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Biomedical subjects

T Madsen

Publications and source records attributed to T Madsen.

At least 19 recordsLinked to original sources

Eccentric rehabilitation exercise increases peritendinous type I collagen synthesis in humans with Achilles tendinosis.

It has been shown that 12 weeks of eccentric heavy resistance training can reduce pain in runners suffering from chronic Achilles tendinosis, but the mechanism behind the effectiveness of this treatment is unknown. The present study investigates the local effect of an eccentric training regime on elite soccer players suffering from chronic Achilles tendinosis on the turnover of the peritendinous connective tissue. Twelve elite male soccer players, of whom six suffered from unilateral tendinosis and six were healthy controls, participated in this study. All participants performed 12 weeks of heavy-resistance eccentric training apart from their regular training and soccer activity. Before and after the training period the tissue concentration of indicators of collagen turnover was measured by the use of the microdialysis technique. After training, collagen synthesis was increased in the initially injured tendon (n=6; carboxyterminal propeptide of type I collagen (PICP): pre 3.9+/-2.5 microg/L to post 19.7+/-5.4 microg/L, P<0.05). The collagen synthesis was unchanged in healthy tendons in response to training (n=6; PICP: pre 8.3+/-5.2 microg/L to post 11.5+/-5.0 microg/L, P>0.05). Collagen degradation, measured as carboxyterminal telopeptide region of type I collagen (ICTP), was not affected by training neither in the injured nor in the healthy tendons. The clinical effect of the 12 weeks of eccentric training was determined by using a standardized loading procedure of the Achilles tendons showing a decrease in pain in all the chronic injured tendons (VAS before 44+/-9, after 13+/-9; P<0.05), and all subjects were back playing soccer following the eccentric training regime. The present study demonstrates that chronically injured Achilles tendons respond to 12 weeks of eccentric training by increasing collagen synthesis rate. In contrast, the collagen metabolism in healthy control tendons seems not to be affected by eccentric training. These findings could indicate a relation between collagen metabolism and recovery from injury in human tendons.

Achilles Tendon↗

MHC class I variation associates with parasite resistance and longevity in tropical pythons.

Using restriction fragment length polymorphism (RFLP) we identified 26 unique major histocompatibility complex (MHC) genotypes in 104 water pythons. We observed a significant independent association between reduced blood parasite load (Hepatozoon sp.) and python body length/age, presence of a specific RFLP fragment (C-fragment) and the overall number of fragments. The parasite has a negative impact on several python life-history traits such as growth, nutritional status and longevity. Thus, the C-fragment could be considered a 'good gene' (a fitness-enhancing genetic element). However, while the number of fragments affected parasite load, the association between level of parasitaemia and fragment number was not linear, and, hence, minimum parasite infection level was achieved at an intermediate number of fragments. Intermediate MHC fragment numbers were also observed among the largest/oldest pythons, suggesting that both a specific fragment and intermediate levels of MHC polymorphism enhanced python longevity. Thus, our results suggest python MHC is subject to both frequency-dependent and balancing selection.

Animals↗

Offspring-driven local dispersal in female sand lizards (Lacerta agilis).

We report on a field study in which determinants of female breeding dispersal (i.e. the shift in the mean home range coordinates between successive breeding events) was investigated. Offspring were released in full sib groups (or half sib ones if there was within-clutch multiple paternity) at a separation distance from the females that varied between 'families'. This allowed for analysis of 'offspring nearness' effects on maternal dispersal. When a female's offspring were released more closely to her, she responded with greater dispersal. Furthermore, when the data set was truncated at 100 m maternal-offspring separation distance at offspring release (because perception at longer distances is likely to be unrealistic), maternal dispersal resulted in greater separation distance between female and offspring in the following year. A corresponding analysis for juveniles revealed no effect of maternal nearness on offspring dispersal but identified a significant effect of clutch size, to our surprise with dispersal declining with increasing clutch size. We discuss this result in a context of the 'public information hypothesis' (reinterpreted for juveniles in a nonsocial foraging species), suggesting that conspecific abundance perhaps acts as an indicator of local habitat quality. Thus, our analysis suggests a microgeographic structuring of the adult female population driven by genetic factors, either through inbreeding avoidance, or from simply avoiding individuals with a similar genotype regardless of their pedigree relatedness, while a nongenetic factor seems more important in their offspring.

