, urinanalysis, hematological and clinical chemistry, or gross pathology, were observed in surviving animals compared to the control groups. Three animals died midway through the observation period (male, 20 g/kg bw/day; male 40 g/kg bw/day; and, female, 10 g/kg bw/day). These animals died without preceding clinical symptoms, histopathological lesions, or evidence of injury to tissue or organs except for signs of suffocation/aspiration congestion, which was concluded to be due to problems with the gavage administration of the fluid test article, and not due to the test article itself. The NOEAL was determined to be 40 g/kg bw/day for male and female rats, which was the highest dose tested. Phylloquinone (vitamin K1) content averaged 21.7 μg/100 g, comparable to amounts found in iceberg lettuce. In conclusion, the results provide additional experimental evidence that MonaVie Active ® juice is non-toxic.

GAMBARAN HEMATOLOGI MENCIT (Mus musculus MODEL TOKSISITAS SUBKRONIS

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Ita Nur Eka Pujiastuti

2017-06-01

Full Text Available Garlic commonly is consumed as medicine to prevent or heal illness or to maintain someone's health. Many societies prefer garlic (Allium sativum among other herbal remedies for cholesterol treatment. It consists of several types, and one of them is single bulb garlic used to treat hypertension. There has been, however, no published research reporting the toxicological properties of single bulb garlic. The purpose of this study was to determine subchronic toxic effects of single bulb garlic administered to mice using hematological parameters. The experiment parameters were hemoglobin and hematocrit levels, the number of erythrocytes and leukocytes. Male mice (Mus musculus strain Balb-C were treated with single bulb garlic extract for 28 days with dosage levels of 0% (N , 0.25% (P1 , 0.5% (P2 , 1% (P3 , and 2% (P4 . Single bulb garlic showed no effect on hemoglobin and hematocrit levels but increased the number of erythrocyte and leucocyte. We concluded that single bulb garlic did not cause subchronic toxic effects.

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

Energy Technology Data Exchange (ETDEWEB)

Poorvu, Philip D. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Sadow, Cheryl A. [Department of Radiology, Brigham and Women' s Hospital, and Harvard Medical School, Boston, Massachusetts (United States); Townamchai, Kanokpis; Damato, Antonio L. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States)

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

International Nuclear Information System (INIS)

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis; Damato, Antonio L.; Viswanathan, Akila N.

2013-01-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy

A 90-day safety study in Sprague-Dawley rats fed milk powder containing recombinant human lactoferrin (rhLF) derived from transgenic cloned cattle.

Science.gov (United States)

Zhou, Cui; Wang, Jian Wu; Huang, Kun Lun; He, XiaoYun; Chen, Xiu Ping; Sun, Hong; Yu, Tian; Che, Hui Lian

2011-10-01

Transgenic cloned animals expressing beneficial human nutritional traits offer a new strategy for large-scale production of some kinds of functional substances. In some cases, the required safety testing for genetically modified (GM) foods do not seem appropriate for human food safety, though regulations do not seem to provide alternatives. A 90-day rat feeding study is the core study for the safety assessment of GM foods. The test material in this 90-day study was prepared nonfat milk powder containing recombinant human lactoferrin (rhLF), which was expressed in transgenic cloned cattle. Groups of 10 male and female Sprague-Dawley rats were given a nutritionally balanced purified diet containing 7.5, 15, or 30% transgenic or conventional milk powder for 90 days. A commercial AIN93G diet was used as an additional control group. Clinical, biological, and pathological parameters were compared between groups. The only significant effect of treatment was higher mean ferritin and Fe(+) concentrations for both male and female rats fed the transgenic milk powder diets, as compared to rats fed nontransgenic milk diets or the commercial diet. The results of the present study are consistent with previous research, which indicates that milk powder containing rhLF derived from healthy transgenic cloned cattle is as safe as conventional milk powder.

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

Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of Sida acuta Burn f . and Sida cordifolia L. (Malvaceae, medicinal plants of Burkina Faso

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Konaté Kiessoun

2012-08-01

Full Text Available Abstract Background Sida acuta Burn f. and Sida cordifolia L. (Malvaceae are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of Sida acuta Burn f. and Sida cordifolia L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso. Method For acute toxicity test, mice were injected different doses of each extract by intraperitoneal route and the LD50 values were determined. For the subchronic toxicity evaluation, Wistar albinos rats were treated by gavage during 28 days at different doses of aqueous acetone extracts and then haematological and biochemical parameters were determined. The analgesic effect was evaluated in mice by the acetic-acid writhing test and by the formalin test. Results For the acute toxicity test, the LD50 values of 3.2 g/kg and 3.4 g/kg respectively for S. acuta Burn f. and S. cordifolia L. were obtained. Concerning the haematological and biochemical parameters, data varied widely (increase or decrease according to dose of extracts and weight of rats and did not show clinical correlations. The extracts have produced significant analgesic effects by the acetic acid writhing test and by the hot plate method (p Conclusion The overall results of this study may justify the traditional uses of S. acuta and S. cordifolia .

Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of Sida acuta Burn f . and Sida cordifolia L. (Malvaceae), medicinal plants of Burkina Faso.

