Abstract:
:The present study evaluated the proconvulsant liability of biapenem, a novel carbapenem antibiotic, in in vitro and in vivo experiments, in comparison with the carbapenems, imipenem/cilastatin and meropenem. Imipenem/cilastatin is a carbapenem antibiotic with known proconvulsive liability in man and in animal experiments. In in vivo studies imipenem/cilastatin, at doses of 400/400 mg/kg i.v., significantly lowered the convulsive threshold of pentylenetetrazol (PTZ) in mice and shifted the dose-response curve of PTZ. The effects of biapenem (400 mg/kg i.v.) and another reference carbapenem, meropenem (400 mg/kg i.v.), in the mouse PTZ model were not significantly different from control. In in vitro experiments the carbapenems were tested for their ability to inhibit [3H]muscimol (1.3 mM) binding to rat brain homogenates at concentrations of 1-10 mM. Similar to in vivo results, when compared to imipenem/cilastatin, biapenem and meropenem did not inhibit [3H]muscimol binding to the GABAA receptor complex in brain homogenates while imipenem/cilastatin exhibited significant inhibition (IC50 = 4.6 mM). These results further confirm the correlation between in vitro GABAA binding and in vivo PTZ convulsive testing with carbapenem antibiotics, and suggest that biapenem possesses a low proconvulsive liability.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Day IP,Goudie J,Nishiki K,Williams PDdoi
10.1016/0378-4274(95)80008-2subject
Has Abstractpub_date
1995-04-01 00:00:00pages
239-43issue
3eissn
0378-4274issn
1879-3169pii
0378-4274(95)80008-2journal_volume
76pub_type
杂志文章abstract::CYP2E1 metabolizes 1,3-butadiene (BD) into genotoxic and possibly carcinogenic 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol (EB-diol). The dose response of DNA and protein adducts derived from BD metabolites increases linearly at low BD exposures and then saturates at higher expos...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.08.025
更新日期:2013-11-25 00:00:00
abstract::A model of the growing small animal skeleton has been developed. The model accurately reproduces a variety of different kinds of measurements made at different ages in different species, as well as reproducing a precise and detailed series of measurements in the growing guinea pig. Of the multiple mechanisms responsib...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(88)90022-7
更新日期:1988-10-01 00:00:00
abstract::It has been reported that lead could induce apoptosis in a variety of cell types. Although mitochondrion is regarded as the most pertinent pathway in mediating apoptosis, the exact mechanisms of lead-induced apoptosis are still largely unknown. Furthermore, there is little information about expressions and regulations...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2006.06.643
更新日期:2006-10-10 00:00:00
abstract::Cadmium is a carcinogenic metal known to increase the expression of several protooncogenes in a variety of cells. although the underlying mechanisms are unknown. Renal mesangial cells are smooth muscle cells in which Ca2+ signaling pathways regulate the induction of c-fos through both cAMP-dependent and mitogen-activa...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00015-0
更新日期:1998-03-16 00:00:00
abstract::We reported earlier that the activation of free-radical-mediated tumor necrosis factor-alpha (TNF-alpha) cascade is the major pathway in the inflammatory lung disease induced by 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog. TNF-alpha induces activating protein 1 (AP-1) activation via phosphorylation of mit...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.07.005
更新日期:2008-09-26 00:00:00
abstract::Both arsenite and benzo(a)pyrene (BaP) are known human carcinogens. Studies on the mode-of-action of arsenite indicate that it can also act as co-carcinogen or as a cancer promoter, and that it can facilitate progression of cancers. Some studies on development of lung cancers have suggested a synergism between arsenit...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.01.004
更新日期:2013-04-12 00:00:00
abstract::Particulate air pollution is associated with cardiovascular morbidity and mortality. Fine particles with a diameter <2.5 microm (PM2.5) have an important role in triggering biological responses. These particles, and particularly the ultrafine fraction (<100 nm) penetrate deeply into the respiratory tract. Recently, we...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2003.12.061
更新日期:2004-04-01 00:00:00
