Biomedical subjects

M Svensson

Publications and source records attributed to M Svensson.

At least 19 recordsLinked to original sources

PubMed2007

Fat cell enlargement is an independent marker of insulin resistance and 'hyperleptinaemia'.

AIMS/HYPOTHESIS: The aim of this study was to explore whether fat cell size in human subcutaneous and omental adipose tissue is independently related to insulin action and adipokine levels. MATERIALS AND METHODS: Fat cells were prepared from abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non-diabetic subjects and from omental biopsies obtained from 37 non-diabetic subjects. Cell size and insulin action on glucose uptake capacity in vitro were assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and adipokines and NEFA were measured. RESULTS: Negative correlations were found between subcutaneous fat cell size and insulin sensitivity assessed as M-value during clamp and as insulin action on glucose uptake in fat cells in vitro. This was seen in non-diabetic subjects after including age, sex and BMI in the analyses. No such relationship was found in type 2 diabetic subjects. In both groups, subcutaneous fat cell size correlated positively and independently with plasma levels of leptin but not to any of the other assessed adipokines. In non-diabetic subjects, omental fat cell size was independently and negatively correlated with insulin action in subcutaneous, but not omental, fat cells in vitro. CONCLUSIONS/INTERPRETATION: Fat cell enlargement is associated with insulin resistance in non-diabetic individuals independently of BMI. This was not seen in type 2 diabetic subjects, suggesting that after development of type 2 diabetes other factors, not related to fat cell size, become more important for the modulation of insulin resistance.

Adipose Tissue↗

PubMed2006

Altered nucleotide sugar metabolism in Streptococcus thermophilus interferes with nitrogen metabolism.

Exopolysaccharide (EPS)-producing Streptococcus thermophilus strains have attracted interest recently, since the EPSs act as natural viscosifiers and texture enhancers of fermented foods. We have previously reported that the low level of EPS production by S. thermophilus LY03 could be improved by altering the activities of enzymes in the central carbon metabolism involved in the nucleotide sugar metabolism. In this study, we observed a reduced growth in milk for the strains with increased UDP-glucose pyrophosphorylase (GalU) activity together with either enhanced phosphoglucomutase activity, and/or enhanced activity of the Leloir enzymes. Rapid growth of these mutants in milk could be restored by the addition of four specific amino acids, i.e. Glu, His, Met, and Val. This amino acid requirement was confirmed in a defined medium. Furthermore, the 31P NMR spectra showed higher levels of the GalU reactants pyrophosphate (PPi) and UDP-glucose in the engineered strain, TMB 6013, compared to the parent strain, LY03. These products plus Glu and the GalU reactant UTP are known to be involved in the nitrogen regulatory system in many bacteria. Thus, these results suggest that the reaction catalyzed by GalU is connected to the nitrogen demand of these engineered strains.

Animals↗

PubMed2005

Testing soccer players.

To cope with the physiological demands of soccer, players must be competent across several fitness components. The use of fitness tests in the laboratory and field assist in examining soccer players' capabilities for performance both at the amateur and elite levels. Laboratory tests provide a useful indication of players' general fitness. Accurate test results can be obtained with the use of a thorough methodology and reliable equipment. Laboratory tests are used sparingly during the season because of the time-consuming nature of the tests. Instead, tests are generally carried out at the start and end of the pre-season period to evaluate the effectiveness of specific training interventions. Field tests provide results that are specific to the sport and are therefore more valid than laboratory tests. The reduced cost, use of minimal equipment and the ease with which tests can be conducted make them more convenient for extensive use throughout the season. Although data from laboratory and field tests provide a good indication of general and soccer-specific fitness, individual test results cannot be used to predict performance in match-play conclusively because of the complex nature of performance in competition. Fitness tests in conjunction with physiological data should be used for monitoring changes in players' fitness and for guiding their training prescription.

Acceleration↗

PubMed2005

Neuronal survival and glial reactions after recurrent laryngeal nerve resection in the rat.

