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Biomedical subjects

J Ostergaard

Publications and source records attributed to J Ostergaard.

At least 19 recordsLinked to original sources

Pre-eclampsia and febrile convulsions.

An association between pre-eclampsia and febrile convulsions has been reported, but the association may not be causal. We compared the risk of febrile convulsions in 14 974 children who had been exposed to pre-eclampsia in fetal life with that of 39 210 unexposed children. Children exposed to pre-eclampsia had a slightly increased risk of febrile convulsions, but the association was apparently caused by a shorter gestation in pre-eclamptic women.

Child, Preschool↗

alpha-Chymotrypsin-catalyzed degradation of desmopressin (dDAVP): influence of pH, concentration and various cyclodextrins.

Desmopressin [1-(mercaptopropanoic acid)-8-D-arginine vasopressin; dDAVP] is a vasopressin analogue with a selective antidiuretic effect. The oral bioavailability of desmopressin is limited due both to its high hydrophilicity leading to a low intestinal permeability and to low enzymatic stability. The degradation of desmopressin was investigated in aqueous buffer solutions (pH 6.00-9.00) containing the enzyme alpha-chymotrypsin at a concentration of 0.50 mg/ml at 37 degrees C. The degradation of desmopressin was also studied in solutions containing alpha-chymotrypsin in the concentration range 0.10-1.00 mg/ml (pH 7.40 and 37 degrees C). The rate of degradation was shown to be highly dependent on both enzyme concentration and pH. Maximal alpha-chymotrypsin activity was observed in the pH range 7.40-8.00. It was observed that phenylalanine was formed during the degradation of desmopressin. Phenylalanine was formed in the amount of 20% in 120 min. In the same time period 95% of desmopressin was degraded. The formation of phenylalanine can be explained from the substrate specificity of alpha-chymotrypsin. Cyclodextrins are known to stabilize drugs including peptides against both chemical and enzymatic degradation. In this study it was shown that hydroxypropyl cyclodextrins (alpha, beta and gamma) stabilized desmopressin against alpha-chymotrypsin-catalyzed degradation. The stabilization was by a factor of 3, 9 and 8 at the concentration 12.5% (w/v) for hydroxypropyl-alpha-cyclodextrin, hydroxylpropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin.

Chymotrypsin↗

Stability and perfusion studies of Desmopressin (dDAVP) and prodrugs in the rat jejunum.

Three aliphatic carboxylic acid esters of the tyrosine phenolic group in Desmopressin (dDAVP) were investigated in vitro for their stability and metabolism in rat gastrointestinal media. The degradation followed strictly first-order kinetics and the prodrugs were quantitatively converted to dDAVP. The n-hexanoyl (II) and n-octanoyl (III) esters were rapidly hydrolysed in 10% rat jejunal fluid showing half-lives of 1.1+/-0.2 min and 1.4+/-0.1 min, respectively. In 5 % rat jejunal homogenate the half-lives were 3.2+/-0.2 min and <30 sec, respectively. The sterically hindered pivalate ester (I) proved to be more stable. The half-lives were 10.3+/-0.3 min in 10% rat jejunal fluid and 1.5+/-0.1 min in 10% rat jejunal homogenate, respectively. The presence of paraoxon, an inhibitor of type B esterases significantly decreased the degradation rate of the pivalate ester (I) in rat jejunal fluid (t1/2 > 5 hrs) indicating that the prodrug is converted to dDAVP by rapid luminal breakdown of the ester bond. It was shown that approximately 13 % of prodrug I disappeared from the gut lumen during a single-pass perfusion experiment in rat jejunum. Our results indicate that the disappearance from the jejunal lumen was primarily caused by degradation of the prodrug to dDAVP by esterases rather than absorption. The better stability of the sterically hindered prodrug (I) indicate that even more sterically hindered prodrugs will be a better choice for a further optimization of stability and lipophilicity, and consequently a potentially improved intestinal absorption of dDAVP.

Animals↗

Duration of breastfeeding and developmental milestones during the latter half of infancy.

