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Biomedical subjects

H Schroeder

Publications and source records attributed to H Schroeder.

At least 19 recordsLinked to original sources
PubMed2006

Randomised phase II study comparing topotecan/carboplatin administration for 5 versus 3 days in the treatment of extensive-stage small-cell lung cancer.

BACKGROUND: Topotecan is an active drug in small-cell lung cancer (SCLC). In our previous study, a combination of topotecan with cisplatin was associated with a median overall survival of 7.6 or 8.7 months, depending on the duration of treatment. We have replaced cisplatin by carboplatin in this trial, with the objective of creating a more convenient schedule for our patients. Furthermore, we have also compared the standard 5-day schedule with an experimental 3-day schedule. PATIENTS AND METHODS: A total of 100 patients with metastatic disease were included. Patients were randomly assigned to receive either topotecan 0.75 mg/m2, days 1-5, and carboplatin AUC 5, day 5 (arm A) or topotecan 1.25 mg/m2, days 1-3, and carboplatin AUC 5, day 3 (arm B). Six cycles were given at a 3-week interval. RESULTS: A total of 91 patients were assessable for response. The response during therapy was 86.9% in arm A and 80.0% in arm B. Median survival in arm A was 11.8 months and in arm B 11.6 months (P=0.37). CONCLUSIONS: The combination of topotecan and carboplatin is active in extensive-disease SCLC. Toxicity and median survival were comparable in both arms. Three days of treatment seems to be similar to the 5-day regimen.

Adolescent↗
PubMed2004

Accelerated kindling development in mu-opioid receptor deficient mice.

The relevance of mu-opioid systems for central excitability and kindling related disturbed learning performance was underlined by investigations using mu-opioid receptor knockout mice. Mice lacking mu-opioid receptors showed an accelerated kindling development induced by the convulsant drug pentylenetetrazol. Blockade of delta-opioid receptors by naltrindole suppressing kindling development in wild-type animals led to a further acceleration of kindled seizure development in the knockout mice. Mice lacking mu-opioid receptors showed such a low learning performance in the shuttle box, that the kindling induced learning deficit as seen in wild-type mice was not detected. The results were discussed on the basis of receptor binding studies with regard to subtypes of glutamatergic receptors, delta-opioid and somatostatin receptors. An increase in glutamate and somatostatin binding could contribute to the enhanced excitability in the-mu-opioid receptor knockout mice.

Animals↗
PubMed2004

Outcome of children with high-risk acute lymphoblastic leukemia (HR-ALL): Nordic results on an intensive regimen with restricted central nervous system irradiation.

BACKGROUND: Improvement in outcome of childhood high-risk (HR) ALL was sought with a very intensive Nordic protocol leaving most patients without CNS-RT. METHODS: A total of 426 consecutive children entered the NOPHO-92 HR-ALL program. HR criteria included WBC > or =50 x 10(9)/L, CNS or testicular involvement, T-cell, lymphomatous features, t(9;22), t(4;11), or slow response. Of these, 152 children had very high risk (VHR) with special definitions. CNS consolidation was based on high-dose MTX (8 g/m2) and ARA-C (12 g/m2) alternating. VHR patients also received cranial RT. RESULTS: The 9-year EFS was 61 +/- 3%, OS 74 +/- 2%, and EFS for T-ALL 62 +/- 4%. Cumulative incidence of isolated CNS relapse was 4.7 +/- 1%, and CNS relapse in total 9.9 +/- 2%. Poor prognostic factors were WBC > or =200 x 10(9)/L and a very slow response. CONCLUSIONS: HR-ALL was successfully treated on the NOPHO-92 regimen, with a relatively low CNS relapse rate for non-irradiated children. WBC > or =200 x 10(9)/L and very slow response emerged as strong poor prognostic factors.

Adolescent↗
PubMed2004

Photocatalytical polishing of paper-mill effluents.