OBJECTIVES/HYPOTHESIS: Complete axonal injury to the recurrent laryngeal nerve (RLN) leads to permanent loss of coordinated function of the intrinsic muscles of the larynx. The aim of the present study was to investigate retrograde reactions, neuronal survival, and glial reactions in the nucleus ambiguus after a distal resection of the RLN to evaluate the potential need for neuroprotective substances. STUDY DESIGN AND METHODS: A segment of the left RLN was resected in 31 adult rats. Before sacrifice of the animals at 2 to 28 days postlesion, the motor neurons in the nucleus ambiguus were retrogradely traced by the use of Fluorogold. Brainstems were isolated and processed for neuron quantification and immunohistochemical analysis. Neuron counts were performed in the nucleus ambiguus on serial sections. Glial reactions were investigated in the nucleus ambiguus using immunohistochemistry. RESULTS: No decrease in the number of motor neurons in the nucleus ambiguus could be demonstrated up to 1 month postlesion. Astroglia and microglia showed increased immunoreactivity at 7 to 14 days postinjury, followed by a slight decline in glial reaction. Microglia revealed no signs of transformation into macrophages during the study period, further indicating the absence of neuronal loss. CONCLUSIONS: Neuronal death does not occur within 1 month postlesion as a result of resection of the RLN in the adult rat, and neuroprotective substances should therefore be of minor value after RLN injury. Glial reactions appear in a similar fashion as after other peripheral nerve lesions not causing neuronal loss.

Animals↗

PubMed2005

Nimodipine and microsurgery induced recovery of the vocal cord after recurrent laryngeal nerve resection.

Transection of the recurrent laryngeal nerve leads to permanent palsy of the vocal cord. Experimental studies have confirmed that nimodipine increases the pace of axonal regeneration. We present a case of a 19-year-old male, suffering a thyroid cancer disease, who was subjected to unilateral resection of the recurrent laryngeal nerve during surgery. The nerve was repaired with a nerve graft and the patient further treated with nimodipine for 3 months. Evaluation of the patient showed normalization of voice, movement of the vocal cord on the injured side, and electromyography evidence of reinnervation of the larynx muscles at 15 months after surgery.

Adenocarcinoma, Papillary↗

PubMed2005

Tissue-specific regulation of lipoprotein lipase in humans: effects of fasting.

BACKGROUND: We have previously reported that the activity of lipoprotein lipase (LPL) measured in postheparin plasma from humans fasted for 30 h is increased relative to the fed state. This is in contrast to laboratory animals, where the strong down-regulation of LPL in their adipose tissue on fasting is reflected in decreased levels of LPL activity in postheparin plasma. MATERIALS AND METHODS: To search for the tissue source of the increase in LPL activity on fasting of humans, young, healthy subjects were fasted for 10, 20 or 30 h, and LPL was measured in plasma (pre- and postheparin) and in biopsies from subcutaneous adipose tissue (abdominal) and from a skeletal muscle (tibialis anterior). Both LPL activity and LPL protein mass were measured in the tissue homogenates. Values after fasting were compared with values from postprandial samples obtained 2 h after a meal. RESULTS: Fasting for up to 30 h did not alter LPL activity in basal plasma (preheparin). LPL activity in postheparin plasma remained unchanged after 10 and 20 h of fasting, but was increased by 50% after 30 h (P < 0.05). Ten hours of fasting caused a 25% (P < 0.05) decrease in LPL activity in subcutaneous adipose tissue, while LPL activity in skeletal muscle remained unchanged. After 30 h of fasting, both LPL activity and mass had decreased by approximately 50% (P < 0.05) in adipose tissue, but had increased by approximately 100% (P < 0.05) in muscle. CONCLUSIONS: The increase in postheparin plasma LPL activity after 30 h of total food deprivation of healthy human subjects seemed to reflect an increased activity and mass of LPL in skeletal muscle.

Adipose Tissue↗

PubMed2004

Oral cancer after using Swedish snus (smokeless tobacco) for 70 years - a case report.

