| 1. |
- Pettersson, Jonas, et al.
(författare)
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Muscular exercise can cause highly pathological liver function tests in healthy men.
- 2008
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 65:2, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- What is already known about this subject • The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. • Physical exercise can result in transient elevations of liver function tests. • There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. What this study adds • Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. • Liver function tests are significantly increased for at least 7 days after weightlifting. • It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10–12 days postexercise. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.
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| 2. |
- Torngren, Kristina, et al.
(författare)
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Association of coronary calcium score with endothelial dysfunction and arterial stiffness
- 2020
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 313, s. 70-75
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The aim of the study was to determine potential associations between endothelial dysfunction and arterial stiffness, measured by peripheral arterial tonometry, and coronary artery calcium score (CACS) assessed by computed tomography (CT). Methods and results: The BIG3 study is a prospective longitudinal, non-interventional, pulmonary-cardiovascular cohort study exploring the three major smoking-induced diseases: cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, in a 45–75 aged cohort (mean 62 years), enriched in smokers. Computed tomography of the chest with assessment of CACS was performed in a selected subset of the participants (n = 2080). Peripheral arterial tonometry (EndoPAT) was used to assess endothelial function and arterial stiffness measured as reactive hyperaemia index (RHI) and augmentation index (AI), respectively. We observed significant associations of CACS, endothelial dysfunction, and arterial stiffness with several risk factors for coronary heart disease including age, sex, BMI, diabetes mellitus, and blood pressure. There was significant association of CACS, classified into three levels of severity, with RHI and AI (p = 0.0005 and p = 0.0009, respectively). For groups of increasing CACS (0, 1–400 and > 400 Agatston score), RHI decreased from median 1.89 (1.58–2.39), and 1.93 (1.62–2.41) to 1.77 (1.51–2.10). AI increased from median 14.3 (5.7–25.2), and 16.4 (8.1–27.6) to 18.0 (9.1–29.2). RHI, but not AI, remained significantly associated with CACS after risk factors adjustment. Conclusions: In this large study of coronary artery calcium and vascular function, we found an association between CACS and both endothelial dysfunction and arterial stiffness, indicating that they may reflect similar mechanisms for development of cardiovascular disease.
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| 3. |
- Wollmer, Per, et al.
(författare)
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Within-session reproducibility of forced oscillometry
- 2021
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:5, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The forced oscillation technique (FOT) provides detailed information about the mechanics of the respiratory system, while requiring minimal co-operation by the patient. FOT may be abnormal in subjects with normal spirometry and appears to be more closely related to airway symptoms. It is, therefore, attractive in epidemiological studies, where a large number of different examinations are made in each subjects in a short period of time. Current technical standards recommend the mean of three consecutive measurements to be used, but there is limited information regarding within-session variability of FOT measurements.OBJECTIVE: The purpose of this study was to examine the within-session variability in FOT measurements in a large, population-based sample.METHODS: We performed three consecutive FOT measurements in 700 subjects using the impulse oscillometry system. The first measurement was compared to the mean of three measurements for resistance at 5 and 20 Hz (R5 and R20, respectively), R5-R20, reactance at 5 Hz (X5) and resonant frequency (fres ).RESULTS: The differences between the first and the mean of three measurements (median, interquartile range) were minimal, for example 0.002, -0.008 to 0.014 kPa L-1 s for R5 and -0.001, -0.008 to 0.005 kPa L-1 s for X5. Findings were numerically similar for men and women as well as for subjects with and without airflow obstruction at spirometry.CONCLUSIONS: We conclude that, whereas in clinical situations, three FOT measurements are to be preferred, a single measurement may suffice in epidemiological studies.
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| 4. |
- Ahlqvist, Emma, et al.
(författare)
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Novel subgroups of adult-onset diabetes and their association with outcomes : a data-driven cluster analysis of six variables
- 2018
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Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 6:5, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.MethodsWe did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations.FindingsWe identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes.InterpretationWe stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.
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| 5. |
- Arner, Anders, et al.
