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Biomedical subjects

L Dencker

Publications and source records attributed to L Dencker.

At least 55 records · Page 3Linked to original sources
PubMed1986

Distribution of tungstate in pregnant mice and effects on embryonic cells in vitro.

Whole-body autoradiography and impulse counting experiments were used to study the distribution and retention of radioactivity in the pregnant mouse after administration of [185W]tungstate. A rapid uptake was found in a number of tissues--skeleton, red pulp of the spleen, adrenal, liver, thyroid, pituitary, and ovary--and in the intestine and kidneys, through which it was rapidly excreted. 185W was also readily transported from mother to fetus, although more in late than in early gestation. The largest metal retention was found in the maternal skeleton, kidneys, and spleen and in the visceral yolk sac epithelium and the skeleton of the fetus. Furthermore, in vitro cytotoxicity experiments showed inhibition by tungstate of cartilage production in limb bud mesenchymal cultures at concentrations similar to those found in vivo.

Animals↗
PubMed1986

Trichloroacetic acid accumulates in murine amniotic fluid after tri- and tetrachloroethylene inhalation.

The distribution of trichloroethylene (Tri) and tetrachloroethylene (Tetra) and their metabolites have been studied in pregnant mice by means of whole-body autoradiography (14C-labelled Tri and Tetra) and gas chromatography, with special emphasis on possible uptake and retention in the foetoplacental unit. Volatile (non-metabolized) activity appeared at short intervals after a 10 min. or 1 hr inhalation period in foetus and amniotic fluid. Most notable, however, was a strong accumulation and retention (peak at 4 hrs) in amniotic fluid of the metabolite trichloroacetic acid (TCA) after inhalation of either of the solvents. The main metabolite of Tri, trichloroethanol (TCE) (or conjugates), did not accumulate specifically as compared to maternal plasma. TCA infused intravenously in the maternal plasma was accumulated in amniotic fluid, but less pronounced than after Tri and Tetra inhalation, indicating that some metabolism of Tri and Tetra to TCA may occur in the foetoplacental unit. The results suggest that TCA may be transported to the foetus partly paraplacentally through foetal membranes and amniotic fluid, with the possibility of foetal swallowing or absorption through the skin. Foetal urinary activity also suggests that circulation between foetus and amniotic fluid may contribute to the long-term retention in the foetoplacental unit. In the mother, after inhalation exposures, and in intraperitoneally injected newborn mice, non-extractable radioactivity was found in the respiratory tract, liver, and kidney, indicating binding to these organs through metabolism.

Amniotic Fluid↗
PubMed1986

Distribution of halothane and the metabolites trifluoroacetic acid and bromide in the conceptus after halothane inhalation by pregnant mice.

Mice in late stage of gestation were exposed to halothane at various concentrations for 1 hr, and were killed at different time intervals after discontinuance of inhalation. The concentration of halothane in maternal plasma decreased rapidly, and in the amniotic fluid the halothane never reached more than 20% of maternal plasma levels. Trifluoroacetic acid (TFA) and bromide, formed mainly by maternal metabolism of halothane, accumulated in foetus and amniotic fluid with time, and reached plateau levels in amniotic fluid between 4 and 24 hrs. TFA infused intravenously to the mother reached higher levels in amniotic fluid after long survival times, than in maternal plasma. Equilibrium dialysis experiments showed that TFA and trichloroacetic acid (TCA) (previously shown to accumulate in amniotic fluid) were bound to amniotic fluid macromolecules only to approximately 20-30 percent. This was at the same magnitude (or lower) as compared to binding in maternal plasma, suggesting that such binding did not contribute to the observed retention in the amniotic fluid. Other possible explanations for the slow accumulation and long-term retention in amniotic fluid are transport by bulk flow via foetus, excretion via foetal urine, or paraplacentally through endometrium and foetal membranes, followed by trapping in the amniotic fluid. The significance of this accumulation of metabolites of halogenated organic solvents and halothane for their foetotoxicity is not clear.

Amniotic Fluid↗
PubMed1986

Renal handling and effects of [3H]digoxin and interactions with quinidine in the avian kidney.