Photocatalytic oxidation (PCO) is a promising technology for purification of biological pretreated wastewater or destruction of non-biodegradable compounds. For this reason PCO has been investigated as a last step of purification of biologically pre-treated paper-mill effluents. The influence of the parameters pH, TiO2-modification, TiO2-concentration, catalyst re-use, concentration of substances to be oxidised (wastewater quality) has been determined. The TOC of the biologically pretreated wasterwater was up to 55 mg L(-1). This wastewater was treated with a previously presented aerated cascade photoreactor which was modified for batch experiments. A high specific oxidation rate of up to 0.76 g TOC m(-2) h(-1) as well as a complete TOC mineralization has been achieved after the optimisation of the process parameters. The complete destruction of recalcitrant compounds will offer the opportunity to reuse the wastewater in the production process. The increase of the BOD5/TOC ratio after a short irradiation period indicates the transformation of recalcitrant organic compounds to better biodegradable intermediates. The use of PCO as a pre-treatment step for the enhancement of the biodegradability of wastewater, containing recalcitrant or inhibitory compounds is an alternative to a long and energy-intensive total pollutant mineralization.

Biodegradation, Environmental↗
PubMed2004

Textile wastewater treatment and reuse by solar catalysis: results from a pilot plant in Tunisia.

Based on results from bench-scale flow-film-reactors (FFR) and aerated cascade photoreactors, a solar catalytic pilot plant has been built at the site of a textile factory. This plant has an illuminated surface area of 50 m2 and is designed for the treatment of 1 m3 h(-1) of wastewater. The preliminary results are presented and compared with a bench-scale FFR using textile wastewater and dichloroacetic acid. Equivalent degradation kinetics were obtained and it was demonstrated that the solar catalytic technology is able to remove recalcitrant compounds and color. However, on-site optimization is still necessary for wastewater reuse and for an economic application.

Catalysis↗
PubMed2003

Effect of cadmium on gonadogenesis and metamorphosis in Pleurodeles waltl (urodele amphibian).

In the amphibian Pleurodeles waltl, steroid hormones play a key role in sex differentiation. Since cadmium has been reported to block receptors of sex steroid hormones, we analyzed the effects of this heavy metal on Pleurodeles larvae gonadogenesis. At stage 42, larvae die in the presence of 10.9 microM Cd in the rearing tap water, with TL(50) of 46.3 h, but the concentration of 5.5 microM is tolerated for more than 60 days. When used at 5.5 microM cadmium accumulation measured by atomic absorption spectrophotometry (AAS) in total homogenates of larvae at stage 54 (after 77 days of exposure to the heavy metal) reached 58.1 microg/g of dry weight. At stage 54, we did not detect inhibitory effects on gonadogenesis in larvae reared in the presence of 5.5 microM Cd since stage 42. When the exposure to 5.5 microM Cd was lengthened after stage 54, metamorphosis was delayed and could not be completed. When larvae were exposed to 10.9 microM Cd from stage 54, metamorphosis did not occur and gonad development was stopped. Our study demonstrates a lack of a direct effect of cadmium on sex determination-differentiation but a strong inhibitory effect on metamorphosis, which impairs further gonadal development.

Analysis of Variance↗
PubMed2003

Use of PCR-RFLP for differentiation of calliphorid larvae (Diptera, Calliphoridae) on human corpses.

Blowfly larvae found on human corpses are important for the estimation of the postmortem interval (PMI) and other questions of forensic relevance. Some of these species are difficult to differentiate morphologically, therefore a molecular method was elaborated for species identification. Specific fragments of the COI and COII region of the mitochondrial DNA (mtDNA) were amplified followed by digestion with different restriction enzymes. Using a 1.3 kb fragment, identification of Lucilia sericata, Calliphora vicina and Calliphora vomitoria was possible by digestion with only one restriction enzyme using either DraI or HinfI. Furthermore, we sequenced 349 bp (a part of the COI and COII regions) from the same three species and found 34 nucleotide distinctions between C. vicina and L. sericata, 30 between C. vomitoria and L. sericata and 15 between the two Calliphora species. These results aid in quick identification of species used for estimation of PMI.

Animals↗
PubMed2002

Larder beetles (Coleoptera, Dermestidae) as an accelerating factor for decomposition of a human corpse.

