Biomedical subjects

J Henriksson

Publications and source records attributed to J Henriksson.

At least 19 recordsLinked to original sources

PubMed2005

Acidosis in muscle tissue distal to vascular contusion despite unchanged global blood flow in rats: an uncoupling of microvascular blood flow and metabolism?

Studies using a contusion trauma model have shown that the femoral artery of the rat remains patent in 85% despite a severe vessel injury. A significant increase in tissue oxygenation (PtO2) has been found despite only a minor effect on blood flow (<20% decrease) on the muscle surface distal to the injury indicating a disturbed relationship between microvascular blood flow and metabolism. The aim of the present study was to further study the interplay between microvascular blood flow and metabolism within the distal muscle using an ethanol clearance technique (blood flow) in conjunction to the determination of an ischemia marker (lactate) by use of microdialysis. Although skeletal muscle blood flow remained unaltered as assessed by ethanol clearance, skeletal muscle lactate levels increased significantly (P<0.001) post-trauma in both legs. The increase was initially higher, faster and the increase over time larger in the trauma leg as compared to the control leg (P<0.001). These findings indicate a systemic effect of the trauma. Further, it suggests a functional impairment of the relationship between microvascular blood flow and/or muscle metabolic processes when the trauma is directed towards the supplying blood vessel. The reason for this anaerobic insult as found in this study compared to the presence of a local increase in PtO2 in the trauma leg as shown in our previous study is suggestive of an microvascular blood flow and tissue metabolism uncoupling.

Acidosis↗

PubMed2005

Local effect of vanadate on interstitial glucose and lactate concentrations in human skeletal muscle.

The aim of this study was to investigate the local effect of the insulin-mimetic agent vanadate on glucose metabolism in human skeletal muscle in vivo. Interstitial concentrations of glucose and lactate were determined by microdialysis at a low flow rate in the quadriceps femoris muscle of 18 men. In the same leg two microdialysis catheters were inserted. In one catheter, the perfusion medium was supplemented with sodium metavanadate (10-100 mM) after a basal period, the other catheter served as control. In the catheter perfused with metavanadate, the interstitial glucose concentration was decreased by 13-50% compared to the control catheter (p<0.05). The lactate concentration was higher in the 50 mM and 100 mM metavanadate catheters compared to control (39-89%, p<0.05). There was no difference between control and metavanadate catheters in urea concentrations. Five of the subjects were insulin-resistant and for them the results were similar, although the effect was somewhat smaller. The decreased interstitial glucose concentration, and the increased lactate concentration, in the vicinity of the microdialysis catheter most likely reflects an increased cellular glucose uptake. The present study thus indicates that vanadate mimics the effect of insulin in human skeletal muscle in vivo.

Adult↗

PubMed2005

A single bout of exercise is followed by a prolonged decrease in the interstitial glucose concentration in skeletal muscle.

AIM: The present study was performed to test the hypothesis that the interstitial glucose concentration in human skeletal muscle is decreased for a prolonged period following a single bout of exercise, while blood flow has returned to resting levels. METHODS: Muscle interstitial concentrations of glucose, lactate, pyruvate and urea were monitored in six healthy individuals during 8 h following a 2-h one-leg exercise session by microdialysis at low perfusion flow rate. Simultaneously the blood flow was measured by the microdialysis ethanol technique. RESULTS: The blood glucose and the control leg interstitial glucose concentrations were stable during the experiment averaging 5.7 +/- 0.1 and 4.1 +/- 0.3 mm, respectively. In contrast, the interstitial glucose concentration in the exercise leg was markedly decreased, averaging 1.9 +/- 0.5 mm, during the first 5.5 h following exercise (P < 0.01), after which it returned towards normal values. Muscle blood flow at the site of the microdialysis catheter, measured as the ethanol outflow-to-inflow ratio, did not change significantly over time in the control or exercise leg and did not differ significantly between the two legs. Interstitial concentrations of lactate, pyruvate and urea were not significantly different between the control and exercise leg. CONCLUSION: The study shows that the interstitial glucose concentration in skeletal muscle is markedly decreased for several hours following a single exercise session. The decreased interstitial glucose concentration may serve to limit the rate of post-exercise muscle glucose uptake to a rate compatible with normal blood glucose levels and may also be speculated to have a positive long-term health implication by augmenting muscle insulin sensitivity.