Renal handling and effects of tritium digoxin and interactions with quinidine in the avian kidney were studied using a modified Sperber technique. Results showed that tritium digoxin was extracted at the peritubular side of the nephron in a process competitively inhibited by increasing amounts of unlabelled digoxin. Light microscope autoradiography showed distinct concentrations of silver grains only over distal tubules in the injected kidney. Inhibition of the proximal tubular transport systems for organic anions and cations, respectively, did not change extraction. Addition of quinidine to the injection solution up to an estimated concentration of 1.4 X 10(-5) M in systemic blood significantly lowered 1 min peritubular extraction of tritium digoxin. However, when the amount of quinidine was further increased, extraction of tritium digoxin augmented significantly. Tritium recovery in urine after renal portal bolus injection of tritiated and unlabelled digoxin already showed a distinct ipsilateral peak 2 min after injection with an equally distinct peak of ipsilateral sodium excretion appearing 1 min later. When quinidine was added to the bolus ipsilateral tritium recovery in urine (0-7 min) was halved, with the true tubular excretion fraction (TTEF) lowered by two-thirds, but without changes in the magnitude of ipsilateral natriuresis. Contralateral natriuresis increased more than four-fold with quinidine in the bolus in spite of unchanged tritium recovery in the urine. Thus, our results show tritium digoxin to be extracted from peritubular blood through a specific process probably localized to the distal nephron of the avian kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

3,3',4,4'-tetrachloro[14C]biphenyl in pregnant mice: enrichment of phenol and methyl sulphone metabolites in late gestational fetuses.

The distribution of radioactivity after injection of 3,3',4,4'-tetrachloro[14C]biphenyl (14C-TCB) in pregnant mice was determined by autoradiography and computer-assisted densitometric analysis. TCB metabolites in fetal tissue were analysed by g.l.c. and g.l.c.-mass spectrometry and compared to the synthesized reference compounds 2-, 5- and 6-methoxy-3,3',4,4'-tetrachlorobiphenyl. The concentration of radioactivity was high in the uterine fluid, and in the fetuses in late gestation. Fetal radioactivity decreased after pretreatment with a high dose of unlabelled TCB. Radioactivity was reversibly bound to fetal tissues. A phenolic metabolite, 3,3',4,4'-tetrachloro-2-biphenylol, and a methylsulphonyl-tetrachlorobiphenyl were found in fetuses in late gestation. No unmetabolized TCB was detected in the fetuses.

Animals↗
PubMed1986

Distribution of chloroform and methyl chloroform and their metabolites in pregnant mice.

The distribution of radioactivity in pregnant mice was registered at different time intervals (0-24 h) after a 10-min period of inhalation of 14C-labelled chloroform and methyl chloroform. Autoradiographic and liquid scintillation methods were used to make possible the distinction between volatile (non-metabolized), water-soluble and firmly tissue-bound radioactivity. Methyl chloroform was retained longer in fat as compared to chloroform. Metabolites of chloroform were present in a much greater abundance than those of methyl chloroform and they were found preferentially in the respiratory tract (nasal mucosa, trachea and bronchi), liver and excretory organs. Tissue-bound activity after chloroform inhalation or i.p. injection to newborn mice was found in the respiratory tract and centrilobular areas of the liver. Volatile radioactivity was observed in the placenta and fetuses at short time intervals after inhalation of both chloroform and methyl chloroform at all stages of gestation. While a low level of radioactive metabolites of methyl chloroform was observed in the fetoplacental unit, metabolites of chloroform accumulated with time. This fact was especially marked in the amniotic fluid, where the peak level of radioactivity was observed at 4 h. In early gestation, metabolites accumulated in the embryonic neural tissues. Tissue-bound metabolites of chloroform were observed in the fetal respiratory epithelium in late gestation, indicating a capacity for drug metabolism in these cells in the late fetal period.

Animals↗
PubMed1985

The role of receptors in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity.

