Biomedical subjects

T Andersson

Publications and source records attributed to T Andersson.

At least 145 records · Page 8Linked to original sources

PubMed1992

Glucocorticoid-mediated potentiation of P450 induction in primary culture of rainbow trout hepatocytes.

Induction of 7-ethoxyresorufin O-deethylase activity (a cytochrome P450IA-dependent activity) by beta-naphthoflavone (0.36 microM) is increased 2-3-fold by dexamethasone or cortisol (10(-9)-10(-7) M) in rainbow trout hepatocyte cultures. This potentiation does not seem to be a time-dependent process and could be a classical glucocorticoid receptor-mediated event resulting in enhanced transcriptional activation of the CYP1A, as previously shown in mammals. Since glucocorticoid levels can increase in fish exposed to pollutants, such steroids may interfere with the induction response to xenobiotics.

Animals↗

PubMed1992

Complement receptor-mediated phagocytosis is associated with accumulation of phosphatidylcholine-derived diglyceride in human neutrophils. Involvement of phospholipase D and direct evidence for a positive feedback signal of protein kinase.

Complement receptor (CR)-mediated phagocytosis is associated with an increased accumulation of diglyceride (sn-1,2-diacylglycerol and/or 1-O-alkyl-2-acyl-glycerol) in human neutrophils. The C3bi-mediated increase in diglyceride (5-20 min) was only partially impaired when phosphoinositide-specific phospholipase C (PLC) activity was abolished by reduction of cytosolic free Ca2+. At an early time point (1 min), however, diglyceride production was barely detectable in control cells, whereas production was considerable in cells with a reduced cytosolic free Ca2+ concentration. C3bi stimulation of 32P-labeled neutrophils caused a rapid and significant breakdown of [32P]phosphatidylcholine (PC) which was not affected by inhibition of Ca(2+)-dependent phosphoinositide-specific PLC. Thus, PC hydrolysis could be involved in C3bi-induced diglyceride formation. Stimulation of cells labeled with [3H]1-O-alkyl-lyso-PC ([3H]alkyl-lyso-PC), resulted in an increased formation of [3H]1-O-alkyl-phosphatidic acid ([3H]alkyl-PA) and a later and slower formation of [3H]1-O-alkyl-diglyceride ([3H]alkyl-diglyceride); this suggests activation of phospholipase D (PLD). When these labeled cells were stimulated in the presence of 0.5% ethanol a marked accumulation of [3H]1-O-alkyl-phosphatidylethanol ([3H]alkyl-PEt) was observed in both controls and calcium-reduced cells, further strengthening the suggested involvement of PLD activity. In parallel with the sustained increase in diglyceride formation, CR-mediated phagocytosis was also associated with phosphorylation of a cellular protein kinase C substrate (MARCKS). Therefore it seems reasonable to suggest a causal relationship between C3bi-induced PLD activation, which results in diglyceride formation, and activation of protein kinase C. In electropermeabilized cells which were incapable of ingesting particles, C3bi particles were still able to activate PLD and induce formation of diglyceride. This signaling event must therefore be triggered by binding of particles to the cell and not by the engulfment process. Most importantly, introduction of the protein kinase C inhibitor peptides, PKC(19-36) and PKC(19-31), into these permeabilized cells resulted in a clear reduction of the C3bi-induced production of diglyceride, indicating that CR-mediated activation of protein kinase C directly triggers a positive feedback mechanism for additional diglyceride formation. Taken together, these data further clarify the mechanisms of CR-mediated diglyceride formation and give added support to the concept that protein kinase C plays an important role in the phagocytic process.

Blotting, Western↗

PubMed1992

Pharmacokinetics of tranexamic acid in patients with ulcerative colitis and in healthy volunteers after the single instillation of 2 g rectally.

