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Biomedical subjects

H Pedersen

Publications and source records attributed to H Pedersen.

At least 19 recordsLinked to original sources
PubMed2003

Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes.

OBJECTIVE: Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus. However, fish oil may have deleterious effects on lipid peroxidation and glycemic control. DESIGN: In this study, 44 type 2 diabetic patients were randomized to vitamin E standardized (53.6 mg/day) supplementation (capsules) with 4 g daily of either fish oil (n=23) or corn oil (n=21) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation. LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu(2+). As a marker of in vivo oxidation malondialdehyde concentration in LDL (LDL-MDA) was measured. RESULTS: Fish oil reduced both mean lag time (before, 57.8; after, 48.8 min, P<0.001) and mean propagation rate (before, 0.018 DeltaOD/min; after, 0.015 DeltaOD/min, P<0.001), whereas corn oil had no influence on lag time and propagation rate. The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment. LDL-MDA changes differed borderline significantly between groups (FO, 110.4 pmol/mg protein; CO, 6.7 pmol/mg protein; P=0.057). Fish oil supplementation had no influence on glycemic control as assessed from HbA(1c) and fasting blood glucose. CONCLUSION: According to our findings, fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles. More studies are needed to clarify the clinical importance of this finding.

Adult↗
PubMed2001

Parenteral water/oil emulsions containing hydrophilic compounds with enhanced in vivo retention: formulation, rheological characterisation and study of in vivo fate using whole body gamma-scintigraphy.

The preparation and characterization of parenteral water-in-oil (w/o) emulsions with a potential for sustained release of hydrophilic drugs was described with emphasis on rheological behaviour and spreading phenomenon after intramuscular (i.m.) injection in rabbit thigh muscle. Both steady state and dynamic rheological parameters were investigated showing Newtonian behaviour at low fraction of disperse phase ratio as opposed to viscoelastic and pseudoplastic behaviour at high fraction of disperse phase. Disappearance and spreading behaviour of hydrophilic radioactive markers, aprotinin (6512 g/mol) and pertechnetate (193 g/mol) entrapped in w/o emulsions from an i.m. injection site was studied by whole body gamma-scintigraphy. The retention of entrapped aprotinin 24 h postinjection was 83 +/- 5% for a low spreading emulsion and 76 +/- 6% for a high spreading emulsion. The corresponding values for pertechnetate were 50 +/- 11 and 23 +/- 2%, respectively. The relatively long retention times were suggested to be related to the good physical stability properties of the present emulsions. It was concluded that the presented w/o emulsions are promising vehicles for sustained release of hydrophilic drugs from an i.m. injection site.

Algorithms↗
PubMed2001

Impact of smoking on the duration of breastfeeding in mothers with insulin-dependent diabetes mellitus.

UNLABELLED: The effect of smoking on breastfeeding was studied in 252 mothers with insulin-dependent diabetes mellitus (IDDM) giving birth in the period 1985-1995 and of whom 31% were classified as White group B, 16% group C, 37% group D and 16% group F or R. As part of a centralized regimen a detailed smoking history was taken during pregnancy. Forty-six percent were smokers. In 1997, a questionnaire was sent out asking for information on the duration of breastfeeding. The response rate was 87%. The duration of breastfeeding was significantly longer in the non-smoking group (p = 0.004). Fifty-five percent of non-smokers versus 33% of smokers were still breastfeeding 4 mo after birth. A strong dose-response relationship was established (p = 0.009). Cox multiple regression analysis showed a significantly negative influence of smoking (p = 0.01) and of hospitalization of the infants during the first year of life (p = 0.02) and a significantly positive influence of maternal age (p = 0.02) and birthweight (p = 0.03) on the length of breastfeeding. The breastfeeding curves for non-smokers and smokers were mainly divergent in the first month after birth, suggesting that the effect of smoking on breastfeeding is mainly exerted during that period. CONCLUSION: Smoking exerted a strong, negative, dose-dependent influence on breastfeeding duration in mothers with IDDM. Given the hazards of smoking, the advantages of breastfeeding and the possible link between being breastfed and later development of diabetes mellitus, these results should be taken into consideration when counselling pregnant women with IDDM about smoking.

Adult↗
PubMed2000

Construction and characterization of an oxalic acid nonproducing strain of Aspergillus niger.

