Biomedical subjects

A Brouwer

Publications and source records attributed to A Brouwer.

172 records · Page 10Linked to original sources

PubMedDate not supplied

Uptake and processing of [3H]retinoids in rat liver studied by electron microscopic autoradiography.

The role of rat liver cell organelles in retinoid uptake and processing was studied by electron microscopic autoradiography. [3H]Retinoids were administered either orally, to make an inventory of the cell organelles involved, or intravenously as chylomicron remnant constituents to study retinoid processing by the liver with time. No qualitative differences were observed between the two routes of administration. Time-related changes in the distribution of grains were studied using chylomicron remnant [3H]retinoids. The percentages of grains observed over cells and the space of Disse at 5 and 30 min after administration were, respectively: parenchymal cells, 72.6 and 70.4%; fat-storing cells, 5.0 and 18.1%, and the space of Disse, 14.4 and 8.9%. Low numbers of grains were observed over endothelial and Kupffer cells. The percentages of grains observed over parenchymal cell organelles were, respectively: sinusoidal area, 59.6 and 34.4%; smooth endoplasmic reticulum associated with glycogen, 13.8 and 13.4%; mitochondria, 5.4 and 13.6%; rough endoplasmic reticulum, 4.2 and 7.3%, and rough endoplasmic reticulum associated with mitochondria, 3.7 and 6.5%. It is concluded that chylomicron remnant [3H]retinoids in combination with electron microscopic autoradiography provide a good system to study the liver processing of retinoids in vivo. These results, obtained in the intact liver under physiological conditions, further substantiate that retinoids are processed through parenchymal cells before storage occurs in fat-storing cell lipid droplets, that retinoid uptake is not mediated through lysosomes and that the endoplasmic reticulum is a major organelle in retinoid processing.

Administration, Oral↗

PubMedDate not supplied

Respiratory activities of hepatocytes isolated from rats of various ages. A brief note.

The ratio between the oxygen consumption of isolated hepatocytes in the presence of an inhibitor of oxidative phosphorylation (oligomycin, atractyloside) and in the presence of an uncoupler (dinitrophenol) is used as an estimation of the respiratory control ratio of mitochondria inside the isolated liver parenchymal cell. No significant age-related decline in the functional integrity of the mitochondria could be detected.

Aging↗

PubMedDate not supplied

The reticuloendothelial system and aging: a review.

This review represents an attempt to summarize and evaluate the literature data on the changes occurring in the reticuloendothelial system (RES) during aging. The RES is briefly introduced with emphasis on cellular composition, function, physiology, regulation and the methods employed for assessment of its functions. The age-related changes in the RES are discussed in terms of endocytotic capacity, antimicrobial and antitumor activity and morphology. In addition, the cooperation between the RES and the immune system in the defence of the body against disease agents is discussed in relation to the increased susceptibility to infectious diseases and tumorigenesis in both man and experimental animals during aging.

Aging↗

PubMedDate not supplied

Report of the WHO working group on the assessment of health risks for human infants from exposure to PCDDs, PCDFs and PCBs.

On Nov. 20-22, 1995, a World Health Organization working group consisting of 12 scientific representatives from 6 different countries met to reassess the health risks to infants associated with perinatal exposure to polyhalogenated aromatic hydrocarbons (PHAHs). Following a review of previous WHO/EURO consultations, as part of their comprehensive programme on PCDDs, PCDFs and PCBs, current exposure information and recent experimental and epidemiologic data were discussed. Exposure assessments within the past decade have revealed that in the case of breast milk samples concentrations of PCDDs/DFs and PCBs have shown a continual decline, in certain countries by up to 50%. New experimental data has revealed that a variety of structural, functional and behaviourial alterations can be induced in rodent species following exposure to PHAHs while a Dutch collaborative PCB/dioxin study has illustrated subtle clinical, endocrine and mental/psychomotor development effects can occur in breast fed infants. The provisional conclusions of the working group were: 1) current evidence does not warrant altering the previous WHO recommendation for promotion/support of breast feeding and 2) based on new clinical data which supports the biological plausibility of certain observed experimental observations, continued and enhanced effort should be directed towards identifying and controlling sources of environmental input for these contaminants.

Animals↗

PubMedDate not supplied

Toxicokinetics of an environmentally relevant mixture of dioxin-like PHAHs with or without a non-dioxin-like PCB in a semi-chronic exposure study in female Sprague Dawley rats.