Topically applied antifibrinolytic drugs may be of value in the control of bleeding in active ulcerative colitis. Any impairment of systemic fibrinolysis in this condition, however, is potentially harmful. Since pharmacokinetic data after the rectal administration of tranexamic acid are non-existent, plasma concentration and recovery in the urine were recorded after a single dose of 2 g tranexamic acid given rectally to five patients with ulcerative colitis and to five healthy volunteers. The median area under the curve was, for the volunteers, 7.64 mg/L x hr (range: 4.43-11.56) and, for the patients, 13.84 mg/L x hr (range: 9.32-50.22) (P less than .05). The median 24-hour recovery in the urine was 0.8% (0.3-1.1) and 2.7% (1.1-4.0), respectively (P less than .05). The median peak plasma concentration was, for the volunteers, 0.40 mg/L (range: 0.20-0.69) 6 hours after administration and, for the patients, 1.10 mg/L (range: 0.53-2.90) 5 hours after administration (P less than .05). The plasma concentrations and recovery in the urine that were observed in the patients and volunteers were low compared with those seen after oral intake of the same dose. The plasma concentrations did not reach levels that were considered liable to impair systemic fibrinolysis.

Administration, Rectal↗

PubMed1992

No influence of single intravenous doses of omeprazole on theophylline elimination kinetics.

The influence of single intravenous doses of omeprazole on the pharmacokinetics of intravenously administered theophylline was studied in eight healthy male volunteers. In a partially randomized three-period crossover design, an IV infusion of theophylline (400 mg over 30 min) was combined with IV omeprazole (either 40 mg over 2.5 min or 80 mg over 5 min) or with IV placebo (over 2.5 min). Theophylline and omeprazole plasma concentrations were measured over 24 hours after the start of the infusions and pharmacokinetic parameters were calculated. The theophylline plasma concentration-time profiles after omeprazole coadministration were virtually identical to the corresponding profile after placebo administration. For each of the pharmacokinetic parameters of theophylline, the 90% confidence intervals of the omeprazole coadministrations were within the 80 to 120% bioequivalence range with respect to the placebo coadministration. Omeprazole plasma concentrations indicated a biexponential decline in most subjects, with a more rapid elimination after the 40-mg than after the 80-mg dose (P less than .01). Doubling the dose caused an almost three-fold increase of AUC resulting in a difference in clearance (P less than .02), whereas the volume of distribution was similar. The results of this study indicate that the metabolism of theophylline is not affected by single intravenous doses of omeprazole. The nonlinear pharmacokinetics of omeprazole are ascribed to saturation of its main metabolizing enzyme, S-mephenytoin hydroxylase.

Adult↗

PubMed1992

Interferon-gamma-like immunoreactivity in sensory neurons may influence the replication of Sendai and mumps viruses.

Rat dorsal root ganglia in tissue culture, which contain an interferon-gamma (IFN-gamma)-like immunoreactive subpopulation of neurons, were infected with paramyxoviruses. Sendai virus caused a substantial neuronal lysis, while the RW strain of mumps virus caused a much less pronounced nerve cell loss. Early during infection, the subpopulation of IFN-gamma-like immunoreactive neurons was less susceptible to mumps virus. Virus antigen was rapidly lost from surviving IFN-gamma-like positive neurons infected with Sendai virus, while this remarkable self-curing effect occurred in both nerve cell populations at later time points after mumps virus infection. By quantitative enzyme-linked immunosorbent assay (ELISA) technique, increased levels of "neuronal IFN-gamma" were recorded at 10 hr and 30 hr after infection with Sendai and mumps virus, respectively. This study indicates a role for the neuronal IFN-gamma-like molecule in determining the outcome of a viral infection in sensory ganglia.

Animals↗

PubMed1992

Lack of effect of omeprazole, cimetidine, and ranitidine on the pharmacokinetics of ethanol in fasting male volunteers.

The effects of three gastric antisecretory drugs on the pharmacokinetics of ethanol have been studied in a randomized crossover experiment. Male medical students (n = 12) took ethanol 0.8 g/kg body weight at 08.00 h after an overnight fast. On seven successive days before drinking ethanol they were given omeprazole 20 mg, cimetidine 800 mg, ranitidine 300 mg, or no drug, with a period of at least 7 days between treatments. The peak blood ethanol concentration of 21.9 to 22.8 mmol.l-1 occurred at 64 to 70 min after the end of drinking. The rate of disappearance of ethanol from the blood ranged from 3.0 to 3.3 mmol.l-1.h-1 and the rate of removal from the whole body ranged from 8.0 to 8.5 g.h-1. The apparent volume of distribution of ethanol was almost the same for all four treatments: mean 0.68 l.kg-1, corresponding to a mean total body water of 44 l (59% body weight). Mean areas under the concentration-time profiles of ethanol ranged from 83 to 87 mmol.l-1.h for the four treatments. It is concluded that omeprazole, cimetidine and ranitidine do not alter the kinetics of a moderate dose of ethanol.