Science.gov (United States)

Konaté, Kiessoun; Bassolé, Imaël Henri Nestor; Hilou, Adama; Aworet-Samseny, Raïssa R R; Souza, Alain; Barro, Nicolas; Dicko, Mamoudou H; Datté, Jacques Y; M'Batchi, Bertrand

2012-08-11

Sida acuta Burn f. and Sida cordifolia L. (Malvaceae) are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of Sida acuta Burn f. and Sida cordifolia L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso. For acute toxicity test, mice were injected different doses of each extract by intraperitoneal route and the LD50 values were determined. For the subchronic toxicity evaluation, Wistar albinos rats were treated by gavage during 28 days at different doses of aqueous acetone extracts and then haematological and biochemical parameters were determined. The analgesic effect was evaluated in mice by the acetic-acid writhing test and by the formalin test. For the acute toxicity test, the LD50 values of 3.2 g/kg and 3.4 g/kg respectively for S. acuta Burn f. and S. cordifolia L. were obtained. Concerning the haematological and biochemical parameters, data varied widely (increase or decrease) according to dose of extracts and weight of rats and did not show clinical correlations. The extracts have produced significant analgesic effects by the acetic acid writhing test and by the hot plate method (p <0.05) and a dose-dependent inhibition was observed. The overall results of this study may justify the traditional uses of S. acuta and S. cordifolia .

A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.

Science.gov (United States)

Wang, B; Liu, Y; Huang, L; Chen, J; Li, J J; Wang, R; Kim, E; Chen, Y; Justicia, C; Sakata, K; Chen, H; Planas, A; Ostrom, R S; Li, W; Yang, G; McDonald, M P; Chen, R; Heck, D H; Liao, F-F

2017-07-01

Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer's disease, without noticeable systemic toxicity. Despite a short half-life of OS47720 in mouse brain, a single intraperitoneal injection induces rapid and long-lasting (>3 days) nuclear activation of the heat-shock factor, HSF1. Mechanistic study indicates that the remedial effects of OS47720 depend upon HSF1 activation and the subsequent HSF1-mediated transcriptional events on synaptic genes. Taken together, this work reveals a novel role of HSF1 in synaptic function and memory, which likely occurs through modulation of the synaptic transcriptome.

Bioregenerative Life Support Experiment for 90-days in a Closed Integrative Experimental Facility LUNAR PALACE 1

Science.gov (United States)

Liu, Hong

A 90-day bioregenerative life support experiment with three-member crew was carried out in the closed integrative experimental facility, LUNAR PALACE 1 regenerating basic living necessities and disposing wastes to provide life support for crew. It was composed of higher plant module, animal module, and waste treatment module. The higher plant module included wheat, chufa, pea, carrot and green leafy vegetables, with aim to satisfy requirement of 60% plant food and 100% O2 and water for crew. The yellow mealworm was selected as animal module to provide partial animal protein for crew, and reared on plant inedible biomass. The higher plant and yellow mealworm were both cultivated and harvested in the conveyor-type manner. The partial plant inedible biomass and human feces were mixed and co- fermented in the waste treatment module for preparation of soil-like substrate by bioconversion, maintaining gas balance and increasing closure degree. Meanwhile, in the waste treatment module, the water and partial nitrogen from human urine were recovered by physical-chemical means. Circulation of O2 and water as well as food supply from crops cultivated in the LUNAR PALACE 1 were investigated and calculated, and simultaneously gas exchange, mass flow among different components and system closure degree were also analyzed, respectively. Furthermore, the system robustness with respect to internal variation was tested and evaluated by sensitivity analysis of the aggregative index consisting of key performance indicators like crop yield, gaseous equilibrium concentration, microbial community composition, biogenic elements dynamics, etc., and comprehensively evaluating the operating state, to number change of crew from 2 to 4 during the 90-day closed experiment period.

Strontium-90 in the diet: results through 1980

International Nuclear Information System (INIS)

Klusek, C.S.

1981-01-01

Estimates of 90 Sr intake via the total diet in New York City and San Francisco have been made since 1960 from quarterly food samplings and average consumption statistics. The dietary intakes of 90 Sr have decreased from the maximum levels attained during 1963 to 1964, but the declines have become more gradual in recent years due to the continuing small amounts of 90 Sr deposition and the little-changing cumulative deposit of 90 Sr in soil. The annual intake in 1980 averaged 6.0 pCi/day (0.22 Bq/day) in New York and 2.5 pCi/day (0.092 Bq/day) in San Francisco, slightly lower than the results of the previous year. Further gradual reductions in 90 Sr intake are anticipated during 1981

Effects of 90-day feeding of transgenic Bt rice TT51 on the reproductive system in male rats.

Science.gov (United States)

Wang, Er Hui; Yu, Zhou; Hu, Jing; Xu, Hai Bin

2013-12-01

Rice is a staple food crop; however, the threat of pests leads to a serious decline in its output and quality. The CryAb/CryAc gene, encodes a synthetic fusion Bacillus thuringiensis (Bt) crystal protein, was introduced into rice MingHui63 to produce insect-resistant rice TT51. This study was undertaken to investigate potential unintended effects of TT51 on the reproductive system in male rats. Male rats were treated with diets containing 60% of either TT51 or MingHui63 by weight, nutritionally balanced to an AIN93G diet, for 90days. An additional negative control group of rats were fed with a rice-based AIN93G diet. Body weights, food intake, hematology, serum chemistry, serum hormone levels, sperm parameters and relative organ/body weights were measured, and gross as well as microscopic pathology were examined. No diet-related significant differences in the values of response variables were observed between rats that were fed with diet containing transgenic TT51, MingHui63 and the control in this 90-day feeding study. In addition, necropsy and histopathology examination indicated no treatment-related changes. The results from the present study indicated that TT51 does not appear to exert any effect on the reproductive system in male rats compared with MingHui63 or the control. Copyright © 2013 Elsevier Ltd. All rights reserved.

Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead.

Science.gov (United States)

Varaksin, Anatoly N; Katsnelson, Boris A; Panov, Vladimir G; Privalova, Larisa I; Kireyeva, Ekaterina P; Valamina, Irene E; Beresneva, Olga Yu

2014-02-01

Rats were exposed intraperitoneally (3 times a week up to 20 injections) to either Cadmium and Lead salts in doses equivalent to their 0.05 LD50 separately or combined in the same or halved doses. Toxic effects were assessed by more than 40 functional, biochemical and morphometric indices. We analysed the results obtained aiming at determination of the type of combined toxicity using either common sense considerations based on descriptive statistics or two mathematical models based (a) on ANOVA and (b) on Mathematical Theory of Experimental Design, which correspond, respectively, to the widely recognised paradigms of effect additivity and dose additivity. Nevertheless, these approaches have led us unanimously to the following conclusions: (1) The above paradigms are virtually interchangeable and should be regarded as different methods of modelling the combined toxicity rather than as reflecting fundamentally differing processes. (2) Within both models there exist not merely three traditionally used types of combined toxicity (additivity, subadditivity and superadditivity) but at least 10 variants of it depending on exactly which effect is considered and on its level, as well as on the dose levels and their ratio. Copyright © 2013 Elsevier Ltd. All rights reserved.

The ampakine, Org 26576, bolsters early spatial reference learning and retrieval in the Morris water maze: a subchronic, dose-ranging study in rats.

Science.gov (United States)

Hamlyn, Eugene; Brand, Linda; Shahid, Mohammed; Harvey, Brian H

2009-10-01

Ampakines have shown beneficial effects on cognition in selected animal models of learning. However, their ability to modify long-term spatial memory tasks has not been studied yet. This would lend credence to their possible value in treating disorders of cognition. We evaluated the actions of subchronic Org 26576 administration on spatial reference memory performance in the 5-day Morris water maze task in male Sprague-Dawley rats, at doses of 1, 3 and 10 mg/kg twice daily through intraperitoneal injection over 12 days. Org 26576 exerted a dose and time-dependent effect on spatial learning, with dosages of 3 and 10 mg/kg significantly enhancing acquisition on day 1. Globally, escape latency decreased significantly as the training days progressed in the saline and Org 26576-treated groups, indicating that significant and equal learning had taken place over the learning period. However, at the end of the learning period, all doses of Org 26576 significantly improved spatial memory storage/retrieval without confounding effects in the cued version of the task. Org 26576 offers early phase spatial memory benefits in rats, but particularly enhances search accuracy during reference memory retrieval. These results support its possible utility in treating disorders characterized by deficits in cognitive performance.

Is Anesthesia Technique Associated With a Higher Risk of Mortality or Complications Within 90 Days of Surgery for Geriatric Patients With Hip Fractures?

Science.gov (United States)

Desai, Vimal; Chan, Priscilla H; Prentice, Heather A; Zohman, Gary L; Diekmann, Glenn R; Maletis, Gregory B; Fasig, Brian H; Diaz, Diana; Chung, Elena; Qiu, Chunyuan

2018-06-01

Postoperative mortality and complications after geriatric hip fracture surgery remain high despite efforts to improve perioperative care for these patients. One factor of particular interest is anesthetic technique, but prior studies on this are limited by sample selection, competing risks, and incomplete followup. (1) Among older patients undergoing surgery for hip fracture, does 90-day mortality differ depending on the type of anesthesia received? (2) Do 90-day emergency department returns and hospital readmissions differ based on anesthetic technique after geriatric hip fracture repairs? (3) Do 90-day Agency for Healthcare Research and Quality (AHRQ) outcomes differ according to anesthetic techniques used during hip fracture surgery? We conducted a retrospective study on geriatric patients (65 years or older) with hip fractures between 2009 and 2014 using the Kaiser Permanente Hip Fracture Registry. A total of 1995 (11%) of the surgically treated patients with hip fracture were excluded as a result of missing anesthesia information. The final study sample consisted of 16,695 patients. Of these, 2027 (12%) died and 98 (< 1%) terminated membership during followup, which were handled as competing events and censoring events, respectively. Ninety-day mortality, emergency department returns, hospital readmission, deep vein thrombosis (DVT) or pulmonary embolism (PE), myocardial infarction (MI), and pneumonia were evaluated using multivariable competing risk proportional subdistribution hazard regression according to type of anesthesia technique: general anesthesia, regional anesthesia, or conversion from regional to general. Of the 16,695 patients, 58% (N = 9629) received general anesthesia, 40% (N = 6597) received regional anesthesia, and 2.8% (N = 469) patients were converted from regional to general. Compared with regional anesthesia, patients treated with general anesthesia had a higher likelihood of overall 90-day mortality (hazard ratio [HR], 1.22; 95

A 56-Day Oral Toxicity Study of the Aqueous Extract of Rapanea melanophloeos (L. Mez in Rats