There is good evidence that the Ah-(TCDD-) receptor plays a role in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its congeners. TCDD and other chlorinated aromatic hydrocarbons with chlorine atoms in lateral positions (2,3,7,8-tetrachlorodibenzofuran, 3,3',4,4'-tetrachloroazoxybenzene, 3,3',4,4'(5,5')-tetra(hexa)chlorobiphenyl), all bind to the receptor and show a similar pattern of toxicity, although there is a wide range in potency. The Ah-receptor is viewed as the major product of the regulatory gene of the Ah-locus in the mouse. Several of the toxicities of TCDD and congeners (teratogenesis, thymic involution and hepatic porphyria) have been shown to segregate with the Ah-locus. In vitro studies using keratinizing cells or fetal thymus organ culture have shown a good correlation between activity as ligands of the receptor and toxicity for the compounds discussed. The great differences in toxic potency of these compounds in vivo may therefore be a result of variation in rate of metabolism and excretion rather than differences in affinity for the Ah-receptor. The physiological role of the Ah-receptor is discussed, whether it has developed as a response to exposure to toxic substances in the environment, as a means of induction of P-450-dependent polysubstrate mono-oxygenase activities in order to make those substances more liable for excretion--or is there a physiological ligand? TCDD has a long half-life in the body, and a sustained competition for binding to the receptor between TCDD and a ligand of importance for normal cell functions may result in toxicities such as the wasting syndrome. This tentative ligand could be of varying importance in different species, which might explain the great variation in sensitivity between species, the hamster being about 5000 times less sensitive than the guinea pig.

Abnormalities, Drug-Induced↗
PubMed1985

Appearance of different lymphoid cells in synovial tissue and in peripheral blood during the course of collagen II-induced arthritis in rats.

The involvement of different sets of lymphoid cells in the development of collagen II-induced arthritis in rats was studied by means of immunohistochemical analyses on frozen sections of tissue from joint biopsy specimens taken at different phases of arthritis development. Particular attention was paid to cells involved in early pannus formation. Accumulation of anti-Ia-reactive cells close to the cartilage surface was seen early in the development of pannus, and the anti-Ia reactive cells could in later phases be seen infiltrating cartilage and crowding bone surfaces at sites of marginal erosion. With the help of monoclonal anti-T-cell subset antibodies and rabbit anti-rat immunoglobulin antiserum, it was demonstrated that synovial infiltration of T lymphocytes, particularly W3/25-reactive T "helper" cells, occurs very early in the development of arthritis, whereas a moderate increase of Ox 8-positive 'suppressor/cytotoxic' T cells and a small number of B cells and plasma cells are seen later in the course of the disease. Levels of Ia-expressing cells and of T cells belonging to different subsets were recorded in peripheral blood by means of immunocytochemical analyses on cell smears; no significant deviations from normal levels were seen during the development of arthritis.

Animals↗
PubMed1985

Distribution of 64Cu in foetal and adult tissues in mice: influence of sodium diethyldithiocarbamate treatment.

64Cu (as 64CuCl2) was given intravenously to male C57BL mice and to pregnant C57BL mice at various stages of gestation. The disposition of the 64Cu in the adult animals and in the foetuses was studied by autoradiography and gamma spectrometry. The effects of treatments with diethyldithiocarbamate (DEDTC) on the disposition of the 64Cu in the animals were also examined. In addition, the ability of Cu to affect chondrogenesis was studied in an embryonic limb bud culture system. The results showed a strong uptake of 64Cu in the liver of the adult animals at all intervals (5 min.-24 hrs). At short survival intervals, there was also an uptake in the kidney cortex, the gastrointestinal mucosa, the adrenal, the pancreas, and the erythrocytes. Exposure to Cu may cause liver and kidney injuries, which may be related to the strong accumulation in these organs. 64Cu passed the placenta to the foetuses at all stages of gestation, although this occurred at a relatively slow rate. Within the foetuses the highest concentrations were found in the liver. Cu was observed to be toxic in the chick limb bud mesenchymal spot culture system although at relatively high concentrations. Foetal malformations and embryotoxicity may therefore be interpreted as a result of direct action of Cu on embryonic structures, although placental and/or maternal influence cannot be excluded. Pre- or posttreatment of the animals with DEDTC, which is a chelating agent, caused a very marked increase in the concentration of 64Cu in most tissues of the adult animals and also an increased foetal uptake of the metal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

In vivo treatment with W3/13 (anti-pan T) but not with OX8 (anti-suppressor/cytotoxic T) monoclonal antibodies impedes the development of adjuvant arthritis in rats.