Larder beetles are known to feed directly upon decomposing carrion, with a preference for dried carrion. Under optimal environmental conditions (dry and warm), they can appear in large numbers. In our case, the mummified corpse of a human male was nearly skeletonized in less than 5 months in his apartment with windows closed and a room temperature between 25 degrees C (near the radiator) and 19.4 degrees C (near the body). There were very few empty fly pupae in the apartment, but a lot of adult hide beetles, their larvae and larval cast skins (exuviae) (Dermestes maculatus DEG.) belonging to the family of the larder beetles (Dermestidae). The beetles skeletonized the human corpse in such a short time because of ideal conditions for them in the apartment (dry and warm) making the body an optimal feeding ground because of his mummification.

Aged↗
PubMed2001

No disadvantage in outcome of using matched unrelated donors as compared with matched sibling donors for bone marrow transplantation in children with acute lymphoblastic leukemia in second remission.

PURPOSE: We evaluated the outcome of children with acute lymphoblastic leukemia (ALL) in second remission (2CR), comparing bone marrow transplantation (BMT) using either matched sibling donors or unrelated donors (URDs). PATIENTS AND METHODS: A total of 65 patients, aged 2 months to 20 years at BMT, with ALL in 2CR underwent allogeneic BMT at seven Nordic centers during 1990 to 1997. Of the first relapses, 85% were in bone marrow; 46% occurred on therapy, and 54%, off therapy. The preparative regimens were cyclophosphamide plus total-body irradiation +/- antithymocyte/antilymphocyte globulin, busulfan plus cyclophosphamide +/- antithymocyte/antilymphocyte globulin, or cytarabine plus total-body irradiation. Of the allografts, 37 were from HLA-matched siblings and 28 were from URDs. RESULTS: In the sibling versus URD graft recipient groups, the posttransplantation 5-year event-free survival was 39% versus 54% (P =.4), the estimated posttransplantation relapse rate was 76% versus 40% (P = not significant [NS]), and the toxic death rate was 19% versus 11% (P = NS). The incidence of significant (grade 2 to 4) acute graft-versus-host disease (GVHD) was 38% versus 64% (P <.05) and was 14% versus 32% (P <.10) for severe (grade 3 to 4) acute GVHD; the incidence of chronic GVHD was 26% versus 57% (P <.05) and was 13% versus 22% (P = NS) for extensive chronic GVHD in the sibling and URD groups. CONCLUSION: BMT with matched URD allografts offers at least equal survival for children with ALL in 2CR, as compared with allografts from matched sibling donors. URD allografts were not associated with a higher toxic mortality rate, although both acute and chronic GVHD were more frequent with URD. Indications for using matched URD allografts in ALL 2CR can be considered the same as for using matched sibling donors.

Adolescent↗
PubMed2001

Loss of locomotor sensitisation in response to morphine in D1 receptor deficient mice.

Mice lacking D1 receptors were used to study the role of these receptors in morphine-induced antinociception and locomotor sensitisation. In the hot-plate test D1 receptor deficient (-/-) and wild-type (+/+) mice showed similar reaction times under basal conditions. A single injection of 1.25 mg/kg and 2.5 mg/kg morphine resulted in a stronger antinociceptive response in D1 receptor deficient mice than in wild-type animals. Tolerance to the analgesic effect did not develop in both groups of animals when 12.5 mg/kg morphine was chronically applied twice daily for 13 days. There was no change in basal locomotor activity between saline-injected wild-type and D1 receptor deficient mice. After chronic treatment wild-type mice showed a continuous increase in locomotor activity, indicating the development of sensitisation. In contrast, a subchronic administration of morphine did not change locomotor activity in mutant mice. The lack of the development of locomotor sensitisation in D1 deficient mice was associated with reduced levels of immunoreactive mu opioid receptors in dorsal striatal patches as compared to wild-type mice. In contrast, no change in the distribution of immunoreactive mu receptors could be detected in areas related to pain pathways such as the spinal cord. Taken together, these results suggest an involvement of D1 receptors in morphine-induced locomotor activity and analgesia.