Whereas the smoking habit has declined significantly in Sweden in recent decades, there has been a marked increase in the consumption of 'snus' (oral moist snuff). The use of this smokeless tobacco, exposing the user locally to carcinogenic nitrosamines, raises the question - will the increasing use of snuff eventually lead to a greater incidence of oral cancer? We report the case of a 90-year-old man who developed a localized squamous cell carcinoma in the gingival fold under the upper lip, at the exact place where he had regularly placed loose oral snuff for 70 years. Although this is a reminder of a prevailing cancer risk, the time frame indicates that the risk is slight. This is consistent with recent epidemiological reports regarding the minor risk of snuff-associated cancer in the Scandinavian countries.

Aged↗

PubMed2003

Higher drive for thinness in adolescent males with insulin-dependent diabetes mellitus compared with healthy controls.

UNLABELLED: Eating behaviour in adolescent males with insulin-dependent diabetes mellitus (IDDM) living in central Sweden was compared with that of healthy age-matched male controls using the Eating Disorder Inventory for Children and an interview. The patients were heavier than controls (p = 0.004) and had higher Drive for Thinness scores (p = 0.002). None was diagnosed as having a current eating disorder. CONCLUSION: The results of the study may indicate an increased risk of future eating disorders in males with IDDM.

Adolescent↗

PubMed2003

Clara cell protein as a biomarker for ozone-induced lung injury in humans.

Exposure to ozone (O3) impairs lung function, induces airway inflammation and alters epithelial permeability. Whilst impaired lung function and neutrophilia have been observed at relatively low concentrations, altered lung epithelial permeability is only seen after high-dose challenges. The appearance of Clara cell protein (CC16) in serum has been proposed as a sensitive marker of lung epithelial injury. Here, the use of CC16 as an injury biomarker was evaluated under a controlled exposure to O3 and the relationship between this marker of lung injury and early lung function decrements was investigated. Subjects (n=22) were exposed on two separate occasions to 0.2 parts per million O3 and filtered air for 2 h. Blood samples were drawn and lung function assessed at 2 h pre-exposure, immediately before and immediately after exposure as well as 2 and 4 h postexposure. O3 increased CC16 serum concentrations at 2 h (12.0+/-4.5 versus 8.4+/-3.1 microg x L(-1)) and 4 h postexposure (11.7+/-5.0 versus 7.9+/-2.6 microg x L(-1)) compared with air concentrations. Archived samples from O3 studies utilising the same design indicated that this increase was sustained for up to 6 h postexposure (9.1+/-2.6 versus 7.1+/-1.7 microg x L(-1)) with concentrations returning to baseline by 18 h (7.7+/-2.9 versus 6.6+/-1.7 microg x L(-1)). In these studies, the increased plasma CC16 concentration was noted in the absence of increases in traditional markers of epithelial permeability. No association was observed between increased CC16 concentrations and lung function changes. To conclude, Clara cell protein represents a sensitive and noninvasive biomarker for ozone-induced lung epithelial damage that may have important uses in assessing the health effects of air pollutants in future epidemiological and field studies.

Adult↗

PubMed2002

A small reduction in glomerular filtration is accompanied by insulin resistance in type I diabetes patients with diabetic nephrophathy.

