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Biomedical subjects

M Sandström

Publications and source records attributed to M Sandström.

49 records · Page 3Linked to original sources

Brainstem response audiometry in chronic Lyme borreliosis.

Auditory brainstem responses (ABR) were investigated in 26 patients with acrodermatitis chronic atrophicans, which is a late manifestation of Lyme borreliosis. Nine of the patients showed pathological ABR, four of them unilaterally and five bilaterally. The main pathological findings were: 1) Poor reproducibility of waves IV-V or of wave V; 2) Increased latency of wave V. After antibiotic treatment, ABR was improved in eight of the nine patients, and in three of them it was normal. In the five patients who did not completely recover, the improvement consisted in better reproducibility and a tendency towards normal wave V latencies. The results of this study indicate that the central nervous system may become involved in patients with acrodermatitis chronica atrophicans.

Adult↗

Cellular metabolism of arsenocholine.

The biotransformation of arsenocholine and arsenobetaine, which are organic arsenic compounds present in certain aquatic organisms, has been studied in vitro using synthetic reference substances. Incubation of arsenocholine with different liver cell fractions showed arsenocholine to be biotransformed only in presence of the mitochondrial fraction. The biotransformation products were arsenobetaine aldehyde, arsenobetaine, trimethylarsine oxide and trimethylarsine. Arsenobetaine was the major metabolite and it was formed via arsenobetaine aldehyde. Trimethylarsine oxide was formed via a side reaction from arsenobetaine aldehyde. Further reduction of trimethylarsine oxide, produced trimethylarsine. In vitro studies of arsenobetaine, did not show any formation of trimethylarsine oxide or trimethylarsine. Furthermore, cytotoxicity of arsenobetaine or arsenocholine in isolated hepatocytes was not observed.

Alcohol Oxidoreductases↗

Biotransformation of dimethylarsinic acid in mouse, hamster and man.

The metabolism of dimethylarsinic acid (DMA) a common pesticide and the main metabolite of inorganic arsenic in mammals, has been studied in mice, hamsters and man. Mice and hamsters were administered a single dose of 74As-DMA (40 mg As/kg body weight) orally, while a human subject ingested DMA corresponding to 0.1 mg As/kg body weight. Ion exchange chromatography, paper electrophoresis, thin layer chromatography as well as arsine generation--gas chromatography combined with atomic absorption spectrophotometry or mass spectrometry were used to characterize the arsenic metabolites in urine and feces collected over 48 hours after treatment. In mice and hamsters 3.5% and 6.4% of the dose, respectively, were excreted in urine in the form of trimethylarsine oxide (TMAO). No TMAO was found in feces. A DMA-complex was detected in urine and feces. It amounted to about 13% of the dose in mice and 15% in hamsters. About 80-85% of the dose was eliminated in urine and feces in the form of unmetabolized DMA. No demethylation of DMA to inorganic arsenic was observed. In man, about 4% of the dose was excreted in urine as TMAO and about 80% as DMA.

Adult↗

Effects of protracted exposure to low intensity radio frequency fields on CHO cells in culture.

This study was performed in order to investigate the biological effects of chronic exposure to low intensity radio frequency fields. By using CHO cells in culture, it was possible to extend exposure to several cell generations. The RF field consisted of a 27 MHz magnetic field (6 A/m), which produces a specific absorption rate of 1 W/kg. Exposure was continued for two to five days. The cells were then studied with respect to certain cell biological parameters: vital staining, plating efficiency, growth rate, volume and physical properties of the intracellular water, as measured by NMR. Scanning electron microscopy studies were also performed. A significant difference between exposed and control cells was found only with respect to intracellular water. A 10% decrease in line width which may indicate a corresponding increase in the spin-spin relaxation time was noted after exposure. A change in the colony forming pattern was also observed in thin cultures after two days of exposure.

Animals↗

Cell physiological effects of radiofrequency electromagnetic fields.

Ovarian and body cavity eggs from R. temporaria were exposed to radiofrequency (rf) electromagnetic fields in the frequency range 10-27 MHz with specific absorption rates (SAR) up to 800 W/kg. The effect of the exposure was investigated by measurement of the water-related cell physiological parameters, isotopic and osmotic water membrane permeability and density of the egg cells. Only the osmotic water permeability, Pf, of ovarian eggs was significantly altered. A decrease of about 30% was seen for SARs of 50 W/kg and exposure times up to 2 h. Tests ruled out that the effect was due to temperature increase during the exposure. The observed decrease of Pf was most likely due to cloudy swelling of the egg cytoplasm resulting from the rf irradiation.

Animals↗

Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression.

Various proteases and their inhibitors have been shown to be important in tumor invasion. Angiogenesis is further a prerequisite for the growth and progression of solid tumors. Since these systems are functionally linked, in situ hybridization and in situ zymography were used to investigate the spatial and temporal expression of factors representative of the plasmin/plasminogen system and of an angiogenic factor in the BT4C glioma model. This tumor is invasive with a high grade of neovascularization. Tissue-type plasminogen activator urokinase-type plasminogen activator and plasminogen activator inhibitor-1 mRNA were expressed in glioma cells during the entire tumor growth. Early in the tumor development the expression was found throughout the small tumor (approximately 10 mm3) while later in the time course the expression was found predominantly in the invasive tumor border of the tumor. The in situ zymography demonstrated that the plasminogen activators were translated into functional proteins. Vascular endothelial growth factor mRNA was expressed following a similar spatial and temporal pattern with an early expression in the entire small tumor while later, in larger tumors, it was exclusively expressed in the invasive tumor edge. In normal brain, the ventricular ependyma, meninges, as well as scattered neurons expressed tissue-type plasminogen activator mRNA. Vascular endothelial growth factor mRNA was observed in the choroid plexus, and in scattered cells in normal brain tissue. Our finding may suggest a functional co-operation of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1 and vascular endothelial growth factor during glioma progression. This model could be of value when evaluating different treatment modalities aimed at blocking the migrating capacity and growth of glial tumors.

Animals↗

Haematological toxicity following different dosing schedules of 5-fluorouracil and epirubicin in rats.

AIM: To study the effects of single and fractionated doses of 5-fluorouracil and epirubicin on the leukocyte counts in rats. METHODS: Six different dosing patterns of each drug were injected within one day. The leukocytes were followed for 11-15 days. Pharmacokinetic models were developed using NONMEM. Quantitative and qualitative pharmacokinetic-pharmacodynamic relationships were investigated. RESULTS: A one-compartment model with non-linear elimination described 5-fluorouracil pharmacokinetics and a three-compartment model described epirubicin concentration data. Sigmoidal or basic Emax-models quantified the relationships between individual AUCs and decreases in leukocytes, for both drugs. Similar relationships between AUC and toxicity were found, regardless of whether the drugs were given as single or fractionated doses. CONCLUSION: Quantitative relationships between AUC and the effect on leukocytes were established for 5-fluorouracil and epirubicin. However, no schedule dependence was indicated for the schedules used in the study.

Animals↗