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Biomedical subjects

T Ekström

Publications and source records attributed to T Ekström.

At least 37 records · Page 2Linked to original sources

Two dimensional protein patterns of bronchoalveolar lavage fluid from non-smokers, smokers, and subjects exposed to asbestos.

BACKGROUND: Bronchoalveolar lavage (BAL) fluid contains a large number of proteins which comprise a potential resource for studying respiratory effects due to occupational and environmental exposures. A study was undertaken to compare protein patterns of BAL fluid from non-smokers, smokers, and subjects exposed to asbestos. METHODS: BAL fluid samples were analysed with two dimensional gel electrophoresis (2-DE). The separated proteins were detected, quantified, and pattern-matched between different individuals with a computerised imaging system designed for evaluations of 2-DE patterns. RESULTS: About 200 different protein spots were detected in each sample of BAL fluid. As is the case with blood plasma, the BAL fluid samples contained large amounts of albumin, transferrin, and immunoglobulins. Higher levels of basic proteins were found in smokers than in non-smokers, while subjects exposed to asbestos had increased amounts of several high molecular weight proteins as well as basic proteins. Lower levels of albumin and higher levels of immunoglobulins were found in smokers than in non-smokers, while higher levels of transferrin were found in asbestos exposed subjects than in unexposed subjects. Moreover, in the group exposed to asbestos differences were found between patients with pleuritis and patients with pleural plaque, and one protein spot was found only in two patients with progressive pleural disease. CONCLUSION: These results suggest that both smokers and asbestos exposed subjects have significant changes in their airway protein expression compared with non-smokers and unexposed subjects. It is inferred that analysis of protein patterns in the BAL fluid with 2-DE may be used to detect and characterise, at a molecular level, respiratory effects due to occupational and environmental exposures.

Adult↗

The effects of long-term oral administration of ethanol on Sprague-Dawley rats--a condensed report.

For a period of 2 years Sprague-Dawley rats received 3% and 1% ethyl alcohol or an equicaloric amount of glucose in a semisynthetic liquid diet. Thereafter the tumour incidence was recorded. For male rats no neoplastic lesions were observed to be related to ethanol exposure. For females, when individual group comparisons were made, an increase in mammary gland tumours was seen for females receiving the low ethanol containing diet. In some tumour frequency comparisons the opposite, namely a decrease in the rate of incidence, was obtained. The overall information seems to indicate the absence of a carcinogenic activity of ethyl alcohol per se after long-term oral administration. Liver and bile duct injury was seen among males. Inflammatory reactions were seen among males in pancreas and for females in the clitoral gland. Hyperplasia was observed in the thyroid gland in both sexes and in the adrenal glands among females. Peripheral nerve degeneration was common in both sexes.

Animals↗

Lack of effect of loratadine on moderate to severe asthma.

BACKGROUND: Antihistamines have been shown to be effective in patients with allergic asthma, but their role in chronic and more severe asthma is uncertain. OBJECTIVES: To evaluate whether loratadine, a selective H1 receptor antagonist, given as an adjunct to standard asthma medication would have any effect in patients with moderate-to-severe asthma. METHODS: Thirty-five patients with moderate-to-severe asthma, most receiving inhaled steroids, were enrolled in this double-blind, crossover study. In addition to their maintenance therapy patients received either loratadine, 20 mg once daily, or placebo for 4 weeks before crossing over to the other preparation for a further 4 weeks. Variables of efficacy were daily and nocturnal respiratory symptoms, lung function (PEF, FEV1, FVC), and bronchodilator use. RESULTS: Three subjects were withdrawn from the study because of deteriorating asthma. There was a trend in favor of loratadine treatment with regard to global assessment of drug efficacy but the difference was not statistically significant. There was no objective improvement in asthma control comparing loratadine with placebo but if each treatment week were compared with the run-in period, PEF was significantly (P < .01) improved during the initial phase of loratadine treatment. This effect gradually decreased with time, suggesting tolerance to any bronchodilatory effect of the antihistamine. CONCLUSION: Loratadine, given as an adjunct to standard asthma therapy, has little if any role to play in the treatment of moderate-to-severe asthma.

