Metabolic alteration in neural tissue of rat embryos exposed to beta-hydroxybutyrate during organogenesis.

Hyperketonemia has been identified as an important factor in diabetic pregnancy affecting growth and development of the offspring. In order to assess the immediate metabolic alterations in embryos caused by excess ketone bodies, we studied rat embryonic neural tissue exposed to a high concentration of beta-hydroxybutyrate in vitro. Beta-hydroxybutyrate inhibited oxygen uptake of the neural tissue of day 9 and day 10 embryos by 12.

Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic rats.

An excess of reactive oxygen species (ROS) has been associated with the increased rate of congenital malformations in experimental diabetic pregnancy. Previous in vitro and in vivo studies show that antioxidants can protect the embryonic development in a diabetic environment. In the present investigation we examined the antiteratogenic capacity of vitamin C, an antioxidative agent not previously evaluated as a dietary supplement in diabetic pregnancy.

The paternal allele of the H19 gene is progressively silenced during early mouse development: the acetylation status of histones may be involved in the generation of variegated expression patterns.

Transcriptional silencing can reflect heritable, epigenetic inactivation of genes, either singly or in groups, during the life-time of an organism. This phenomenon is exemplified by parent-of-origin-specific inactivation events (genomic imprinting) for a subset of mammalian autosomal genes, such as H19. Very little is known, however, about the timing and mechanism(s) of silencing of the paternal H19 allele during mouse development.

Increase of bikunin and alpha1-microglobulin concentrations in urine of rats during pregnancy is due to decreased tubular reabsorption.

Bikunin and alpha1-microglobulin are two plasma proteins of about 25 kDa which are made in the liver from a common precursor. The concentration of bikunin in human urine has been shown to increase several fold during various conditions of stress. The mechanism behind this increase is unknown.

Retinoid binding proteins in mouse yolk sac and chorio-allantoic placentas.

In the adult, as well as in the embryo, a number of specific extra- and intracellular binding proteins such as the plasma retinol binding protein (RBP), the cellular retinol binding protein type I (CRBP I), and also the cellular receptors for RBP are thought to regulate transport and metabolism of retinol (vitamin A). Since the regulation of materno-fetal transport of vitamin A is not well understood, we examined the localization of these proteins during the development of the mouse chorio-allantoic and yolk sac placentas. The labyrinthine region of the chorio-allantoic placenta, where exchange of substances can occur between the maternal and fetal circulations, did not contain RBP (mRNA or protein) or antigen(s) similar to the bovine RBP-receptor p63, whereas the visceral endoderm of the yolk sac placenta, the second site for materno-fetal transport, did.

Vitamin E decreases the occurrence of malformations in the offspring of diabetic rats.

An association between excess oxygen radical activity and disturbed embryogenesis in diabetic pregnancy has been suggested. In the present study, the protective capacity of vitamin E with different treatment regimens was investigated in early and late pregnancy of streptozotocin-induced diabetic rats. Daily gavaging of 0.

[Neurosyphilis 12 years after treatment of primary infection in a meanwhile HIV infected patient].

A 33-year-old male HIV-positive patient developed pure right motor hemiplegia due to meningovascular neurosyphilis. 12 years ago he was successfully treated for early syphilis with a single dose of 2.4 million units penicillin G benzathine without subsequent evidence of new infection or disease progression.

Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia.

The vascular endothelial growth factor (VEGF) family has recently been expanded by the isolation of two additional growth factors, VEGF-B and VEGF-C. Here we compare the regulation of steady-state levels of VEGF, VEGF-B and VEGF-C mRNAs in cultured cells by a variety of stimuli implicated in angiogenesis and endothelial cell physiology. Hypoxia, Ras oncoprotein and mutant p53 tumor suppressor, which are potent inducers of VEGF mRNA did not increase VEGF-B or VEGF-C mRNA levels.

The Swedish Environmental Specimen Bank--application in trend monitoring of mercury and some organohalogenated compounds.

The Environmental Specimen Bank (ESB) at the Swedish Museum of Natural History, Stockholm, constitutes a base for ecotoxicological research as well as for spatial and trend monitoring of contaminants in Swedish fauna. Since the 1960s, tissue samples from more than 150000 organisms have been collected from different groups of animals, habitats and types of landscape. Samples from the ESB have been utilized for retrospective studies of trace elements, organohalogenated compounds and radionuclides.

Detection of Francisella tularensis in ulcers of patients with tularemia by PCR.

The diagnosis of human cases of tularemia is usually confirmed by the demonstration of an antibody response to Francisella tularensis, which occurs about 2 weeks after the onset of disease. Due to a high risk of infection in the laboratory, cultivation of the causative agent tends to be avoided. During an outbreak in Sweden, the use of PCR for diagnosing the ulceroglandular form of tularemia was evaluated.

Purification and characterization of substance P endopeptidase activities in the rat spinal cord.

Two enzymes with substance P degrading activity were purified from the membrane bound fraction of the rat spinal cord. The purified enzymes were characterized with regard to biochemical and kinetic properties. One of the enzymes exhibited close similarity to neutral endopeptidase 24.

In vitro effects of inogatran, a selective low molecular weight thrombin inhibitor.

