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Biomedical subjects

L Dencker

Publications and source records attributed to L Dencker.

102 records · Page 6Linked to original sources
PubMed1976

Uptake of 14C-labelled chloroquine and an 125I-labelled chloroquine analogue in some polypeptide hormone producing cell systems.

After the injection of 14C-labelled chloroquine and the 125I-labelled chloroquine analogue 4-(31-dimethylaminopropylamino)-7-iodoquinoline [125I]DAPQ into mice, rats and a monkey the distribution of the radioactivity was studied by autoradiographical methods. A high and persistent uptake occurred in some endocrine cell systems, such as the pancreatic islets, the hypophysis, the adrenal medulla and the thyroid (in cells that were probably identical with the parafollicular cells). The melanin-containing tissues were the only ones which showed a higher uptake and retention of radioactivity. The above mentioned endocrine cells and the melanocytes have a common embryological origin and common morphological and cytochemical characteristics. They have been called the APUD (Amine Precursor Uptake and Decarboxylation)-cell series. It is proposed that the polypeptide hormone producing cells and the melanocytes may use a similar mechanism for accumulating chloroquine and (as shown earlier) also some other drugs such as nicotine, alprenolol, local anesthetics and atropine. These drugs however, accumulate stronger within the melanocytes and become bound to the melanin for a long time. The ability to accumulate these drugs may be considered another characteristic of the APUD-cell series.

Adrenal Medulla↗
PubMed1975

Distribution of labeled chloroquine in the inner ear.

Autoradiography of the inner ear was performed at varying intervals following intravenous injection of either chloroquine tagged with carbon 14 (14C), or an iodine 125 (125l)-labeled analogue of chloroquine, in rats. In pigmented rats a strong accumulation and retention was noted in the melanin-bearing tissues. In the inner ear there was a very high concentration in the melanin-containing tissues, eg, the stria vascularis and the planum semilunatum. A strong retention was found in these structures 13 days after injection. Accumulation was not observed in the endolymph nor in the perilymph. No accumulation was found in the inner ear of an albino rat. The ototoxic effects of chloroquine may be caused by an accumulation of the drug in the melanin-containing structures in the inner ear, leading to pathological changes in these tissues and secondary lesions in the receptor cells.

Animals↗
PubMed1975

Distribution of an 125I-labelled chloroquine analogue in a pregnant macaca monkey.

Whole body autoradiography of a pregnant monkey (Macaca irus) of late gestation was performed 72 h after an intravenous injection of the 125I-labelled chloroquine analogue 4-(3-dimethylaminopropylamino)-7-iodoquinoline (DAPQ). The overall distribution pattern in the monkey was similar to that which was earlier observed in rodents. A few species differences, however, were found in the monkey as compared to the rodents: a high accumulation in the inner part of the adrenal cortex, a high level in the central nervous system, and generally a higher retention in the tissues. The accumulation in the adrenal cortex may be of significance for the cortisone-like effects of the 4-aminoquinolines in rheumatoid arthritis and allied conditions. The fact that no accumulation was found in the adrenal cortex of mice and rats indicates that these species may not be appropriate in studies on the mechanisms involved in the anti-inflammatory action of the 4-aminoquinolines. As was earlier observed in small rodents the melanin containing structures accumulated the drug. In both the mother and the fetus a high concentration was thus seen in the uveal tract of the eye, in the inner ear (in the stria vascularis of the cochlea and the planum semilunatum of the ampullae) and in the hair follicles. This accumulation can be related to reported disturbances--also transplacentally induced--in vision and hearing.

Animals↗
PubMed1975

Studies on the renal uptake of vitamin D3 in the mouse and the quail.

The renal uptake of labelled vitamin D3 was studied in the mouse and the quail. Upon the administration of labelled vitamin D3 autoradiographic experiments showed a specific accumulation of radioactivity in the proximal tubuli of the mouse kidney. This was still obvious 18 days after the administration. In the quail, on the other hand, the uptake in the kidney did not exceed the level of the blood. In the mouse there was a slow increase in the amount of steriod in the kidney after the injection of vitamin D3, a maximum being reached 24 hours after the administration. The amount of steroid which accumulated in the kidney was largely proportional to the injected dose of the vitamin-from doses at 4.8 ng to 4.8 mug. Column chromatography showed that most of the renal vitamin D3, was present in a non-metabolized form. Cellular fractionation showed that most radioactivity in the kidney was present in the mitochondrial and microsomal fractions. Upon sonication of the fractions most radioactivity was still bound to these particles.