(författare)
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Calcium transients and the effect of a photolytically released calcium chelator during electrically induced contractions in rabbit rectococcygeus smooth muscle
- 1998
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Ingår i: Biophysical Journal. - 1542-0086 .- 0006-3495. ; 75:4, s. 1895-1903
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Tidskriftsartikel (refereegranskat)abstract
- Intracellular Ca2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22 degreesC. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca2+] increased during activation; the increase in [Ca2+] preceded force development by approximately 2 s. After cessation of stimulation Ca2+ fell, preceding the fall in force by approximately 4 s. The fluorescence properties of fura-2 were determined with time-resolved spectroscopy using synchrotron light at the MAX-storage ring, Lund, Sweden. The fluorescence decay of free fura-2 was best described by two exponential decays (time constants approximately 0.5 and 1.5 ns) at low Ca2+ (pCa 9). At high Ca2+ (pCa 4.5), fluorescence decay became slower and could be fitted by one exponential decay (1.9 ns). Time-resolved anisotropy of free fura-2 was characteristic of free rotational motion (correlation time 0.3 ns). Motion of fura-2 could be markedly inhibited by high concentrations of creatine kinase. Time-resolved spectroscopy measurements of muscle fibers loaded with fura-2 showed that the fluorescence lifetime of the probe was longer, suggesting an influence of the chemical environment. Anisotropy measurements revealed, however, that the probe was mobile in the cells. The Ca2+-dependence of contraction and relaxation was studied using a photolabile calcium chelator, diazo-2, which could be loaded into the muscle cells in a similar manner as fura-2. Photolysis of diazo-2 leads to an increase in its Ca2+-affinity and a fall in free Ca2+. When muscles that had been loaded with diazo-2 were illuminated with UV light flashes during the rising phase of contraction, the rate of contraction became slower, suggesting a close relation between intracellular Ca2+ and the cross-bridge interaction. In contrast, photolysis during relaxation did not influence the rate of force decay, suggesting that relaxation of these contractions is not determined by the rate of Ca2+ removal or due to an increased Ca2+ sensitivity, but instead is limited by other processes such as deactivation by dephosphorylation or detachment of tension-bearing cross-bridges, possibly regulated by thin filament systems.
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| 6. |
- Arner, Anders, et al.
(författare)
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Cross-bridge cycling in smooth muscle: a short review
- 1998
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 164:4, s. 363-372
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Tidskriftsartikel (refereegranskat)abstract
- This review is focused on the cross-bridge interaction of the organized contractile system of smooth muscle fibres. By using chemically skinned preparations the different enzymatic reactions of actin-myosin interaction have been associated with mechanical events. A rigor state has been identified in smooth muscle and the binding of ATP causes dissociation of rigor cross-bridges at rates slightly slower than those in skeletal muscle, but fast enough not to be rate-limiting for cross-bridge turn over in the muscle fibre. The release of inorganic phosphate (Pi) is associated with force generation, and this process is not rate-limiting for maximal shortening velocity (Vmax) in the fully activated muscle. The binding of ADP to myosin is strong in the smooth muscle contractile system, a property that might be associated with the generally slow cross-bridge turn over. Both force and Vmax are modulated by the extent of myosin light chain phosphorylation. Low levels of activation are considered to be associated with the recruitment of slowly cycling dephosphorylated cross-bridges which reduces shortening velocity. The attachment of these cross-bridge states in skinned smooth muscles can be regulated by cooperative mechanisms and thin filament associated systems. Smooth muscles exhibit a large diversity in their Vmax and the individual smooth muscle tissue can alter its Vmax under physiological conditions. The diversity and the long-term modulation of phenotype are associated with changes in myosin heavy and light chain isoform expression.
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| 7. |
- Arner, Anders, et al.
(författare)
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Effects of Ca2+ on force-velocity characteristics of normal and hypertrophic smooth muscle of the rat portal vein
- 1985
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 124:4, s. 525-533
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Tidskriftsartikel (refereegranskat)abstract
- Portal hypertension was induced in rats by partial ligation of the hepatic branches of the portal vein. After 5 days of hypertension the portal veins were taken out and mounted for isometric and quick-release experiments. Portal veins from sham-operated normal rats served as controls. The ligated veins had an increased cross-sectional area, indicating smooth-muscle hypertrophy. Although the absolute magnitude of active force of these veins was increased, the active force per cross-sectional area was decreased, indicating an alteration in the properties of the contractile system. No difference in the Ca2+ concentration-response relations to K+-activated intact control and hypertrophic veins was found. In chemically skinned preparations, devoid of functional plasma membranes, the hypertrophic veins had similar Ca2+ sensitivity (in the presence of I microM calmodulin) but a lower force per cross-sectional area. Force-velocity relations were determined in K+-activated intact preparations. In control veins a reduction in extracellular Ca2+ was associated with a significant reduction in both isometric force and maximal shortening velocity (Vmax). In hypertrophic veins the decreased isometric force at maximal activation was associated with a low Vmax. A comparison between hypertrophic and submaximally stimulated control vessels showed corresponding Vmax and isometric force values. We conclude that the low isometric force of hypertrophic veins is associated with a lower rate of cross-bridge turnover. This could be an effect of alterations in the activation mechanisms or in the intrinsic properties of the contractile system itself.
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| 8. |
- Arner, Anders, et al.