Aspergillus niger produces oxalic acid as a by-product which causes problems with downstream processing of industrial enzymes. To overcome this problem the oah gene encoding oxaloacetate hydrolase (EC 3.7.1.1) was disrupted in a glucoamylase-producing strain of A. niger and the resulting strain was incapable of producing oxalic acid. The strain with the disrupted gene was compared with the wild-type strain producing oxalic acid in batch cultivations. The specific growth rate of both strains was 0.20 h(-1). The citric acid yields were identical, but the glucoamylase yield was only 50% in the disruptant compared with the wild-type strain. Batch experiments with 13C-labeled glucose as substrate were carried out to determine the metabolic fluxes through the central metabolism. The two strains had almost identical metabolic fluxes, which suggested that it was possible to disrupt the oah gene without pleiotropic consequences. The flux through the pentose phosphate pathway was around 60% of the glucose uptake for both strains, which suggested that a sufficient supply of NADPH was available for biosynthesis.

Aspergillus niger↗
PubMed2000

Glucoamylase production in batch, chemostat and fed-batch cultivations by an industrial strain of Aspergillus niger.

The Aspergillus niger strain BO-1 was grown in batch, continuous (chemostat) and fed-batch cultivations in order to study the production of the extracellular enzyme glucoamylase under different growth conditions. In the pH range 2.5-6.0, the specific glucoamylase productivity and the specific growth rate of the fungus were independent of pH when grown in batch cultivations. The specific glucoamylase productivity increased linearly with the specific growth rate in the range 0-0.1 h(-1) and was constant in the range 0.1-0.2 h(-1). Maltose and maltodextrin were non-inducing carbon sources compared to glucose, and the maximum specific growth rate was 0.19 +/- 0.02 h(-1) irrespective of whether glucose or maltose was the carbon source. In fed-batch cultivations, glucoamylase titres of up to 6.5 g l(-1) were obtained even though the strain contained only one copy of the glaA gene.

Aspergillus niger↗
PubMed2000

The influence of nitrogen sources on the alpha-amylase productivity of Aspergillus oryzae in continuous cultures.

The influence of the nitrogen source on the alpha-amylase productivity of Aspergillus oryzae was quantified in continuous cultivations. Both inorganic and complex nitrogen sources were investigated and glucose was used as the carbon and energy sources. For production of alpha-amylase, nitrate was shown to be inferior to ammonia as a nitrogen source. A mixture of ammonia and complex nitrogen sources, such as yeast extract or casein hydrolysate, was better than with ammonia as the sole nitrogen source. Even a low concentration of casein hydrolysate (0.05 g l(-1)) resulted in a 35% increase in the alpha-amylase productivity. The higher alpha-amylase productivity during growth on casein hydrolysate was not caused by increased transcription of the alpha-amylase genes but was caused by a faster secretion of alpha-amylase or by a lower binding of alpha-amylase to the biomass.

Aspergillus oryzae↗
PubMed2000

Cloning and characterization of oah, the gene encoding oxaloacetate hydrolase in Aspergillus niger.

The enzyme oxaloacetate hydrolase (EC 3.7.1.1), which is involved in oxalate formation, was purified from Aspergillus niger. The native enzyme has a molecular mass of 360-440 kDa, and the denatured enzyme has a molecular mass of 39 kDa, as determined by gel electrophoresis. Enzyme activity is maximal at pH 7.0 and 45 degrees C. The fraction containing the enzyme activity contained at least five proteins. The N-terminal amino acid sequences of four of these proteins were determined. The amino acid sequences were aligned with EST sequences from A. niger, and an EST sequence that showed 100% identity to all four sequences was identified. Using this EST sequence the gene encoding oxaloacetate hydrolase (oah) was cloned by inverse PCR. It consists of an ORF of 1227 bp with two introns of 92 and 112 bp, respectively. The gene encodes a protein of 341 amino acids with a molecular mass of 37 kDa. Under the growth conditions tested, the highest oah expression was found for growth on acetate as carbon source. The gene was expressed only at pH values higher than 4.0.