Adult↗

PubMed1992

Subcellular fractionation of rainbow trout gonads with emphasis on microsomal enzymes involved in steroid metabolism.

Rainbow trout gonads were subfractionated by differential centrifugation with emphasis on obtaining preparations suitable for the study of steroid-metabolizing enzymes. A fractionation scheme was evaluated for the mature testis and for 3 ovarian developmental stages. The distribution of cell organelles among the fractions was determined using enzyme-markers and electron microscopy. The fractionation scheme was found to be suitable for separating mitochondria and microsomes which were recovered at similar yields to those that had been reported for other extraheptic fish tissues. Fractionation of the mature ovary was fraught with problems probably because a large yolk protein cytosole fraction interfered with the recovery of microsomes. However, no difference in the specific activity of microsomal NADPH-cytochrome c-reductase between the various organ preparations was evident. The testis microsomes contained detectable amounts of cytochrome P450, whereas its content in the various ovary microsomes was too low to be detected. Progesterone 17 alpha-hydroxylase was detected in microsomes from testes and early developing ovaries, and microsomal aromatase activity was present in microsomes from early developing, mature and postovulatory ovaries. Furthermore, the testis microsomes contained a highly active UDP glucuronosyltransferase with testosterone used as a substrate.

Animals↗

PubMed1992

Expression of P4501A1 in a primary culture of rainbow trout hepatocytes exposed to beta-naphthoflavone or 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Primary cultures of rainbow trout hepatocytes were used to study the expression of CYP1A1 mRNA, its protein product (P4501A1), and catalytic activities (7-ethoxy-resorufin-O-deethylase, EROD) during a 96-h period after exposure of cells to beta-naphthoflavone (BNF) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatocytes were isolated from immature rainbow trout by a two-step perfusion method and incubated at 10 degrees C. Cells were exposed to the inducers for 48 h after 24 h of preculturing. The EROD activity of BNF-treated hepatocytes was higher than that of the control hepatocytes 12 h after addition of the inducer. Activities peaked after 48 h and had declined to control levels after 72 h. EROD activity in TCDD-treated cells was significantly elevated after 12 h, but in contrast to BNF-exposure, activities continued to increase during the experimental period. The content of P4501A1 protein, measured with an indirect ELISA technique (using anti-codP4501A1 IgG), increased linearly during the first 12 h and remained constant thereafter. In TCDD-exposed cells the immunochemically determined P4501A1 levels changed in parallel with EROD activity. CYP1A1 mRNA levels, determined by Northern blot and slot-blot analyses (using the trout P4501A1 cDNA pSg15 probe), were hardly detectable in control cells. In BNF- and TCDD-treated cells a 2.8-kb mRNA band was detected by the probe 6 h before the protein and catalytic activities became detectable. The elevated levels of CYP1A1 mRNA were sustained more effectively by TCDD than by BNF. In addition, a second mRNA band at 1.9 kb was seen. The results suggest that transcriptional activation is probably the prime factor even though post-transcriptional events may be involved in the regulation of P4501A1 induction by PAHs in rainbow trout hepatocytes.

Animals↗

PubMed1992

Toxic effects of bleached and unbleached paper mill effluents in primary cultures of rainbow trout hepatocytes.