abstract::Male C57B1/6N mice, 8-10 weeks old were given a single oral dose of 0, 1.0 or 3.0 mg/kg body weight of trimethyltin hydroxide (TMT). Levels of ornithine decarboxylase (ODC) activity were measured in several brain areas, 1, 2 and 7 days later. The lower dose of TMT produced a decrease of ODC in the caudate nucleus and ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90042-7
更新日期:1987-03-01 00:00:00
abstract::The oral LD50 of hymenoxon in Swiss white mice was found to be 241 +/- 37 mg/kg. No significant sex differences were observed. Pretreatment of male mice for 3 days using doses of 50 and 100 mg/kg hymenoxon failed to alter significantly pentobarbital sleeping time. Hymenoxon was found to be a direct-acting mutagen in t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(81)90016-3
更新日期:1981-12-01 00:00:00
abstract::We observed transient excretion of dark-brown urine after acute exposure to cobalt in rats and investigated the mechanism of it. We injected cobalt into rats s.c. at a dose of 15 mg/kg and collected urine, peripheral blood, and organ samples at the indicated times after injection. Biochemical and histopathological exa...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.03.018
更新日期:2004-08-01 00:00:00
abstract::Male Swiss OF1 mice received a single oral dose of either 80 mg/kg hexachloro-1,3-butadiene (HCBD) or 40 mg/kg methyl mercury (MeHg). Examination of cryostat kidney sections stained for alkaline phosphatase (APP) revealed damage to about 50% of the proximal tubules after 8 h. Treatment with the organic anion transport...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(88)90184-1
更新日期:1988-01-01 00:00:00
abstract::Phosgene Oxime (CX, Cl2CNOH), a halogenated oxime, is a potent chemical weapon that causes immediate acute injury and systemic effects. CX, grouped together with vesicating agents, is an urticant or nettle agent with highly volatile, reactive, corrosive, and irritating vapor, and has considerably different chemical pr...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2017.11.011
更新日期:2018-09-01 00:00:00
abstract::Regions with heavy industry are in many ways regions of crisis. The health of the population is primarily affected by the different air pollutants. Dust, with all its organic (dioxins and furans) and inorganic (heavy metals) contents, makes up the greatest part of the air-borne pollutants. The influence on health of e...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(96)03731-9
更新日期:1996-11-01 00:00:00
abstract::Dichloromethane (DCM) elimination and carboxyhemoglobin (COHb) generation were examined in adult female SD rats pretreated with a glutathione (GSH) depletor(s). Rats were treated with either buthionine sulfoximine (BSO; 2 mmol/kg, i.p.), diethylmaleate (DEM; 3 mmol/kg, i.p.), phorone (PHO; 1 mmol/kg, i.p.) or BSO plus...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(01)00523-9
更新日期:2002-03-24 00:00:00
abstract::Results of health survey and biological monitoring in pesticide formulators exposed to a combination of pesticides, an organophosphorus (OP) insecticide (phorate) and a persistent chlorinated insecticide (technical hexachlorocyclohexane; HCH; BHC) are reported. Exposure of 160 workers to a combination of pesticides (m...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(86)90075-5
更新日期:1986-10-01 00:00:00
abstract::Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 0, 2.5, 5.0, 7.5 or 10.0 mg/kg on days 7-15 of pregnancy. Maternal toxicity occurred in the 7.5 and 10.0 mg/kg groups as evidenced by a significant increase in maternal death and decrease in food consumption and body weight gain...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(91)90047-a
更新日期:1991-11-01 00:00:00
abstract::International scientific committees, regional scientific committees such as those of the European Union, and national regulatory agencies generally use the uncertainly factor approach for establishing acceptable or tolerable intakes of substances that exhibit thresholds of toxicity. No observed adverse effect levels (...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2008.06.003
更新日期:2008-08-15 00:00:00
abstract::Acrylonitrile (ACN) is a widely used intermediate in the manufacture of plastics, acrylic fibers, synthetic rubbers and resins that are used in a variety of products including food containers and medical devices. ACN is a possible human carcinogen and a documented animal carcinogen, with the stomach being an important ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.10.018