Analgesics, Opioid↗
PubMed2000

Free radical production and changes in superoxide dismutases associated with hypoxia/reoxygenation-induced apoptosis of embryonic rat forebrain neurons in culture.

Following hypoxia/reoxygenation (6h/96h), cultured neurons from the embryonic rat forebrain undergo delayed apoptosis. To evaluate the participation of oxidative stress and defense mechanisms, temporal evolution of intraneuronal free radical generation was monitored by flow cytometry using dihydrorhodamine 123, in parallel with the study of transcriptional, translational, and activity changes of the detoxifying enzymes Cu/Zn-SOD and Mn-SOD. Two distinct peaks of radical generation were depicted, at the time of reoxygenation (+ 27%) and 48 h later (+ 25%), respectively. Radical production was unaffected by caspase inhibitors YVAD-CHO or DEVD-CHO, which prevented neuronal damage, suggesting that caspase activation is not an upstream initiator of radicals in this model. Cell treatment by vitamin E (100 microM) displayed significant neuroprotection, whereas the superoxide generating system xanthine/xanthine oxidase induced apoptosis. Transcript and protein levels of both SODs were reduced 1 h after the onset of hypoxia, but activities were transiently stimulated. Reoxygenation was associated with an increased expression (139%), but a decreased activity (21%) of the inducible Mn-SOD, whereas Cu/Zn-SOD protein and activity were low and progressively increased until 48 h post-hypoxia, when the second rise in radicals occurred. In spite of a temporal regulation of SODs, which parallels radical formation, oxidative stress might account for neurotoxicity induced by hypoxia.

Aerobiosis↗
PubMed2000

High-performance liquid chromatographic analysis of muscular interstitial arginine and norepinephrine kinetics. A microdialysis study in rats.

Complex interactions between the L-arginine/nitric oxide synthase (NOS) pathway and the sympathetic nervous system have been reported. Methods capable of measuring L-arginine and norepinephrine (NE) have mainly been reported for plasma. We report the use of the microdialysis technique combined with high-performance liquid chromatography (HPLC) for measurement of both L-arginine and NE within the same tissue microdialysis sample. The microdialysis probe consisted of linear flexible probes (membrane length: 10 mm, outside diameter: 290 microm, molecular weight cut-off 50 kDa). The method used for L-arginine measurement was HPLC with fluorescence detection, giving a within-run and a between-day coefficient of variation of 2.9 and 12.8%, respectively. The detection limit was 0.5 pM/20 microl injected for L-/D-arginine. The method used for NE measurement was HPLC with electrochemical detection. The coefficients of variation were 4% for within-assay precision and 7.5% for between-assay precision. The detection limit for NE was 1 fmol/20 microl injected. The microdialysis technique coupled with HPLC system was validated in vivo to measure muscular interstitial concentrations of both arginine and NE under baseline conditions and after intravenous infusion of 500 mg/kg of L-arginine or D-arginine. In conclusion, the microdialysis technique coupled to HPLC allows the simultaneous measurements of both L-arginine and NE within the same tissue microenvironment and will enable the study of the complex interactions between the L-arginine/NO pathway and sympathetic nervous system within the interstitial space of different organs.

Animals↗
PubMed2000

Differential effects of acyl-CoA binding protein on enzymatic and non-enzymatic thioacylation of protein and peptide substrates.

Both enzymatic and autocatalytic mechanisms have been proposed to account for protein thioacylation (commonly known as palmitoylation). Acyl-CoA binding proteins (ACBP) strongly suppress non-enzymatic thioacylation of cysteinyl-containing peptides by long-chain acyl-CoAs. At physiological concentrations of ACBP, acyl-CoAs, and membrane lipids, the rate of spontaneous acylation is expected to be too slow to contribute significantly to thioacylation of signaling proteins in mammalian cells (Leventis et al., Biochemistry 36 (1997) 5546-5553). Here we characterized the effects of ACBP on enzymatic thioacylation. A protein S-acyltransferase activity previously characterized using G-protein alpha-subunits as a substrate (Dunphy et al., J. Biol. Chem., 271 (1996) 7154-7159), was capable of thioacylating short lipid-modified cysteinyl-containing peptides. The minimum requirements for substrate recognition were a free cysteine thiol adjacent to a hydrophobic lipid anchor, either myristate or farnesyl isoprenoid. PAT activity displayed specificity for the acyl donor, efficiently utilizing long-chain acyl-CoAs, but not free fatty acid or S-palmitoyl-N-acetylcysteamine. ACBP only modestly inhibited enzymatic thioacylation of a myristoylated peptide or G-protein alpha-subunits under conditions where non-enzymatic thioacylation was reduced to background. Thus, protein S-acyltransferase remains active in the presence of physiological concentrations of ACBP and acyl-CoA in vitro and is likely to represent the predominant mechanism of thioacylation in vivo.