Adult↗

PubMed2002

Chromosomal size variation in Trypanosoma cruzi is mainly progressive and is evolutionarily informative.

The evolutionary significance of chromosome size polymorphism was explored in a representative panel of 26 Trypanosoma cruzi stocks. We tested a progressive model (aCSDI) assuming that the larger the size difference between homologous chromosomes, the more divergent the parasites are. This was contrasted with a non-progressive model (Jaccard's distance), in which any chromosome size difference has the same weight. ACSDI-based dendrograms were very similar to those built-up from multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD) data: structuring in 2 major lineages (T. cruzi I and T. cruz II) and 5 small subdivisions within T. cruzi II was identical, and branching was very similar. Furthermore, a significant correlation (P < 0.001) was observed between aCSDI and phenetic distances calculated from MLEE and RAPD data. In contrast, analysis of chromosome size polymorphism with Jaccard's distance generated dendrograms with relatively long branches, causing most branching points to cluster close together, which generates statistically uncertain branching points. Our results thus support a model of progressive chromosome size-variation and show that despite an extensive polymorphism, chromosomal sizes constitute valuable characters for evolutionary analyses. Furthermore, our data are consistent with the clonal evolution model previously proposed for T. cruzi.

Animals↗

PubMed2002

Microdialysis in human skeletal muscle: effects of adding a colloid to the perfusate.

Microdialysis catheters (CMA-60 with a polyamide dialysis membrane; 20,000-molecular wt cutoff) were either immersed in an external medium or were inserted in the quadriceps femoris muscle of healthy subjects, using perfusate with or without dextran 70. Varying the position of the outflow tubing induced changes in hydrostatic pressure. The sample volumes were significantly smaller in catheters perfused without a colloid compared with those perfused with a colloid [11-50% (in vitro) and 8-59% (in vivo) lower than in colloid-perfused catheters with the same position of the outflow tubing]. The sample volumes were also significantly smaller when the dialysis membrane was influenced by maximal hydrostatic pressure (above position) compared with minimal hydrostatic pressure (below position) [7-38% (in vitro) and 3-46% (in vivo) lower than in catheters in the below position with the same perfusion fluid]. In vivo, glucose concentration at a perfusion flow rate of 0.33 microl/min was higher when the catheters were perfused without a colloid [18-28% higher than in colloid-perfused catheters with the same position of the outflow tubing (P < 0.001)] than with a colloid. A corresponding difference also tended to occur with lactate, glycerol, and urea. At 0.16 microl/min, the glucose concentration was the same irrespective of whether fluid loss had been counteracted by colloid inclusion or by lowering of outlet tubing. The mechanism behind the observed concentration difference is thought to be a higher effective perfusion flow rate when fluid loss is prevented at low-perfusion flows. This study shows that fluid imbalances can have important implications for microdialysis results at low-perfusion flow rates.

Adult↗

PubMed2001

Bacterial senescence: protein oxidation in non-proliferating cells is dictated by the accuracy of the ribosomes.

We have investigated the causal factors behind the age-related oxidation of proteins during arrest of cell proliferation. A proteomic approach demonstrated that protein oxidation in non-proliferating cells is observed primarily for proteins being produced in a number of aberrant isoforms. Also, these cells exhibited a reduced translational fidelity as demonstrated by both proteomic analysis and genetic measurements of nonsense suppression. Mutants harboring hyperaccurate ribosomes exhibited a drastically attenuated protein oxidation during growth arrest. In contrast, oxidation was augmented in mutants with error-prone ribosomes. Oxidation increased concomitantly with a reduced rate of translation, indicating that the production of aberrant, and oxidized proteins, is not the result of titration of the co-translational folding machinery. The age-related accumulation of the chaperones, DnaK and GroEL, was drastically attenuated in the hyperaccurate rpsL mutant, demonstrating that the reduced translational fidelity in growth-arrested cells may also be a primary cause for the induction of the heat shock regulon. The data point to an alternative way of approaching the causal factors involved in protein oxidation in eukaryotic G(0) cells.