Animals↗

Family and population effects on disease resistance in a reptile.

Despite its importance in evolutionary biology, studies of the pattern of disease resistance in natural populations are rare. In this paper, we report patterns of infection of a viral eye disease in juvenile Swedish common lizards (Lacerta vivipara). Females were sampled at random from natural populations immediately prior to parturition with equal exposure of pathogens for all lizards once in captivity. No causative agents could be found that linked risk of disease to maternal/interfollicular transfer of pathogens. The results show that a major factor influencing offspring susceptibility is family identity, suggesting heritable variation in pathogen resistance. Our interpopulation comparison provides additional support for a link between genetics and disease resistance. Lizards in northern Sweden were not only more susceptible to the disease but were also more health compromised once infected, with relatively more reduced growth rate and increased mortality than lizards from the south. This scenario suggests that southern lizards have been under selection for resistance to this pathogen, whereas northern lizards have not, or at least not to the same degree. Thus, this study confirms the importance of genetic (family) effects on pathogen resistance with variation in this trait among natural populations.

Animals↗

C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease.

The acute-phase reactant C-reactive protein (CRP) has emerged as an independent risk factor for coronary artery disease. Experimental and clinical studies provide evidence of anti-inflammatory effects of n-3 polyunsaturated fatty acids (PUFA) derived from fish. We have studied the effect of marine n-3 PUFA on CRP levels in 269 patients referred for coronary angiography because of clinical suspicion of coronary artery disease. All patients filled out a food questionnaire regarding fish intake. The n-3 PUFA content of granulocyte membranes was determined and the concentration of CRP in serum was measured using a highly sensitive assay. The results were related to angiographic findings. CRP was significantly higher in patients with significant coronary stenoses than in those with no significant angiographic changes (p <0.001), but the CRP levels were not associated with the number of diseased vessels. Subjects with CRP levels in the lower quartile had a significantly higher content of docosahexaenoic acid (DHA) in granulocytes than subjects with CRP levels in the upper quartile (p = 0.02), and in a multivariate linear regression analysis, DHA was independently correlated to CRP (R(2) = 0.179; p = 0.003). The inverse correlation between CRP and DHA may reflect an anti-inflammatory effect of DHA in patients with stable coronary artery disease and suggest a novel mechanism by which fish consumption may decrease the risk of coronary artery disease.

Adult↗

Marine n-3 fatty acids: basic features and background.

There is some evidence from epidemiology that intake of n-3 polyunsaturated fatty acids (PUFA) from seafood may protect against coronary artery disease (CAD). This hypothesis is further supported from animal data showing a beneficial effect of n-3 PUFA on thrombosis and atherosclerosis in animals fed fish oils in most, but not all, studies. There are several mechanisms by which an increased intake of marine n-3 PUFA may protect against CAD; the most universal finding is a reduction of plasma triglycerides. It is puzzling, however, that a very low amount of n-3 PUFA, with no known beneficial biochemical effects, seems to be cardioprotective. It has therefore been of paramount interest to perform clinical trials. Such evidence and trials are discussed in later chapters, and the results have been very encouraging.

Animals↗

Effects of sludge-amendment on mineralization of pyrene and microorganisms in sludge and soil.

Hydrophobic contaminants sorb to sludge in wastewater treatment plants and enter the soil environment when the sludge is applied to agricultural fields. The mineralization of pyrene was examined in soil, in sludge mixed homogeneously into soil, and in sludge-soil systems containing a lump of sludge. Sludge-amendment enhanced the mineralization of pyrene in the soil compared to soil without sludge, and the most extensive mineralization was observed when the sludge was kept in a lump. The number of protozoa, heterotrophic bacteria and pyrene-mineralizing bacteria was much higher in the sludge compared to the soil. The amendment of sludge did not affect the number of protozoa and bacteria in the surrounding soil, which indicated that organic contaminants in the sludge had a little effect on the number of protozoa and bacteria in the surrounding soil.