Acetyltransferases↗
PubMed2000

Lack of expression of long-term potentiation in the dentate gyrus but not in the CA1 region of the hippocampus of mu-opioid receptor-deficient mice.

The possible involvement of the mu-opioid receptor subtype in mechanisms of long-term potentiation (LTP) of the lateral perforant pathway to the dentate gyrus neurons, as well as of the Schaffer collateral-commissural input of CA1 neurons, was investigated using mu-opioid receptor-deficient mutant mice. In transversal hippocampal slices from mice lacking the mu-opioid receptor (MOR) only a short potentiation in the dentate gyrus after tetanization of the lateral perforant pathway was found. In contrast, the loss of the mu-opioid receptor in the CA1 region did not affect the potentiation of the field potentials induced by tetanization of the Schaffer collaterals. In parallel experiments, the application of 10 microM of the selective MOR-antagonist, funaltrexamine, decreased LTP in the dentate gyrus of wild-type mice but again did not alter the potentiation of the field potentials in the CA1. The loss of MOR-binding in the hippocampus was accompanied by a reduction in D2-binding sites indicating a possible compensatory role of the dopaminergic system. The D1- and glutamate binding was not affected. These observations confirm earlier results with pharmacological blockade of opioid receptors in the dentate gyrus and demonstrate an essential role of MOR activation for the generation of LTP in the dentate gyrus of the mouse but not necessarily in the CA1 region.

Action Potentials↗
PubMed2000

Morphine self-administration in mu-opioid receptor-deficient mice.

Morphine-induced place preference was demonstrated recently in wild-type mice, whereas this conditioned behaviour was not observed in mu-opioid receptor-deficient mice. In the present study, we investigated locomotor effects of subcutaneously (s.c.) injected morphine as well as intracerebroventricular (i.c.v.) morphine self-administration in mu-opioid receptor-knockout mice. After s.c. morphine injection, locomotor activity significantly increased in wild-type animals. As expected, in the self-administration test the rate of self-administration constantly increased in wild-type mice reflecting reward effects of morphine. This increase was independent of locomotor/motor activity. In contrast, self-administration rates and locomotor/motor activity significantly decreased in the receptor-deficient animals. It was shown that this aversive effect might partly be due to kappa-opioid receptor interaction.

Analysis of Variance↗
PubMed2000

Body distribution of 3H-labelled dalargin bound to poly(butyl cyanoacrylate) nanoparticles after i.v. injections to mice.

The blood-brain barrier (BBB) limits the penetration of substances into the brain. Because many drugs, particularly peptides, therefore can not be delivered to the brain, carrier systems were developed to overcome this problem. In earlier studies we demonstrated central analgesic effects of a peptide, dalargin (dal), after systemic administration when this substance was bound onto the surface of polybutylcyanoacrylate nanoparticles and coated with polysorbate 80 but not when it was given alone. The aim of the present study was to investigate the body distribution of 3H-labelled dal bound to nanoparticles compared to unbound dal after i.v. injection in mice. The radioactivity in several tissues, including the brain, was separated in subcellular preparations and was measured after a single i.v. injection over time. Dal radioactivity level in brain preparations was 3 times higher when the drug was bound to nanoparticles whereas the first pass pathway in liver was reduced. The results support previous data that nanoparticles can be used to transport peptides across the BBB.

Animals↗