Aspergillus niger↗
PubMed1999

Decay of the GRB 990123 optical afterglow: implications for the fireball model

Broad-band (ultraviolet to near-infrared) observations of the intense gamma ray burst GRB 990123 started approximately 8.5 hours after the event and continued until 18 February 1999. When combined with other data, in particular from the Robotic Telescope and Transient Source Experiment (ROTSE) and the Hubble Space Telescope (HST), evidence emerges for a smoothly declining light curve, suggesting some color dependence that could be related to a cooling break passing the ultraviolet-optical band at about 1 day after the high-energy event. The steeper decline rate seen after 1.5 to 2 days may be evidence for a collimated jet pointing toward the observer.

Journal Article↗
PubMed1999

Polarimetric constraints on the optical afterglow emission from GRB 990123

Polarization of the optical emission from GRB 990123 was measured on 24.17 January 1999 universal time with the Nordic Optical Telescope. An upper limit of 2.3% on the linear polarization was found. Accurate polarization measurements provide important clues to the blast wave geometry and magnetic field structure of gamma-ray bursts (GRBs). The lack of detectable polarization for GRB 990123 indicates that the optical afterglow was produced by a blast wave of unknown geometry with an insignificant coherent magnetic field or by a beamed outflow at high Lorentz factor seen at a small viewing angle. Such a collimated jet would help solve the problem of energy release in this exceptionally luminous cosmological burst.

Journal Article↗
PubMed1999

Spectroscopic limits on the distance and energy release of GRB 990123

An optical spectrum of the afterglow from the unusually bright gamma-ray burst GRB 990123 obtained on 24.25 January 1999 universal time showed an absorption system at a redshift of z = 1.600. The absence of a hydrogen Lyman alpha forest sets an upper limit of z < 2.17, whereas ultraviolet photometry indicates an upper limit of z < 2.05. The probability of intersecting an absorption system as strong as the one observed along a random line of sight out to this z is at most a few percent, implying that GRB 990123 was probably at z = 1. 600. Currently favored cosmological parameters imply that an isotropic energy release equivalent to the rest mass of 1.8 neutron stars (4.5 x 10(54) erg) was emitted in gamma rays. Nonisotropic emission, such as intrinsic beaming, may resolve this energy problem.

Journal Article↗
PubMed1999

Synthesis and muscarinic receptor pharmacology of a series of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine bioisosteres of arecoline.

A series of O- and ring-alkylated derivatives of 4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol was synthesized via treatment of appropriately substituted 4-benzylamino-1,2,5,6-tetrahydropyridine-3-carboxamides with hydrogen sulfide and subsequent ring closure by oxidation with bromine. The muscarinic receptor affinity as well as estimated relative efficacy and subtype selectivity of this series of bicyclic arecoline bioisosteres were determined using rat brain membranes and a number of tritiated muscarinic receptor ligands. The effects at the five cloned human muscarinic receptor subtypes of a selected series of chiral analogues, with established absolute stereochemistry, were studied using receptor selection and amplification technology (R-SAT). The potency, relative efficacy, and receptor subtype selectivity of these compounds were related to the structure of the O-substituents and the position and stereochemical orientation of the piperidine ring methyl substituents.

Animals↗
PubMed1999

Identification of enzymes and quantification of metabolic fluxes in the wild type and in a recombinant aspergillus oryzae strain

Two alpha-amylase-producing strains of Aspergillus oryzae, a wild-type strain and a recombinant containing additional copies of the alpha-amylase gene, were characterized with respect to enzyme activities, localization of enzymes to the mitochondria or cytosol, macromolecular composition, and metabolic fluxes through the central metabolism during glucose-limited chemostat cultivations. Citrate synthase and isocitrate dehydrogenase (NAD) activities were found only in the mitochondria, glucose-6-phosphate dehydrogenase and glutamate dehydrogenase (NADP) activities were found only in the cytosol, and isocitrate dehydrogenase (NADP), glutamate oxaloacetate transaminase, malate dehydrogenase, and glutamate dehydrogenase (NAD) activities were found in both the mitochondria and the cytosol. The measured biomass components and ash could account for 95% (wt/wt) of the biomass. The protein and RNA contents increased linearly with increasing specific growth rate, but the carbohydrate and chitin contents decreased. A metabolic model consisting of 69 fluxes and 59 intracellular metabolites was used to calculate the metabolic fluxes through the central metabolism at several specific growth rates, with ammonia or nitrate as the nitrogen source. The flux through the pentose phosphate pathway increased with increasing specific growth rate. The fluxes through the pentose phosphate pathway were 15 to 26% higher for the recombinant strain than for the wild-type strain.