Bacterial Proteins↗

PubMed2001

Effects of concentric and eccentric contractions on phosphorylation of MAPK(erk1/2) and MAPK(p38) in isolated rat skeletal muscle.

1. Exercise and contractions of isolated skeletal muscle induce phosphorylation of mitogen-activated protein kinases (MAPKs) by undefined mechanisms. The aim of the present study was to determine exercise-related triggering factors for the increased phosphorylation of MAPKs in isolated rat extensor digitorum longus (EDL) muscle. 2. Concentric or eccentric contractions, or mild or severe passive stretches were used to discriminate between effects of metabolic/ionic and mechanical alterations on phosphorylation of two MAPKs: extracellular signal-regulated kinase 1 and 2 (MAPK(erk1/2)) and stress-activated protein kinase p38 (MAPK(p38)). 3. Concentric contractions induced a 5-fold increase in MAPK(erk1/2) phosphorylation. Application of the antioxidants N-acetylcysteine (20 mM) or dithiothreitol (5 mM) suppressed concentric contraction-induced increase in MAPK(erk1/2) phosphorylation. Mild passive stretches of the muscle increased MAPK(erk1/2) phosphorylation by 1.8-fold, whereas the combination of acidosis and passive stretches resulted in a 2.8-fold increase. Neither concentric contractions, nor mild stretches nor acidosis significantly affected phosphorylation of MAPK(p38). 4. High force applied upon muscle by means of either eccentric contractions or severe passive stretches resulted in 5.7- and 9.5-fold increases of phosphorylated MAPK(erk1/2), respectively, whereas phosphorylation of MAPK(p38) increased by 7.6- and 1.9-fold (not significant), respectively. 5. We conclude that in isolated rat skeletal muscle an increase in phosphorylation of both MAPK(erk1/2) and MAPK(p38) is induced by mechanical alterations, whereas contraction-related metabolic/ionic changes (reactive oxygen species and acidosis) cause increased phosphorylation of MAPK(erk1/2) only. Thus, contraction-induced phosphorylation can be explained by the combined action of increased production of reactive oxygen species, acidification and mechanical perturbations for MAPK(erk1/2) and by high mechanical stress for MAPK(p38).

Acids↗

PubMed2000

A microdialysis method for the in situ investigation of the action of large peptide molecules in human skeletal muscle: detection of local metabolic effects of insulin.

The possibility of using microdialysis catheters with a large pore size dialysis membrane (100 kDa) to investigate the action of macromolecules perfused into the interstitial space of peripheral tissues was explored. This was made possible by increasing the colloid osmotic pressure of the perfusate with 40 g/l of dextran-70 to prevent perfusate loss across the dialysis membranes. Microdialysis catheters were inserted into the quadriceps femoris muscle of 13 human subjects. With different perfusion flow rates (1. 33, 0.66, 0.33 and 0.16 microl/min) the recorded concentrations of glucose, lactate, and urea were in agreement with values previously obtained using a conventional membrane with a smaller pore size (20 kDa) [Rosdahl H, Hamrin K, Ungerstedt U, Henriksson. J Am J Physiol 1998;274:E936-45.]. When insulin was added to the perfusate, the concentration of glucose was significantly reduced, indicating that insulin diffuses across the dialysis membrane and has cellular effects that can be simultaneously recorded. The present findings are the first documentation on the use of microdialysis to study the local metabolic action of large peptide molecules in human tissues and may open new avenues for in-vivo metabolic research.

Adult↗

PubMed2000

The tyrosine aminotransferase from Trypanosoma rangeli: sequence and genomic characterization.

