Detection of titanium particles in human liver and spleen and possible health implications

Background: Titanium dioxide (TiO2) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO2 to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO2 particle...

Feasibility of SPECT-CT imaging to study the pharmacokinetics of antisense oligonucleotides in a mouse model of Duchenne muscular dystrophy

Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using...

Elevation of cartilage AGEs does not accelerate initiation of canine experimental osteoarthritis upon mild surgical damage

Osteoarthritis is a highly prevalent disease, age being the main risk factor. The age-related accumulation of advanced-glycation-endproducts (AGEs) adversely affects the mechanical and biochemical properties of cartilage. The hypothesis that accumulation of cartilage AGEs in combination with surgically induced damage predisposes to the...

A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes for soman in multiple species

A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(±)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 × LD50), medium (2-3 × LD50) and high (6 × LD50) levels...

Application of physiologically based toxicokinetic modelling to study the impact of the exposure scenario on the toxicokinetics and the behavioural effects of toluene in rats

The toxicity of inhalatory exposure to organic solvents may not only be related to the total external dose, but also to the pattern of exposure. In this study physiologically based toxicokinetic (PBTK) modelling has been used to study the impact of the exposure scenario on the toxicokinetics and the behavioural effects of the model solvent...

Toxicogenomics of bromobenzene hepatotoxicity: A combined transcriptomics and proteomics approach

Toxicogenomics is a novel approach integrating the expression analysis of thousands of genes (transcriptomics) or proteins (proteomics) with classical methods in toxicology. Effects at the molecular level are related to pathophysiological changes of the organisms, enabling detailed comparison of mechanisms and early detection and prediction of...

Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers

Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although ω-3 PUFAs may influence oxidative stress. We examined the effect of supplementation on a range of indicators of ultraviolet...

In vitro intestinal lead uptake and transport in relation to speciation

Children might be exposed substantially to contaminants such as lead via soil ingestion. In risk assessment of soil contaminants there is a need for information on oral bioavailability of soilborne lead. Oral bioavailability can be seen as the result of four steps: (1) soil ingestion; (2) mobilization from soil during digestion, i.e.,...

Toenail selenium levels and the subsequent risk of prostate cancer: A prospective cohort study

Results of a randomized controlled trial have suggested a protective effect of selenium against prostate cancer. Few other prospective studies have been conducted to confirm or refute this. The association between prostate cancer and baseline toenail selenium level was evaluated in the Netherlands Cohort Study, conducted among 58,279 men, aged...

Association between toenail scandium levels and risk of acute myocardial infarction in European men: The EURAMIC and Heavy Metals Study

The association between scandium status and risk of acute myocardial infarction (MI) was examined in a multicentre case control study in 10 centres from Europe and Israel. Scandium in toenails was assessed in 684 cases and 724 controls less than 70 years of age. Mean concentrations of toenail scandium were 6.74 μg/kg in cases and 7.75 μg/kg in...

Age-related accumulation of Maillard reaction products in human articular cartilage collagen

Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage....

Determinants of p,p'-dichlorodiphenyldichloroethane (DDE) concentration in adipose tissue in women from five European cities

To identify the determinants of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE) in adipose tissue in subjects who participated in a cross- sectional study, we analyzed fatty acids, antioxidants, and p,p'-DDE in aspirates of adipose tissue of 328 postmenopausal women from 5 European countries. The overall mean of p,p'-DDE concentration was 1.66 μg...

Pharmacokinetics of cisplatin with and without amifostine in tumour- bearing nude mice

Amifostine (Ethyol, WR-2721) is in use in the clinic as a protector against platinum-induced toxicities. We have previously reported that amifostine induced a potentiation of the antitumour activity of carboplatin in human ovarian cancer xenografts. An influence of amifostine on the pharmacokinetics of carboplatin, resulting in higher platinum...

Disposition of [14C]γ-cyclodextrin in germ-free and conventional rats

The absorption, disposition, metabolism, and excretion of 14C-labeled γ-cyclodextrin ([14C]γ-CD) was examined in four separate experiments with Wistar rats. In experiment 1, [14C]γ-CD (25 μCi, 600 mg/kg body wt) was administered intravenously to four male and four female conventional rats. In experiment 2, [14C]γ- CD (25 μCi, 1000 mg/kg body wt)...

Enhancement of tissue-type plasminogen activator levels by retinoids in rat tissues in vivo

Fluorometric determination of retinol in human tear fluid using high-performance liquid chromatography

A fast and sensitive high-performance liquid chromatographic (HPLC) method for the determination of vitamin A (all-trans retinol) in 50 ??l human tear fluid is described. After deproteinization with ethanol and extraction with n-hexane, retinol is separated from the extract on a straight-phase HPLC column and detected fluorometrically. Vitamin A...

Kinetic profile in blood and brain of the cholinesterase reactivating oxime HI-6 after intravenous administration to the rat

The kinetic profile of the oxime HI-6, a potent cholinesterase reactivator, after iv administration of 0.1325 mmol/kg (50 mg/kg) to rats is described. The blood concentrations measured over a period of 300 min can be described by a two-compartment open model. Excretion occurred only by the kidney. Approximately 60% was excreted in unmetabolized...