Agriculture↗

Heart rate variability and n-3 polyunsaturated fatty acids in patients with diabetes mellitus.

OBJECTIVES: Dietary n-3 polyunsaturated fatty acids (PUFA) derived from fish may reduce the incidence of sudden cardiac death (SCD). The aim of the present study was to examine associations between n-3 PUFA and 24-h heart rate variability in patients with type 1 and type 2 diabetes mellitus (DM). DESIGN: Observational study. SETTING: The out-patient's diabetic clinic at Hjørring Hospital, Hjørring, Denmark. SUBJECTS: Forty-three patients with type 1 DM and 38 patients with type 2 DM. MAIN OUTCOME MEASURES: The patients fulfilled a food-questionnaire regarding fish consumption, whilst the content of n-3 PUFA in platelets was measured and 24-h heart rate variability (HRV) was obtained. RESULTS: The patients fish consumption was strongly related to their content of n-3 PUFA in platelets. Furthermore, in patients with type 1 DM a close positive association was found between the content of n-3 PUFA in platelets and 24-h HRV. This association was not significant in patients with type 2 DM. CONCLUSIONS: The positive association between n-3 PUFA in platelets and HRV may indicate a beneficial effect of n-3 PUFA on HRV in patients with type 1 DM. Further studies are warranted to clarify whether supplementation with n-3 PUFA reduce the risk of SCD amongst patients with DM.

Adult↗

Mineralization of organic contaminants in sludge-soil mixtures.

The mineralization of 14C-labeled linear alkylbenzene sulfonate (LAS), nonylphenol (NP), nonylphenol-di-ethoxylate (NP2EO), di-(2-ethylhexyl)phthalate (DEHP), pyrene, and 1,4-dichlorobenzene (DCB) was investigated in different sludge-soil mixtures and soils. Under aerobic conditions, the mineralization of LAS, NP, and NP2EO was between 50 and 81% of the added amounts after two months, while DEHP and pyrene were mineralized more slowly. The mineralization of the model chemicals was indirectly affected by the amount of sludge in the test mixtures. A higher content of sludge in the mixtures reduced the overall concentration of oxygen, which resulted in a decrease of the mineralization of several of the model chemicals. In sludge-soil mixtures with predominantly anaerobic conditions, the mineralization was slower for all of the chemicals with the exception of DEHP and DCB. The mineralization of DCB was enhanced in mixtures with a high sludge content. No pronounced difference in the mineralization of the model chemicals (except DEHP) was observed when the sludge was mixed with three different agricultural soils.

Aerobiosis↗

Fate and effects of esfenvalerate in agricultural ponds.

The fate of esfenvalerate was investigated by sampling and chemical analysis after spraying of an artificial pond (25 g a.i./ha) and in the laboratory with [14C]esfenvalerate by trapping of 14CO2 and fractionation of the sediment. The effects were investigated on pelagic communities in enclosures in a natural lake and in the laboratory on surface (Cymatia coleoptrata) and sediment (Chironomus riparius) insects. The latter were used in sediment-plus-water and in water-only tests, measuring effects on emergence and mortality. The measurements in the artificial pond indicated exposure concentrations in the surface microlayer, water column, and sediment of 0.4 microgram/L, 0.05 microgram/L, and 9 micrograms/kg dry weight, respectively, two weeks after application. The degradation studies showed a limited mineralization (26.5%) of [chorophenyl-14C]esfenvalerate during 112 d. Part of the substance was transformed to water-soluble compounds (18.1%) or compounds attached to fulvic acids (26.2%), humic acids (14.2%), or nonextractable sediment constituents (8.8%). The formulated product Sumi-Alpha 5 FW caused 100% mortality to Cymatia coleoptrata after surface application of 0.13 g a.i/ha. Effects on zooplankton were recorded at 0.005 microgram/L of esfenvalerate. The 96-h median lethal concentration for first-instar larvae of Chironomus riparius was 0.13 microgram/L, whereas the delayed emergence lowest-observed-effect concentration was 0.8 microgram/L.

Agriculture↗

Toxicity of linear alkylbenzene sulfonates and nonylphenol in sludge-amended soil.