The complete sequence and genomic characterization of the tyrosine aminotransferase (TAT) gene from Trypanosoma rangeli is reported. The gene was found to be organized in a tandem multicopy gene array. A homologous mRNA species (2.5 kb) was identified in the epimastigote form of the parasite. From the deduced amino acid sequence, the gene encodes a protein of 420 amino acids with a predicted molecular mass of 46.4 kDa and a theoretical pI of 6.23. A high sequence identity was found with the Trypanosoma cruzi, human and rat enzymes. All the essential residues for TAT enzymatic activity are conserved, as well as a pyridoxal-phosphate attachment site typical of class-I aminotransferases. The recombinant enzyme was recognized by a monoclonal antibody against the T. cruzi enzyme. Additionally, the recombinant protein showed enzymatic activity when incubated with L-tyrosine and 2-oxoglutaric acid as substrates.

Amino Acid Sequence↗

PubMed2000

Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle.

The mitogen-activated protein (MAP) kinase pathways have been highlighted as a possible link between exercise and adaptive changes in skeletal muscle. In this study, the effect of exercise intensity on the activation of the ERK/MAP kinase pathway was investigated in human skeletal muscle. One-leg exercise at low (40% maximal oxygen consumption, VO2max for 30 min) and high (75% VO2max for 30 min) intensity resulted in 11.5+8. I-fold and 39.7+/-6.3-fold (mean +/-SEM) increases in ERK1/2 phosphorylation (P<0.001), respectively. The phosphorylation of MEK1/2, the upstream kinase of ERK1/2, increased with exercise intensity (P<0.05) to 2.5+/-0.9 and 4.8+/-1.1 times the basal level at the low and high intensity, respectively. The statistical analysis revealed a systematic difference between basal, low and high intensity exercise levels for both kinases. There was no change in the phosphorylation of either kinase in the non-exercised leg. The phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB), a possible downstream target of the ERK/MAP kinase signalling pathway, was unaffected by exercise. The phosphorylation of ERK1/2 was significantly higher in purified freeze-dried compared to crude wet muscle after exercise, whereas the opposite pattern was observed for CREB. In conclusion, phosphorylation of ERK1/2 and MEK1/2 increases in an exercise intensity-dependent manner in human skeletal muscle and this seems to originate in the muscle fibres themselves.

Adult↗

PubMed2000

Differential activation of mitogen-activated protein kinase signalling pathways by isometric contractions in isolated slow- and fast-twitch rat skeletal muscle.

Activation of mitogen-activated protein (MAP) kinases has been implicated in the signal transduction pathways linking exercise to adaptive changes of muscle protein expression. In the present study, we investigated whether contractions of isolated muscles induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 MAPK in a fibre-type dependent manner. Slow-twitch (soleus) and fast-twitch (epitrochlearis, extensor digitorum longus) rat skeletal muscles were exposed to intermittent tetanic stimulation. Compared with the contralateral non-stimulated muscle, contractions increased ERK1/2 phosphorylation to the same extent in fast- and slow-twitch muscles. Significant increase in phosphorylation of p38 MAPK was observed in the fast-twitch muscles only. The total amount of ERK1/2 and p38 MAPK proteins was higher in the slow-twitch soleus muscle. In conclusion, MAP kinase signalling pathways are differentially activated and expressed in slow- and fast-twitch muscles. In addition, this activation is owing to muscle contraction per se and do not demand additional external influence.

Animals↗

PubMed2000

Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes.

Manganese (Mn), administered intranasally in rats, is effectively taken up in the CNS via the olfactory system. In the present study, Mn (as MnCl(2)) dissolved in physiological saline, was instilled intranasally in rats at doses of 0 (control), 10, 250, or 1000 microg. At the start of the experiment each rat received an intranasal instillation. Some rats were killed after one week without further treatment (the 1-w group), whereas the remaining rats received further instillations after one and two weeks and were killed after an additional week (the 3-w group). The brains were removed and either used for ELISA-determination of the astrocytic proteins glial fibrillary acidic protein (GFAP) and S-100b or histochemical staining of GFAP and S-100b, microglia (using an antibody against the iba1-protein) and the neuronal marker Fluoro-Jade. There were no indications that the Mn induced neuronal damage. On the other hand, the ELISA showed that both GFAP and S-100b decreased in the olfactory cortex, the hypothalamus, the thalamus, and the hippocampus of the 3-w group. The only effect observed in the 1-w group was a decrease of S-100b in the olfactory cortex at the highest dose. The immunohistochemistry showed no noticeable reduction in the number of astrocytes. We assume that the decreased levels of GFAP and S-100b are due to an adverse effect of Mn on the astrocytes, although this effect does not result in astrocytic demise. In the 3-w group, exposed to the highest dose of Mn, increased levels of GFAP and S-100b were observed in the olfactory bulbs, but these effects are probably secondary to a Mn-induced damage of the olfactory epithelium. Our results indicate that the astrocytes are the initial targets of Mn toxicity in the CNS.