Animals↗
PubMed1975

Possible mechanisms of cadmium fetotoxicity in golden hamsters and mice: uptake by the embryo, placenta and ovary.

Pregnant golden hamsters and mice of different gestational ages were injected intravenously with 109CdCl(2). The whole animal or the uterus and embryos were submitted to autoradiography. Cadmium administered on the 8th day accumulated in the primitive gut of the embryos. No cadmium was detected in the embryos after administration on or after the 9th day (hamster) and 11th day (mouse). This finding can be explained by the ability of cadmium to pass from the yolk-sac cavity into the primitive gut (where it is absorbed) before the closure of the vitelline duct but not later. This uptake by the embryo might explain the severe malformations produced by cadmium given on the 8th day as compared with the 9th day in the hamster. Cadmium is also heavily accumulated in the decidua (mainly the antimesometrial part), the yolk sac, the ectoplacental cone, and later in the chorioallantoic placenta-possibly disturbing the maternal-embryonic relationship and fetal nutrition. A high accumulation in the CL and the follicles and in the pituitary may also disturb reproductive function.

Animals↗
PubMedDate not supplied

Behavioural effects of prenatal metallic mercury inhalation exposure in rats.

The effects of administration by inhalation of metallic mercury vapour (Hg0) to pregnant rats, approximately corresponding to doses of 0.2 mg Hg0/kg/day (high dose) or 0.07 mg Hg0/kg/day (low dose), on the developmental and behavioural repertoire of the offspring were studied. Exposure occurred during days 11-14 plus 17-20 of gestation. The dose levels were selected so as not to induce maternal toxicity. Maturation variables such as surface righting, negative geotaxis, pinna unfolding, and tooth eruption revealed no differences between Hg0-treated offspring and controls. Tests of spontaneous motor activity showed that the Hg0-treated offspring were hypoactive at 3 months of age but hyperactive at 14 months. In spatial learning tasks the prenatally exposed offspring showed retarded acquisition in the radial arm maze but no differences in circular swim maze. A simple test of learning, habituation to a novel environment (activity chambers), indicated a reduced ability to adapt. These data suggest that prenatal exposure to Hg0 vapour results in similar behaviour changes in the offspring as reported for methylmercury.

Administration, Inhalation↗
PubMedDate not supplied

Prenatal coexposure to metallic mercury vapour and methylmercury produce interactive behavioural changes in adult rats.

Pregnant rats were 1) administered methyl mercury (MeHg) by gavage, 2 mg/kg/day during days 6-9 of gestation, 2) exposed by inhalation to metallic mercury (Hg degrees) vapour (1.8 mg/m3 air for 1.5 h per day) during gestation days 14-19, 3) exposed to both MeHg by gavage and Hg degrees vapour by inhalation (MeHg + Hg degrees), or 4) were given combined vehicle administration for each of the two treatments (control). The inhalation regimen corresponded to an approximate dose of 0.1 mg Hg degrees/kg/day. Clinical observations and developmental markers up to weaning showed no differences between any of the groups. Testing of behavioural function was performed between 4 and 5 months of age and included spontaneous motor activity, spatial learning in a circular bath, and instrumental maze learning for food reward. Offspring of dams exposed to Hg degrees showed hyperactivity in the motor activity test chambers over all three parameters: locomotion, rearing and total activity; this effect was potentiated in the animals of the MeHg + Hg degrees group. In the swim maze test, the MeHg + Hg degrees and Hg degrees groups evidenced longer latencies to reach a submerged platform, which they had learned to mount the day before, compared to either the control or MeHg groups. In the modified, enclosed radial arm maze, both the MeHg + Hg degrees and Hg degrees groups showed more ambulations and rearings in the activity test prior to the learning test. During the learning trial, the same groups (i.e., MeHg + Hg degrees and Hg degrees) showed longer latencies and made more errors in acquiring all eight pellets. Generally, the results indicate that prenatal exposure to Hg degrees causes alterations to both spontaneous and learned behaviours, suggesting some deficit in adaptive functions. Coexposure to MeHg, which by itself did not alter these functions at the dose given in this study, served to significantly aggravate the changes.

