Abstract:
:Drugs intended for use in preventing allograft rejection in transplant patients are likely to be administered chronically; thus, it is normally expected that sponsors would conduct nonclinical studies to determine the carcinogenic potential of candidate compounds. For pharmaceuticals other than biologic agents, this would mean that rodent carcinogenicity bioassays would be performed under most circumstances. Immunosuppressant drugs have presented unique challenges with respect to the issue of carcinogenicity bioassays. The pharmacological activity of therapeutic immunosuppressants is thought to make them highly likely to act as promoters/cocarcinogens, even in the absence of genotoxic activity. Thus, it is assumed that this class of drug would represent a carcinogenic hazard in the absence of confirmatory standard rodent bioassay data. In addition, rodents typically have been sensitive to the pharmacological/toxicological effects of immunosuppressants. It has proven to be difficult, therefore, to conduct life-time bioassays at doses reasonably equivalent to those that would be used clinically. For this and other reasons, alternative models might be more appropriate for risk assessment with this class of drugs.
journal_name
Hum Exp Toxicoljournal_title
Human & experimental toxicologyauthors
Hastings KLdoi
10.1191/096032700678815837subject
Has Abstractpub_date
2000-04-01 00:00:00pages
261-5issue
4eissn
0960-3271issn
1477-0903journal_volume
19pub_type
杂志文章,评审abstract::The regulation of osteoblast proliferation is a key factor in maintaining bone mass. The enhancement of this process can be achieved by stimulating the proliferation of these cells. Mechanical stimulation is one of the important enhancing factors, but the exact cellular mechanisms of mechanical stimulation, i.e., mech...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/0960327103ht362oa
更新日期:2003-05-01 00:00:00
abstract::Two previously healthy women developed nausea, vomiting, headache and dizziness for several days, a massive hair loss about 2 weeks later and a discoloration of the fingernails. Detailed diagnostic procedures did not reveal any pathological results. Therapeutic measures did not show any effect. Thallium and arsenic we...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327109360046
更新日期:2010-05-01 00:00:00
abstract::Celecoxib has been shown to have antitumor effect in previous studies but the mechanisms are unclear. The effect of celecoxib on cytosolic Ca(2+) concentrations ([Ca(2+)]i) and viability in HA59T human hepatoma cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. Celecoxib ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327112472996
更新日期:2014-11-01 00:00:00
abstract::Cisplatin is an effective anticancer drug used against a variety of cancers. The full therapeutic potential of cisplatin is often hampered due to concurrent development of various side effects in the hosts. Rutin, a naturally occurring bioflavonoid shows several pharmacological activities. It has been earlier reported...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327120947793
更新日期:2020-08-13 00:00:00
abstract::In Southern Africa, the medicinal plant Warburgia salutaris is commonly used for the treatment of inflammatory and other diseases. The methanol extracts of W. salutaris were investigated with regard to a) production of proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma; b) a...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327108099536
更新日期:2008-11-01 00:00:00
abstract::Acute exposure to systemic poisons represents an important challenge in clinical toxicology. We aimed to analyze the potential role of cardiac biomarkers, routine laboratory tests, and clinical scores as morbidity and in-hospital mortality predictors in patients intoxicated with various systemic poisons. We conducted ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327116660866
更新日期:2017-07-01 00:00:00
abstract:OBJECTIVES:Pesticide poisoning stands as a major public health issue worldwide. The objective of this study was to examine the epidemiologic characteristics of pesticide-related hospitalizations in South Korea. METHODS:Data from the Korea National Hospital Discharge Survey were analyzed to describe the epidemiologic c...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327111431709
更新日期:2012-08-01 00:00:00
abstract::The study was done to find out whether subacute exposure to supercypermethrin forte (SCM) affected cellular and humoral immunity. Groups of 10 male Wistar rats were given SCM by gavage for 28 days at 12.5 mg kg-1 day-1 (1/14 LD50), 8.75 mg kg-1 day-1 (1/20 LD50) and 4.38 mg kg-1 day-1 (1/40 LD50) and the response of s...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719501400502
更新日期:1995-05-01 00:00:00
abstract::The National Toxicology Program (NTP) Technical Reports online database was reviewed to find chemicals that were reported to show clear evidence of carcinogenicity in the NTP rodent studies and for which data on human exposure could be found. Six representative compounds were selected. Three volatile compounds: ethyl ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/0960327103ht374oa