Administration, Intranasal↗

PubMed2000

Effects of exercise on mitogen- and stress-activated kinase signal transduction in human skeletal muscle.

Exercise/contraction is a powerful stimulator of mitogen-activated protein (MAP) kinase cascades in skeletal muscle. Little is known regarding the physiological activation of enzymes downstream of MAP kinase. We investigated whether acute exercise results in activation of mitogen- and stress-activated kinases (MSK) 1 and 2, p90 ribosomal S6 kinase (p90rsk), and MAP kinase-activated protein kinase 2 (MAPKAPK2). Muscle biopsies were obtained from healthy volunteers before, during, and after 60 min one-leg cycle ergometry, from exercising and resting legs. MSK1 and MSK2 activities were increased 400-500% and 200-300%, respectively, in exercised muscle (P < 0.05 vs. rest). A dramatic increase in activity of p90rsk (MAPKAPK1) (>2,500%), and to a lesser extent MAPKAP2 (300%), was noted with exercise (P < 0.05 vs. rest). MSK1, MSK2, p90rsk, and MAPKAP2 activities were sustained throughout exercise. Exercise-induced activation of these enzymes was limited to working muscle, indicating that local rather than systemic factors activate these signaling cascades. Thus physical exercise leads to activation of multiple enzymes downstream of MAP kinase.

Adult↗

PubMed1999

Transport of manganese via the olfactory pathway in rats: dosage dependency of the uptake and subcellular distribution of the metal in the olfactory epithelium and the brain.

The dosage dependency of the uptake of Mn from the olfactory epithelium via olfactory neurons into the brain was studied after intranasal administration of the metal in rats. The results indicate that the Mn transport is saturable both regarding the uptake into the olfactory epithelium and the transfer to the olfactory bulb. Further, our data indicate that Mn moves relatively freely from the olfactory bulb to the olfactory cortex at an amount dependent on the level of influx into the bulb. The transport to the rest of the brain was related to the amounts in the olfactory bulb and the olfactory cortex, but the relative proportion reaching this area increased with increasing doses. Cell fractionations showed that the Mn was present both in the cytosol and in association with various cell constituents. Gel filtrations of the cytosol on a Superdex 30 column showed that about 20% of the Mn in the brain and about 3% in the olfactory epithelium was eluted together with high-molecular-weight materials (MW > 10,000), whereas the rest was eluted in the total volume and may represent unbound metal. It is likely that the metal has been loosely associated with protein(s) or other constituents at the application to the column, but that this association is too loose to be retained during the passage through the column. Our results show that the olfactory neurons provide a pathway with a considerable capacity to transport Mn into the brain. We propose that the neurotoxicity of inhaled Mn is related to an uptake via this route.

Administration, Intranasal↗

PubMed1999

[Current knowledge on muscle training: endurance and strength yield complementary effects].

Both endurance and strength training are generally agreed to be necessary components of a balanced fitness programme. These two types of training are complementary; strength training improves neuromuscular function, prevents injuries, and is a prerequisite for effective endurance training. Whereas endurance training results in high energy expenditure during exercise, strength training, being associated with increased muscle mass, may result in increased energy expenditure at rest. In conjunction with endurance training, the most striking finding in skeletal muscle is its remarkable adaptability. Indeed, it is usually possible for the muscles to acquire the characteristics necessary to meet prevailing functional demands. This is true even if the demand is continuous contractile activity, 24 hours a day, week after week. The physiological effects of strength training are the result of hypertrophy of individual motor units, mostly comprising type II (fast-twitch) fibres, but are also secondary to neural changes affecting the recruitment and frequency modulation of motor units and co-ordination.

