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Biomedical subjects

M Söderberg

Publications and source records attributed to M Söderberg.

At least 37 records · Page 2Linked to original sources
PubMed1996

Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis.

Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic patients, the percentage of eosinophils correlated with ECP in bronchial lavage fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of eosinophilic activation. A negative correlation was found for the percentage of eosinophils in BBB with levels of provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) for the asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy method appears to give information on the changes present in superficial bronchial epithelium in inflammatory airways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma.

Administration, Inhalation↗
PubMed1994

Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting--the Nordic experience.

An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Isoprenoids in aging and neurodegeneration.

During aging the human brain shows a progressive increase in levels of dolichol, a reduction in levels of ubiquinone, but relatively unchanged concentrations of cholesterol and dolichyl phosphate. In a neurodegenerative disease, Alzheimer's disease, the situation is reversed with decreased levels of dolichol and increased levels of ubiquinone. The concentrations of dolichyl phosphate are also increased, while cholesterol remains unchanged. This study shows that the isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging and that this disease cannot, therefore, be regarded as a result of premature aging. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of glycosylation in the diseased brain and the increase in the endogenous anti-oxidant ubiquinone an attempt to protect the brain from oxidative stress, for instance induced by lipid peroxidation.

Adult↗
PubMed1994

Content and fatty acid composition of cardiolipin in the brain of patients with Alzheimer's disease.

The frontal, temporal and occipital cortex from human brains affected by Alzheimer's disease were analyzed for their contents and fatty acid compositions of cardiolipin. Phospholipids were purified using an HPLC system and cardiolipin was found to be present in the same amount (on a protein basis) as in age-matched controls. One-third of the total fatty acyl moieties of this phospholipid were saturated, one-third monounsaturated and one-third polyunsaturated. In affected brain regions the levels of certain polyunsaturated fatty acids displayed moderate decreases, not exceeding 10-15%. However, the total amount of polyunsaturated fatty acids decreased by only 9%. These results demonstrate that the amount and structure of brain cardiolipin are not modified to any great extent in connection with Alzheimer's disease.

Aged↗
PubMed1993

Phase I study of tauromustine administered in a weekly schedule.

Tauromustine was administered orally in weekly doses with interindividual dose escalation to patients with disseminated malignant melanoma. The dose in the first cohort of 6 patients was 20 mg/m2/week. The dose escalation was 5 mg/m2/week. The limit of tolerance was 55 mg/m2/week. 99 patients completed at least 8 weeks of treatment and eight dose levels were evaluated for toxicity. Reversible thrombocytopenia, and to a lesser degree leukopenia, were dose limiting. From a starting dose of 40 mg/m2/week, the long-term tolerated dose was 35 mg/m2/week, thus achieving a considerable increase of dose intensity without a significant increase of toxicity by employing this weekly schedule of tauromustine.

Administration, Oral↗
PubMed1993

Inhaled methacholine does not influence the cellular composition of bronchoalveolar lavage fluid.

A methacholine or a histamine test is often used to quantitate bronchial responsiveness, in studies investigating the influence of various inhaled stimuli on the responsiveness and composition of bronchoalveolar lavage (BAL) fluid. Histamine has been shown to evoke an inflammatory cell response in BAL fluid. In order to test the influence of the methacholine test on the cellular composition of BAL fluid, we investigated 14 healthy, nonsmoking volunteers with a methacholine test 24 h before performing a BAL. The results showed no significant changes in the cellular composition of BAL fluid, as compared with control BAL in the same persons.

Administration, Inhalation↗
PubMed1993

Bronchial mucosal structure after histamine inhalation.