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Hesbon Z. Amenya

2016-01-01

Full Text Available Rapanea melanophloeos is a tropical tree that is extensively utilized in African traditional medicine to treat helminthiases, tuberculosis, and heart-water. As with many other medicinal plants, there is insufficient information regarding the safety of therapeutic R. melanophloeos extracts. An aqueous extract of R. melanophloeos stem bark was administered to Sprague Dawley rats at doses of 100 mg/kg, 300 mg/kg, and 1000 mg/kg for 56 days to characterize its potential toxicity after prolonged dosing. Blood samples were obtained fortnightly for serum chemistry and hematology, while organs were collected at the end of the study. The extract caused an increase in organ weight indices of the kidneys and testis at 300 mg/kg and 1000 mg/kg. Hematological and biochemical examination revealed a drop in leukocyte counts and the hematocrit at 1000 mg/kg dose level, while there was a general but nondose-related elevation in alkaline phosphatase activity. There were time-associated variations in the hematological and clinical chemistry parameters at days 28, 42, and 56 in all dose levels, but most values remained within physiological limits. No pathological lesions were evident at histopathology after treatment with the extract. Our data shows that the aqueous extract of R. melanophloeos is not likely to be toxic at the doses tested and provides support to its medicinal use.

Toxicity of middle distillates from dermal exposure.

Science.gov (United States)

Koschier, F J

1999-02-01

/developmental toxicity (OECD Guideline 421) or neurotoxicity (TSCA Guidelines on subchronic inhalation and neurotoxicity studies). These studies demonstrated that the highest dose level of kerosine does not induce reproductive/developmental or neurotoxicity effects by skin exposure in rodent studies. The dermal NOEL for HDS kerosine in rats was > or = 494 mg/kg for both neurotoxicity, and reproductive/developmental toxicity.

In Utero Domoic Acid Toxicity: A Fetal Basis to Adult Disease in the California Sea Lion (Zalophus californianus

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Tanja S. Zabka

2008-06-01

Full Text Available California sea lions have been a repeated subject of investigation for early life toxicity, which has been documented to occur with increasing frequency from late February through mid-May in association with organochlorine (PCB and DDT poisoning and infectious disease in the 1970's and domoic acid poisoning in the last decade. The mass early life mortality events result from the concentrated breeding grounds and synchronization of reproduction over a 28 day post partum estrus cycle and 11 month in utero phase. This physiological synchronization is triggered by a decreasing photoperiod of 11.48 h/day that occurs approximately 90 days after conception at the major California breeding grounds. The photoperiod trigger activates implantation of embryos to proceed with development for the next 242 days until birth. Embryonic diapause is a selectable trait thought to optimize timing for food utilization and male migratory patterns; yet from the toxicological perspective presented here also serves to synchronize developmental toxicity of pulsed environmental events such as domoic acid poisoning. Research studies in laboratory animals have defined age-dependent neurotoxic effects during development and windows of susceptibility to domoic acid exposure. This review will evaluate experimental domoic acid neurotoxicity in developing rodents and, aided by comparative allometric projections, will analyze potential prenatal toxicity and exposure susceptibility in the California sea lion. This analysis should provide a useful tool to forecast fetal toxicity and understand the impact of fetal toxicity on adult disease of the California sea lion.

Inhibition of larval development of the marine copepod Acartia tonsa by four synthetic musk substances

DEFF Research Database (Denmark)

Wollenberger, Leah; Breitholtz, M.; Kusk, Kresten Ole

2003-01-01

A nitro musk (musk ketone). and three polycyclic musks (Tonalide(TM), Galaxolide(TM) and Celestolide(TM)) were tested for acute and subchronic effects on a marine crustacean, the calanoid copepod Acartia tonsa. Sublethal effects on A. tonsa larvae were investigated with a rapid and cost effective...... bioassay, which is based on the easily detectable morphological change from the last nauplius to the first copepodite stage during copepod larval development. The inhibition of larval development after 5 days exposure was a very sensitive endpoint, with 5-d-EC(50)-values as low as 0.026 mg/l (Tonalide...... of synthetic musks, for which there is little published ecotoxicological information available regarding Crustacea. It is suggested that subchronic and chronic copepod toxicity tests should be used more frequently for risk assessment of environmental pollutants. (C) 2002 Elsevier Science B.V. All rights...

An estimate of equatorial wave energy flux at 9- to 90-day periods in the Central Pacific

Science.gov (United States)

Eriksen, Charles C.; Richman, James G.

1988-01-01

Deep fluctuations in current along the equator in the Central Pacific are dominated by coherent structures which correspond closely to narrow-band propagating equatorial waves. Currents were measured roughly at 1500 and 3000 m depths at five moorings between 144 and 148 deg W from January 1981 to March 1983, as part of the Pacific Equatorial Ocean Dynamics program. In each frequency band resolved, a single complex empirical orthogonal function accounts for half to three quarters of the observed variance in either zonal or meridional current. Dispersion for equatorial first meridional Rossby and Rossby gravity waves is consistent with the observed vertical-zonal coherence structure. The observations indicate that energy flux is westward and downward in long first meridional mode Rossby waves at periods 45 days and longer, and eastward and downward in short first meridional mode Rossby waves and Rossby-gravity waves at periods 30 days and shorter. A local minimum in energy flux occurs at periods corresponding to a maximum in upper-ocean meridional current energy contributed by tropical instability waves. Total vertical flux across the 9- to 90-day period range is 2.5 kW/m.

