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Biomedical subjects

C Pettersson

Publications and source records attributed to C Pettersson.

At least 19 recordsLinked to original sources
PubMed2002

Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters.

A comparison of platinum-group element (PGE) emission between gasoline and diesel engine catalytic converters is reported within this work. Whole raw exhaust fumes from four catalysts of three different types were examined during their useful lifetime, from fresh to 80,000 km. Two were gasoline engine catalysts (Pt-Pd-Rh and Pd-Rh), while the other two were diesel engine catalysts (Pt). Samples were collected following the 91441 EUDC driving cycle for light-duty vehicle testing, and the sample collection device used allowed differentiation between the particulate and soluble fractions, the latter being the most relevant from an environmental point of view. Analyses were performed by inductively coupled plasma-mass spectrometry (ICP-MS) (quadrupole and high resolution), and special attention was paid to the control of spectral interference, especially in the case of Pd and Rh. The results obtained show that, for fresh catalysts, the release of particulate PGE through car exhaust fumes does not follow any particular trend, with a wide range (one-two orders of magnitude) for the content of noble metals emitted. The samples collected from 30,000-80,000 km present a more homogeneous PGE release for all catalysts studied. A decrease of approximately one order of magnitude is observed with respect to the release from fresh catalysts, except in the case of the diesel engine catalyst, for which PGE emission continued to be higher than in the case of gasoline engines. The fraction of soluble PGE was found to represent less than 10% of the total amount released from fresh catalysts. For aged catalysts, the figures are significantly higher, especially for Pd and Rh. Particulate PGE can be considered as virtually biologically inert, while soluble PGE forms can represent an environmental risk due to their bioavailability, which leads them to accumulate in the environment.

Air Pollutants↗
PubMed2001

Altered insulin receptor processing and function in scrapie-infected neuroblastoma cell lines.

The underlying neurochemical changes contributing to prion-induced neurodegeneration remain largely unknown. This study shows that scrapie infection induced a 2-fold increase of insulin receptor (IR) protein and aberrantly processed IR beta-chain in scrapie-infected N2a neuroblastoma cells (ScN2a) as measured by Western blot of immunoprecipitated IR, in the absence of increased IR mRNA. Elevated IR protein level was further confirmed in an independently scrapie-infected neuroblastoma cell line N1E-115 (ScN1E-115). Proliferation studies showed that the increased IR level in ScN2a did not result in an increased insulin-mediated cell growth compared to normal N2a cells. Binding studies indicated that this apparent paradox was due to a 65% decrease in specific [(125)I]insulin binding sites in ScN2a when compared to the amount of immunoreactive IR, although the IR binding affinity was unchanged. Analysis of insulin stimulated IR tyrosine phosphorylation showed a slight but not significant reduction in ScN2a, when related to the increased level of immunoreactive IR. However, comparing the IR tyrosine phosphorylation to the loss of binding sites in ScN2a, we demonstrated an increased IR tyrosine phosphorylation of the remaining functional IR. In addition to these differences in IR properties, the basal extracellular signal regulated kinase-2 (ERK2) phosphorylation detected by Western blot, was significantly elevated and the insulin stimulated ERK2 phosphorylation was subsequently decreased in ScN2a. Together, these data show that scrapie infection affects the level and processing of the IR and signal transduction mediated by the IR in neuroblastoma cells, as well as induces an elevated basal ERK2 phosphorylation. Aberrant regulation of neuroprotective receptors may contribute to neurodegeneration in prion diseases.

Animals↗
PubMed2001

Up-regulation of functionally impaired insulin-like growth factor-1 receptor in scrapie-infected neuroblastoma cells.

A growing body of evidence suggests that an altered level or function of the neurotrophic insulin-like growth factor-1 receptor (IGF-1R), which supports neuronal survival, may underlie neurodegeneration. This study has focused on the expression and function of the IGF-1R in scrapie-infected neuroblastoma cell lines. Our results show that scrapie infection induces a 4-fold increase in the level of IGF-1R in two independently scrapie-infected neuroblastomas, ScN2a and ScN1E-115 cells, and that the increased IGF-1R level was accompanied by increased IGF-1R mRNA levels. In contrast to the elevated IGF-1R expression in ScN2a, receptor binding studies revealed an 80% decrease in specific (125)I-IGF-1-binding sites compared with N2a cells. This decrease in IGF-1R-binding sites was shown to be caused by a 7-fold decrease in IGF-1R affinity. Furthermore, ScN2a showed no significant difference in IGF-1 induced proliferative response, despite the noticeable elevated IGF-1R expression, putatively explained by the reduced IGF-1R binding affinity. Additionally, IGF-1 stimulated IGF-1Rbeta tyrosine phosphorylation showed no major change in the dose-response between the cell types, possibly due to altered tyrosine kinase signaling in scrapie-infected neuroblastoma cells. Altogether these data indicate that scrapie infection affects the expression, binding affinity, and signal transduction mediated by the IGF-1R in neuroblastoma cells. Altered IGF-1R expression and function may weaken the trophic support in scrapie-infected neurons and thereby contribute to neurodegeneration in prion diseases.

