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U J Eriksson

Publications and source records attributed to U J Eriksson.

At least 91 records · Page 5Linked to original sources
PubMed1987

Mechanisms of congenital malformations in diabetic pregnancy.

The reasons for the increased rate of congenital malformations in diabetic pregnancy are unclear. Several different teratological agents may be considered. In clinical investigations and animal experimentation hyperglycemia and hypoglycemia, hyperketonemia, altered trace metal metabolism, and a genetic predisposition have been suggested to be of significance in the teratogenic process of diabetic pregnancy. Studies of these possible etiological factors have so far failed to reveal a single agent or mechanism as the most important. The diabetic pregnancy, therefore, appears to be of multifactorial origin.

3-Hydroxybutyric Acid↗
PubMed1986

Diabetes in pregnancy: influence of genetic background and maternal diabetic state on the incidence of skeletal malformations in the fetal rat.

Female Sprague-Dawley rats from two different substrains (denoted U and H rats) were made manifest diabetic (MD) with a single iv injection of streptozotocin 2-4 weeks before mating. In some MD animals insulin treatment was started 1-3 weeks before mating (denoted MDI rats) and in a majority of these animals the treatment was interrupted during two days of pregnancy, i.e. gestational days 2 + 3, 4 + 5, 6 + 7, 8 + 9 or 10 + 11. The pregnant rats were killed on gestational day 20. The offspring of MD and MDI rats of the U substrain showed skeletal malformations (micrognathia and sacral dysgenesis) at a rate up to 19%, whereas the MD and MDI fetuses of the H strain did not display any skeletal malformations. Offspring of the U strain with sacral dysgenesis exhibited lack of a tail and no staining of osseous and cartilagenous tissue in the sacral-caudal region, suggesting total absence of vertebrae. The offspring of the diabetic U rats tended to be more readily resorbed, were smaller and tended to have slightly larger placentae than those of the diabetic H rats. The severity of the diabetic state in pregnant and nonpregnant female rats--as reflected by body and kidney weights, blood levels of HbA1c, carbohydrate and lipid metabolites--did not differ significantly between the U and H rats. These results are in concert with the notion that congenital malformations result from a teratogenic insult in a genetically predisposed organism. The described malformation-prone rat strain (U) may be a suitable model for the future elucidation of teratological mechanisms in diabetic pregnancy.

Animals↗
PubMed1986

Fetal lung maturation in diabetic pregnancy.

The increased incidence of the idiopathic respiratory distress syndrome (IRDS) in infants of diabetic mothers may be explained by preterm delivery and asphyxia but the metabolic derangement per se may also be responsible for the inadequate production of surfactant. Experimental studies of the underlying mechanisms in the lungs of fetuses of pregnant diabetic rats have shown a decreased formation of the two major surfactant phospholipids disaturated phosphatidyl choline and phosphatidyl glycerol. In addition, the activities of key enzymes responsible for the production of these phospholipids are decreased in the fetal lung tissue. Inadequate utilization of pulmonary glycogen for surfactant biosynthesis has also been observed. Furthermore, experimental studies support that other changes than fetal hyperinsulinaemia are needed to produce a state of disturbed surfactant production. In human diabetic pregnancy strict metabolic control allows the fetal lungs to mature in a near-normal fashion. The presence of phosphatidyl glycerol in the amniotic fluid seems to be the best available predictor of lung maturity in diabetic pregnancy, in which both the lecithin/sphingomyelin ratio and amniotic fluid cytology may result in false-positive and false-negative values. The trend towards extension of delivery to term will undoubtedly diminish the need for estimation of fetal lung maturity by amniocentesis. Avoiding preterm delivery and adhering to strict metabolic control of the maternal diabetes would be expected to decrease the neonatal respiratory problems in diabetic pregnancy.

Amniotic Fluid↗
PubMed1986

Increased accumulation of sorbitol in offspring of manifest diabetic rats.

The effects of maternal diabetes on somatic development and activity of the polyol pathway were investigated during early and late gestation in a rat model for diabetic pregnancy. We studied embryo-fetal growth, mortality, and malformation rate in the offspring of nondiabetic rats and in the offspring of diabetic rats either treated with an aldose reductase inhibitor during gestation or left untreated. The numbers of embryo-fetal resorptions and malformations were significantly increased in the diabetic groups compared with the controls despite maternal treatment with the aldose reductase inhibitor. The sorbitol content of embryos and membranes from the diabetic rats in early gestation was increased 3-5 times over the control values. Similarly, elevated sorbitol levels were observed in the fetal livers and placentas of the diabetic rats in late gestation. Administration of the aldose reductase inhibitor to the pregnant diabetic rats normalized the sorbitol levels in the embryos and their membranes, whereas the sorbitol contents of the fetal livers and placentas were significantly lowered but not completely corrected. Furthermore, in the diabetic groups, no differences in sorbitol levels could be demonstrated between malformed and nonmalformed offspring. The results of this study suggest that enhanced polyol metabolism leading to increased sorbitol accumulation is present in the embryos of diabetic mothers as early as organogenesis. This accumulation is apparently not a major factor in the early developmental disturbances (e.g., growth perturbations and congenital malformations) of diabetic pregnancy.