BACKGROUND: Insulin sensitivity and insulin clearance are compromised in end-stage renal disease but it has not been fully established whether they are altered in earlier stages of diabetic nephropathy. DESIGN: We studied three groups of patients with type 1 diabetes; 10 with no sign of nephropathy, 11 with albuminuria (> 20 microg min-1) but normal glomerular filtration rate (GFR) and eight with a small reduction in GFR, (43-73 mL min-1 1.73 m-2). The groups were matched for age (range 36-61 years), body mass index (BMI), diabetes duration and glycaemic control. The euglycaemic hyperinsulinaemic clamp technique was utilized to study insulin sensitivity (M-value) and metabolic clearance rate for insulin. Needle biopsies from abdominal subcutaneous fat tissue were obtained to study insulin binding, insulin degradation, insulin-stimulated glucose uptake and anti-lipolysis in adipocytes in vitro. RESULTS: Patients with reduced GFR were more insulin-resistant (M-value 5.7 +/- 0.7 mg kg LBM-1 min-1) than those without nephropathy (9.6 +/- 0.7, P = 0.001) and those with only albuminuria (8.9 +/- 1.2, P = 0.044). In all subjects taken together there was a strong association between insulin sensitivity and GFR (r = 0.46, P = 0.012). Patients with reduced GFR displayed no significant difference in insulin clearance (12.2 +/- 1.6 mL kg-1 min-1) compared to controls (13.8 +/- 1.3) but a slightly lower insulin clearance than patients with only albuminuria (16.6 +/- 1.0, P = 0.027). There were no significant differences between patient groups in the adipocyte studies in vitro, i.e. with respect to insulin binding, insulin degradation and the effects of insulin on glucose uptake and lipolysis. This is compatible with humoral factors causing whole-body insulin resistance and in the group with reduced GFR, we found that serum parathyroid hormone, interleukin-6 and tumour necrosis factor-alpha levels were elevated whereas the morning cortisol was decreased. CONCLUSIONS: In type 1 diabetes, the appearance of albuminuria does not seem to alter insulin sensitivity and clearance. A marked insulin resistance but no consistent impairment in insulin clearance seems to accompany progression to a stage with a slight reduction in GFR. These alterations are not accompanied by general defects in insulin target cells. Instead, alterations in the regulation of insulin-antagonistic hormones and cytokines could potentially contribute to the development of insulin resistance in diabetic nephropathy.

Adipose Tissue↗

PubMed2002

Comparison of the Rear Impact Biofidelity of BioRID II and RID2.

Researchers worldwide try to define a unique test procedure for the assessment of whiplash protection of seats and restraint systems in low speed rear-end impact. Apart from valid injury criteria and uniform crash conditions, there is no clear answer to the question, which dummy to use. There are two impact dummies currently available, which have been designed for rear-end impact testing: BioRID and RID2. Both dummies have been evaluated in several test programs, however, both dummies have never been compared with each other in the test conditions, which form the basis of their design. BioRID was based on and validated against volunteer tests performed by Davidsson and Ono, while RID2 was designed with and validated against PMHS tests done by Bertholon and compared to volunteer tests reported by Van den Kroonenberg. This paper compares the responses of both rear impact dummies and the Hybrid III for the test conditions mentioned above. The setup of Davidsson used a rigid seat with flexible back and head restraint panels, while the setups from Ono and Bertholon used a rigid seat without a head restraint, in spite of being not representative for real car seats. This configuration creates a well defined test environment which will not affect nor obscure the dummy response Results of the performance of both rear impact dummies and the Hybrid III in comparison to the human responses will be presented in this paper. The results show that both rear impact dummies are capable of simulating rear impact responses, especially the head-neck kinematics. A difference in load pattern was found, which could be relevant when injury criteria will be based on neck forces and/or torques. Moreover, the dummies show a different interaction with the seat back, illustrated by the differences in T1 kinematics: BioRID shows larger T1 rotation and more ramping up than RID2, while spine straightening is comparable for both dummies. The current study showed good scores for both dummies in the setup on which they are based. The biofidelity score of BioRID is slightly better than for RID2, while the performance of the Hybrid III is relatively poor. However, repeatability, reproducibility and handling are not part of the evaluation, even though they are important for the practical use of the dummies.

Journal Article↗

PubMed2001

Glutamate release from adult primary sensory neurons in culture is modulated by growth factors.

The aim of this study was to examine possible modulatory effects of some trophic molecules, i.e. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF), on potassium (K(+))-, bradykinin (BK)- or capsaicin (CAPS)-evoked release of glutamate (GLU) from dorsal root ganglion (DRG) neurons in vitro. BK (0.5 and 1 microM) induced a dramatic and significant increase in glutamate release. Neither CAPS nor K(+) (60 mM) produced any significant increase of GLU release vs. basal levels during a 5-min stimulation. The BK-evoked release of GLU was almost completely blocked by HOE 140, a selective BK2-receptor antagonist at high doses. Basal release of GLU was significantly reduced in cultures grown in the presence of bFGF, whereas BDNF and NGF had no significant effect. Incubation with growth factors generally decreased the BK-stimulated GLU release, an effect most pronounced for bFGF, which completely blocked BK-stimulated release. The rise in intracellular [Ca(2+)] following stimulation with BK (100 nM-1 microM), potassium (60 mM) or ATP (10 microM) was also studied using a Ca(2+)-sensitive indicator, Fura-2, in cultures grown in basal medium with or without bFGF. None of the bFGF-treated cells exhibited strong Ca(2+) responses to BK or ATP stimulation, while 10-20% of the responding cells grown in basal medium exhibited strong responses. The K(+)-induced increase of [Ca(2+)] did not vary between the different groups. The present findings suggest that sensory neurotransmission involving glutamate may be modulated by growth factors and that regulation of intracellular Ca(2+) homeostasis may be a contributing factor.