Animals↗
PubMed2001

Non-aqueous capillary electrophoretic separation of enantiomeric amines with (-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid as chiral counter ion.

(-)-2,3:4,6-Di-O-isopropylidene-2-keto-L-gulonic acid [(-)-DIKGA] has been introduced as a chiral counter ion in non-aqueous capillary electrophoresis. High enantioresolutions (R(s)> or =3) were obtained for amines, e.g., pronethalol, labetalol and bambuterol. Methanol containing NaOH and (-)-DIKGA was used as the background electrolyte. The counter ion concentration and the nature of the injection medium were found to affect the chiral separation. Covalent coating of the fused-silica capillary reduced the electro-osmotic flow resulting in improved enantioresolutions.

Amines↗
PubMed2000

Cellulases from the fungi Phanerochaete chrysosporium and Trichoderma reesei as chiral selectors in capillary electrophoresis: applications with displacer plugs and sample preconcentration.

The cellulases CBH 58 from the fungus Phanerochaete chrysosporium and CBH I from the fungus Trichoderma reesei were compared as chiral selectors in capillary electrophoresis (CE) applying the partial filling technique. Amines, e.g., norephedrine, two bambuterol analogs, as well as acids, e.g., di-p-toluoyl tartaric acid and dibenzoyl tartaric acid, which could not be enantioseparated in the liquid chromatographic use of the selectors, could be separated in the corresponding CE experiments. Due to the very high enantioselectivities, terbutaline, alprenolol and propranolol could be completely enantioresolved with selector plugs shorter than the sample plugs. The affinity of propranolol to CBH 58 was so high at pH 7.0 that neither of the enantiomers reached the detector; therefore, a plug of the displacing disaccharide cellobiose was injected after the sample to elute the propranolol enantiomers. The enantiomers could also be made to leave the capillary at opposite ends, thereby causing an infinite enantioresolution. A new preconcentration technique was introduced, which takes advantage of the very high affinity of propranolol to CBH 58 and the eluting ability of cellobiose. A 12.5 cm long plug of rac-propranolol could be preconcentrated and enantioseparated in a single procedure.

Cellulase↗
PubMed2000

Low level exposure to cadmium and early kidney damage: the OSCAR study.

OBJECTIVES: To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium. METHODS: Early kidney damage in 1021 people, occupationally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC (alpha(1)-microglobulin) in urine to assess tubular proteinuria. RESULTS: There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjustment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine. CONCLUSION: Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated.

Adult↗
PubMed2000

Low-level cadmium exposure and osteoporosis.

Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia. We have examined whether long-term low-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16-81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age. There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (> or = 3 nmol/mmol creatinine) compared with the lowest dose group (< 0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.5-3 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.

Absorptiometry, Photon↗
PubMed1999

Chromatographic evaluation of structure selective and enantioselective retention of amines and acids on cellobiohydrolase I wild type and its mutant D214N.

The mechanisms of structure selective and enantioselective retentions of amines and acids on two chiral stationary phases based on wild type cellobiohydrolase I (CBH I) and its mutant D214N have been investigated. All the amino alcohols tested had an enantioselective site that overlaps with the catalytically active site of CBH I, whereas the enantioselectivity of prilocaine was not affected by the mutation. The hydroxyl group of the amino alcohols did not seem to be an important contributor to the total binding strength whereas a bromo substituent in the aromatic ring promotes a high enantioselectivity (alpha=7.05). Interestingly, the chiral recognition site of the acid warfarin overlaps with the binding site of the amino alcohols. Di-p-toluoyltartaric acid and dibenzoyltartaric acid were strongly retained probably due to electrostatic attraction, but no enantioselectivity was observed. The difference in retention characteristics for the amino alcohols on the two stationary phases was strongly pH-dependent. A change in elution order of different amino alcohols occurred when changing the pH from 5.0 to 7.0. The difference between the two phases was lower at low pH. The retention times could also be affected by ionic strength and by use of cellobiose as a mobile phase additive but no indication of ion-pair retention of the amines was observed, when adding hexanesulphonate as counter ion to the mobile phase. The temperature dependence of the retention of the enantiomers of propranolol at pH 7.0 on the mutant D214N was similar to what was earlier observed on the wild type CBH I at lower pH.