Toxic effects of unbleached (sulfate or sulfite) and bleached (sulfate) paper mill effluents were studied in a primary culture of rainbow trout liver cells. The effluents and control water from a clean area were extracted with diethyl ether and added to the cultures dissolved in dimethyl sulfoxide. Plasma membrane integrity was studied by measuring lactate dehydrogenase (LDH) leakage. The cellular content of glutathione (GSH) was used as an indicator of oxidative stress and the formation of reactive intermediates. Dose-response studies indicated that unbleached effluents contained more potent toxic substances than bleached effluents. Both unbleached and bleached effluents contained organic diethyl ether-extractable substances which increased cytochrome P450-dependent 7-ethoxyresorufin-O-deethylase (EROD) activities. The inducing effects were seen at concentrations substantially lower than those decreasing GSH content and increasing LDH leakage. Possible EROD inducing substances in bleached effluents are chlorinated organic compounds. Inducing compounds in unbleached effluents are yet to be identified. Furthermore, at higher concentrations the effluents contained substances that inhibited the cytochrome P450 system. The results show that the trout primary hepatocyte cultures afford a convenient in vitro method for screening cytochrome P450 inducing components extracted from industrial effluents to investigate mechanisms by which wastewaters cause injury in cells.

Abietanes↗

PubMed1992

Protein C in patients with alcoholic cirrhosis and other liver diseases.

The coagulation inhibitor protein C was measured in 151 patients with various liver diseases. The protein C level was significantly decreased in patients with alcoholic cirrhosis (n = 73) compared to patients with steatosis (n = 24) (40 +/- 2%) vs. 88 +/- 4%, mean S.E., p less than 0.001). It was also decreased in cases of acute liver damage (n = 8) and in patients with non-alcoholic cirrhosis (n = 15) (35 +/- 7% and 36 +/- 4%, respectively). A significant correlation was found between protein C and Normotest, antithrombin, heparin cofactor II, (r = 0.83, r = 0.82, r = 0.81, respectively, p less than 0.001). There was also a significant correlation between protein C and serum concentrations of albumin (r = 0.61, p less than 0.001), but a negative association to bilirubin (r = -0.56). No significant association was found between protein C and aspartate aminotransferase, alaline aminotransferase, and gamma-glutamyltranspeptidase. In conclusion, protein C is low in advanced liver diseases and gives the same amount and type of information as Normotest, antithrombin and heparin cofactor II.

Acute Disease↗

PubMed1992

Octreotide and interferon alfa: a new combination for the treatment of malignant carcinoid tumours.

24 patients with malignant carcinoid tumours received octreotide and interferon alfa (IFN-alpha). All the patients initially received octreotide 50-100 micrograms, twice daily. When progressive symptoms or increasing biochemical markers were observed, the daily dose was raised to a median 300 micrograms. If the initial dose proved ineffective or if no improvement was seen after escalation, IFN-alpha was added (median 9 MU subcutaneously per week). After the addition of IFN-alpha, 17 of the 22 patients (77%) with elevated urinary 5-hydroxyindoleacetic acid showed a significant (> 50%) reduction. Only 1 patient progressed and 4 had continuously stable biochemical disease. No significant reduction in tumour size was noted; in 5 patients, the tumour continued to grow despite decreasing hormone levels. 18 patients had carcinoid syndrome when IFN-alpha was added in 10 (56%) symptoms ameliorated. Thus, the addition of IFN-alpha is beneficial for patients with malignant carcinoid tumours that progress and/or who do not respond to octreotide.

Adult↗

PubMed1992

Effects of ethanol on the chemotactic peptide-induced second messenger generation and superoxide production in polymorphonuclear leukocytes.

The generation of oxygen radicals by polymorphonuclear leukocytes (PMNL) plays a pivotal role for host defense. Since ethanol reduced FMLP- but not PMA-induced superoxide ion (O2-) formation by PMNL, the effects of ethanol on second messenger systems in PMNL were studied. FMLP induced a biphasic rise in cytosolic calcium concentrations, [Ca2+]i. Ethanol treatment abolished the second phase (believed to reflect Ca2+ influx), an effect also observed in PMNL treated with La3+ or suspended in Ca(2+)-free buffer. The FMLP-induced inositol trisphosphate generation was unaffected by ethanol, whereas diacylglycerol formation was, as expected, markedly reduced. Propranolol, an inhibitor of diacylglycerol formation from phosphatidic acid, caused a prolonged transmembrane influx of Ca2+ and partially reversed the inhibitory effect of ethanol on FMLP-induced O2- production. Thus, the ability of ethanol to inhibit FMLP-induced O2- generation in neutrophils seems to be due to both impaired influx of Ca2+ across the plasma membrane and reduced phospholipase D-mediated generation of phosphatidic acid.