The application of sewage sludge to agricultural land brings several chemicals to the soil ecosystem. Linear alkylbenzene sulfonates (LAS) and nonylphenol (NP) are frequently found in sludge at relatively high concentrations. The toxic effects of LAS and NP to two soil invertebrates (Folsomia candida and Enchytraeus albidus) and five different microbial processes (aerobic respiration, nitrification, denitrification, anaerobic CH4 production, and anaerobic CO2 production) were investigated in sludge-soil mixtures. Median lethal concentrations (LC50 values) and median effective concentrations (EC50 values) were quite similar and calculated to be in the range of 1,143 to 1,437 and 71 to 437 mg/kg (dry wt) for LAS and NP, respectively. The EC50 values for nitrification and CH4 production were 431 and 277 mg/kg, respectively, for LAS and 343 and 754 mg/kg, respectively, for NP. Aerobic respiration and denitrification were not inhibited at the tested concentrations. The results show that NP was more toxic than LAS to both F. candida and E. albidus, whereas LAS was more toxic than NP to the anaerobic CH4 production. The safety margins between the lowest 10% effective concentration (EC10) and the estimated environmental concentration were a factor of 11 for LAS and 510 for NP when the concentrations of the contaminants corresponded to the current Danish cutoff values of 1,300 mg/kg for LAS and 30 mg/kg for NP.

Agriculture↗

Testosterone, ticks and travels: a test of the immunocompetence-handicap hypothesis in free-ranging male sand lizards.

The immunocompetence-handicap hypothesis suggests that androgen-dependent male characters constitute honest signals of mate and/or rival quality because of the imposed costs through immune suppression associated with elevated testosterone levels. We demonstrate in a field experiment that male sand lizards (Lacerta agilis) exposed to elevated testosterone suffered from increased mass loss and tick load compared to control males. Although the first of these two results could be due to an elevated basal metabolic rate from increased plasma testosterone levels, the increased parasite load was statistically independent of the loss in body condition and is likely to be due to compromised immune function. Testosterone-treated males showed greater mobility than control males, and greater mobility resulted in higher mating success. Our experiment thus lends support to the immunocompetence-handicap hypothesis, suggesting that male testosterone levels have been moderated by balancing selection for reproductive success and sustained immune function.

Animals↗

The effects of dilution on the outcome of pooled plasma testing with HIV type 1 (HIV-1) RNA genome amplification as compared to the outcome of individual-unit testing with other HIV-1 markers.

BACKGROUND: Proposed testing of large plasma pools with genome amplification technology (GAT) for detection of transfusion-transmissible viruses may have unanticipated complications not associated with individual unit testing. One such potential complication, the effect of dilution resulting from pool formation, was the subject of the present study. STUDY DESIGN AND METHODS: Specimens from three plasma donor HIV type 1 (HIV-1) seroconversion panels were tested with a quantitative HIV-1 RNA GAT assay (lower detection limit, 400 copies). GAT results were compared to HIV-1 p24 antigen and anti-HIV-1/2 enzyme immunoassay results. Effects of dilution on the detection of GAT-positive panel specimens were assessed by terminal dilution with pooled volunteer-donor EDTA plasma samples. RESULTS: Low HIV-1 RNA copy numbers (755 and 890 copies/0.1-mL input) that were detectable in two individual plasma specimens before HIV-1 p24 antigen were subsequently undetectable by GAT upon dilution with an equal volume of nonreactive plasma from a single donor. HIV-1 RNA at higher copy numbers (15,500 copies/0.1-mL input) in an HIV-1 p24 antigen-reactive and anti-HIV-1/2-nonreactive specimen was undetectable when diluted to 1-in-50 (1-in-50). Terminal dilution of seven HIV-1 RNA-containing plasma panel specimens indicated a proportional loss of HIV-1 RNA detectability with increasing dilution. CONCLUSION: GAT for detection of HIV-1 RNA in individual specimens was more sensitive than other HIV markers. For pooled plasma testing, GAT-independent constraints, such as effects of dilution, may preclude the use of GAT detection as a replacement for individual unit testing with HIV serologic assays.

Gene Amplification↗

Quantitative evaluation of flow patterns in perfusion cannulae by a new magnetic resonance imaging method.