Using combined bio-omics methods to evaluate the complicated toxic effects of mixed chemical wastewater and its treated effluent

International Nuclear Information System (INIS)

Zhang, Yan; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang

2014-01-01

Highlights: • Mice exposed to mixed chemical wastewater and its treated effluent for 90 days. • Hepatic transcriptomic alterations were analyzed by digital gene expression. • Serum metabolomic alterations were analyzed by proton nuclear magnetic resonance. • The water samples induced disruption of lipid metabolism and hepatotoxicity. • Omics approaches are valuable to evaluate the complicated toxicity of wastewater. - Abstract: Mixed chemical wastewaters (MCWW) from industrial park contain complex mixtures of trace contaminants, which cannot be effectively removed by wastewater treatment plants (WWTP) and have become an unignored threat to ambient environment. However, limited information is available to evaluate the complicated toxic effects of MCWW and its effluent from wastewater treatment plant (WTPE) from the perspective of bio-omics. In this study, mice were exposed to the MCWW and WTPE for 90 days and distinct differences in the hepatic transcriptome and serum metabolome were analyzed by digital gene expression (DGE) and proton nuclear magnetic resonance ( 1 H-NMR) spectra, respectively. Our results indicated that disruption of lipid metabolism in liver and hepatotoxicity were induced by both MCWW and WTPE exposure. WTPE is still a health risk to the environment, which is in need of more attention. Furthermore, we demonstrated the potential ability of bio-omics approaches for evaluating toxic effects of MCWW and WTPE

Using combined bio-omics methods to evaluate the complicated toxic effects of mixed chemical wastewater and its treated effluent

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yan; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang, E-mail: hqren@nju.edu.cn

2014-05-01

Highlights: • Mice exposed to mixed chemical wastewater and its treated effluent for 90 days. • Hepatic transcriptomic alterations were analyzed by digital gene expression. • Serum metabolomic alterations were analyzed by proton nuclear magnetic resonance. • The water samples induced disruption of lipid metabolism and hepatotoxicity. • Omics approaches are valuable to evaluate the complicated toxicity of wastewater. - Abstract: Mixed chemical wastewaters (MCWW) from industrial park contain complex mixtures of trace contaminants, which cannot be effectively removed by wastewater treatment plants (WWTP) and have become an unignored threat to ambient environment. However, limited information is available to evaluate the complicated toxic effects of MCWW and its effluent from wastewater treatment plant (WTPE) from the perspective of bio-omics. In this study, mice were exposed to the MCWW and WTPE for 90 days and distinct differences in the hepatic transcriptome and serum metabolome were analyzed by digital gene expression (DGE) and proton nuclear magnetic resonance ({sup 1}H-NMR) spectra, respectively. Our results indicated that disruption of lipid metabolism in liver and hepatotoxicity were induced by both MCWW and WTPE exposure. WTPE is still a health risk to the environment, which is in need of more attention. Furthermore, we demonstrated the potential ability of bio-omics approaches for evaluating toxic effects of MCWW and WTPE.

28-Day oral (gavage) toxicity studies of green tea catechins prepared for beverages in rats.

Science.gov (United States)

Chengelis, Christopher P; Kirkpatrick, Jeannie B; Regan, Karen S; Radovsky, Ann E; Beck, Melissa J; Morita, Osamu; Tamaki, Yasushi; Suzuki, Hiroyuki

2008-03-01

The beneficial health effects associated with drinking green tea are widely considered to be due primarily to tea catechins. Heat treatment of marketed green tea beverages for sterilization causes epimerization and/or polymerization of tea catechins. Safety studies on heat-treated tea catechins are limited. The objective of the present study was to evaluate potential adverse effects, if any, of two standardized green tea catechin (GTC) preparations: one that underwent heat sterilization (GTC-H) and one that was not heat-sterilized (GTC-UH). A decaffeinated preparation of the GTC-H (GTC-HDC) was also evaluated to ascertain if any effects were due to caffeine. The GTC preparations were administered to rats once daily at levels up to 2000 mg/kg/day for 28 days. There were no deaths attributable to the GTC preparations. The clinical condition of the animals, functional observational battery, motor activity, clinical pathology evaluations, organ weights, and gross necropsy findings were unaffected by any of the GTC preparations. GTC-HDC or GTC-UH dosing had no effects on body weights or microscopic findings, whereas lower body weights and food consumption were observed in the 1000 and 2000 mg/kg/day GTC-H group males. The no observed-adverse-effect level (NOAEL) for localized gastric effects for GTC-H was 1000 mg/kg/day. No other target organs were identified. Thus, the NOAEL for systemic toxicity following oral administration was 2000 mg/kg/day for GTC-H, GTC HDC, and GTC-UH under the conditions of this study.

Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer

International Nuclear Information System (INIS)

Knox, S J.; Goris, M L.; Tempero, M.; Weiden, P L.; Gentner, L.; Breitz, H.; Adams, G. P.; Axworthy, D.; Gaffigan, S.; Bryan, K.; Fisher, Darrell R.; Colcher, D; Horak, I D.; Weiner, L M.