Female Sprague Dawley rats were treated subcutaneously for 20 weeks with an environmentally relevant mixture of dioxin-like PHAHs with (PHAH+) or without (PHAH-) 2,2',4,4',5,5'-hexachlorobiphenyl. The hepatic retention (% of given dose) of the various PHAH congeners differed considerably and in the following order: 2,3,4,7,8-pentachlorodibenzofuran (30.5-43.1%), 3,3',4,4',5-pentachlorobiphenyl (12.8-17.6%), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (6.9-10.8%), 2,3,7,8-tetrachlorodibenzo-p-dioxin (3.2-4.5%), 2,3,3',4,4',5-hexachlorobiphenyl (1.0-1.7%), 2,2',4,4',5,5'-hexachlorobiphenyl (0.5-0.8%) and 2,3',4,4',5-pentachlorobiphenyl (0.2-0.4%). A decrease of the hepatic retention of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF was found at increasing doses of the PHAH+ mixture. 2,2',4,4',5,5'-Hexachlorobiphenyl increased the hepatic retention (1.3-2 times) of all congeners in the PHAH+ group, compared to the TEQ equivalent dosed PHAH- group. No interactions were observed on the ethoxyresorufin-O-deethylase activity.

Animals↗

PubMedDate not supplied

Validation and use of the CALUX-bioassay for the determination of dioxins and PCBs in bovine milk.

There is a strong need for the development of relatively cheap and rapid bioassays for the determination of dioxins and related compounds in food. A newly developed CALUX (Chemical-Activated LUciferase gene eXpression) bioassay was tested for its possible use to determine low levels of dioxins in bovine milk. Data show that this mammalian cell-based test is very sensitive for 2,3,7,8-substituted dioxins and related PCBs, thereby reflecting the relative potencies of these compounds in comparison to TCDD (TEF-values). The limit of detection was about 50 fg of TCDD. Furthermore, the response obtained with a mixture of dioxins was additive, in accordance with the TEF-principle. Milk fat was isolated by centrifugation followed by clean-up of the fat with n-pentane, removal of the fat on a 33% H2SO4 silica column, and determination of Ah receptor agonist activity with the CALUX-bioassay. An equivalent of 67 mg fat was tested per experimental unit, resulting in a limit of quantification around 1 pg i-TEQ/g fat. To investigate the performance of the method, butter fat was cleaned and spiked with a mixture of 17 different 2,3,7,8-substituted PCDD and PCDF congeners at 1, 3, 6, 9, 12 and 15 pg TEQ/g fat, as confirmed by GC/MS. In this concentration range, the method showed a recovery of TEQs around 67% (58-87%). The reproducibility, determined in three independent series showed a CV varying between 4% and 54%, with the exception of the sample spiked at 1 pg i-TEQ (CV 97%). The repeatability determined with the sample spiked at 6 pg i-TEQ/g showed a CV of 10%. Testing of 22 bovine milk samples, taken at different sites in The Netherlands, in the CALUX-assay showed combined dioxin and dioxin-like PCB levels equivalent to 1.6 pg TCDD/g fat (range 0.2-4.6). GC/MS analysis of these samples revealed an average level of 1.7 pg i-TEQ/g fat, varying between 0.5 and 4.7 pg i-TEQ/g fat. All five samples showing a GC/MS determined dioxin content of more than 2 pg i-TEQ/g fat gave a response in the CALUX-assay corresponding to more than 2 pg TCDD/g fat. These data clearly show that the CALUX-bioassay is a promising method for the rapid and low cost screening of dioxins in bovine milk.

Animals↗

PubMedDate not supplied

Characterization in vitro of interaction of human apolipoprotein E-free high density lipoprotein with human hepatocytes.

Characterization of the interaction of iodinated apolipoprotein (apo) E-free high density lipoprotein (HDL) with cultured human hepatocytes provides evidence for a saturable, Ca2(+)-independent, high affinity binding site with an apparent km value of 20 micrograms/ml of apolipoprotein. Nitrated HDL and low density lipoprotein (LDL) did not compete for the binding of HDL, in contrast to very low density lipoprotein (VLDL). It is suggested that VLDL competition is exerted by the presence of apo Cs. Degradation of HDL was relatively low and in some cases not detectable. In cases where degradation was found, inhibitors of the lysosomal pathway of protein degradation had no effect, while LDL degradation was inhibited more than 80%. In the presence of 10 microM of monensin, the cell-association of HDL was unaffected, but the degradation was inhibited by 30%. Under similar conditions, LDL association was inhibited by 40% and LDL degradation, by 90%. Incubation of human hepatocytes with fluorescently labeled HDL (Dil-HDL) revealed (in contrast to Dil-LDL) mainly strong membrane-bound fluorescence and hardly any labeling of small intracellular vesicles. It is concluded that human hepatocytes possess a specific high affinity site for human HDL with recognition properties similar to those described earlier on rat hepatocytes. No evidence that the binding of HDL is actively coupled to uptake and lysosomal degradation could be obtained, indicating that binding of LDL and HDL to human hepatocytes is coupled differently to intracellular pathways.

