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Biomedical subjects

M Berg

Publications and source records attributed to M Berg.

At least 145 records · Page 8Linked to original sources

Food-induced increase in bioavailability of 5-methoxypsoralen.

5-Methoxypsoralen (5-MOP) in combination with ultraviolet light exposure is used for the treatment of psoriasis. The effect of food on the pharmacokinetics of 5-MOP was evaluated in a randomized, crossover study in nine healthy subjects. Each subject received the tablets with a standardized breakfast or under fasting conditions. The food had a dramatic effect on the bioavailability of 5-MOP. Five of the subjects showed no measurable quantities (detection limit of the analytical technique 1 ng.ml-1) of 5-MOP when the drug was given under fasting conditions. However, plasma peak concentration within the range 37-144 ng.ml-1 (median 102 ng.ml-1) was measured when the drug was taken with food. The time for the plasma peak concentration was within the range 2.0-5.1 h (median 3.0 h) under non-fasting conditions. The elimination half-life was within the range 1.4-2.7 h (median 1.9 h). We conclude that it is imperative that 5-MOP tablets are administered together with food.

5-Methoxypsoralen↗

Principles and practices of medicine. The co-existence of various anemias.

The medical textbooks in our university library present 'principles' as the basis which underlies medical 'practice'. In this article it is argued that this helps different medical logics to co-exist. The example analyzed is that of anemia in the Netherlands. Currently this is defined pathophysiologically, statistically and clinically. These three definitions are intertwined with different strategies for the creation of normal hemoglobin levels and the detection of patients with anemia. The discrepancies between them, however, do not lead to the controversies that might be expected by those who believe in consistency. Instead, the rhetoric of principles-and-practice helps to bring about peaceful co-existence.

Adult↗

Evolution of H3N8 equine influenza virus from 1963 to 1991.

The antigenic properties of H3N8 influenza viruses isolated from outbreaks of equine influenza in Sweden between 1979 and 1991 have been studied in hemagglutination inhibition tests with polyclonal and monoclonal antisera, and antigenic drift of the virus has been demonstrated. To clarify the basis of the antigenic drift, amino acid sequences of the globular head regions (HA1) of the hemagglutinin membrane glycoproteins of virus strains from 1979, 1984, 1988 and 1990 have been deduced from the nucleotide sequences of the hemagglutinin genes, and the sequence information has been used to construct a phylogenetic tree of H3N8 equine influenza strains. Several strains from previous studies have been included to give a clearer picture of viral evolution in an international context.

Amino Acid Sequence↗

Characterization of differentiation factor/leukaemia inhibitory factor effect on lipoprotein lipase activity and mRNA in 3T3-L1 adipocytes.

Alterations in lipid metabolism characterized in major part by a decrease in lipoprotein lipase (LPL) activity in adipose tissue are a central feature of cachexia from chronic infection or malignancy. These metabolic derangements may be mediated in large part through endogenous host proteins produced in response to various pathological stimuli. Differentiation factor/leukaemia inhibitory factor (D-factor) is a cytokine whose functions overlap those of tumour necrosis factor-alpha (TNF), IL-6 and IL-1. Recombinant murine D-factor produced a dose- and time-dependent inhibition of heparin-releasable LPL activity in differentiated 3T3-L1 adipocytes. Although 2-10 fold less potent than recombinant murine TNF, D-factor inhibited LPL activity at concentrations of 1-10 ng/ml. When added together, D-factor and TNF produced a synergistic inhibition of LPL activity. Interleukin 6 (IL-6) was 100-fold less potent than D-factor; 0.1 ng/ml of D-factor or 10 ng/ml of IL-6 caused a 50% inhibition of LPL activity. D-factor and TNF increased IL-6 production in 3T3-L1 cells. Ten ng/ml of D-factor or 1.0 ng/ml of TNF stimulated the release of < 1 ng/ml of IL-6 and inhibited LPL activity to 11 +/- 3% and 3 +/- 2% of control, respectively, whereas 50 ng/ml of recombinant IL-6 was required to decrease LPL activity to 24 +/- 19% of control. TNF produced a marked decrease in LPL mRNA, whereas D-factor had minimal or no effect at doses which inhibited LPL activity almost completely. Western blot analysis of cell extracts showed that TNF caused a greater decrease in LPL protein production than D-factor.2+ with TNF, may contribute to the manifestations of cachexia.

3T3 Cells↗

Synthetic lipopeptide Pam3CysSer(Lys)4 is an effective activator of human platelets.

Lipopeptide analogues of the NH2-terminus of bacterial lipoprotein are known to induce activation of macrophages, neutrophils, and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-( S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3CysSer(Lys)4] on several functions of human platelets. Pam3CysSer(Lys)4 led to the aggregation of platelets and induced the secretion of serotonin with an effectiveness similar to thrombin. These cellular effects of Pam3CysSer(Lys)4 were concentration dependent, being half maximal at 2-3 microM and maximal at 10-30 microM. Another lipopeptide also induced platelet aggregation and serotonin secretion but was less potent and less effective than Pam3CysSer(Lys)4. The lipid moiety and the peptide moiety of Pam3CysSer(Lys)4 alone were without any effect. Lipopeptides also stimulated tyrosine phosphorylation of several proteins with molecular masses similar to those found to be tyrosine phosphorylated in response to thrombin, and Pam3CysSer(Lys)4 led to an increase in the cytosolic calcium concentration. All studied responses of platelets to lipopeptides were inhibited by the prostacyclin receptor agonist cicaprost. Taken together, our data show that lipopeptides are effective activators of human platelets and that this activation is susceptible to the action of physiological platelet inhibitors.

