Gijsbert van der Voet

• Toxicologist at Leiden University Medical Centre

Background: The majority of modern war wounds are characterized by high-energy blast injuries containing a wide range of retained foreign materials of a metallic or composite nature. Health effects of retained fragments range from local or systemic toxicities to foreign body reactions or malignancies, and dependent on the chemical composition and...

Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing...

This manuscript has been reviewed in accordance with the policy of the Armed Forces Institute of Pathology and the Department of Defense, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Department of the Army or the Department of Defense, nor does mention of trade names or...

This chapter discusses effects of metals on human body. Many studies have documented an increased cancer risk—particularly lung and bladder—among workers in the aluminum industry. While workers in the aluminum industry are heavily exposed to fluorides, these studies have assumed that the main chemicals causing the cancer are polycyclic aromatic hyd...

This chapter discusses results of the studies conducted on metals. Aluminum compounds are used as phosphate binders and as adjuvants in vaccines. Aluminium is also part of dental and medical implant material such as glass ionomer cement. Current evidence suggests that aluminum from adjuvants in vaccines can persist at the site of injection for year...

The use of dietary supplements has grown dramatically in the last decade. A large number of dietary and herbal supplements escape regulatory and quality control; components of these preparations are poisonous and may contain, among other toxins, heavy metals. Uncontrolled use of dietary and herbal supplements by special populations, such as the mil...

In our previous study in rats acutely exposed to As, we observed an effect of As on neurofilaments in the sciatic nerve. This study deals with the effects of inorganic As in Wistar rats on the cytoskeletal protein composition of the sciatic nerve after subchronic intoxication. Sodium meta-arsenite (NaAsO2) dissolved in phosphate-buffered saline (PB...

Arsenic (As) has been shown to alter one or more DNA repair processes. Excision repair cross-complementing 1 and 2 (ERCC1 and ERCC2) have shown to be associated with arsenic-induced toxicity and carcinogenicity. In this study, we investigated cytotoxic effects of various As metabolites in relation to two nucleotide excision repair genes: ERCC1 and...

In recent studies we have demonstrated that arsenic (As) metabolites change the composition of neuronal cytoskeletal proteins in vivo and in vitro. To further examine the mechanism of arsenic-induced neurotoxicity with various arsenate metabolites (iAsV, MMAV and DMAV) and arsenite metabolites (iAsIII, MMAIII and DMAIII), we investigated the role o...

The Epidemiological Study Air Disaster in Amsterdam (ESADA) aimed to assess long-term health effects in professional assistance workers involved in the 1992 air disaster in Amsterdam. As part of ESADA indications of nephrotoxicity due to exposure to uranium from the balance weights of the crashed aircraft were assessed. Data of a historically defin...

Arsenic (As) is one of the oldest poisons known to men. Its applications throughout history are wide and varied: murder, make-up, paint and even as a pesticide. Chronic As toxicity is a global environmental health problem, affecting millions of people in the USA and Germany to Bangladesh and Taiwan. Worldwide, As is released into the environment by...

Tungsten and tungsten compounds are considered toxicologically relatively safe. Concern regarding the potential health and environmental effects of depleted uranium and lead in military applications has lead many countries to explore the possibility of applying toxicologically safer metals. Heavy metal tungsten alloy-based munitions have been there...

Neurological studies indicate that the central (CNS) and peripheral nervous system (PNS) may be affected by arsenic (As). As-exposed patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison to healthy subjects. As may play a role in the disruption of neuroskeletal integrity, but the mechanisms by...

Exposure to arsenic compounds may lead to skin and lung cancer and various disorders such as vascular disease and peripheral neuropathy in humans. Peripheral arsenic neurotoxicity has been demonstrated clinically and in electrophysiological studies. Patients intoxicated with arsenic show neurological symptoms in their feet and hands. These patients...

Een verhoging van nikkel in het bloed is alleen een indicatie voor blootstelling. Een schatting van het gezondheidsrisico is louter met dit gegeven niet te maken, omdat bloedspiegels slechts in bijzondere gevallen correleren met gezondheidseffecten. Interpretatie van de bloedspiegel is mogelijk na het zoeken van uitsluitsel omtrent acute dan wel ch...

To study mercury levels in hair from mothers and newborns in Surinam. Hair and urine was collected from thirty-nine mothers of different ethnicity and hair from their newborns. The women delivered in a large hospital in the capital. Mercury analysis was performed. Fourteen (36%) of the mothers had elevated Hg concentrations in the hair as compared...

We describe a fetus with a hypoplastic right ventricle detected by prenatal ultrasound examination. A possible causal relationship with prenatal valproate exposure is discussed.