(författare)
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Energy turnover and lactate dehydrogenase activity in detrusor smooth muscle from rats with streptozotocin-induced diabetes
- 1993
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 147:4, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- Force generation and tissue glucose metabolism were measured in the urinary bladder smooth muscle from rats with streptozotocin-induced diabetes (7-8 wk duration). Bladder wet wt was almost 4-fold higher in the diabetic animals compared with the untreated controls. Morphological analysis showed that the growth was associated with hypertrophy of the smooth muscle component in the bladder wall. Force generation of isolated bladder strip preparations was measured in vitro at different ambient oxygen tensions. Activation of intramural nerves, with electrical field stimulation, induced contractions that were unaffected by reduction of oxygen tension down to PO2 100 mmHg for both control and diabetic muscle strips. At zero PO2 force was reduced by approximately 10-20%, in both groups. High-K+ solution induced 'tonic' contractions that were slightly more inhibited by lowering PO2. At intermediate PO2 (between 100 and 20 mmHg) the diabetic muscle gave slightly higher force. At zero PO2 no significant difference could be detected between strips from control and diabetic animals. Oxygen consumption and lactate production in the preparations were determined at a PO2 of 290 mmHg and related to the volume of smooth muscle. At zero PO2, lactate formation increased 3- to 4-fold. The metabolic tension cost was lower at zero PO2. No differences in basal and contraction related metabolic rates could be detected between the two groups under normoxic and anoxic conditions. The maximal activity of lactate dehydrogenase (LDH) determined in tissue samples was about 2-fold higher in the diabetic bladder muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 9. |
- Arner, Anders, et al.
(författare)
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Metabolism and force in hypertrophic smooth muscle from rat urinary bladder
- 1990
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Ingår i: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 258:5 Pt 1, s. 923-932
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Tidskriftsartikel (refereegranskat)abstract
- Ten days of urinary outlet obstruction in the rat induced a threefold increase in bladder weight. Active force of control and hypertrophic bladder muscle strips was measured at varying PO2 levels after high-K+, carbachol, or electrical field stimulation. Highest force output was obtained with carbachol. Force per muscle area was lower in the hypertrophic muscles. The basal rates of oxygen consumption and lactate formation were similar in the two groups. The metabolic tension cost (ATP turnover/active force) was similar in the two groups for activation with high K+ and carbachol. In anoxia the active force decreased, but this was less pronounced in the hypertrophied muscle. Hypertrophied muscle could, in contrast to the controls, maintain a sustained K+ contracture in anoxia. Basal metabolic rates and tension cost were markedly reduced in anoxia for both groups. The lower force per area with unaltered tension cost, in hypertrophic muscles under all experimental conditions, may reflect unaltered intrinsic properties of the contractile system, although the amount of contractile material has decreased relative to cell volume. The increased resistance to anoxia may reflect a metabolic adaptation to impaired oxygen supply to the hypertrophied tissue.
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| 10. |
- Arner, Anders, et al.
(författare)
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Structural and mechanical adaptations in rat aorta in response to sustained changes in arterial pressure
- 1984
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 122:2, s. 119-126
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Tidskriftsartikel (refereegranskat)abstract
- Structural and mechanical adaptations in response to sustained changes in arterial pressure were studied on abdominal aorta of the male rat. Two models were used: 1. Aortic ligature (L), immediately below the renal arteries producing hypotension distal to the knot (duration before sacrifice 6 weeks or 3 months). 2. One-clip renal hypertensive rats (H) (duration 6 weeks). Normotensive sham-operated rats (C) served as controls. At sacrifice mean tail artery pressure was L: 58 +/- 1, C: 110 +/- 3, and H: 163 +/- 5 mmHg (SE, N=6). Segments of abdominal aorta were mounted in vitro for determination of their length-tension relations (activation: High-K+ solution with 2.5 mM Ca2+). At end of experiments the vessels were supramaximally stimulated at optimal circumference (1o) for active force (activation: High-K+ solution with 10 mM Ca2+, and 10(-5) M noradrenaline), and then fixated for light and electron microscopy. Passive and active length-tension relations were shifted towards lower and higher circumference values for hypo- and hypertensive vessels, respectively. The 1o values were L: 3.60 +/- 0.13, C: 4.44 +/- 0.19, and H: 4.91 +/- 0.29 mm. The media thickness at 1o was reduced in L: 56.0 +/- 3.3, and increased in H: 81.3 +/- 2.4 compared to C: 73.4 +/- 1.8 micron. Maximal active wall stress was L: 46.6 +/- 9.8, C: 74.2 +/- 7.0, and H: 83.8 +/- 7.7 mN/mm2. Intracellular volume (ICV) in the media was L: 30 +/- 2, C: 45 +/- 3, and H: 44 +/- 1% (n=4 for each).
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