1999-01-01

A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biotin (Y-90-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients were treated with a single dose of 110 mCi/m 2 (mean administered dose, 106.5-10.3 mCi/m 2 ) of Y-90-DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administered 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients received biotin-DOTA-labeled with 110 mCi/m 2 Y-90. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed. Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 4 thrombocytopenia. The overall response rate was 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20 weeks. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs

Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

Energy Technology Data Exchange (ETDEWEB)

Yan, Yuan-Horng [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Charles, Chou C.-K. [Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan (China); Wang, Jyh-Seng [Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Li, Ya-Ru; Lo, Kai [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

2014-12-01

Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic

Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

International Nuclear Information System (INIS)

Yan, Yuan-Horng; Charles, Chou C.-K.; Wang, Jyh-Seng; Tung, Chun-Liang; Li, Ya-Ru; Lo, Kai; Cheng, Tsun-Jen

2014-01-01

Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM 2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM 2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m 3 , respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic homeostasis, was

An analysis of lethal and sublethal interactions among type I and type II pyrethroid pesticide mixtures using standard Hyalella azteca water column toxicity tests.

Science.gov (United States)

Hoffmann, Krista Callinan; Deanovic, Linda; Werner, Inge; Stillway, Marie; Fong, Stephanie; Teh, Swee

2016-10-01

A novel 2-tiered analytical approach was used to characterize and quantify interactions between type I and type II pyrethroids in Hyalella azteca using standardized water column toxicity tests. Bifenthrin, permethrin, cyfluthrin, and lambda-cyhalothrin were tested in all possible binary combinations across 6 experiments. All mixtures were analyzed for 4-d lethality, and 2 of the 6 mixtures (permethrin-bifenthrin and permethrin-cyfluthrin) were tested for subchronic 10-d lethality and sublethal effects on swimming motility and growth. Mixtures were initially analyzed for interactions using regression analyses, and subsequently compared with the additive models of concentration addition and independent action to further characterize mixture responses. Negative interactions (antagonistic) were significant in 2 of the 6 mixtures tested, including cyfluthrin-bifenthrin and cyfluthrin-permethrin, but only on the acute 4-d lethality endpoint. In both cases mixture responses fell between the additive models of concentration addition and independent action. All other mixtures were additive across 4-d lethality, and bifenthrin-permethrin and cyfluthrin-permethrin were also additive in terms of subchronic 10-d lethality and sublethal responses. Environ Toxicol Chem 2016;35:2542-2549. © 2016 SETAC. © 2016 SETAC.

The effects of stress on alcohol consumption: mild acute and sub-chronic stressors differentially affect apomorphine susceptible and unsusceptible rats.

NARCIS (Netherlands)

Kam, E.L. van der; Coolen, J.C.; Ellenbroek, B.A.; Cools, A.R.

2005-01-01

The aim of this study was to investigate the effects of mild acute and mild sub-chronic challenges on alcohol intake and preference in the genetically selected ratlines of apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) animals. Animals from both lines were subjected to

Comparative effects of inhaled relatively insoluble forms of 90Y, 144Ce, and 90Sr on canine peripheral lymphocyte function

International Nuclear Information System (INIS)

Benjamin, S.A.; Jones, R.K.; Snipes, M.B.; Lustgarten, C.S.

1976-01-01

Dogs that have inhaled relatively insoluble forms of either alpha- or beta-emitting radionuclides manifest a peripheral lymphopenia, the development and course of which depends on both total dose and dose rate. The remaining peripheral lymphocytes in dogs exposed to longer lived beta-emitting radionuclides showed a depressed function as measured by the ability to respond to plant mitogens in vitro. This experiment was designed to evaluate the effect of dose rate on peripheral lymphocyte function by exposing dogs to aerosols of radionuclides with varied effective half-lives in the lung: 90 Y (2.6 days), 144 Ce (170 days), and 90 Sr (650 days). Three groups of four adult beagle dogs each were exposed by inhalation to 90 Y, 144 Ce, or 90 Sr in fused-clay particles. Two controls were matched with each group. Initial lung burdens and initial dose rates to the lung were 520 to 610 μCi/kg of body weight and 2200 to 2600 rads/day in the 90 Y group, 33 to 60 μCi/kg and 200 to 350 rads/day in the 144 Ce group, and 25 to 32 μCi/kg and 130 to 170 rads/day in the 90 Sr group. Hematologic parameters and lymphocyte function as measured by the ability of lymphocytes to respond to plant mitogen stimulation were evaluated on a weekly or biweekly basis for 8 weeks after exposure and on a monthly basis thereafter. The 90 Y-exposed dogs showed a marked lymphopenia within 1 week with a return to control levels by 20 weeks after exposure. The remaining peripheral lymphocytes, however, showed no functional changes in these dogs. Animals exposed to 144 Ce or 90 Sr developed a progressive and persisent lymphopenia and showed functional depression of the remaining lymphocytes as well. The relationships among dose pattern, lymphopenia, and lymphocyte-function depression are discussed

Implementation of a Total Hip Arthroplasty Care Pathway at a High-Volume Health System: Effect on Length of Stay, Discharge Disposition, and 90-Day Complications.

Science.gov (United States)

Featherall, Joseph; Brigati, David P; Faour, Mhamad; Messner, William; Higuera, Carlos A