Several studies have suggested that breastfeeding has a long-term influence on brain development. However, interpretation of these findings is complicated by the presence of many potential confounding factors. Only a few studies have examined infants before 1 y of age, although very early assessment might reduce the role of environmental influence. We investigated the association between exclusive breastfeeding and three developmental milestones related to general and fine motor skills and early language development at the age of 8 mo. We followed 1656 healthy, singleton, term infants, with a birthweight of at least 2500 g, born between May 1991 and February 1992 in Aarhus, Denmark. Information was collected at 16 wk gestation, at delivery and when the infant was 8 mo old. Motor skills were evaluated by measurement of crawling and pincer grip. Early language development was defined as the ability to babble in polysyllables. The proportion of infants who mastered the specific milestones increased consistently with increasing duration of breastfeeding. The relative risk for the highest versus the lowest breastfeeding category was 1.3 (95% CI: 1.0-1.6) for crawling, 1.2 (95% CI: 1.1-1.3) for pincer grip and 1.5 (95% Cl: 1.3-1.8) for polysyllable babbling. Little change was found after adjustment for confounding. In conclusion, our data support the hypothesis that breastfeeding benefits neurodevelopment.

Breast Feeding↗

Ascorbate biosynthesis in Arabidopsis cell suspension culture.

The biosynthesis of L-ascorbic acid (L-AA) in an Arabidopsis (L.) Heynh. cell suspension culture was studied by quantifying the effects of incubation with a range of potential biosynthetic precursors, analogs, and inhibitors on the intracellular levels of reduced and oxidized forms of L-AA. Our results support the recently published biosynthetic pathway of L-AA from L-galactose (G.L. Wheeler, M.A. Jones, N. Smirnoff [1998] Nature 393: 365-369), but suggest that Arabidopsis cell suspension culture simultaneously contains two other routes leading to L-AA. The possible physiological significance of these alternate routes is discussed.

Arabidopsis↗

Smoking during pregnancy and babbling abilities of the 8-month-old infant.

Animal experiments suggest that the fetal brain is sensitive to nicotine. Although much attention has been given to the relation between cigarette smoking during pregnancy and neurodevelopment in children, this remains controversial. Our study describes the relationship between maternal cigarette smoking during pregnancy and babbling abilities of the 8-month-old infant. In a longitudinal cohort, information was collected at the 16th week of gestation, at delivery and when the infant was about 8 months old. At this age babbling abilities of the infant were evaluated by a health visitor during a home visit. Singleton infants without any disability born at Aarhus University Hospital, Denmark, 1991-92 and still living in the Community of Aarhus at the age of 8 months were eligible (n = 2302). Complete follow-up was obtained for 1871 children (81.3%). A dose-response-like relationship between number of cigarettes smoked per day during pregnancy and babbling abilities was found after controlling for potential confounders. Smoking 10 or more cigarettes per day during pregnancy almost doubled the risk (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.1-3.6) of the infant being a non-babbler at the examination at 8 months. Among children who were breast fed for less than 4 months this risk was even higher (OR = 2.7, CI 1.3-5.8).

Bias↗

Isolation of a cDNA coding for L-galactono-gamma-lactone dehydrogenase, an enzyme involved in the biosynthesis of ascorbic acid in plants. Purification, characterization, cDNA cloning, and expression in yeast.

L-Galactono-gamma-lactone dehydrogenase (EC 1.3.2.3; GLDase), an enzyme that catalyzes the final step in the biosynthesis of L-ascorbic acid was purified 1693-fold from a mitochondrial extract of cauliflower (Brassica oleracea, var. botrytis) to apparent homogeneity with an overall yield of 1.1%. The purification procedure consisted of anion exchange, hydrophobic interaction, gel filtration, and fast protein liquid chromatography. The enzyme had a molecular mass of 56 kDa estimated by gel filtration chromatography and SDS-polyacrylamide gel electrophoresis and showed a pH optimum for activity between pH 8.0 and 8.5, with an apparent Km of 3.3 mM for L-galactono-gamma-lactone. Based on partial peptide sequence information, polymerase chain reaction fragments were isolated and used to screen a cauliflower cDNA library from which a cDNA encoding GLDase was isolated. The deduced mature GLDase contained 509 amino acid residues with a predicted molecular mass of 57,837 Da. Expression of the cDNA in yeast produced a biologically active protein displaying GLDase activity. Furthermore, we identified a substrate for the enzyme in cauliflower extract, which co-eluted with L-galactono-gamma-lactone by high-performance liquid chromatography, suggesting that this compound is a naturally occurring precursor of L-ascorbic acid biosynthesis in vivo.

Amino Acid Sequence↗

Amino acid sequences of three acyl-binding/lipid-transfer proteins from rape seedlings.