The involvement of phenotypically defined cells in the pathogenesis of adjuvant arthritis in rats has been investigated in two different ways. Firstly, immunohistochemical methods have been used to characterize the cellular composition of the arthritic synovial tissue, in particular the pannus tissue close to the destroyed cartilage. It is shown that T-helper lymphocytes dominate the lymphoid infiltrates, and that large numbers of cells expressing Ia are present in the pannus. Secondly, different anti-T cell monoclonal antibodies have been injected into rats in vivo and disease course and phenotypes of synovial cells investigated after different types of treatment. It is shown that the injection of W3/13 (anti-pan T-cell antibodies) delays the development of adjuvant arthritis, whereas a complete elimination of the suppressor/cytotoxic T-cell subset after injection of OX8 antibodies does not affect the disease course.

Animals↗
PubMed1985

Renal handling of 125I-labelled insulin in the hen.

Renal handling of 125I-insulin was studied using a modification of the Sperber technique. Results showed 125I-insulin to be extracted at the peritubular side of the nephron in a process that was competitively inhibited by increasing amounts of unlabelled insulin, but not ACTH, in the injection mixture. When unlabelled insulin instead was injected 30 sec after the labelled insulin it showed significantly less interference with peritubular extraction of 125I-insulin, indicating strong attachment to the cell membrane or possible internalization of 125I-insulin into proximal tubular cells. Light microscope autoradiography 1 min after injection of 125I-insulin showed grains over proximal tubules only. On the ligated side localization was preferably peritubular while on the control side it was luminal. Electron microscope autoradiography showed sparsely distributed grains, however, frequently located over basal parts of proximal tubular cells. Pretreatment with lysine hydrochloride lowered renal extraction of 125I-insulin and increased urinary recovery of iodine label bilaterally. 125I-glucagon and 125I-C-peptide were not extracted from the peritubular circulation. In conclusion, the model has provided evidence of a rapid and significant peritubular extraction of 125I-insulin by proximal tubular cells in a process probably involving specific insulin receptors. Following receptor binding probably only minor amounts of 125I-insulin enters the proximal tubular cells, while the greater part is degraded at the cell surface or released into the circulation.

Adrenocorticotropic Hormone↗
PubMed1985

Fetal thymus organ culture as an in vitro model for the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

Fetal thymuses from C57BL/6 (B6) and DBA/2J (D2) mice from gestation day 14 or 15 were explanted and grown for 2 and 6 days in culture in the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and a number of its congeners, known ligands of the Ah receptor (Ah, designating genetic locus for aryl hydrocarbon responsiveness). TCDD and 2,3,7,8-tetrachlorodibenzofuran (TCDBF) showed the same toxicity to B6 thymuses with a 50% inhibition of lymphoid development (EC50) at 10(-10) M concentration. 3,3',4,4'-Tetrachloroazoxybenzene (TCAOB) was only 2-10 times less effective, while the EC50 of 3,3',4,4'-tetrachlorobiphenyl (TCB) was around 10(-8) M (100 times higher than that of TCDD). TCBs with chlorine atoms in the position close to the biphenyl bridge were nontoxic even at 10(-5) M concentration. Thymuses exposed to TCDD, TCDBF, and TCAOB in vivo at teratogenic doses given to the mothers and explanted 24-48 hr later were smaller and inhibited in their early in vitro growth, but recovered slowly (less rapid for TCDD) as judged by lymphoid cell counts and [3H]thymidine incorporation. These results indicate a good correlation for this group of compounds between their activity as ligands of the Ah receptor and toxicity in vitro. Other ligands of the Ah receptor, namely 3-methylcholanthrene and beta-naphthoflavone, were inactive at the highest concentrations tested (10(-6) M). Thymuses from D2 mice, considered Ah receptor-defective, were nonsensitive to TCDD at the concentrations used (up to 3 X 10(-8) M) after 2 days in culture, indicating more than 100 times lower sensitivity as compared to B6 thymuses. After 6 days in culture, their sensitivity was however only 1 order of magnitude lower than that of B6 thymuses. Therefore "low sensitivity" of D2 thymuses may be at least partially overcome by prolonged exposure to TCDD in vitro.

Animals↗
PubMed1984

Metabolism of arsenocholine in mice, rats and rabbits.