更新日期:2012-01-25 00:00:00
abstract::In C57BL/6 mice, aryl hydrocarbon hydroxylase (AHH) increased 1 day after treatment with 3-methylcholanthrene, and induction of UDP-glucuronyl transferases for 3-hydroxybenzo(a)pyrene, p-nitrophenol and bilirubin in the liver microsomes was observed 2 to 5 days later. In DBA/2 mice, neither AHH nor transferase activit...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(80)90146-0
更新日期:1980-01-01 00:00:00
abstract::Human fetuses and neonates are particularly vulnerable to methylmercury (MeHg)-induced brain damage and are sensitive even to low exposure levels. Previous work of our group evidence that prenatal exposure to MeHg causes cognitive and behavioral alterations and disrupt hippocampus signaling. The current study aimed to...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.12.006
更新日期:2018-03-01 00:00:00
abstract::(1) The hypothesis that inhalational anesthetics affect G-protein linked alpha2 adrenergic signaling pathway was investigated using human platelets as a model system. (2) Alpha2 receptor stimulation by UK-14304, a potent and selective agonist, inhibits cAMP production induced by prostaglandin I2 (PGI2). (3) Brief stim...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00174-x
更新日期:1998-11-23 00:00:00
abstract::To help minimize errors and confusion in the scientific literature, a few principles can be followed. The original intent and hypothesis of each study should be made clear, and deviations from the initial purpose should be stated. The hypothesis-testing portions of the research need to be clearly differentiated from t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03554-0
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:GAPDH, well known for its house-keeping functions, has also been shown to be involved in cell injury, apoptosis and death under conditions of stress such as starvation, chemical injury and oxidative stress. This study examines the effect of GAPDH knockdown on cell injury in response to Rotenone. METHODS:GAP...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.02.017
更新日期:2015-05-05 00:00:00
abstract::To characterize the accumulated hazards associated with the inhalation of gases typical of combustion products, a time-integrated value known as the fractional effective dose (FED) is used. This FED is maintained by the International Organization for Standardization (ISO) and made publicly available as the Standard IS...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.09.012
更新日期:2016-11-16 00:00:00
abstract::Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneou...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.10.009
更新日期:2011-01-15 00:00:00
abstract::Xenobiotic exposure is a risk factor in the etiology of neurodegenerative disease. It was recently hypothesized that restricted exposure during brain development could predispose for a neurodegenerative disease later in life. As neuroinflammation contributes to progressive neurodegeneration, it is suspected that neuro...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.02.001
更新日期:2014-10-15 00:00:00
abstract::Arsenic (As), a ubiquitous toxic metal, is an important environmental and industrial pollutant throughout the world. Inorganic As (iAs) is usually more harmful than organic ones and with a high risk of diabetes incidence by exposure. However, the toxicological effects of iAs on growth and function of pancreatic β-cell...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.11.019
更新日期:2011-02-25 00:00:00
abstract::Besides hepatotoxicity, paracetamol may exert nephrotoxic effects in experimental animals and man. The present study in rats shows that cholestyramine given 4 and 24 h after paracetamol provided protection against both hepato- and nephrotoxicity; this was evidenced by reduced increments in plasma enzyme activities (SD...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(89)90073-8
更新日期:1989-05-01 00:00:00
abstract::Lithocholic acid (LCA) supplementation in the diet results in intrahepatic cholestasis and bile infarcts. Previously we showed that an innate immune response is critical for cholestatic liver injury in the bile duct ligated mice. Thus, the purpose of this study was to investigate the role of neutrophils in the mechani...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.04.001
更新日期:2014-07-03 00:00:00
abstract::Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expres...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2005.10.024
更新日期:2006-06-01 00:00:00