Energy Metabolism↗

PubMed1999

Microdialysis of skeletal muscle at rest.

Techniques in human skeletal muscle research are by necessity predominantly 'descriptive'. Microdialysis has raised high expectations that it could meet the demand for a method that allows 'mechanistic' investigations to be performed in human skeletal muscle. In the present review, some views are given on how well the initial expectations on the use of the microdialysis technique in skeletal muscle have been fulfilled, and the areas in which additional work is needed in order to validate microdialysis as an important metabolic technique in this tissue. The microdialysis catheter has been equated to an artificial blood vessel, which is introduced into the tissue. By means of this 'vessel' the concentrations of compounds in the interstitial space can be monitored. The concentration of substances in the collected samples is dependent on the rate of perfusate flow. When perfusate flow is slow enough to allow complete equilibration between interstitial and perfusate fluids, the concentration in the perfusate is maximal and identical to the interstitial concentration. Microdialysis data may be influenced by changes in blood flow, especially in instances where the tissue diffusivity limits the recovery in vivo, i.e. when recovery in vitro is 100%, whereas the recovery in vivo is less than 100%. Microdialysis data indicate that a significant arterial-interstitial glucose concentration gradient exists in skeletal muscle but not in adipose tissue at rest. While the concentrations of glucose and lactate in the dialysate from skeletal muscle are close to the expected values, the glycerol values obtained for muscle are still puzzling. Ethanol added to the perfusate will be cleared by the tissue at a rate that is determined by the nutritive blood flow (the microdialysis ethanol technique). It is concluded that microdialysis of skeletal muscle has become an important technique for mechanistic studies in human metabolism and nutrition.

Blood Flow Velocity↗

PubMed1999

Endothelin plays an important role in the endothelium-dependent vasodilatation in the human forearm.

UNLABELLED: Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mainly by local infusion of a muscarinic-receptor agonists in the forearm. It has been postulated that the function of the vasodilator nitric oxide (NO) can be evaluated with this technique. However, the role of the vasoconstrictor endothelin in this model has not been investigated. METHODS: Ten male hypertensive and seven male normotensive subjects were subjected to measurements of forearm blood flow (FBF) by venous occlusion plethysmography during local intra-arterial infusion of metacholine (4 microg/min) or nitroprusside (10 microg/min). In parallel, forearm venous plasma endothelin (ir-ET) was determined. RESULTS: Metacholine and nitroprusside increased FBF 2.3 and 2.2 times the baseline level (6.6+/-2.8 SD ml/min/100 ml tissue) in hypertensive subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 ml tissue) for both drugs in the normotensive subjects. None of the drugs induced any significant changes in ir-ET levels in any of the groups (baseline 1.5+/-0.4 pmol/l in hypertensive and 1.1+/-1.2 pmol/l in normotensive subjects). However, in the hypertensive subjects, the individual change in venous ir-ET levels during infusion with metacholine, but not with nitroprusside, was inversely related to the degree of vasodilatation induced by this agent (r = -0.71, p < 0.02). A similar correlation coefficient (r=-0.69) was found in healthy subjects. CONCLUSION: Muscarinic-receptor-agonist-stimulated vasodilatation in the human forearm, thought mainly to reflect NO synthesis, was inversely related to the change in endothelin levels, suggesting an important role for this endothelium-derived vasoconstrictor in this model of EDV.

Adult↗

PubMed1998

[Regular physical activity reduces the risk of cardiovascular disease. Overweight is increasing--we have to exercise!].

Epidemiological findings have shown strong inverse correlation to exist between the level of physical activity and the risk of ischaemic heart disease. Although the mechanism underlying the beneficial effect of physical activity is incompletely understood, available data suggest the risk reduction to be mainly due to decreased development of arteriosclerosis, but that reduced thrombogenesis and myocardial oxygen requirement, and enhanced myocardial vascularisation are contributory factors. In all likelihood, these factors, combined with reduced sympatho-adrenal activity during exercise in the trained state, explain the association of regular physical exercise with a decreased risk of fatal cardiac arrhythmia.

Cardiovascular Diseases↗