Adolescent↗

Dose potency relationship of terbutaline inhaled via Turbuhaler or via a pressurized metered dose inhaler.

OBJECTIVE: The relative dose potency of cumulative doses of terbutaline sulfate inhaled via Turbuhaler and via a pressurized metered dose inhaler was estimated with respect to lung efficacy and systemic effect. METHODS: The study was an open, crossover, randomized, multicenter study including 31 adult patients with asthma [forced expiratory volume in one second (FEV1), 65% of predicted]. The patients inhaled terbutaline doses of 0.125, 0.125, 0.25, 0.5, 1.0, and 2.0 mg (a total of 4 mg) at 30-minute intervals. Lung function [FEV1, forced vital capacity (FVC), forced expiratory flow at 75% of FVC (FEF75%), and peak expiratory flow (PEF)], and systemic effect variables (serum potassium, tremor, pulse, blood pressure) were monitored prior to the first inhalation and 15 to 25 minutes after each inhaled dose. RESULTS: The mean relative dose potency of terbutaline inhaled via Turbuhaler compared with pressurized metered dose inhaler was 1.5 (95% confidence interval: 1.2 to 1.8) with respect to FEV1 and serum potassium, respectively. The corresponding relative dose potencies for PEF, FVC, and FEF75% were 1.0, 1.2, and 1.6, respectively, with no statistically significant difference between the two devices. No differences between the devices were evident with regard to blood pressure and pulse. CONCLUSION: The results suggest that Turbuhaler is more efficient in the delivery of inhaled terbutaline to the lungs compared with the conventional pressurized metered dose inhaler.

Administration, Inhalation↗

Intermittent 50 Hz magnetic field and skin tumor promotion in SENCAR mice.

A number of epidemiological studies have indicated association between exposure to extremely low frequency electromagnetic fields and a variety of cancers, including leukaemia and brain tumours among residentially exposed children and among occupationally exposed adults. In order to test if intermittent magnetic fields (MF) act as a tumour promoter, a long-term skin carcinogenicity study of 50 Hz sinusoidal MF with flux densities of 50 muT and 0.5 mT, continuous as well as with an intermittence of 15 s on/off, was performed. Female SENCAR mice were divided into eight groups of 50 animals in each and treated according to an initiation- promotion scheme. 7,12-dimethylbenz[a] anthracene (DMBA) in acetone was applied to the dorsal skin at a subcarcinogenic dose, as an initiator and exposure to MF was performed for 19-21 h/day during 104 weeks starting 1 week after the initiator treatment. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as a positive control for skin tumour promoting activity. Two animals from each group were assigned for skin hyperplasia analysis at 2, 6, 12, 18 and 21 months. The animals were observed daily. The appearance of skin lesions and neoplasms were carefully followed and histopathological diagnosis was made for all neoplasms present at death. The experiment was terminated after 105 weeks. DMBA-treatment alone yielded altogether two skin tumours in two tumour-bearing animals and the animals exposed to acetone alone had one skin tumour. The animals exposed to continuous fields showed no skin tumour. Five animals exposed to 0.5 mT on/off had a total of 13 skin tumours and in the group exposed to 50 microT on/off four animals had a total of four skin tumours. The on/off exposed groups differed significantly from the continuously exposed groups (P = 0.014) but the difference between the on/off exposure groups and the DMBA group was not statistically significant when tumour-bearing animals and cumulated skin tumours were compared. There was a statistically significant dose trend (P = 0.045) with flux density and Tesla-h for intermittent MF exposure for cumulated skin tumours per tumour-bearing animals. The epithelial thickness of DMBA + MF-treated animals was of the same magnitude as for DMBA-treated animals indicating that, in the case of a promoting effect being present, another mechanism than one involving sustained hyperplasia may be involved.

9,10-Dimethyl-1,2-benzanthracene↗

Rat liver foci study on coexposure with 50 Hz magnetic fields and known carcinogens.