Animals↗

PubMed2001

Allantoin formation and urate and glutathione exchange in human muscle during submaximal exercise.

Seven males performed two exhaustive cycling bouts (EX1 and EX2) at a work-rate of 90% of maximal oxygen uptake, separated by 60 min. During EX1 there was a significant accumulation of urate (from 0.16 +/- 0.02 to 0.27 +/- 0.03 micromol/kg d.w.) and allantoin (from 0.39 +/- 0.05 to 0.69 +/- 0.14 micromol/kg d.w.) in the muscle. An uptake of urate was observed in early recovery from EX1 (0-9 min: 486 +/- 136 micromol; p <.05). There was no exchange of total glutathione or cysteine over the muscle either during or after exercise, and muscle and plasma total glutathione remained unaltered (p <.05). The glycogen levels were lowered by 40% at the onset of EX2, yet the level of oxidative stress in EX1 and EX2 was similar as evidenced by a similar increase in muscle allantoin in both exercise bouts. The data suggest that urate is utilized as antioxidant in human skeletal muscle and that reactive oxygen species are formed in muscle during intense submaximal exercise. No net exchange of glutathione appears to occur over the muscle either at rest, during exercise or in recovery. Moreover, when an exhaustive exercise bout is repeated with lowered glycogen levels, the level of oxidative stress is not different than that of the first bout.

Adenosine Triphosphate↗

PubMed2001

Small-scale analysis of exopolysaccharides from Streptococcus thermophilus grown in a semi-defined medium.

BACKGROUND: Exopolysaccharides (EPSs) produced by lactic acid bacteria are important for the texture of fermented foods and have received a great deal of interest recently. However, the low production levels of EPSs in combination with the complex media used for growth of the bacteria have caused problems in the accurate analysis of the EPS. The purpose of this study was to find a growth medium for physiological studies of the lactic acid bacterium Streptococcus thermophilus, and to develop a simple method for qualitative and quantitative analysis of EPSs produced in this medium. RESULTS: A semi-defined polysaccharide medium was developed and evaluated on six strains of Streptococcus thermophilus. The EPSs were analysed using a novel protocol incorporating ultracentrifugation for the removal of interfering sugars, hydrolysis and analysis of the monomer composition by High Performance Anion-Exchange Chromatography with pulsed amperometric detection. The medium and analysis method allowed accurate quantification and monomer analysis of 0.5 ml samples of EPSs from tube cultures. CONCLUSIONS: The presented medium should be useful for physiological studies of S. thermophilus, and, in combination with the method of analysis of EPS, will allow downscaling of physiological studies and screening for EPSs.

Culture Media↗

PubMed2001

Nimodipine promotes regeneration and functional recovery after intracranial facial nerve crush.

The calcium flow inhibitor, nimodipine, has been shown to promote motor neuron survival in the facial nucleus after intracranial facial nerve transection. However, it has not been known whether the neuroprotective effects primarily involve survival of nerve cell bodies or outgrowth and/or myelination of nerve fibers. Here, we studied the effects of nimodipine in a different injury model in which the facial nerve was unilaterally crushed intracranially. This lesion caused complete anterograde degeneration and partial retrograde degeneration that were studied with a combination of several stereological methods. Nimodipine did not attenuate the modest lesion-induced neuronal loss (13%) but accelerated the time course of functional recovery and axonal regrowth, inducing increased numbers and sizes of myelinated axons in the facial nerve. It is interesting to note that nimodipine also enlarged the axons and the myelin sheaths in the nonlesioned facial nerve, which points to the possibility of using this substance for new clinical applications to promote axonal growth and remyelination.