The thrombin inhibitor inogatran is a synthetic peptidomimetic with a molecular weight of 439 dalton. In vitro studies have shown that inogatran is a classical competitive inhibitor of the active site of thrombin with a Ki of 15 x 10(-9) mol/l. Inogatran doubles the thrombin clotting time in human plasma at 20 x 10(-9) mol/l, APTT at 1.

Altered metabolism and superoxide generation in neural tissue of rat embryos exposed to high glucose.

Oxygen uptake and glucose utilization of embryonic and fetal neural tissue of normal and diabetic rat pregnancy were studied. Exposure to 50 mM glucose inhibited oxygen uptake of embryonic neural tissue of normal rats by 28% at gestational day 9 (P < 0.001) and 20% at days 10-12 and 15 (P < 0.

Teratogenic effect of diabetic serum is prevented by supplementation of superoxide dismutase and N-acetylcysteine in rat embryo culture.

Congenital malformations are more common in offspring of diabetic mothers than offspring of non-diabetic mothers. The precise cell biological mechanism leading to the increased incidence of congenital malformations in diabetic pregnancy is not known. In previous studies increased glucose and beta-hydroxybutyrate concentrations were found to cause embryonic dysmorphogenesis.

In vitro regulation of insulin release and biosynthesis of fetal rat pancreatic cells explanted on pregnancy day 16.

Although the morphological development of the fetal pancreatic B cell has been studied in considerable detail, knowledge about the functional maturation, particularly in early stages of development, is still poor. The present paper describes a method for monolayer culture of fetal rat islet cells which allows a study of the regulation of insulin biosynthesis, release and content during critical stages of embryonic and fetal development. Suspensions of pancreatic cells were prepared from rat fetuses on pregnancy day 16 and cultured for 3 days.

Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring.

The increased incidence of congenital malformations in diabetic pregnancy may be associated with an excess of free oxygen radicals in the embryo. We have previously blocked the dysmorphogenesis of rat embryos exposed to high glucose and beta-hydroxybutyrate concentrations in vitro by increasing the antioxidant capacity of the conceptus. In the present study, we attempted to diminish the teratogenic process in vivo in a rat model of diabetic pregnancy.

Effect of butylated hydroxytoluene on alpha-tocopherol content in liver and adipose tissue of rats.

Female rats were fed an antioxidant supplemented diet containing butylated hydroxytoluene (BHT; 0.5% and 1.0%) with or without vitamin E acetate (0.

Primary structure of human 11-cis retinol dehydrogenase and organization and chromosomal localization of the corresponding gene.

The universal chromophore of visual pigments in higher animals is 11-cis retinaldehyde. The final step in the biosynthetic pathway generating this compound is catalyzed by 11-cis retinol dehydrogenase, a membrane-bound enzyme abundantly expressed in the retinal pigment epithelium of the eye. In this work we demonstrate that the primary structure of human 11-cis retinol dehydrogenase is highly conserved with 91% identity to the bovine enzyme.

Lifelong consequences of metabolic adaptations in utero?

Dr. Phillips argues that insulin resistance in adult life may be the price the developing fetus has to pay in return for a short-term successful adaptation to undernutrition in utero. The concept is interesting, and, indeed, challenging.

Reversed-phase high-performance liquid chromatography combined with tandem mass spectrometry in studies of a substance P-converting enzyme from human cerebrospinal fluid.

The application of reversed-phase HPLC in combination with micro-electrospray mass spectrometry to study a substance P (SP)-hydrolysing endoprotease in human cerebrospinal fluid (hCSF) is reported. The enzyme was partially purified from the hCSF specimens by ion-exchange chromatography and molecular sieving. During the purification procedure the enzyme activity was monitored by measuring the formation of the SP-fragment 1-7 from SP by radioimmunoassay.

Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform.

A second isoform and the genomic structures of mouse and human vascular endothelial growth factor B are described. Both genes consist of seven coding exons and span about 4 kilobases of DNA. The two identified isoforms of vascular endothelial growth factor B are generated by alternative splicing where different splice acceptor sites in exon 6 introduce a frameshift and a partial use of different but overlapping reading frames.

Nuclear import of cellular retinoic acid-binding protein type I in mouse embryonic cells.

Using confocal microscopy we show that cellular retinoic acid-binding protein type I (CRABP I), expressed in several embryonic cell types, displays a compartmentalized subcellular distribution. The protein was excluded from the nucleus in some cells, while in others it accumulated in the nucleus. In the rat cerebellar cell line ST15A, which expresses CRABP I, the protein was found in the cytoplasm with a prominent nuclear exclusion.

Cyanide detoxification in rats exposed to acetonitrile and fed a low protein diet.

Different neurological syndromes have been associated with exposure to cyanide. Dietary cyanide exposure from cassava roots combined with a low intake of the sulfur amino acids necessary for cyanide detoxification has been implicated in the causation of konzo, an upper motoneuron disease identified in Africa. We have investigated the effect of a low protein diet on the capacity for cyanide detoxification.

Clinical outcome in four children with metachromatic leukodystrophy treated by bone marrow transplantation.

Four children with metachromatic leukodystrophy (MLD) underwent allogeneic bone marrow transplantation between 1988 and 1993. No effect on the natural course of the disease was observed in two children with late infantile and juvenile MLD. They had moderate neurological symptoms at the time of BMT and were followed for 7 and 6 years, respectively.