Nephrotoxicity is the most important dose-limiting factor in cisplatin based anti-neoplastic treatment. Pretreatment with bismuth salts, used as pharmaceuticals to treat gastric disorders, has been demonstrated to reduce cisplatin-induced renal cell death in clinical settings and during in vivo and in vitro animal experiments. To investigate the ge...

The population of Curaçao, Netherlands Antilles (133,000) shows a very high prevalence of end-stage renal disease (approximately 1 per 1,000). These patients are often treated chronically with haemodialysis. As the drinking water on the island is prepared by distillation of sea water, the haemodialysis fluid used to be prepared with tap water witho...

Despite the abundance of aluminum (Al) in nature, it has no known biological function in humans. On the contrary, wide ranges of toxic effects of Al to hundreds of cellular processes both in man and animals have been demonstrated in plants and aquatic animals in nature, experimental animals by several routes of exposure, and under different clinica...

Colloidal bismuth subcitrate (CBS), a drug for treatment of peptic ulcers, has been reported in the literature to be nephrotoxic in humans when taken in high overdoses. To investigate the mechanism of bismuth nephropathy, we developed an animal model by feeding rats single doses of CBS containing 3.0 mmol Bi/kg body weight. Terminal deoxyribonucleo...

The nephrotoxicity of single high doses of bismuth (Bi)-containing therapeutic drugs is characterized morphologically by detachment of proximal tubular epithelial cells (PTECs) from each other, followed by cell death. We investigated whether Bi nephrotoxicity is mediated by changes in the distribution of proteins involved in intercellular adhesion....

In Curaçao, distilled seawater from the water plant was used without further purification for hemodialysis for several decades. A new distribution pipe supplying water to a dialysis center on the island was installed in May 1996. To protect it from corrosion, this pipe was lined on the inside with a cement mortar. Because of the aggressiveness of t...

Overdosing of colloidal bismuth subcitrate (CBS), used to treat peptic ulcers and Helicobacter pylori infections, has been reported to result in serious, though reversible, nephrotoxicity in humans. However, little is known about the nature of the renal damage induced by bismuth (Bi), and no well-described experimental model exists. Single large or...

Bismuth induced nephrotoxicity has been reported to occur after acute overdoses of Bi-containing therapeutic drugs. We studied the development of bismuth induced nephropathy and bismuth biokinetics in rats. Bismuth nephropathy was induced in 33 young adult female Wistar rats weighing ca. 175 g by feeding them a single overdose of colloidal bismuth...

The role of fluoride in aluminium neurotoxicity was studied using an in vitro system of cultured hippocampal neurons from foetal rats. Sodium fluoride (50 microM) and aluminium chloride (12.5 microM) were administered alone or in a specific combination (50 + 12.5 microM) in a 14-day culture in a chemically defined medium before staining of neurofil...

Arsenic compounds continue to be used as therapeutic agents, being old drugs for new indications, such as various categories of leukemia. Their use to treat acute promyelocytic leukemia is recent and is indicated when resistance develops against first line treatment with all-trans retinoic acid. Bismuth remains a part of some regimens for the eradi...

Suriname is experiencing a revival of small scale gold mining activities, with about 10,000 to 15,000 workers involved in 1996. The estimated production in 1995 is at least 10,000 kg crude gold. Gold is extracted with mercury and methods used are comparable with those described for gold mining in the Amazon Basin. Since no data exist on the interna...

Two groups of 12 human volunteers, who had been treated with colloidal bismuth subcitrate, because of Helicobacter pylori-associated gastritis, participated in the study. The patients received a single dose of meso-2,3-dimercaptosuccinic acid (DMSA) or D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS) at a dose of 30 mg kg-1 in a randomized single b...

Aluminum (Al) is recognized as a toxin in patients with deficient renal function. Moreover, Al may play a role in some neurodegenerative diseases. It is hypothesized that more than one intestinal absorption mechanism exists for Al, related to various intraluminal chemical species, and that Al shares intestinal transport routes for essential inorgan...

Aluminium is produced from the mineral bauxite. Occupational exposure is reported during the industrial processing of aluminium and is associated with pulmonary and neurotoxicity. However, data on exposure and toxicity of workers in the open bauxite mining industry do not exist. Therefore, a study was performed to explore aluminium exposure in empl...

The detection of low levels of iron overload by magnetic resonance imaging. Eight consecutive patients suspected of having idiopathic haemochromatosis. Comparison of signal intensity ratios and absolute iron content of liver. There was a good correlation between the signal intensity ratios and iron content in the range 2-30 micrograms Fe/mg dry wei...