Acids↗
PubMed1998

Protection of metabolic and exercise capacity in unselected weight-losing cancer patients following treatment with recombinant erythropoietin: a randomized prospective study.

This study was aimed at evaluating whether anemia could be prevented in unselected weight-losing cancer patients on anti-inflammatory treatment by early and prophylactic treatment with recombinant human erythropoietin (rhEPO) and whether such a benefit could be translated into improved physical function and metabolic efficiency. One hundred eight cancer patients who experienced progressive cachexia due to solid, mainly gastrointestinal tumors were randomized to receive twice daily a cyclo-oxygenase inhibitor (controls; indomethacin, 50 mg twice a day) or indomethacin and erythropoietin, provided on individual basis to prevent development of progressive anemia (study patients; indomethacin, 50 mg twice a day plus rhEPO; range, 12,000-30,000 units per week). All patients were treated and followed up until death or to preterminal stage. Biochemical tests (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurements of respiratory gas exchanges before and during exercise were performed before institution of treatments and then at regular intervals during the treatment period (2-30 months after start). Study and control patients did not differ in survival. rhEPO prevented development of anemia during the entire observation period. This was associated with a significantly more preserved maximum exercise capacity in study patients compared to control patients during the follow-up period (101 +/- 10 versus 66 +/- 6 W; P < 0.0001), based on more effective ventilation and whole-body respiratory gas exchanges. These improvements were also evident when exercise performance was normalized to lean body mass, an indirect measure of the skeletal muscle mass. The metabolic efficiency, expressed as oxygen uptake per watt produced, was also significantly preserved in rhEPO-treated patients compared to controls (14.1 +/- 1.1 versus 16.3 +/- 0.9 ml O2/W, P < 0.05). Our results demonstrate that institution of early and prophylactic rhEPO treatment to patients with progressive cancer prevents development of tumor-induced anemia. This achievement was associated with a better preserved exercise capacity, which is explained in part by improved whole-body metabolic and energy efficiency during work load.

Aged↗
PubMed1997

Enantioresolution of disopyramide by capillary affinity electrokinetic chromatography with human alpha1-acid glycoprotein (AGP) as chiral selector applying a partial filling technique.

A method using alpha1-acid glycoprotein (AGP) as chiral selector for disopyramide by means of affinity electrokinetic chromatography has been developed. In order to avoid UV absorbance interferences, less than the effective length of the capillary was filled with the chiral selector. The electrophoretic conditions were chosen to give opposite migration directions for the chiral selector and the analyte; AGP migrated away from the detector. Enantiomers of disopyramide were separated on a methylcellulose-coated capillary with 20 cm length to the detector. The enantioresolution of the solute was affected by the concentration of the chiral selector, the plug length of the selector in the capillary, and the applied voltage. Resolution factors and migration times decreased with reduction of the plug length, while the efficiency of the separation system and peak performance were improved by decreasing the separation zone. A special feature of the technique is an enhanced selectivity due to increasing separation of the enantiomers when the fastest has migrated from the selector zone, while the second one still is retained. Equations relating selectivity and resolution with the difference in effective plug lengths between the two enantiomers are developed. Optimized conditions yielding complete resolution, requiring an 0.75 mM AGP plug of only 4.5 cm effective length, also gave high efficiencies (about 400,000 plates/m) for both enantiomer peaks.

Chromatography↗
PubMed1996

Diversity and distribution of subterranean bacteria in groundwater at Oklo in Gabon, Africa, as determined by 16S rRNA gene sequencing.