Administration, Inhalation↗
PubMedDate not supplied

Placental accumulation of 57Co-vitamin B12 in mice studied by light- and electron-microscopic autoradiography.

Pregnant C57BL mice on day 18 of gestation were injected with 0.114 micrograms cyanocobalamin-57Co and killed either 40 min or 3 h later. Radioactivity measurements showed that the placenta was the organ with the highest concentration. Light- and electron-microscopic autoradiography of the placental labyrinth showed heavy accumulation of radioactivity in the second (middle) trophoblastic cell layer in the barriers between the maternal and fetal circulations. Silver grains were mainly associated with the folded plasma membrane deep in the cytoplasm or with vesicles, indicating a cellular uptake by pinocytosis. The cytosolic accumulations present may be derived from cellular metabolic sites, such as that of protein synthesis.

Animals↗
PubMedDate not supplied

Retinoid binding proteins-expression patterns in the human placenta.

The present study examined the expression and occurrence of different retinoid binding proteins in human first trimester and term placenta. At both stages, messenger RNA for the serum transport vehicle for retinol, retinol-binding protein (RBP), was detected only in decidual cells of the basal plate. In contrast, immunoreactive RBP (irRBP) was present in syncytiotrophoblast, core mesenchyme and lumen of vessels in placental villi and in mesenchyme and decidual cells of the basal plate. In villi of term placentae, however, staining for irRBP was lost in syncytiotrophoblasts and villous core mesenchyme. A putative placental RBP-receptor, approx 60-65kDa, was detected in the villous syncytiotrophoblast of both stages investigated. Immunoreactivity for the cellular retinol binding protein type I (CRBP I), was found in villous stromal cells and in decidual cells of the basal plate in sections of first trimester and term placenta. These results may suggest that maternal RBP-retinol is transferred across the chorionic villi to the fetal/villous circulation and that villous absorption of the complex is mediated via a placental RBP-receptor. Moreover, binding and possibly also metabolism of retinol may occur in the CRBP I positive villous stromal cells and decidual cells of the basal plate. In the latter, release of placental RBP-retinol may also be anticipated.

Allantois↗
PubMedDate not supplied

Retinoid-binding proteins in craniofacial development.

Cephalic neural crest cells are known to form the frontonasal mesenchyme and contribute to the mesenchyme of the visceral arches. Retinoids affect neural crest cells and their derivatives during development, and thus cause craniofacial, thymus, and conotruncal heart malformations. In addition, retinoids induce malformations of the central nervous system (CNS). Retinoic acid (RA) and its congeners accumulate in a saturable manner in neural crest and neural crest-derived cells, in the hindbrain, and the spinal cord of mouse embryos. Cellular retinoic acid-binding protein (CRABP) was localized by immunohistochemistry in the same areas as were the labelled RA congeners. Thus, CRABP and RA congeners were found in the transitional zone between surface ectoderm and neuropeithelium, from where neural crest cells are known to emanate (day 8 1/2). Later, specific labelling was found in the frontonasal mesenchyme and in the visceral arches. Also in the trunk, neural crest cells were labelled. In CNS, strong staining was seen in the rhombomeres (especially numbers 4-6) of the hindbrain and in the spinal cord. Retinol and cellular retinol-binding protein (CRBP) were more evenly distributed, with exception of surface ectoderm, epithelium of gut, and myocardium, where CRBP was specifically expressed. These findings are discussed in relation to the differential expression of nuclear RA receptors and homeobox genes in the craniofacial region and in the hindbrain. It is possible that RA is important for the normal pattern formation in these regions and acts as a morphogen as previously proposed in limb development.

Animals↗