Animals↗

PubMed2001

Probing inhibitor-induced conformational changes along the interface between tissue factor and factor VIIa.

Upon injury of a blood vessel, activated factor VII (FVIIa) forms a high-affinity complex with its allosteric regulator, tissue factor (TF), and initiates blood clotting. Active site-inhibited factor VIIa (FVIIai) binds to TF with even higher affinity. We compared the interactions of FVIIai and FVIIa with soluble TF (sTF). Six residues in sTF were individually selected for mutagenesis and site-directed labeling. The residues are distributed along the extensive binding interface, and were chosen because they are known to interact with the different domains of FVIIa. Fluorescent and spin probes were attached to engineered Cys residues to monitor local changes in hydrophobicity, accessibility, and rigidity in the sTF--FVIIa complex upon occupation of the active site of FVIIa. The results show that inhibition of FVIIa caused the structures around the positions in sTF that interact with the protease domain of FVIIa to become more rigid and less accessible to solvent. Thus, the presence of an active site inhibitor renders the interface in this region less flexible and more compact, whereas the interface between sTF and the light chain of FVIIa is unaffected by active site occupancy.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Differential involvement of dendritic cell subsets during acute Salmonella infection.

Within murine CD11c(+) dendritic cells (DC), CD8alpha+, CD8alpha-CD4+, and CD8alpha-CD4- subsets are defined. This study characterized the localization, number, and function of these subsets during acute Salmonella typhimurium infection. Immunohistochemical and flow cytometric analyses of spleens from mice orally infected with virulent S. typhimurium revealed that in situ redistribution and alteration in the absolute number and function of DC occurred in a subset-specific manner during infection. CD8alpha-CD4+ DC present at B cell follicle borders in the spleen of naive mice were absent 5 days post-Salmonella infection, despite no overall change in the absolute number of CD8alpha-CD4+ splenic DC. CD8alpha+ and CD8alpha-CD4- DC were prominently associated with the red pulp, and the frequency of these cells increased strikingly 5 days post-Salmonella infection. Significant quantitative increases in both CD8alpha+ and CD8alpha-CD4- subsets were associated with the in situ redistribution. Examination of Salmonella-infected TAP1(-/-)/beta(2)-microglobulin(-/-) mice, which lack CD8alpha+ T cells, confirmed the differential subset-specific modulations in the DC populations both in situ and quantitatively. Ex vivo intracellular cytokine analysis showed significantly increased frequencies of CD8alpha(+) DC producing TNF-alpha at days 2 and 5 postinfection. In contrast, CD4+ DC producing TNF-alpha were transiently increased followed by a significant reduction. No significant increase in IL-12p40 or IL-10 production by splenic DC was detected during the first 5 days post-S. typhimurium infection. Together these data reveal differential modulation of splenic DC subsets with regard to organization, number, and cytokine production during the course of acute Salmonella infection.

Acute Disease↗

PubMed2001

pap genotype and P fimbrial expression in Escherichia coli causing bacteremic and nonbacteremic febrile urinary tract infection.

Escherichia coli strains from patients with febrile urinary tract infections (n=73) were examined for pap genotype and P fimbrial expression in relation to bacteremia and patients' background variables. Most isolates were pap(+) by DNA hybridization (n=51), and 36 were papG(IA2)(+) and 18 prsG(J96)(+) by polymerase chain reaction. The pap and papG genotypes of the infecting strain were shown to vary with host compromise, sex, and age. Bacteremia in noncompromised patients was caused by papG(IA2)(+) strains, but compromised hosts carried a mixture of papG(IA2)(+), prsG(J96)(+), and pap(-) strains. Women of all ages were infected with papG(IA2)(+) strains. Infected men carried prsG(J96)(+) or pap(-) strains and were older, and most had compromising conditions. papG(IA2)(+) strains predominated among patients with medical illness, whereas prsG(J96)(+) strains predominated among patients with urinary tract abnormalities. These findings emphasize the strong influence of host factors on the selection of E. coli strains causing febrile urinary tract infections.

Adhesins, Bacterial↗