Animals↗
PubMed1986

Induction of skeletal malformations in the offspring of rats fed a zinc deficient diet.

Pregnant rats were subjected to a trace metal poor diet (1.2 ppm zinc, 5.9 ppm copper, 40 ppm manganese) during the entire gestation. The rat mothers did not gain weight during pregnancy and showed decreased liver weight and lowered serum glucose levels on gestational day 20. The offspring exhibited decreased body and placental weights, delayed ossification of the skeleton, and an increased resorption rate. We also found 4% skeletal malformations in the offspring (0% in the controls), which closely resembled a type of malformation previously encountered in rats when the mother was manifest diabetic (i.e. sacral dysgenesis). The zinc levels were decreased and manganese levels increased to the same extent in offspring of trace metal restricted (this study) and manifest diabetic rats (previous studies). Furthermore, when pregnant rats on the trace metal restricted diet were resupplemented with 75 ppm zinc in the drinking water the offspring largely normalized their somatic and placental growth, skeletal maturation, as well as their zinc and manganese levels. In addition, the fetuses of the zinc resupplemented rats did not show any malformations. The possibility of common teratological mechanisms in maternal diabetes and trace metal deficiency may therefore be considered.

Animals↗
PubMed1985

Congenital malformations in diabetic pregnancy: the clinical relevance of experimental animal studies.

The aim of this work was to present recent observations on the occurrence of malformations in the offspring of diabetic rats and to discuss these findings in the light of present clinical experience. Comparison of malformation rates between different substrains of Sprague-Dawley rats showed marked differences in the occurrence of diabetes-induced malformations. These findings suggest that congenital malformations in diabetic pregnancy may result from a teratological insult in genetically predisposed individuals. Recent clinical reports seem to link facial malformations to an increased incidence of sacral-caudal malformations in human diabetic pregnancy. The present rat model, which expresses both these aberrations--micrognathia and sacral dysgenesis--may therefore be a useful tool in studies of the aetiological relationships between disturbed maternal metabolism and skeletal malformations in the offspring. Malformations in fetuses of diabetic animals seem to arise from teratogenic insult(s) early in pregnancy. Hyperglycemia and hyperketonemia may both singly, and in combination, be of teratological significance. Insulin itself does not appear to be directly teratogenic. Furthermore, there is evidence to suggest that disturbed levels of trace metals, primarily zinc, may be a significant factor in the production of congenital malformations. The increased rate of malformations in diabetic pregnancy, therefore, appears to be multifactorial in origin.

Animals↗
PubMed1985

Estimation of gestational age by amniocentesis.

We have previously demonstrated that gestational age can be estimated from a diagram in which the percentage of lipid-carrying cells (amniotic fluid cytology) and the creatinine concentration in the amniotic fluid are plotted. Using this diagram for the purpose of dating, a comparison was made with prediction of gestational age by early ultrasound (biparietal diameter, BPD). Dating by the two methods showed a high correlation (r = 0.72) in 53 samples from 48 pregnancies and the two methods were in agreement within 2 weeks in 94%. In one third of infants with a low birth weight for age, however, amniotic fluid tests overestimated gestational age in comparison with early BPD. It is suggested that this disparity may be due to a combination of influence of early growth retardation on the BPD and accelerated maturation accompanying intrauterine growth retardation. Prior to elective delivery in pregnancies with uncertain dates and when an early ultrasonic examination has not been performed dating by amniotic fluid tests is reliable and is particularly useful.

Amniocentesis↗
PubMed1985

The development of antioxidant enzymatic defense in the perinatal rat lung: activities of superoxide dismutase, glutathione peroxidase, and catalase.

This report describes the development of superoxide dismutase, glutathione peroxidase, and catalase activities in fetal (days 16-22) and neonatal (day 2 postpartum) lungs of normal rats. Each of the enzymes showed an individual pattern of development in the perinatal period. Glutathione peroxidase activity increased by 135% (p less than 0.001) during the last 3 days before birth, catalase activity by 105% (p less than 0.01) during the first 2 postnatal days, and the activity of superoxide dismutase by 52% (p less than 0.05) from gestational day 19 to 2 days after birth. Contamination by superoxide dismutase from blood in the lung samples accounted for less than 2% of the activity. In contrast, not less than 10-30% of glutathione peroxidase and catalase originated from the blood; and corrections were made for this source of error in each sample.