The distribution, retention and biotransformation of arsenocholine, an organic arsenic compound present in certain seafood, have been studied in rats, mice and rabbits by use of synthesized 73 As-labelled arsenocholine. Orally administered arsenocholine was almost completely absorbed from the gastro-intestinal tract in mice and rats. In all species 70--80% of the administered dose was excreted in the urine within 3 days, [73 As] arsenobetaine was the main urinary metabolite; [73 As] arsenocholine was found in the urine of the first day only. No degradation to inorganic arsenic, mono- or dimethylarsenic acids, or trimethylarsine oxide was observed. In the tissues the 73 As activity retained was found in the form of [73 As] arsenobetaine and [73 As arsenophospholipids. Tissues with longest retention times were prostate, epididymis, testes, myocardium, liver, adrenal cortex, pancreas, dental pulp and pituitary gland.

Animals↗
PubMed1984

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced cleft palate in the mouse: evidence for alterations in palatal shelf fusion.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes a high percentage of cleft palate in fetuses when administered during organogenesis in certain strains of mice including the C57BL/6J, but not in certain other strains (AKR/J). The purpose of the present study was to examine various biochemical and morphological aspects of TCDD-induced changes in the developing palatal shelves. Our results indicate that when TCDD (100 micrograms/kg) was given on individual days between days 8 and 10 of gestation, a high percentage of cleft palate was observed. Receptors specific for TCDD were detected in the C57BL/6J but not AKR/J palatal shelves. The amount of TCDD receptors is highest in the palatal shelves on day 13 as compared to other embryonic tissues including the liver. Examination of cryostat sections taken from embryos during the time of palatal elevation and fusion demonstrated that TCDD does not interfere with growth, elevation, or initial contact of the palatal shelves, but does interfere with firm adhesion and/or degeneration of the medial epithelial cells. Our results suggest that TCDD exerts a direct effect on the embryonic palatal shelves which results in formation of cleft palate.

Animals↗
PubMed1984

Accumulation of toxic metals in male reproduction organs.

Occupation exposure to metals has been related to impaired reproduction in males. This report summarizes autoradiographic studies on the distribution of cadmium (Cd), chromium (Cr) and arsenic (As) in the testis and epididymis of rodents. Cd and Cr strongly accumulated in the interstitial tissues, indicating an effect on hormone production (Leydig cells) and blood supply or both. Arsenic accumulated in the lumen of the duct of epididymis causing long-term exposure of the semen.

Animals↗
PubMed1984

Teratological studies on the TCDD congener 3,3',4,4'-tetrachloroazoxybenzene in sensitive and nonsensitive mouse strains: evidence for direct effect on embryonic tissues.

The teratogenicity of 3,3',4,4'- tetrachloroazoxybenzene ( TCAOB ), a TCDD congener, was studied in Ah-responsive (C57BL and NMRI) and non-responsive (DBA/2J and AKR/ NBom ) strains of mice. In the responsive strains, the TCAOB produced cleft palate and hydronephrosis in 50-90% of the offspring at a dose level of 6-8 mg/kg b.w. in the absence of apparent maternal toxicity. Day 11 was shown to be the day of highest sensitivity (palatal closure occurs at day 14) in the C57BL strain. Higher doses (16 mg/kg b.w.) produced high rate of fetal death both in responsive (C57BL; 60%) and non-responsive (DBA; 40%) strains. These doses induced cleft palate in 95% of the surviving C57BL fetuses but failed to do so in the DBA strain. The non-sensitivity of the DBA and AKR strains appeared to segregate as a dominant trait. Backcrosses between NMRI X DBA F1 generation and NMRI showed an intermediate sensitivity. It was shown that the genotype of the embryo was of ultimate importance for the development of cleft palate. There appeared however to be an additional host (maternal) factor as well, because the offspring of NMRI females mated with NMRI X DBA F1 males showed a higher rate of cleft palate as compared to those of the crossing between NMRI X DBA F1 females and NMRI males. Light and scanning electron microscopy indicated that the apical epithelial cells of the secondary palates failed to follow the normal pattern of programmed cell death, suggesting a similar mechanism of pathogenesis as previously described for TCDD.

Animals↗