The arterial cannula is a critical part of any extracorporeal circulation system due to the high flow rates which must pass a small cross-sectional area, resulting in high blood velocities. The aim of this study was to examine whether high-field magnetic resonance scanning is applicable for detailed mapping of velocity fields around the tip of such arterial cannulae in vitro. The investigated cannula was an angled, open-tip traditional design aortic cannula with an internal tip diameter of 5.5 mm. The velocity fields were measured at two different flow rates (2 and 4 l/min) at various positions in the lumen and outside the cannula using magnetic resonance imaging (MRI). All three components of the velocity vectors were measured. The study showed that MRI can provide a clear quantitative visualization of the velocity field around the tip of arterial cannulae at lower flow rates. At higher flow rates it can provide information about localization of regions with turbulent or disturbed flow.

Catheterization↗

Automatic detection of esophageal pressure events. Is there an alternative to rule-based criteria?

Ambulatory long-term motility recording is used increasingly for evaluation of esophageal function. The enormous amount of motility data recorded by this method demands subsequent computer analysis. One of the most crucial steps of this analysis becomes the process of automatic selection of relevant pressure peaks at the various recording levels. Until now, this selection has been performed entirely by rule-based systems, requiring each pressure deflection to fit within predefined rigid numerical limits in order to be detected. However, due to great variations in the shapes of the pressure curves generated by muscular contractions, rule-based criteria do not always select the pressure events most relevant for further analysis. We have therefore been searching for a new concept for automatic event recognition. The present study describes a new system, based on the method of neurocomputing. A large sample of normal esophageal pressure deflections was used as a "learning set," and the performance of the trained neural networks was subsequently verified on different sets of data from normal subjects. Our trained networks detected pressure deflections with sensitivities of 0.79-0.99 and accuracies of 0.89-0.98, depending on the recording level within the esophageal lumen. The neural networks often recognized peaks that clearly represented true contractions but that had been rejected by a rule-based system. We conclude that neural networks have potentials for automatic detections of esophageal, and possibly also other kinds of gastrointestinal, pressure variations.

Adult↗

Anaerobic biodegradation potentials in digested sludge, a freshwater swamp and a marine sediment.

An anaerobic gas production test was used for determining the potential biodegradation of 22 organic chemicals under methanogenic conditions. Nine of the examined chemicals were extensively mineralized (> 75%) both in sewage sludge and in a freshwater swamp indicating good agreement between biodegradation potentials in these habitats. Samples from a marine sediment showed a less extensive mineralization of most of the test chemicals, and lag periods of several weeks often preceded net gas production. As marine sediments usually contain sulfate at the time of collection, the assessment of biodegradation potentials in such environments is probably more reliable when using a method based on sulfate reduction instead of methanogenic gas production. The results of the tests indicate that the commonly recommended washing of sludge solids can be eliminated by applying a more diluted inoculum.

Anaerobiosis↗

An LI and ML motif in the cytoplasmic tail of the MHC-associated invariant chain mediate rapid internalization.

Invariant chain (Ii) is a transmembrane protein that associates with the MHC class II molecules in the endoplasmic reticulum. Two regions of the 30 residue cytoplasmic tail of Ii contain sorting information able to direct Ii to the endocytic pathway. The full-length cytoplasmic tail of Ii and the two tail regions were fused to neuraminidase (NA) forming chimeric proteins (INA). Ii is known to form trimers and when INA was transfected into COS cells it assembled as a tetramer like NA. The INA molecules were targeted to the endosomal pathway and cotransfection with Ii showed that both molecules appeared in the same vesicles. By labelling the INA fusion proteins with iodinated antibody it was found that molecules with either endocytosis signal were expressed at the plasma membrane and internalized rapidly. Point mutations revealed that an LI motif within the first region of the cytoplasmic tail and an ML motif in the second region were essential for efficient internalization. The region containing the LI motif is required for Ii to induce large endosomes but a functional LI internalization motif was not fundamental for this property. The cytoplasmic tail of Ii is essential for efficient targeting of the class II molecules to endosomes and the dual LI and ML motif may thus be responsible for directing these molecules to the endosomal pathway, possibly via the plasma membrane.

Amino Acid Sequence↗