Ammonium Chloride↗

PubMedDate not supplied

Interactions of persistent environmental organohalogens with the thyroid hormone system: mechanisms and possible consequences for animal and human health.

Several classes of environmental contaminants have been claimed or suggested to possess endocrine-disrupting potency, which may result in reproductive problems and developmental disorders. In this paper the focus is on the multiple and interactive mechanisms of interference of persistent polyhalogenated aromatic hydrocarbons (PHAHs) and their metabolites with the thyroid hormone system. Evidence suggests that pure congeners or mixtures of PHAHs directly interfere with the thyroid gland; with thyroid hormone metabolizing enzymes, such as uridine-diphosphate-glucuronyl transferases (UGTs), iodothyronine deiodinases (IDs), and sulfotransferases (SULTs) in liver and brain; and with the plasma transport system of thyroid hormones in experimental animals and their offspring. Changes in thyroid hormone levels in conjunction with high PHAH exposure was also observed in captive as well as free ranging wildlife species and in humans. Maternal exposure to PHAHs during pregnancy resulted in a considerable fetal transfer of hydroxylated PHAHs, which are known to compete with thyroxine (T4) for plasma transthyretin (TTR) binding sites, and thus may be transported to the fetus with those carrier proteins that normally mediate the delivery of T4 to the fetus. Concomitant changes in thyroid hormone concentrations in plasma and in brain tissue were observed in fetal and neonatal stages of development, when sufficient thyroid hormone levels are essential for normal brain development. Alterations in structural and functional neurochemical parameters, such as glial fibrillary acidic protein (GFAP), synaptophysin, calcineurin, and serotonergic neurotransmitters, were observed in the same offspring up to postnatal day 90. In addition, some changes in locomotor and cognitive indices of behavior were observed in rat offspring, following in utero and lactational exposure to PHAHs. Alterations in thyroid hormone levels and subtle changes in neurobehavioral performance were also observed in human infants exposed in utero and through lactation to relatively high levels of PHAHs. Overall these studies indicate that persistent PHAHs can disrupt the thyroid hormone system at a multitude of interaction sites, which may have a profound impact on normal brain development in experimental animals, wildlife species, and human infants.

Animals↗

PubMedDate not supplied

Kupffer cells and the acute phase response: the effect of aging.

Aging is associated with a significant increase in the susceptibility to scepsis and endotoxin induced shock in both man and experimental animals. In this study, some metabolic, heamodynamic and other pathophysiological factors possibly involved in the increased mortality of aged rats after endotoxin administration were investigated. The results indicate that older rats display an overall decrease in the capacity to maintain homeostasis after endotoxin challenge, which is expressed by severe disregulation of body temperature (hypothermia), glucose metabolism (hypoglycemia), tissue perfusion (fibrinolytic and anti-fibrinolytic factors) and severe tissue damage. Although a slight decrease in the clearance of endotoxin from the circulation was noted in old rats, alterations in the secondary response, evoked by stimulated macrophages and other cells appear to be more important in the age-related increase in susceptibility.

Acute-Phase Reaction↗

PubMedDate not supplied

Long-term alterations in regional brain serotonin metabolism following maternal polychlorinated biphenyl exposure in the rat.

Pregnant Wistar WU rats were administered PCBs (0, 5 or 25 mg Aroclor 1254 per kg body weight) by gavage on day 10 to 16 of gestation. Levels of biogenic amines were measured in the lateral olfactory tract, prefrontal cortex, striatum, hippocampus and hypothalamus in male and female offspring 21 and 90 days after birth. 5-Hydroxyindole acetic acid (5-HIAA) concentrations and the ratio of 5-HIAA/5-hydroxytryptamine (5-HT, serotonin) were significantly increased in the lateral olfactory tract, prefrontal cortex and hippocampus on postnatal day 90 in male and female offspring following maternal PCB treatment. No effects were observed on regional brain levels of dopamine, 3,4-dihydroxyphenylacetic acid, norepinephrine and homovanillic acid. The results indicate that pre- and postnatal exposure to Aroclor 1254 results in regionally specific long-term alterations in the serotonergic system.

Animals↗