The complete amino acid sequence of three acyl-binding/lipid-transfer proteins, AB/LTP I, AB/LTP II and AB/LTP III from germinated rape seeds were determined. AB/LTP I and AB/LTP II consist of 93 residues and the M(r) was determined as 9408 by mass spectrometry and calculated as 9406.8 from the sequence. AB/LTP III consists of 92 residues and the M(r) was determined as 9424 by mass spectrometry and calculated as 9422.8 from the sequence. The primary structures were determined by automated Edman degradations of the intact proteins and peptides obtained from digestion with trypsin and endoproteinase Asp-N and cyanogen bromide cleavage. Use of 252Cf plasma-desorption mass spectrometry facilitated the identification and verification of peptides.

Amino Acid Sequence↗

Acyl-binding/lipid-transfer proteins from rape seedlings, a novel category of proteins interacting with lipids.

From rape (Brassica napus) seedlings proteins able to bind fatty acids and their CoA-esters were purified by gel filtration and cation-exchange chromatography. Among the four proteins detected, one of them (peak IV) appeared purified to homogeneity. This protein is a monomer with a molecular mass of about 9 kDa, as estimated by gel filtration and by polyacrylamide gel electrophoresis. The isoelectric point of the rape protein was higher than 10.5 as determined by chromatofocusing. The pure rape protein appeared furthermore to be able to transfer several phospholipids (phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine) between membranes. The rape protein, having a multifunctional property, was thus called acyl-binding/lipid-transfer protein (AB-LTP). In order to compare this protein to plant lipid-transfer proteins (LTPs), its structure was determined. The amino acid analysis of the rape AB-LTP revealed a high amount of alanine, an absence of histidine and tryptophan and the presence of eight cysteine residues. The N-terminal amino acid sequence of the rape protein revealed a high homology to plant LTPs. These observations led us to propose that the rape AB-LTPs belong to a category of plant proteins interacting with lipids and playing a role in the fatty acid dynamics.

Amino Acid Sequence↗

Cystosarcoma phylloides with lobular and ductal carcinoma in situ.

Malignant change of the epithelium in cystosarcoma phylloides is a rare occurrence, the most frequent occurrence being infiltrating carcinoma of various types and lobular carcinoma in situ, while ductal carcinoma in situ is much more rare. We describe a case of lobular and ductal carcinoma in situ in the same case of cystosarcoma phylloides.

Aged↗

Anaesthesia with flunitrazepam and ketamine.

A randomized study of 96 women undergoing hysterectomy was used to compare two anaesthetic techniques: flunitrazepam, ketamine and nitrous oxide in oxygen; and pethidine, thiopentone, nitrous oxide in oxygen and halothane. The techniques exerted small, but significantly different influences on heart rate and arterial pressure. Significantly more patients complained of nausea and vomiting on awakening after inhalation anaesthesia. Amnesia after operation lasted significantly longer after flunitrazepam combined with ketamine and nitrous oxide in oxygen.

Adult↗

Thermal problems in plethysmography and pressure/volume recording.

Where volume changes are recorded as the concomitant changes in pressure, modern, fast-responding pressure transducers might record not only the pressure changes due to volume changes in the measured object but also the heat of compression, showing itself as an overshoot or hysteresis phenomenon in the calibration curves. Introduction of an effective heat sink (e.g. copper mesh) within the air space in the plethysmograph might absorb this heat and thereby diminish the overshoot phenomena. The effect is not of practical importance in classical venous occlusion plethysmography where rapid changes only contribute to a smaller part of the total volume change during venous occlusion. When rapid changes, as in volume pulse recordings, are to be evaluated, the effect must be taken into consideration and should be reduced.

Blood Pressure Determination↗

Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial.

A double-blind controlled trial based on 140 women undergoing abortus provocatus was employed to study whether the frequency of side effects after administration of the anaesthetic Ketalar (ketamine) could be reduced by a con-current dose of Rohypnol (flunitrazepam). The control group was given ketamine alone. The dosage of ketamine was 2 mg/kg body weight, supplemented if necessary by 1 mg/kg, in combination with either 2 mg flunitrazepam or placebo. No other anaesthetics were used. On several counts, the combination of ketamine and flunitrazepam was proved to reduce the adverse reactions seen with ketamine alone. Motor restlessness and confusion in the awakening state occurred with significantly less severity and frequency. Amnesia for dreams was significantly more frequent. Memory of dreams was often unpleasant after ketamine alone. The influence on pulse rate was significantly smaller and no significant changes in systolic blood pressure were seen, whereas a significant increase occurred with ketamine alone. Less pronounced fluctuations in diastolic blood pressure occurred with the combination ketamine-flunitrazepam. Respiratory rate increased significantly with both treatments, but respiratory minute volume was lower with the ketamine-flunitrazepam combination.

Abortion, Induced↗