This paper describes how ground water was sampled, DNA extracted, amplified and cloned and how information available in the ribosomal 16S rRNA gene was used for mapping diversity and distribution of subterranean bacteria in groundwater at the Bangombé site in the Oklo region. The results showed that this site was inhabited by a diversified population of bacteria. Each borehole was dominated by species that did not dominate in any of the other boreholes; a result that probably reflects documented differences in the geochemical environment. Two of the sequences obtained were identified at genus level to represent Acinetobacter and Zoogloea, but most of the 44 sequences found were only distantly related to species in the DNA database. The deepest borehole, BAX01 (105 m), had the highest number of bacteria and also total organic carbon (TOC). This borehole harboured only Proteobacteria beta group sequences while sequences related to Proteobacteria beta, gamma and delta groups and Gram-positive bacteria were found in the other four boreholes. Two of the boreholes, BAX02 (34 m) and BAX04 (10 m) had many 16S rRNA gene sequences in common and also had similar counts of bacteria, content of TOC, pH and equal conductivity, suggesting a hydraulic connection between them.

Acinetobacter↗
PubMed1995

Enantiomeric separation of basic drugs using N-benzyloxycarbonylglyclyl-L-proline as counter ion in methanol.

Direct separation of enantiomeric amines using mainly N-benzyloxycarbonylglycyl-L-proline (L-ZGP) but also N-benzyloxycarbonylglyclglcyl-L-proline (L-ZGGP) as the chiral counter ion in methanol is described. The solid phase was Hypercarb porous graphitic carbon. Several amines of pharmacological interest (e.g., alprenolol, sotalol, terbutaline, promethazine and trimipramine) were separated with high enantioselectivity (alpha = 1.16-1.98) using L-ZGP and L-ZGGP as chiral selectors. In accordance with ion-pair chromatography, the retention of the enantiomeric amines was found to increase with increasing concentration of the anionic form of L-ZGP. Addition of a base (sodium hydroxide or an alkylamine) in excess of L-ZGP gave rise to a decrease in retention and enantioselectivity. The enantioselective retention was also affected by adding 2-propanol or acetonitrile to the mobile phase.

Chromatography, Liquid↗
PubMed1993

Enantioselective high-performance liquid chromatographic determination of (SR)- and (RS)-mefloquine in plasma using N-benzyloxycarbonyl-glycyl-L-proline as chiral counter ion.

A stereoselective HPLC method is described for the determination of (SR)- and (RS)-mefloquine in plasma. The direct chiral separation is carried out on a Hypercarb-S column (porous graphitised carbon) with N-benzyloxycarbonyl-glycyl-L-proline (L-ZGP) as a chiral counter-ion in a reversed-phase system. The sample work-up included protein precipitation by addition of zinc sulphate and acetonitrile followed by liquid-liquid extraction with methyl-tert.-butyl ether. After evaporation of the organic phase, the residue is dissolved in the mobile phase and injected onto the column. Analyses of the enantiomers in plasma after a single oral dose of mefloquine indicates that the pharmacokinetics of the two enantiomers are different. The method is validated by determining the absolute recovery, linearity, accuracy, precision and inter- and intra-assay variation.

Calibration↗
PubMed1992

Separation of (R)- and (S)-naproxen using micellar chromatography and an alpha 1-acid-glycoprotein column: application for chiral monitoring in human liver microsomes by coupled-column chromatography.

A column-switching system for fast determination of (R)- and (S)-naproxen in liver microsomes has been developed. The centrifuged sample was injected directly onto a pre-column with octadecylcoated silica. The retained analytes were then directed to an alpha 1-AGP column using a mobile phase composed of phosphate buffer (pH 6.5), dimethylocytylamine (30 mM) and the nonionic surfactant, Tween 20 (40 g/l). The method gave high absolute recoveries and good repeatabilities: 99.6% (1.7% relative standard deviation) and 94.9% (2.4% R.S.D.) for the (R)- and (S)-naproxen, respectively. The use of a surfactant in combination with an aliphatic amine in the mobile phase involves reduced retention times with retained enantioselectivity. Furthermore, the presence of the surfactant makes it possible to inject biological samples directly into the chromatographic system.

Chemistry Techniques, Analytical↗
PubMed1990

(R)- and (S)-5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT): assessment of optical purities and dopaminergic activities.

Racemic 5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT), a potent and selective dopamine (DA) D2-receptor agonist, was resolved into the enantiomers by a new method. The enantiomers of 5-OH DPAT were determined by chiral ion-pair chromatography using N-benzyloxycarbonylglycyl-L-proline as the counter ion. The enantiomeric purity of (R)-5-OH DPAT was found to be greater than 99.7%. The ability of the enantiomers to change the rat brain DOPA levels was evaluated in vivo. The results indicate that (R)-5-OH DPAT is a weakly potent DA D2-receptor antagonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