Animals↗
PubMed1985

Is there an animal model for gestational diabetes?

This article reviews the effects of pregnancy on carbohydrate metabolism and insulin production in the normal rat and discusses some animal models of potential value for the study of gestational diabetes mellitus (GDM). Against the background of current clinical and laboratory experiences it is suggested that GDM reflects a deficiency in islet B-cell proliferation in response to the increased insulin requirement during pregnancy. Although this hypothesis lends itself for testing in animal experiments, a suitable animal model for GDM needs to be described.

Animals↗
PubMed1984

Diabetes in pregnancy: retarded fetal growth, congenital malformations and feto-maternal concentrations of zinc, copper and manganese in the rat.

The possible relationship between trace metal alterations, disturbed somatic growth and congenital malformations in diabetic pregnancy was studied in an animal model in which skeletal malformations are known to occur in the offspring of experimentally diabetic rats. The diabetic state was induced with streptozotocin more than 2 weeks before mating. In some of the diabetic animals, a zinc supplement in the drinking water (1 ppm or 15 ppm) was given during pregnancy. The contents of zinc, copper and manganese in the maternal livers and whole fetuses were examined on gestational days 18, 20 and 22. The resorption and malformation rates were significantly increased in the diabetic groups. In addition, the fetuses of the diabetic rats exhibited marked growth retardation at all times compared to the normal offspring whether or not the mothers were zinc-treated. There was an excessive accumulation of zinc, copper and manganese in the maternal livers of the diabetic rats. In the offspring of the diabetic rats, however, the total-body concentration of zinc was strikingly decreased. The fetal zinc deficiency in the diabetic group persisted despite maternal zinc supplement during pregnancy. The copper concentrations in the fetuses of normal and diabetic mothers were largely similar, whereas the fetal manganese concentrations were increased in the fetuses of diabetic rats. The findings are compatible with the view that trace metal aberrations may be related to the disturbed fetal growth, and furthermore, that these changes in trace metal levels may also be of teratogenic importance in diabetic pregnancy.

Animals↗
PubMed1984

Diabetes in pregnancy: decreased placental blood flow and disturbed fetal development in the rat.

Placental blood flow was measured with the aid of radioactive microspheres, in normal (N) and manifest diabetic (MD) rats, and related to fetal body growth and incidence of congenital malformations. The total blood flow in the placentae of the MD rats was decreased to about one-half of the normal flow on gestational days 20 and 22. The placentae of the MD offspring were enlarged, whereas the fetuses in this group were smaller than normal. Thus, the placental blood flow per placental weight was drastically decreased in the MD fetuses on both days 20 and 22. In contrast, the placental blood flow per fetal weight was not different in the N and MD groups on gestational day 20 whereas it was decreased in the MD offspring on gestational day 22. Placental blood flow in the malformed fetuses of the MD group did not differ significantly from that in the nonmalformed MD fetuses.

Animals↗
PubMed1984

Amniotic fluid C-peptide and phosphatidyl glycerol in diabetic pregnancy.

The concentrations of C-peptide and phosphatidylglycerol in the amniotic fluid were determined in 36 pregnant diabetic women. Twenty-one patients who were being treated with insulin for gestational diabetes as well as 15 patients who were insulin dependent were studied. All patients were subjected to a program of strict metabolic control, and amniocentesis was performed at gestational week 36-37. Phosphatidyl glycerol was present in the amniotic fluid in 15 cases and absent in 21. The mean concentration of C-peptide did not differ whether phosphatidyl glycerol was present or absent. (C-peptide: 0.56 +/- 0.06 and 0.43 +/- 0.05 nmol/l respectively). Although the mean value for amniotic fluid C-peptide in both groups was close to that in diabetic pregnancies with an uneventful neonatal outcome, it was significantly higher than that in non-diabetic pregnancies, indicating minor fetal hyperinsulinemia. The level of C-peptide in the amniotic fluid showed a correlation to the subsequent birthweight of the infant (r = 0.50; p less than 0.01). It is concluded that with rigorous metabolic control of the pregnant diabetic patient, the presence or absence of phosphatidyl glycerol, as an index of fetal lung maturity, is apparently not related to the level of C-peptide in the amniotic fluid.

Amniocentesis↗
PubMed1984

Growth retardation during early organogenesis in embryos of experimentally diabetic rats.