Blood Platelets↗

Ultraviolet A phototherapy and trimethylpsoralen UVA photochemotherapy in polymorphous light eruption--a controlled study.

Twenty-two patients with polymorphous light eruption were prophylactically treated with ultraviolet A (UVA) with and without trimethylpsoralen in the first randomized double-blind study in this subject. Twelve of the patients were treated during 2 consecutive springs with placebo during one spring and psoralens during the other. Eighteen of the patients improved after the therapy, but there was no clear-cut difference between the 2 regimens. As many as 12 patients got light eruptions during the treatment, but all but one continued with the therapy. This study indicates that UVA alone is as good prophylactic therapy for polymorphous light eruption as PUVA with trimethylpsoralen. However, because of the high incidence of provoked eruptions during therapy, the treatment may be difficult to handle for the patients themselves, at least during the initial treatment.

Adult↗

Treatment of psoriasis with psoralens and ultraviolet A. A double-blind comparison of 8-methoxypsoralen and 5-methoxypsoralen.

Thirty-eight patients with plaque-type psoriasis were enrolled in a double-blind psoralen plus ultraviolet A (PUVA) treatment study comparing the efficacy and side effects of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP). Patients treated with 8-MOP healed significantly faster than those on 5-MOP for 6 weeks of treatment, but there was no significant difference after 9 weeks. There was no significant difference in side effects between the two groups, but nausea tended to be more common in the 8-MOP group. One patient on 5-MOP had signs of toxic hepatitis. The importance for maximizing absorption of taking 5-MOP with food is stressed, and PUVA treatment should be given 3 h after intake of the drug.

5-Methoxypsoralen↗

[Transitory evoked otoacoustic emissions in patients with cerebellopontile angle tumors].

Click-evoked transitory otoacoustic emissions (TEOAE) were recorded in 34 patients suspected of having an acoustic neuroma with consequent hearing loss. Measurements took place one day prior to transtemporal removal of tumor. The evoked otoacoustic emissions were compared to hearing thresholds of the pure-tone audiogram. In 31 of the 34 patients tested, the spectrum of the emissions corresponded to the audiogram, in that an emission was not detectable at frequencies with a hearing loss exceeding 30 dB HL. Three patients showed good emissions in spite of a demonstrable hearing loss. This can be expected when only retrocochlear lesions are present. These results suggest that in most cases the hearing loss accompanying a retrocochlear process is combined with secondary lesions of the cochlea and is rarely due to isolated retrocochlear malfunction.

Adult↗

A paradox after systemic kainate injection in rats: lesser damage of hippocampal CA1 neurons after higher doses.

The pyramidal neuron loss in dorsal rat hippocampus was determined 4 days after i.p. administration of 10 or 20 mg/kg kainic acid (KA). Histological examination revealed that subtotal-to-total loss of the pyramidal neurons in both the CA3 and CA1 regions of hippocampus was produced after 10 mg/kg KA. At the higher dose, severe damage was evident in the CA3 region while no or only sporadic damage was observed in the CA1 region. These findings suggest that the high KA dose damaged the CA3 pyramidal neurons before excitatory input through the Schaffer collaterals produced irreversible damage to the CA1 pyramidal neurons.

Animals↗

The effects of long-term treatment with the 5-HT1A receptor agonist 8-OH-DPAT and the 5-HT2/1C receptor agonist DOI in the neonatal rat.

The rat pup ultrasonic call was used to study the effects of acute and long-term treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) during the neonatal period. Acute administration of 8-OH-DPAT and DOI reduced the number of ultrasonic calls. The reduction induced by 8-OH-DPAT and DOI was antagonized by the 5-HT1A antagonist (S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin ((S)-UH-301) and the 5-HT2 antagonist ketanserin, respectively. The long-term treatments were started on postnatal day 1. On postnatal day 7, the response of the long-term DOI-treated group was clearly attenuated in comparison to that of the acute DOI-treated group. In contrast, no tolerance to the effect of 8-OH-DPAT was achieved after an analogous treatment. The data indicate that there is a diversity in the ontogeny of the ability to develop tolerance to 5-HT1A agonists in comparison to 5-HT2/1C agonists.

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

Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia.

D factor, also known as leukemia inhibitory factor, is a pleiotropic cytokine whose role during acute injury and inflammation is not known. Intraperitoneal administration of Escherichia coli endotoxin induced D factor gene expression in mice, and passive immunization against D factor protected them from the lethal effects of endotoxin and blocked endotoxin-induced increases in serum levels of interleukin 1 and 6. Peak levels of tumor necrosis factor and interferon gamma were not affected. These results indicate that D factor is an essential early mediator of the inflammatory cytokine response and therefore may be important in the pathogenesis of the many inflammatory conditions, such as sepsis, arthritis, allograft rejection, and cancer immunotherapy.