A study was performed to investigate possible interactions by magnetic fields (MF) with the processes of initiation and promotion of chemically induced preneoplastic lesions in rat liver. Male Sprague-Dawley rats were subjected to a 70% partial hepatectomy followed after 24 h by i.p. injection of diethylnitrosamine (DENA) as a tumour initiator. Starting one week after the DENA-treatment phenobarbital (PB) was given to promote growth of enzymatically altered foci of liver cells. MF was applied immediately after the partial hepatectomy and continued until sacrifice after 12 weeks of PB exposure. Homogenous horizontal AC magnetic fields with a frequency of 50 Hz and flux densities of 0.5 mu T or 0.5 mT were used. The rats coexposed with MF and DENA plus PB did not gain weight as much as the rats exposed to the chemical agents only. The MF-exposure also resulted in a slight reduction in size and numbers of the focal lesions. The results suggest an interaction of MF with the processes of chemical carcinogenesis either as a result of stress or depending on effects on the proliferation of preneoplastic cells.

Animals↗

Structure and regulation of expression of the acetylcholinesterase gene.

Acetylcholinesterase, an enzyme essential for the termination of the action of acetylcholine, is encoded by a single gene. Alternative mRNA processing gives rise to the expression of enzyme forms with three distinct carboxyl-termini. These structural differences govern the cellular disposition of the expressed enzyme but do not influence catalytic activity. Alternative polyadenylation signals give rise to distinct 3' non-coding regions which are likely to affect mRNA stability. Alternative splicing also occurs at the 5' end of the gene where two promoter regions can be identified. Hence, regulation of expression of the gene occurs at 3 levels, transcriptional through alternative promoters, translational by affecting mRNA stability and processing of distinct mRNAs and post-translationally by giving rise to distinct peptide chains which are processed differently. Recombinant DNA studies have also been extended to modifying protein structure through site-specific mutagenesis and studying the function of the mutant enzymes.

Acetylcholinesterase↗

A study on skin tumour formation in mice with 50 Hz magnetic field exposure.

In order to test the possibility that magnetic fields (MF) act as a tumour promoter, a long-term skin carcinogenicity study of 50 Hz sinusoidal MF with flux densities of 50 microT and 0.5 mT was performed in female NMRI mice. 7,12-dimethylbenz[a]anthracene (DMBA) in acetone was applied to the dorsal skin, as an initiator, and exposure to MF was performed for 19 (weekdays) or 21 h/day (weekends and holidays) for 103 weeks starting one week after the initiator treatment. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as a positive control for skin tumour promoting activity. MF was also evaluated for complete carcinogenic action in groups of mice that were treated with acetone only. Six animals from each group were taken for skin hyperplasia analysis and were killed after 9, 26 and 52 weeks. The appearance of skin lesions were carefully followed and histopathological diagnosis was made for all neoplasms present at death. The statistical analyses on occurrence of skin tumour bearing animals and cumulated skin tumours, with corrections for survival did not reveal a difference between the controls and the MF exposed groups. The epithelial thickness of DMBA + MF-treated animals was of the same magnitude as for DMBA-treated animals. Leukaemia was a little more frequent among animals exposed to 0.5 mT MF compared to the control animals. However this difference was not statistically significant.

9,10-Dimethyl-1,2-benzanthracene↗

A clinical comparison of hydrocortisone butyrate with oxytetracycline/hydrocortisone acetate-polymyxin B in the local treatment of acute external otitis.

In a single blind, randomized study, 46 patients with acute external otitis were treated with either oxytetracycline/hydrocortisone with polymyxin B (TPB) or hydrocortisone-17-alpha-butyrate eardrops for 7 days. Pseudomonas pyocyanea, Staphylococcus epidermidis and Staph. aureus were the microorganisms most frequently found in the ear canal. Fungi were not found in any culture. The overall cure rate was 80%. No significant difference in therapeutic efficacy was noted between the preparations except regarding Staph. aureus, which was cultured from 17% of the patients. Although the butyrate solution did not contain any antibiotic supplement, it seemed to be more effective than TPB in treating the staphylococcal infections. These findings suggest that such other factors as the hydrogen ion concentration, the steroid potency or the vehicle per se are of importance for the successful treatment of acute external otitis.

Acute Disease↗

Effects of ranitidine treatment on patients with asthma and a history of gastro-oesophageal reflux: a double blind crossover study.