2018-06-01

Standardized care pathways are evidence-based algorithms for optimizing an episode of care. Despite the theoretical promise of care pathways, there is an inconsistent literature demonstrating improvements in patient care. The authors hypothesized that implementing a care pathway, across 11 hospitals, would decrease hospital length of stay (LOS), decrease postoperative complications at 90 days, and increase discharges to home. A multidisciplinary team developed an evidence-based care pathway for total hip arthroplasty (THA) perioperative care. All patients receiving THA in 2013 (pre-protocol, historical control), 2014 (transition), and 2015 (full protocol implementation) were included in the analysis. Multivariable regression assessed the relationship of the care pathway to 90-day postoperative complications, LOS, and discharge disposition. Cost savings were estimated using previously published postarthroplasty episode and per diem hospital costs. A total of 6090 primary THAs were conducted during the study period. After adjusting for the covariates, the full protocol implementation was associated with a decrease in LOS (mean ratio, 0.747; 95% confidence interval [CI; 0.727, 0.767]) and an increase in discharges to home (odds ratio, 2.079; 95% CI [1.762, 2.456]). The full protocol implementation was not associated with a change in 90-day complications (odds ratio, 1.023; 95% CI [0.841, 1.245]). Payer-perspective-calculated theoretical cost savings, including both index admission and postdischarge costs, were $2533 per patient. The THA care pathway implementation was successful in reducing LOS and increasing discharges to home. The care pathway was not associated with a change in 90-day complications; further targeted interventions in this area are needed. Despite care standardization efforts, high-volume hospitals and surgeons had higher performance. Extrapolation of theoretical cost savings indicates that widespread THA care pathway adoption could lead to national

Deposition, clearance, and shortening of Kevlar para-aramid fibrils in acute, subchronic, and chronic inhalation studies in rats.

Science.gov (United States)

Kelly, D P; Merriman, E A; Kennedy, G L; Lee, K P

1993-10-01

The deposition and clearance of lung-deposited Kevlar para-aramid fibrils (subfibers) have been investigated as part of a subchronic and chronic inhalation toxicity testing program. Fibrils recovered from lung tissue in para-aramid-exposed Sprague-Dawley rats were microscopically counted and measured after exposures to airborne fibrils which were about 12 microns median length (ML) and < 0.3 micron median diameter. In each of three studies lung-recovered fibrils were progressively shorter with increasing residence time in the lungs. Twenty-eight days after a single 6-hr exposure at 400 respirable fibrils per cubic centimeter (f/cm3) the ML of recovered fibrils decreased to about 5 microns. Twenty-four months after a 3-week exposure to 25 or 400 f/cm3, fibrils reached about 2 microns ML. After 2 years of continuous exposure at 2.5, 25, or 100 f/cm3 or 1 year exposure plus 1 year recovery at 400 f/cm3, fibril ML approached 4 microns. In the 2-year study, the lung-fiber accumulation rate/exposure concentration was similar for the three highest concentrations and was about 3 x greater than that seen at 2.5 f/cm3, indicating that concentrations of about 25 f/cm3 or more may overwhelm clearance mechanisms. Time required for fibrils to be reduced to < 5 microns in the lung was markedly less at lower exposure concentration and shorter exposure time. The primary shortening mechanism is proposed to be long fibril cutting by enzymatic attack at fibril defects. However, length-selective fibril deposition and clearance may contribute to shortening in the first few days after exposure. The enzymatic cutting hypothesis is supported by measured increases in numbers of short fibers following cessation of exposures, continued shortening of the fibril length distribution up to 2 years following exposure, and in vitro fibril shortening after 3 months in a proteolytic enzyme preparation. The conclusion is that para-aramid fibrils are less durable in the lungs of rats than expected from

Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.

Science.gov (United States)

Levesque, Shannon; Surace, Michael J; McDonald, Jacob; Block, Michelle L

2011-08-24

Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m³ significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

Directory of Open Access Journals (Sweden)

McDonald Jacob

2011-08-01

Full Text Available Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3 by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3 in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may

Clinical outcomes of Y90 radioembolization for recurrent hepatocellular carcinoma following curative resection

Energy Technology Data Exchange (ETDEWEB)

Ali, Rehan; Riaz, Ahsun; Gabr, Ahmed; Abouchaleh, Nadine; Mora, Ronald; Al Asadi, Ali [Northwestern University, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Caicedo, Juan Carlos; Abecassis, Michael; Katariya, Nitin [Northwestern University, Department of Surgery, Division of Transplant Surgery, Chicago, IL (United States); Maddur, Haripriya; Kulik, Laura [Northwestern University, Department of Medicine, Division of Hepatology, Chicago, IL (United States); Lewandowski, Robert J. [Northwestern University, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Chicago, IL (United States); Salem, Riad [Northwestern University, Department of Radiology, Section of Interventional Radiology, Chicago, IL (United States); Northwestern University, Department of Surgery, Division of Transplant Surgery, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Chicago, IL (United States)

2017-12-15

To assess safety/efficacy of yttrium-90 radioembolization (Y90) in patients with recurrent hepatocellular carcinoma (HCC) following curative surgical resection. With IRB approval, we searched our prospectively acquired database for patients that were treated with Y90 for recurrent disease following resection. Baseline characteristics and bilirubin toxicities following Y90 were evaluated. Intention-to-treat overall survival (OS) and time-to-progression (TTP) from Y90 were assessed. Forty-one patients met study inclusion criteria. Twenty-six (63%) patients had undergone minor (≤3 hepatic segments) resection while 15 (37%) patients underwent major (>3 hepatic segments) resections. Two patients (5%) had biliary-enteric anastomoses created during surgical resection. The median time from HCC resection to the first radioembolization was 17 months (95% CI: 13-37). The median number of Y90 treatment sessions was 1 (range: 1-5). Ten patients received (entire remnant) lobar Y90 treatment while 31 patients received selective (≤2 hepatic segments) treatment. Grades 1/2/3/4 bilirubin toxicity were seen in nine (22%), four (10%), four (10%), and zero (0%) patients following Y90. No differences in bilirubin toxicities were identified when comparing lobar with selective approaches (P = 0.20). No post-Y90 infectious complications were identified. Median TTP and OS were 11.3 (CI: 6.5-15.5) and 22.1 months (CI: 10.3-31.3), respectively. Radioembolization is a safe and effective method for treating recurrent HCC following surgical resection, with prolonged TTP and promising survival outcomes. (orig.)