Animals↗

Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation.

There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Equine influenza virus from the 1991 Swedish epizootic shows major genetic and antigenic divergence from the prototype virus.

The antigenic properties of H3N8 equine influenza virus from the Swedish epizootic of 1991 differ from those of A/eq 2/Fontainebleau/79 (representative of the Swedish vaccine strain) in hemagglutination inhibition tests. The amino acid sequence of the hemagglutinin (HA) of an isolate from the 1991 outbreak was deduced from the nucleotide sequence and comparison was made to the A/eq 2/Fontainebleau/79 strain. Twenty-three amino acid substitutions were found, 10 mapping onto areas of the HA known to bind antibodies in human H3 influenza viruses. The amino acid changes together with the serological data suggest that a major antigenic drift has taken place in equine H3N8 viruses in Sweden and we conclude that recent strains of the virus must be incorporated into vaccines on a regular basis if epizootics of equine influenza are to be controlled in the future.

Amino Acid Sequence↗

Nail varnish allergy with far-reaching consequences.

Contact allergy to nail varnish is well-known, and toluene-sulphonamide formaldehyde resin (TSAfr) was identified as the main allergen in 1943. During the period October 1989-December 1991 we identified 18 cases of contact allergy to nail varnish. The aim of the study was to describe the clinical picture, patch-test results, course and socio-medical consequences. Seventeen of the 18 patients were patch-test positive to TSAfr and 17/18 were positive to their own nail varnishes. Fourteen of the 18 were also positive to one or more substances in the standard patch-test series. The lesions were scattered, involving the face, eyelids, neck and hands. Periungual lesions were recorded in 11/18. The dermatitis resolved within a few weeks when the use of nail varnish was stopped. The socio-medical consequences of contact allergy to nail varnish had been severe: sick leave (nine cases), hospitalization (four cases), cessation of visual-display-unit (VDU) work (two cases), and job-loss (two cases). Our conclusions are that contact allergy to nail varnish and TSAfr is common; the socio-medical consequences may be severe; periungual lesions occur more frequently than previously stated, and the presence of other contact allergies makes the diagnosis easy to miss. TSAfr should be included in the standard patch-test series and patients should also be tested with their own nail varnishes. The study illustrates the need for mandatory declaration of the ingredients of cosmetics, as is required in the U.S.A.

Adult↗

Clinical significance of outcome in long-term follow-up of borderline patients at a day hospital.

All borderline patients admitted at a day hospital during a 6-year period were followed up with a postal questionnaire after 3-10 years. Patients who had chosen to leave the treatment within 4 months were analyzed as a separate group, and these drop-outs and the remaining patients were compared with a group of well-adjusted people who were assumed to represent the functional norm. The patients who remained in treatment were clearly posited at a level of functioning between the norm and the drop-outs, although the variation among them was quite large. Depending on the stringency and content of the criterion of clinical significance, 25-75% of the patients remaining in treatment fell within the range of the norm group versus 20-50% of the drop-outs. The patients who had benefited most since termination had differed favorably from the other patients already at admission to treatment, but not as much as had the drop-outs. The drop-outs, however, at admission also had more ambivalent or negative attitudes towards treatment.

Adult↗

Kainic acid-induced seizures and brain damage in the rat: different effects of NMDA- and AMPA receptor antagonists.

We have studied the effect of two glutamate receptor antagonists on seizures and hippocampal neurone loss in the rat after systemic kainic acid administration. Intraperitoneal injection of the novel AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolproprionic acid) receptor antagonist NBQX (6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione) (30 mg/kg x 3 and 15 mg/kg x 3) administered 30 and 15 min. before and simultaneously with injection of kainic acid (5 mg/kg) intraperitoneally, dramatically enhanced the toxicity of kainic acid leading to death of all animals. When the NBQX dose was reduced to 8 mg/kg x 3, all animals survived and neurone damage in the hippocampus did not differ from control animals. When NBQX (30 mg/kg x 3) was administered 30- or 60 min after injection of kainic acid (8 mg/kg) intraperitoneally, no changes were observed concerning survival rates, seizure generation and neurone loss. Post-kainic acid treatment with the non-competitive NMDA receptor antagonist MK-801 (0.5 mg/kg and 1.0 mg/kg), 30 and 60 min. after intraperitoneally injection of kainic acid 8 mg/kg, abolished seizures in all animals and the neurone damage in the hippocampus was completely prevented. The results emphasize the importance of the NMDA-receptor activation for seizure generation and subsequent brain damage after intraperitoneally kainic acid. The paradoxical, unexpected effects of NBQX contrast to the protective effect of this compound after cerebral ischaemia and hypoglycaemia, conditions which are also characterized by glutamate-mediated damage. One possible explanation of the lowered seizure threshold to kainic acid after NBQX could be that NBQX is blocking AMPA receptors on interneurones more efficiently than on pyramidal cells.

Animals↗