Journal Article↗
PubMed1999

Metabolites of [(14)C]-5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2,3, 6-tetrahydropyridine in mice, rats, dogs, and humans.

The M1 muscarine agonist, 5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2, 3,6-tetrahydropyridine (Lu 25-109), is extensively metabolized in mice, rats, dogs, and humans. The metabolite profile after an oral dose of [(14)C]Lu 25-109 was determined in plasma and in urine. Lu 25-109 was metabolized by N-demethylation (Lu 25-077), N-oxidation (Lu 32-181), and N-deethylation (Lu 31-126). In addition, combined N-demethylation and N-deethylation (Lu 31-190), and formation of a pyridine derivative took place (Lu 31-102). Lu 25-109 was also oxidized to pyridinium (Lu 29-297), 3-hydroxy-pyridinium (Lu 35-080), N-deethyl-2-pyridone (Lu 35-026), and a glucuronide of a 4, 6-dihydroxy-pyridinium ("m/z 398") compounds. A glucuronide of a dihydroxylated dihydro-pyridine compound ("m/z 400") was isolated from human urine, but not fully identified. In vitro studies were undertaken to elucidate the order of formation of the metabolites. In human plasma, the concentrations of Lu 25-109 and the pharmacologically active N-demethyl metabolite (Lu 25-077) were small compared with the N-oxide (Lu 32-181) and the N-deethyl-2-pyridone (Lu 35-026) at the first sample time (0.75 h). The N-deethyl metabolite (Lu 31-126) was the major component in human plasma between 3 and 10 h postdose. The major human metabolites in urine (Lu 32-181, Lu 35-026, and Lu 31-126) and the minor metabolites (Lu 25-077, Lu 35-080, Lu 31-190, and Lu 29-297) were all present in urine from rats, dogs, and mice, whereas m/z 398 was present in only mice and humans, and Lu 31-102 in only rats. The minor human metabolite m/z 400 was not detected in mice, rats, or dogs.

Animals↗
PubMed1998

A method for directed evolution and functional cloning of enzymes.

A general scheme is described for the in vitro evolution of protein catalysts in a biologically amplifiable system. Substrate is covalently and site specifically attached by a flexible tether to the pIII coat protein of a filamentous phage that also displays the catalyst. Intramolecular conversion of substrate to product provides a basis for selecting active catalysts from a library of mutants, either by release from or attachment to a solid support. This methodology has been developed with the enzyme staphylococcal nuclease as a model. An analysis of factors influencing the selection efficiency is presented, and it is shown that phage displaying staphylococcal nuclease can be enriched 100-fold in a single step from a library-like ensemble of phage displaying noncatalytic proteins. Additionally, this approach should allow one to functionally clone natural enzymes, based on their ability to catalyze specific reactions (e.g., glycosyl transfer, sequence-specific proteolysis or phosphorylation, polymerization, etc.) rather than their sequence- or structural homology to known enzymes.

Amino Acid Sequence↗
PubMed1998

[Congenital bilateral perisylvian syndrome].

The congenital bilateral perisylvian syndrome is characterized by pseudobulbar palsy, moderate delay in mental and motor development and epilepsy. Three characteristic case stories are presented. Epileptic seizures are most frequently generalized: tonic, astatic, atypical absences and tonic-clonic seizures. Partial seizures are less frequent. Seizure control is often unsatisfactory. Neuroimaging demonstrates thickening of the cerebral cortex in the perisylvian area bilaterally; these changes together with the clinical picture establish the diagnosis. The etiology is unknown.

Abnormalities, Multiple↗
PubMed1998

Photometry and spectroscopy of the GRB 970508 optical counterpart

An optical transient within the error box of the gamma ray burst GRB 970508 was imaged 4 hours after the event. It displayed a strong ultraviolet excess, and reached maximum brightness 2 days later. The optical spectra did not show any emission lines, and no variations on time scales of minutes were observed for 1 hour during the decline phase. According to the fireball and afterglow models, the intensity should rise monotonically before the observed optical maximum, but the data indicate that another physical mechanism may be responsible for the constant phase seen during the first hours after the burst.

Journal Article↗