The Effect of Subchronic Administration of the Aqueous and Hydro-alcoholic Extracts of Crocus sativus from Estahbanat, Fars Province, on Mice

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M Emamghoreishi

2012-02-01

Full Text Available Background & aim: In Iranian traditional medicine, Crocus sativus L. has been defined as an exultant plant. The present study was undertaken to determine the effect of subchronic administration of aqueous and hydro-alcoholic extracts of Crocus sativus on mice. Methods: The effect of subchronic i.p. administration of different doses of the aqueous extract (50, 100, 200, 400 mg/kg or water and the hydro-alcoholic extract (100, 200, 400, 800 mg/kg or water of Crocus sativus stigma on immobility, climbing, and swimming behaviors were evaluated in the forced swimming test in mice. Fluoxetine (20 mg/kg and imipramine (15 mg/kg were used as reference drugs. Additionally, the effect of both plant preparations on spontaneous activity was examined. The collected data was analyzed using One-way ANOVA. Results: The aqueous extract at doses of 50 and 100 mg/kg produced a significant reduction in immobility along with an increase in climbing behavior which is similar to those which have been observed with imipramine. The hydro-alcoholic extract did not show significant effects on immobility, climbing and swimming behaviors of all studied doses, compared to control group. The aqueous extract of all studied doses and the hydro-alcoholic extract at dose of 1600 mg/kg decreased spontaneous activity. Conclusion: The results of this study suggests that the aqueous, but not hydro-alcoholic, extract of Crocus sativus stigma from Estahbanat in Fars province, in subchronic administration possess an antidepressant-like activity which may be mediated through norepinephrine system.

Bound residues of 14C-carbofuran and 14C-malathion in stored soybean seeds and their toxicological effects on mice

International Nuclear Information System (INIS)

Mahdy, F.; Taha, H.

2005-01-01

Soybeans treated with 1 4C -carbofuran or 1 4C -malathion at a dose of 30 mg/kg and stored for 30 weeks showed that the organophosphorus insecticide malathion had a higher binding tendency to soybean seeds than the carbamate insecticide carbofuran. The amount of malathion bound 1 4C -residues were almost three times higher (as percentage of applied dose) than carbofuran bound residues. Sub-chronic feeding experiments on mice for 90 days with a diet containing the bound 1 4C -residues at a dose of 0.91 and 2.39 ppm/day/mouse for carbofuran and malathion, respectively, caused non-significant symptoms of toxicity during the period of the experiment. A slight inhibition in plasma and erythrocyte choline esterase activities was observed during the second and third months in both treated mice fed on carbofuran or malathion. Liver enzymes, total protein, albumin, cholesterol, triglycerides and kidney functions showed non-significant differences from control values in case of mice fed on 1 4C -bound carbofuran residues. However, these mentioned blood parameters showed only slight increase, as compared with controls, in treated mice fed on 1 4C -bound malathion residues

Ovarian condition of Holstein dairy cows between 30 and 90 days postpartum in the microregion of Uberlândia, MG

Directory of Open Access Journals (Sweden)

Anderson Kloster Munhoz

2014-01-01

Full Text Available Anestrous postpartum is a state of complete sexual inactivity without estrous manifestations and the return of ovarian activity in postpartum may be negatively affected by several factors, such as negative energy balance (NEB, loss of body condition score (BCS, season in which the calving occurs, nutritional deficiencies, dystocic calving, retained placenta, uterine infections and metabolic diseases. This study aimed to evaluate the effects of BCS and number of days in milk (DIM on ovarian cyclicity of Holstein dairy cows. Ovarian conditions of 168 cows between 30 to 90 days in milk (DIM were evaluated twice by ultrasonography with seven days of interval and cows were classified in four categories: ovaries with presence of small follicles (Category 1: up to 10 mm; ovaries with medium follicles (Category 2: 10 to 18 mm; ovaries with large follicles (Category 3: over 20 mm and ovaries with presence of corpus luteum (CL (Category 4. The cows classified in categories 1, 2 and 3 were considered in anestrous. Data were analyzed by logistic regression at Minitab (P<0.05. As a result 15 cows (8.93% were in Category 1, 34 (20.24% in Category 2, 4 (2.38% in Category 3 and 115 (68.45% in Category 4. There was no effect (P>0.05 of DIM in the percentage of cycling cows, however there was a tendency (P=0.074 that cows with greater BCS (≥ 2.75 had a higher cyclicity rate (74.44% vs. 61.54% than cows with lower BCS. Days in milk effect was not detected in cyclicity rate in cows between 30 and 90 DIM, but there was a tendency of Holstein cows with greater body condition score to had higher cyclicity rate.

Comparative chronic toxicity of imidacloprid, clothianidin, and thiamethoxam to Chironomus dilutus and estimation of toxic equivalency factors.

Science.gov (United States)

Cavallaro, Michael C; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

2017-02-01

Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to

Phytotherapeutic activity of curcumol: Isolation, GC-MS identification, and assessing potentials against acute and subchronic hyperglycemia, tactile allodynia, and hyperalgesia.