更新日期:2003-09-01 00:00:00
abstract::Tripartite motif-containing protein 24 (TRIM24) has currently emerged as a crucial cancer-related gene present in a wide range of human cancer types. However, the involvement of TRIM24 in acute myeloid leukemia (AML) has not been well investigated. The present study aims to investigate the significance, cellular funct...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327120938845
更新日期:2020-12-01 00:00:00
abstract::Puerarin, a potent free radicals scavenger, has been demonstrated to have protective efficacy in oxidative damage induced by nephrotoxins. In the present study, the attenuating effect of puerarin (PU) on lead (Pb)-induced apoptosis and oxidative stress was investigated in cultured primary rat proximal tubular (rPT) ce...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327114521048
更新日期:2014-10-01 00:00:00
abstract::We describe two cases of chemical necrotizing fasciitis in the upper extremities, anterior chest wall and epigastric region of the abdominal wall caused by household insecticide injection. We suggest that surgical debridement can be successfully performed in the subacute period under close observation in hemodynamical...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/0960327102ht308cr
更新日期:2002-12-01 00:00:00
abstract::1. Six healthy male volunteers received intravenous injections of 26Al as citrate. Accelerator mass spectrometry and gamma-ray spectrometry were used to determine levels of the tracer in blood and excreta at times up to 5-6 d. 2. There was a rapid clearance from blood (mean 2% of injection remaining after 1 d) and maj...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719501400707
更新日期:1995-07-01 00:00:00
abstract::A four-fold increase in the iron content of normal subjects was detected in plasma after 5 hours of iron administration. Iron supplementation had a surprisingly erratic effect on four patients with hepatomegaly secondary to heart insufficiency, since the increase in the iron content in the plasma after iron-dextran ad...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/0960327103ht372oa
更新日期:2003-07-01 00:00:00
abstract::Cultures of bovine pulmonary endothelial (BPE) cells were exposed to LC70 doses of ricin or abrin (15.5 and 4.5 pM respectively) over a period of up to 40 h. The viability of the cultures (as determined by the neutral red (NR) dye retention assay) declined after 6 h exposure to the toxins. From 15 h onwards, cellular ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719601500513
更新日期:1996-05-01 00:00:00
abstract::In the 1980s, villages in the Kurdistan region of Iraq were exposed to chemical weapons (CWs), which killed and injured thousands of civilians. There has been no clinical assessment of the long-term effects of CWs exposure on those injured. We report the first such evaluation of CW effects on long-term health of child...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327117734620
更新日期:2018-08-01 00:00:00
abstract::The study of Jayjock and Lewis, 'Implication of Hormesis for Industrial Hygiene', represents a challenge for the scientific community to consider hormesis as a possible working hypothesis for redefining risk assessment strategy for low-dose exposures in the realm of industrial hygiene. This invited commentary aims at ...
journal_title:Human & experimental toxicology
pub_type: 评论,杂志文章
doi:10.1191/0960327102ht269xx
更新日期:2002-07-01 00:00:00
abstract::1. The reactivating and therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-/2-hydroxyiminomethylpyridinium/-4-/carbamoylpyridinium/- 2-butene dibromide), against organophosphate sarin was compared with presently used oximes (pralidoxime, obidoxime, methoxime) and H oximes (HI-6, HLö-7) ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/096032799678845106
更新日期:1999-09-01 00:00:00
abstract::1. This study examines the effect of treating rats with gentamicin (80 mg kg-1 day-1 intramuscularly (i.m.), for 6 days) alone or with either L-thyroxine or the anti-thyroid drug carbimazole. 2. Gentamicin produced significant increases in serum creatinine and urea concentrations, and significantly reduced the activit...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719501400103
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:The objective of the present study was to determine oxidant and antioxidant status in infants with hyperbilirubinemia and/or kernicterus and to find whether there is a relationship between bilirubin level and oxidant/antioxidant status. PATIENTS:The study includes 69 full-term newborns (neonates with hyperbi...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327111401638
更新日期:2011-11-01 00:00:00
abstract::Changes required for the explicit recognition of hormesis are outlined for both ecotoxicology and ecological risk assessment (ERA). A major research need is the extension of hormesis beyond chemical stressors to abiotic (e.g., habitat) and biotic stressors (e.g., species introductions, organism interactions). An overr...