Embryos from rats rendered diabetic with streptozotocin for 1 wk or more before conception were examined on day 11.5 of gestation (i.e., at the 26-29-somite stage of normal rat embryonic development). The studies were designed to assess whether poorly regulated maternal diabetes is associated with demonstrable abnormalities even during this early phase of embryogenesis. We found that manifest retardations in growth and development were invariably present as judged by significant reductions in crown-rump length and somite number, respectively. Total protein and DNA content of the embryos were also reduced, although not symmetrically, so that protein/DNA ratios were increased. Gross dysmorphogenic lesions in neural tissue disproportional to the overall growth retardation at 11.5 days could not be demonstrated. The findings suggest that maternal diabetes can compromise intra-uterine growth and development during the period preceding and coinciding with the establishment of circulation in the allantoic placenta. The possible multifactorial determinants remain to be elucidated. It also remains to be established whether the early embryotoxicity provides a setting conducive to the increased dysmorphogenesis that is traditionally recognized during the later stages of pregnancy complicated by diabetes.

Animals↗
PubMed1984

Fetal maturation in strictly controlled diabetic pregnancy.

In 56 strictly controlled diabetic pregnancies, altogether 60 amniotic fluid samples were analysed for their content of lipid-carrying cells and the presence of phosphatidylglycerol. The outcome of the amniotic fluid tests was examined for its association to macrosomia and to minor neonatal complications such as hypoglycaemia, hypocalcaemia, respiratory disturbances and hyperbilirubinaemia. The predictive value of these tests was nil, since all cases of neonatal complications occurred in the group showing maturity in tests at week 37. At term, phosphatidylglycerol was detected in 80% of the pregnancies, a finding corresponding to our observations in non-diabetic pregnancies. Lipid-carrying cells were present in quantities indicating maturity (greater than or equal to 10%) in 65% of the pregnancies at term, compared with 87% in non-diabetic pregnancies, suggesting a somewhat disturbed skin maturation secondary to the maternal diabetic state. The failure of these tests to predict neonatal complications indicates that other factors may be of more importance for the occurrence of these disorders than those aspects of final functional maturation of the fetus that are reflected in these two particular maturity tests.

Adult↗
PubMed1983

Development of phosphatidyl glycerol biosynthesis in the lungs of fetuses of diabetic rats.

The lungs of fetuses of streptozotocin-diabetic rats were examined for their ability to incorporate U-14C-glucose into phosphatidyl choline, phosphatidyl glycerol, phosphatidyl inositol and lysophosphatidyl choline. In the lungs of control rats an increased biosynthesis of phosphatidyl glycerol in late pregnancy suggested a close association between the production of this phospholipid and the terminal maturation of the fetal lung. In the offspring of diabetic rats the incorporation of 14C-glucose into phosphatidyl choline, lysophosphatidyl choline and phosphatidyl glycerol was markedly decreased compared with the control rats on gestational day 20, whereas no difference was seen at day 22. Insulin treatment of the pregnant rats restored the biosynthesis of phosphatidyl choline and lysophosphatidyl choline towards normal on gestational day 20, while the ratio of phosphatidyl glycerol to phosphatidyl inositol incorporation of 14C-glucose was decreased, suggesting that the biosynthesis of phosphatidyl glycerol is more sensitive than that of phosphatidyl choline and lysophosphatidyl choline to the metabolic disturbances inherent in maternal diabetes. The delayed fetal pulmonary maturation occurred without fetal hyperinsulinism which suggests that this latter feature may not be of crucial significance in the aetiology of the respiratory distress syndrome.

Animals↗
PubMed1983

Diabetes in pregnancy. Skeletal malformations in the offspring of diabetic rats after intermittent withdrawal of insulin in early gestation.

Precise timing of the teratogenic period in diabetic pregnancy is of clinical importance since correction of the glucose intolerance during this period may protect the offspring from malformations. An experimental approach to elucidate this problem with regard to skeletal development was made in groups of pregnant streptozotocin-diabetic rats (MDI), which were treated with daily insulin injections except for a 2-day period in the first half of pregnancy. The degree of metabolic derangement was estimated by measurements of serum glucose concentrations. During the insulin-free period, the rats showed severe hyperglycemia (greater than 20 mM) while during ongoing insulin treatment, only brief periods of hyper- or hypoglycemia were observed. Insulin treatment was withdrawn successively between gestational days 3 and 12. Control groups consisted of normal pregnant rats (N) or pregnant rats with manifest diabetes (MD) without insulin treatment. The serum glucose levels of the N animals were below 6 mM while those of the MD animals were above 25 mM throughout pregnancy. Skeletal malformations in the viable offspring were recorded on gestational day 20 after Alizarin staining of calcified ossification centers, which also allowed an estimate of skeletal development as a whole. Untreated diabetes in the MD rats induced a high rate of fetal resorptions, a decrease in fetal weight and viability, as well as retardation of skeletal development. Intermittent insulin treatment in the MDI rats ameliorated, but did not abolish, these changes. In the MD group 9 of 48 viable fetuses showed severe malformations of either the lower jaw (micrognathia) or of the lumbosacral region (caudal dysgenesis).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