Forty eight patients with moderate to severe asthma were enrolled in a double blind crossover study designed to evaluate the effects of ranitidine treatment, 150 mg twice daily for four weeks, on gastro-oesophageal reflux, asthma control, and bronchial reactivity. All 48 had a history of reflux symptoms and 27 had in addition reflux associated respiratory symptoms. Thirty two patients had objective evidence of acid reflux on 24 hour pH monitoring (pH of less than 4 for more than 1% of the 24 hours) and 27 patients had a positive result in the acid perfusion test. Reflux symptoms were significantly improved after ranitidine treatment. Ranitidine treatment was associated with modest improvements in nocturnal asthma and daily use of inhaled bronchodilator drugs but there was no significant change in bronchial reactivity, lung function, peak flow, or the number of eosinophils in the blood. Comparisons between the effect of ranitidine treatment on asthma control were performed between patients with and without a history of reflux associated respiratory symptoms, with and without a positive result in the acid perfusion test, and with and without objective evidence of gastro-oesophageal reflux. A history of reflux associated respiratory symptoms was the only factor that predicted an improvement in asthma control after ranitidine treatment. These results indicate that antireflux treatment will produce only small improvements in asthma control in asthmatic patients with a history of gastro-oesophageal reflux.

Airway Resistance↗

Increased bronchial reactivity and potentiated skin responses in hypertensive subjects suffering from coughs during ACE-inhibitor therapy.

The aim of this study was to investigate whether ACE-inhibitors could influence bronchial reactivity and interfere with inflammatory skin responses. Ten hypertensive subjects, who had reacted with coughs during ACE-inhibitor therapy, were treated in a double-blind crossover fashion for two weeks with enalapril and with placebo. Enalapril reduced the PC20 value for histamine and augmented the dermal response. Circulating eosinophilic leukocyte level in venous blood dropped markedly after the histamine bronchoprovocation performed during enalapril treatment. Plasma substance P was reduced after histamine provocation performed during placebo treatment, whereas this reduction was abolished by enalapril. In this study, we have demonstrated ACE-inhibitor-induction of moderately increased bronchial reactivity in subjects with suspected ACE-inhibitor-elicited coughs. It is suggested that coughing during ACE-inhibitor therapy is due to an increased inflammatory state in the airways.

Aged↗

Esophageal acid perfusion, airway function, and symptoms in asthmatic patients with marked bronchial hyperreactivity.

It is believed that GER can trigger asthma by the stimulation of acid-sensitive receptors in the esophagus. The aim of this study was to determine whether esophageal acid stimulation in asthmatic patients can provoke clinically detectable bronchospasm and if a possible response is correlated to bronchial reactivity. Eight patients with chronic asthma and GER disease were investigated on three occasions with a histamine challenge test followed by acid provocation of the esophagus. Assessment of bronchial function was made by FEV1, chest auscultation, and respiratory symptoms. While symptoms and signs of bronchoconstriction induced by esophageal acid stimulation were not detected clinically on any occasion, there was a significant correlation between histamine reactivity and the subclinical bronchospasm following acid provocation. It is concluded that esophageal acid stimulation during daytime in the majority of asthmatic patients is not a strong and immediate trigger of asthma.

Aged↗

Influence of theophylline on gastro-oesophageal reflux and asthma.

The aim of the study was to determine whether gastro-oesophageal (GO)-reflux was increased by normal maintenance doses of theophylline, and if so, whether this was detrimental to lung function in asthmatic patients with symptoms of reflux. In 25 patients with moderate or severe bronchial asthma and a history of respiratory symptoms aggravated by reflux, two consecutive oesophageal 24-h pH recordings were made, one with and the other without their ordinary dose of slow release theophylline. The theophylline treatment caused a significant increase in total reflux time and reflux symptoms but did not worsen the asthma. Patients with subtherapeutic serum levels showed significant improvement in lung function and those with therapeutic serum levels did not. It is concluded that theophylline, in view of its potential to exacerbate GO-reflux, should be used with caution as maintenance therapy in asthmatic patients with GO-reflux.

Asthma↗