Calcium↗

PubMed1992

Myofibromatosis-like hemangiopericytoma metastasizing as differentiated vascular smooth-muscle and myosarcoma. Myopericytes as a subset of "myofibroblasts".

A thyroid hemangiopericytoma that was resected in a 5-year-old boy recurred insidiously in the larynx 8 years later. Marked cicatricial mucosal inflammation prevented a definitive pathologic diagnosis of recurrence until a nodule grew to obstruct the airway 15 years after initial surgery. After excision of the nodule, a larger sarcomatous metastasis was discovered in the upper esophagus and resected, but the patient eventually succumbed to widespread disease at the age of 20 years. The original tumor contained atypical pericytes and bundles of hyalinizing smooth muscle abutting on "staghorn vessels," a pattern similar to infantile myofibromatosis. Desmin immunostaining was negative in the pericytes but positive in smooth-muscle cells dispersed singly as well as in bundles. Both elements reacted strongly for vimentin and the alpha-isoform of actin (alpha-SMA) found in normal smooth muscle and pericytes. A third cell type showing dendritic processes and immunoreactivity for all three antigens was interpreted as a myopericyte. Spindled cells in multiple subsequent mucosal biopsy specimens stained retrospectively also positive for these antigens. Large bundles of vascular smooth muscle surrounded by radiating myocytes characterized the occluding laryngeal nodule. In the esophageal metastasis, which showed no histologic features typical of hemangiopericytoma, numerous mitotically active, small, vimentin+, desmin+, alpha-SMA+ cells often maintained shortened processes and tended to form nodular aggregates about capillaries. Single rows of pericytes accreted to endothelial tubes. Ultrastructurally, some cells contained myofilaments and irregular dense material or showed rare cell junctions and variable investment by a basal lamina.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

PubMed1992

Malignant melanoma of the nasal cavity and nasopharynx treated with cisplatin and accelerated hyperfractionated radiation.

Primary malignant melanoma of the nasal cavity and paranasal sinuses is an uncommon disease, accounting for only 0.5-2% of all malignant melanomas. The primary treatment has been surgery. The frequency of local recurrence is high and recurrence is also the major determinant of treatment failure. Here we report on six patients with locally advanced disease, four of whom were too advanced for surgery, who were treated with accelerated hyperfractionated radiation in combination with cis-platinum. Three of four patients treated for local recurrent disease achieved a local cure and died of disseminated disease after 9-21 months. One patient given preoperative cisplatin and radiation is still alive with no evidence of disease 34 months after the completion of treatment. The present protocol may be a useful approach to obtain local control with the possibility of long-term cure.

Aged↗

PubMed1992

Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects.

Twelve Caucasian healthy men and women, of whom six were poor metabolizers (PMs) and six were extensive metabolizers (EMs) of S-mephenytoin, together with 13 Chinese healthy men and women (five PMs and eight EMs), received a single oral 20 mg dose of omeprazole. Plasma levels of omeprazole and its two main metabolites, omeprazole sulphone and hydroxyomeprazole, were determined by HPLC. The mean (+/- SD) area under the plasma concentration-time curve (AUC) for omeprazole was 11.1 +/- 2.6 and 0.9 +/- 0.4 microM h in the Caucasian PMs and EMs, respectively. Corresponding values for elimination half-life were 2.3 +/- 0.4 and 0.7 +/- 0.4 h. In the Chinese PMs and EMs the AUC of omeprazole as 13.3 +/- 5.6 and 2.6 +/- 1.8 microM h. The AUCs of omeprazole were significantly higher in the Chinese EMs than in the Caucasian EMs possibly due to the higher proportion of heterozygotes in the former than in the latter group. The elimination half-life in the Chinese PMs and EMs was 2.4 +/- 0.2 and 0.8 +/- 0.2 h--similar to the observations in the Caucasian subjects. The maximum plasma concentration of hydroxyomeprazole was five-fold and four-fold higher in EMs compared to PMs among Caucasians and Chinese, respectively. The elimination half-life of the hydroxy metabolite was also longer in PMs than in EMs in both populations. The ratio between AUC for omeprazole and AUC for hydroxyomeprazole was 11.9 +/- 2.1 and 0.6 +/- 0.1 in Caucasian PMs and EMs, respectively. Corresponding values in the Chinese were 13.1 +/- 2.9 and 1.6 +/- 0.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