journal_title:Human & experimental toxicology
pub_type: 杂志文章,评审
doi:10.1191/096032701718120337
更新日期:2001-10-01 00:00:00
abstract::1-Bromopropane (1-BP) is an increasingly used chemical solvent for cleaning metals and gradually replacing spraying adhesives. Workers exposed to 1-BP (WBP) showed nervous system dysfunction and other symptoms. This study focused on the proteomic change between healthy individuals (HIs), WBP and poisoned patients with...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327117689911
更新日期:2018-01-01 00:00:00
abstract::Vulpinic acid, a lichen compound, has been shown to have many beneficial effects and its medicinal value increases day by day. As in atherosclerosis, endothelial damage is the basis of many diseases. The aim of this study is to investigate the effects of vulpinic acid against oxidative stress damage induced by hydroge...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327119833745
更新日期:2019-06-01 00:00:00
abstract::Resveratrol, a grape skin and red wine-derived polyphenolic phytoalexin, exhibits hormetic action delivering numerous health benefits at lower doses while being detrimental at higher doses. Epidemiologic and clinical trials need to be based on the clear understanding of hormetic health benefits of resveratrol. ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327110383626
更新日期:2010-12-01 00:00:00
abstract::Airborne mono-2-ethylhexyl phthalate (MEHP) was studied for acute airway effects using a bioassay with BALB/c mice. Concentration- and time-dependent effects were obtained by continuous monitoring of the breathing pattern during exposure to 0.3-43.6 mg/m3 MEHP for 60 min. Additionally, inflammatory effects of MEHP wer...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/0960327104ht486oa
更新日期:2004-11-01 00:00:00
abstract:INTRODUCTION:Accidental toxicity by organophosphate (OP) agents may occur among farmers during spraying season due to improper use and handling. Plasma cholinesterase (ChE) activity measurement is recommended to monitor the extent of exposure to the OP agent. The aim of the current study was to measure plasma ChE activ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115584990
更新日期:2016-03-01 00:00:00
abstract::The effect of sympathomimetic intervention with dopamine or dobutamine on the myocardial uptake of d-propoxyphene was investigated experimentally in rats. The d-propoxyphene (19 mg kg-1 h-1) was continuously infused, intravenously, over 45 min. After 20 min of infusion the rats were given either dopamine (12.5 microgr...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719101000203
更新日期:1991-03-01 00:00:00
abstract::Pharmacological potential of curcumin was assessed in PC12 cells against hydrogen peroxide (H(2) O(2)) exposure. In MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and lactate dehydrogenase (LDH) assays, 24-hour exposure of H(2)O(2) (0.5 mM and above) was found to be cytotoxic. A significant (p < 0...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327110371696
更新日期:2011-03-01 00:00:00
abstract::As an input to dose assessments, measurements have been made of the clearance of Pu and Am after subcutaneous implantation in rats for six particulate materials and one dust from the Maralinga test sites. The tissue distribution of Pu and Am were measured in groups of six animals at one month and 6 months after implan...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719301200410
更新日期:1993-07-01 00:00:00
abstract::The purpose of the present study is to establish a new animal model of azithromycin (AZ)-induced liver injury and study the molecular pathological change during the process. First, mice were respectively injected intraperitoneally with AZ of different high doses. Our results showed that 800 mg/kg AZ injection signific...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115595684
更新日期:2016-05-01 00:00:00