Evaluation of the amount of bismuth (Bi) absorbed from the gastrointestinal tract is important for assessment of the possible risks associated with the use of Bi compounds in the treatment of gastrointestinal disorders. We compared the absorption of Bi from media containing the equivalent of 1 g of elemental Bi from either Bi subnitrate (BSN), Bi s...

Deposition of aluminum in the body is responsible for the development of dialysis-related diseases in patients with renal dysfunction and may play a role in the development of certain neurodegenerative disorders. Although citric acid is known to be a strong enhancer of gastrointestinal absorption of aluminum, its effect on aluminum distribution and...

Aluminum (Al) has been observed to cause neurofilament protein accumulation in both experimental animals and cultured cells. Impairment of axonal transport is thought to be a mechanism of toxicity. Inhibition of the degradation of neurofilament proteins, however, resulting in accumulation of these proteins may be an alternative mechanism for Al tox...

Aluminium (Al) accumulation occurs in the liver of renal patients and in patients on parenteral nutrition. Human hepatotoxicity is not proven. The role of the liver in storage and biotransformation of Al and in development of osteo- and neurotoxicity is not clarified as yet. The aim of the present investigation was to study the storage of Al in tot...

The intestinal absorption of aluminium can contribute significantly to systemic exposure to this element. Aluminium can be absorbed not only from oral pharmaceuticals but also from solid food and drinking water. The absorption process is not restricted to patients with kidney disorders; other groups of patients and healthy subjects are not excluded...

Bismuth-containing medicines have been used for years, but there is a lack of clinically applicable methods for measuring bismuth in body fluids. We describe a sensitive, accurate and precise method for analysis of bismuth in blood and serum, which is suitable both for monitoring purposes and for further investigations into the biokinetics and safe...

Doses of 4-6 mg kg-1 c-DDP given 6 months before renal irradiation caused only a modest increase in functional radiation damage (DEF 1.1). These effects could be explained by additive toxicities and the damage was much less than when c-DDP was given 3-6 months after irradiation. Pharmacokinetic studies did not demonstrate any decrease in the rate o...

A two-year-old male Barsoi dog was presented after a two-week period of muscle twitching and convulsions during exercise, which worsened to a state of tetraparesis and coma. Removal of a gastric foreign body, containing aluminium, resolved the presenting signs. Parallel with this clinical recovery the elevated serum levels of aluminium decreased to...

The binding of aluminium in rat serum was studied. Rats were loaded intraperitoneally with different doses of aluminium(III)chloride 4 times during one week, before being killed by cardiac puncture. One ml of serum was applied to a Sephacryl S-200 SF column and 70 fractions were collected. In the collected fractions, the distribution of aluminium w...

To improve the accuracy and precision of the assay of aluminum in brain tissue, we modified for application to brain samples from rats and humans the wet-digestion method of Trapp et al. (Biol Psychiatry 1978; 13:709-18), established the contribution of contamination, and examined the effect of precipitation of nonoxidizable fatty residues on the a...

To improve the accuracy and precision of the assay of aluminum in brain tissue, we modified for application to brain samples from rats and humans the wet-digestion method of Trapp et al. (Biol Psychiatry 1978; 13:709-18), established the contribution of contamination, and examined the effect of precipitation of nonoxidizable fatty residues on the a...

The effect of aluminum (Al) was studied in an in vitro system of cultured hippocampal neurons from fetal rats in a chemically defined medium. Neuronal aggregates interconnected by neurites were detected light and electron microscopically in control and Al-treated cultures. In the Al-treated cultures disruptions of the fibers were observed proximal...

The effects of citric acid and dinitrophenol on the mucosal uptake of aluminum (Al) and its appearance in the portal and systemic blood were investigated to establish the energy dependence of these processes. Therefore, the rat small intestine was perfused in situ with media containing 20 mmol Al/liter, with or without 5 mmol citric acid/liter, and...

In a group of 19 rheumatoid arthritis (RA) patients with normal renal function, serum levels of aluminium (A1S) were monitored during treatment with drugs containing this metal (Al). The A1S levels during treatment were significantly higher (0.005>p>0.01) than those before treatment, i.e. 19.4 (SEM 2.3)μg/1 and 12.3 (1.7), respectively. This increa...

To investigate the association of serum copper and zinc with mortality from cancer and cardiovascular disease, the authors performed a case-control analysis of data obtained in a Dutch prospective follow-up study. Cancer (n = 64) and cardiovascular disease (n = 62) deaths and their matched controls were taken from a cohort of 10,532 persons examine...

The effect of iron (Fe) on the intestinal absorption of aluminum (A1) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The gut was perfused with media containing 0.0, 10.0, 15.0, 20.0, and 25.0 mmol/liter Al chloride and 5 mmol/liter Fe(II) or Fe(III) chloride at pH 3.0. Neith...