Previous studies have shown an increased number of inflammatory cells and an increased level of hyaluronan in the bronchoalveolar lavage (BAL) fluid, 24 h after the inhalation of histamine. In the present report, the influence of histamine inhalation on the bronchial mucosa was, therefore, investigated in 20 subjects. Scanning electron microscopy (SEM) revealed that small areas of the mucosal surface were altered or lacked cilia more frequently in the bronchial biopsies taken 24 h after the inhalation of histamine than in the control biopsies. In contrast, light and transmission electron microscopy revealed no increase in epithelial damage and no changes in the subepithelial morphology. The results indicate that inhalation of histamine does not significantly alter the structure of the bronchial mucosa, which means that bronchial biopsies can be taken for routine morphological examination within 24 h after a histamine test. When using the biopsies in research, one should consider the possible influence of the histamine test.

Adult↗
PubMed1992

Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of Alzheimer's type.

The lipid compositions of 10 different brain regions from patients affected by Alzheimer's disease/senile dementia of Alzheimer's type were analyzed. The total phospholipid amount decreased somewhat in nucleus caudatus and in white matter. The cortical areas that are morphologically affected by Alzheimer's disease, i.e., frontal and temporal cortex and the hippocampus, showed elevated contents of lipid solvent-extractable phosphatidylinositol. Sphingomyelin content was decreased in regions rich in myelin. There was a 20-50% decrease in dolichol amount in all investigated parts of the brain, but no change was seen in the polyisoprenoid pattern. Levels of alpha-unsaturated polyprenes were decreased in Alzheimer brains. Dolichyl-phosphate content increased in most regions, up to 100%. In both control and Alzheimer tissue almost all of the dolichyl-phosphate was covalently bound, apparently through glycosylation. Cholesterol amounts were highly variable but mostly unchanged, whereas ubiquinone concentrations increased by 30-100% in most regions in brains affected by Alzheimer's disease. These results demonstrate that both phospholipids and neutral lipids are modified in brains affected by Alzheimer's disease/senile dementia of Alzheimer's type.

Aged↗
PubMed1992

Ubiquinone, dolichol, and cholesterol metabolism in aging and Alzheimer's disease.

The lipid compositions of various regions of the human brain were investigated during aging and in Alzheimer's disease. The phospholipid amounts and compositions remained unchanged during aging. There were, however, considerable differences both in phospholipid composition and amount when the various regions were compared. The level of dolichol increased severalfold in all regions up to the age of 70, but there was no further elevation thereafter. The ubiquinone level decreased significantly in all parts of the brain upon aging. In Alzheimer's disease, the dolichol level was decreased in all regions, and particularly, in those affected by the disease. In contrast, the dolichyl-P concentration increased in those regions that exhibited morphological changes. There was no modification in cholesterol distribution, but a significant elevation in ubiquinone content was observed in most regions. The only phospholipid whose level was elevated was phosphatidylinositol, and only in those parts of the brain that were affected. The content of polyunsaturated fatty acids in phosphatidylethanolamine was greatly decreased in connection with the disease, with a parallel increase in the saturated portion. The results indicate that Alzheimer's disease results in specific and significant changes in the levels of lipid products of the mevalonate pathway in the brain.

Aged↗
PubMed1991

Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease.

The two major phospholipid classes, namely, phosphatidylethanolamines (PE) and phosphatidylcholines (PC), were studied in four different regions of human brain, i.e., in frontal gray matter, frontal white matter, hippocampus and in pons. The fatty acid (FA) compositions of these phospholipids were found to be specific for the different regions. PC contains mostly saturated and 18:1 FA, while PE is rich in polyunsaturated FA. Aging has no influence on the FA compositions, while in Alzheimer's disease (AD) PE is modified in all four regions, particularly in frontal gray matter and in hippocampus. The abundance of the major monounsaturated FA of PE, 18:1, is not significantly altered in Alzheimer's disease, but there is a substantial increase in the relative amounts of the saturated components 14:0, 16:0 and 18:0. This is paralleled by a decrease in the polyunsaturated FA 20:4, 22:4 and 22:6. It is not clear whether the changes observed are specific for AD. Changes in saturated/polyunsaturated FA ratio are likely to influence cellular function, which in turn may cause certain neural deficiencies. The findings do not support the hypothesis that AD reflects an accelerated aging process.

Adult↗
PubMed1991

Effect of cetirizine on histamine-induced bronchoconstriction and bronchoalveolar cells.