A study of the interaction of omeprazole and warfarin in anticoagulated patients.

1. Thirty-five patients on continuous therapy with warfarin were given omeprazole 20 mg once daily and placebo each for 3 weeks according to a two-centre randomised double-blind cross-over design. 2. Blood samples were obtained once weekly during the run-in and follow-up periods as well as during the first 2 weeks of each treatment period, and twice during the last week of each treatment period. Plasma concentrations of R- and S-warfarin were measured by h.p.l.c. and the anticoagulant effect was assessed using the Trombotest. 3. Twenty-eight patients were evaluated. The mean plasma concentration of R-warfarin was increased by 9.5% during omeprazole treatment compared with placebo, while that of S-warfarin, the more active isomer, was unaffected. The coagulation time was not significantly changed (106 s during omeprazole and 98 s during placebo). Corresponding TT-values (Trombotest) were 8.8 and 9.9 (NS).

Adult↗

PubMed1992

Enrichment of metabolites in the cerebrospinal fluid of cod (Gadus morhua) following oral administration of hexachlorobenzene and 2,4',5-trichlorobiphenyl.

The disposition of 14C-labelled hexachlorobenzene (HCB) and 2,4',5-trichlorobiphenyl (triCB) was studied in cod (Gadus morhua) and rainbow trout (Oncorhynchus mykiss). For both compounds tape section autoradiography revealed substantial amounts of radiolabelled material in the central nervous system (CNS) of cod, whereas only traces of radioactivity were observed in the CNS of rainbow trout. Furthermore, an enrichment of radiolabelled compound in the cerebrospinal fluid (CSF) was observed in the cod, whereas no radioactivity could be detected in the CSF of rainbow trout. According to autoradiography, the CNS of cod dosed with HCB contained the parent compound, whereas the major part of radioactivity in CSF was due to HCB metabolites. Thin-layer chromatography of extracts from cod dosed with triCB showed the presence of parent compound in the CNS, whereas part of the radioactivity in the CSF was due to triCB metabolites. The activities of cytochrome P-450 and UDP-glucuronosyltransferase in the CNS of cod and rainbow trout were determined in microsomal and mitochondrial fractions. Both species expressed activities which were in the same order of magnitude as those reported for the corresponding fractions from rat brain. Incubation of triCB with cod brain mitochondria and microsomes resulted in the formation of two polar metabolites. It is suggested that cod may be more vulnerable than rainbow trout regarding neurotoxicological effects of HCB, triCB and related environmental pollutants.

Administration, Oral↗

PubMed1992

In vivo microdialysis estimation of histamine in human skin.

Microdialysis, a new bioanalytical sampling technique, enables the measurement of substances in the extracellular space. This study investigates the use of the technique in the in vivo measurement of histamine levels in human skin. Microdialysis probes are equipped at the tip with a semipermeable polycarbonate membrane which permits the passive diffusion of substances. 16 probes were inserted, via a guide, into the skin of the ventral forearm of 8 patients or volunteers. The probe was perfused at a flow of 5 microliters/min, with samples being collected at intervals of 10 min and analysed by RIA technique. The mean histamine level in the first 10-min sample following probe insertion was 39.4 nM. The mean histamine value fell with successive 10-min samples (8.8, 4.6, 2.3 nM). An equilibration period of 40 min following probe insertion is suggested for histamine studies, where provocation of the skin is to be performed. Microdialysis appears to be a promising new tool for quantitative and chronological studies of cutaneous inflammatory mediators.

Dialysis↗