Aluminium (AlS) and zinc (ZnS) concentrations in serum were measured in patients with rheumatoid arthritis (RA) with and without Al-containing drugs and compared with levels in healthy controls. In RA patients without Al-containing antacids, the AlS levels did not differ from those of the healthy controls (mean 9.9, SEM 0.9 microgram/l and mean 8.6...

To study the mechanism of intestinal aluminium (Al) absorption, an experimental investigation into the uptake of Al from the rat gut was undertaken. The small intestine was perfused in situ for 60 min with isotonic media containing 4.63, 9.25, and 18.50 mmol/l Al chloride at pH 4.0 and 7.0. Portal and systemic blood were sampled and analysed for it...

During the past decade, aluminium (Al) has been shown to possess a potential for systemic toxicity. Renal patients form a high-risk group for Al poisoning, and biological monitoring is indicated to diagnose and prevent toxicity. Electrothermal atomic absorption spectrometry is the analytical method of choice for measuring Al levels. Special precaut...

The intestinal absorption of aluminum (Al) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The jejunum-ileum was perfused with media containing 4.63, 9.25 and 18.50 mmol l-1 Al chloride at pH 4.0 and 7.0. Both mucosal retention was not affected by pH but at lower pH more Al w...

The intestinal absorption of aluminium (Al) from the antacid hydrotalcite (UltacitR) was compared with that from algeldrate (Algeldratum des-acidans) in 8 healthy human subjects in a crossover study. The level of Al in serum (AlS) was increased in 7 out of 8 subjects 7 hr after intake of 6 g algeldrate while AlS did not rise after intake of 8 g hyd...

1 It is common use to monitor body burdens of toxic trace metals by measuring concentrations in whole blood. To monitor aluminium (Al) body burden in renal patients on haemodialysis, which is a high-risk group for Al poisoning, the concentrations of Al in plasma (AIP) or serum (AlS) are determined rather than Al in whole blood (AlB). 2 To evaluate...

The antibacterial efficacy of azlocillin against Pseudomonas aeruginosa was quantitatively assessed in short-term growth curves in vitro and in a short-term thigh muscle infection in granulocytopenic mice. Ticarcillin was used as the reference drug. The antibacterial effect in vitro was expressed as the difference between the logarithms of the num...

A simple, time-saving procedure to measure aluminum (AI) in whole blood, plasma, and water samples of low ionic strength by flameless atomic absorption spectrometry is presented. With this procedure, an analagous pretreatment is given to all samples. Moreover, the pretreated samples are analyzed using an identical program of the atomic absorption s...

To study the mechanism of intestinal aluminium (Al) absorption, an experimental investigation into the uptake of Al from the rat gut was undertaken. The small intestine was perfused in situ for 60 min with isotonic media containing 4.63, 9.25, and 18.50 mmol/l Al chloride at pH 4.0 and 7.0. Portal and systemic blood were sampled and analysed for it...

Aluminium (Al) intoxication in dialysis patients is held to be caused not only by Al in the dialysis fluid but also by Al from orally administered phosphate binders. Studies on Al absorption in patients and healthy individuals as well as in animals are still scarce, and do not provide sufficient data to characterize the absorption process. This pap...

We are presenting a quantitative determination of the effect of granulocytes, monocytes and lymphocytes on the course of infection during antibiotic treatment. The animal model was a short-term infection of the thigh muscle in normal or irradiated mice. Two kinds of antibiotics were used: tobramycin for Pseudomonas aeruginosa infections and ampicil...

The antibacterial activity of mecillinam and ampicillin, alone and in combination, against Escherichia coli was quantitated and compared in vitro and in vivo. Minimum inhibitory concentrations (MICs) were determined for both antibiotics individually and combined. Two-hour growth curves were established in vitro. A quadratic fit to these growth curv...

The ampicillin susceptibility of Escherichia coli showing morphological changes after pretreatment with low concentrations of mecillinam (spherical forms) or ampicillin (filaments) was compared in vitro and in vivo in short term experiments. Normal non-pretreated bacteria and mecillinam- or ampicillin-pretreated bacteria were cultured in vitro in t...

The relative antibacterial efficacy of amoxycillin ampicillin was compared in vitro and in vivo against a strain of Escherichia coli in short-term experiments (hours). The quadratic fit to the growth curves in vitro in the presence of the antibiotic gave concentration dependent parameters. The concentration effect curves for both antibiotics showed...

To quantify the relative antibacterial efficacy of beta-lactam antibiotics in vitro, a mathematical description of bacterial growth was developed. Curves of growth in the presence of the antibiotic are expressed as quadratic functions of time, with initial growth rate (ko) and rate of change of growth (a) as concentration dependant variables. For t...

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