The effect of the histamine H1 receptor antagonist (cetirizine) on histamine-induced bronchoconstriction and inflammatory cells in bronchoalveolar lavage fluid was studied in 12 healthy volunteers. In previous studies we have observed an increased number of inflammatory cells, albumin and hyaluronan in the bronchoalveolar lavage (BAL) fluid 24 h after an inhalation challenge test with histamine-chloride. In the present study certirizine blocked the histamine-induced bronchoconstriction but did not influence the cell counts in the bronchoalveolar lavage fluid. Our result suggests that the histamine-induced bronchoconstriction but not the recruitment of inflammatory cells in the BAL fluid is mediated by histamine H1 receptors.

Adult↗
PubMed1990

Uptake and metabolism of dolichol and cholesterol in perfused rat liver.

The uptake of dolichol and cholesterol by perfused rat liver was studied. When these radioactive lipids were incorporated into egg phosphatidylcholine liposomes, both dolichol and cholesterol appeared initially in the supernatant and in the microsomal fraction and, later on, in the mitochondrial-lysosomal fraction. The lipids taken up were esterified to some extent, but no phosphorylation of dolichol occurred. Incorporation of dolichol and cholesterol into lipoproteins increased the efficiency of uptake, which was receptor-mediated in this case. Accumulation of these lipids occurred in lysosomes followed by a transport to the endoplasmic reticulum (ER). Both labeled dolichol and cholesterol appeared in the bile. In the case of dolichol, the majority of this radioactivity was not associated with the original substance itself, and probably represented lipid-soluble catabolites. In the case of cholesterol, most of the radioactivity was associated with bile acids. It appears that, in contrast to the receptor-mediated uptake of lipoproteins from the perfusate, the uptake of liposomal lipids involves a different mechanism. After association with the plasma membrane, the lipids enter into the cytoplasm and are transported to the ER and later to the lysosomes.

Animals↗
PubMed1990

Lipid compositions of different regions of the human brain during aging.

The neutral and phospholipid compositions of various regions of the human brain were analyzed using autopsy material covering the life period between 33 and 92 years of age. The protein content was also measured and, on a weight basis, this content is unchanged in the cerebellum, pons, and medulla oblongata, whereas in the 90-year-old group it decreases in the hippocampus, gray matter, and nucleus caudatus. In white matter, the protein content decreases continuously with age. The phospholipid composition is characteristic of the region investigated, but remains unchanged during aging. The total phospholipid content exhibits only a 5-10% decrease in the oldest age group. The content of dolichol and its polyisoprenoid pattern are also characteristic of the region analyzed. Between 33 and 92 years of age, the amount of dolichol in all portions of the brain increases three- to fourfold, but the isoprenoid pattern remains constant. The level of dolichyl-P varies between different regions, but only a moderate increase is seen with age. Ubiquinone content is highest in the nucleus caudatus, gray matter, and hippocampus, and in all areas this content is decreased to a great extent in the oldest age groups. All regions of the human brain are rich in cholesterol, but alterations in the amount of this lipid are highly variable during aging, ranging from no change to a 40% decrease.

Adult↗
PubMed1990

Plasma pharmacokinetics of Idarubicin and its 13-hydroxymetabolite after intravenous and oral administration under fasting and non-fasting conditions.

The plasma pharmacokinetics of Idarubicin and its 13-hydroxy-metabolite have been studied in 10 patients with solid tumours after intravenous and oral administration under fasting and non-fasting conditions in a randomized cross-over design. The plasma concentration time curves of Idarubicin after intravenous administration could be described by the open two or three compartment models. No pharmacokinetic modelling of Idarubicin was possible after oral administration. After oral administration of Idarubicin, the amount of intact drug was higher under non-fasting conditions. The extensive and long-lasting appearance of Idarubicinol suggests that this cytotoxic metabolite is of major clinical importance in i.v. and oral therapy with Idarubicin. The pharmacokinetics of Idarubicinol was not affected by food intake.

Administration, Oral↗