Biomedical subjects

Magnus Andersson

Publications and source records attributed to Magnus Andersson.

23 records · Page 2Linked to original sources

PubMed2003

Nitric oxide metabolite determinations reveal continuous inflammation in multiple sclerosis.

Nitric oxide (NO) is formed as a consequence of induction of the iNOS enzyme during inflammatory disorders. To investigate NO production in multiple sclerosis (MS), we determined the concentrations of its oxidation products (NOx) in the cerebrospinal fluid (CSF) and plasma of 61 MS patients. The patients were divided into three groups on the basis of their clinical disease activity. The total levels of NOx in CSF were significantly increased in all MS groups as compared to healthy controls and tension headache patients. CSF nitrite correlated with clinical disease activity. At exacerbation, the CSF nitrite levels exceed the plasma level. This suggests that clinical disease activity is due to a CNS inflammatory response, which is more intense and qualitatively different from that during clinical stable phases. This study supports NO involvement in the pathogenesis of MS and determination of nitrite levels may be useful a surrogate marker for disease activity.

Adult↗

PubMed2003

No influence of ethnic origin on the pharmacokinetics and pharmacodynamics of melagatran following oral administration of ximelagatran, a novel oral direct thrombin inhibitor, to healthy male volunteers.

OBJECTIVE: To determine the influence of ethnic origin on the pharmacokinetic and pharmacodynamic properties of melagatran after oral administration of ximelagatran, a novel oral direct thrombin inhibitor. STUDY DESIGN: This was an open-label, non-randomised study with a single study session. SUBJECTS: Thirty-six young healthy male subjects living in France were divided equally according to their ethnic origin (African, Asian and Caucasian). METHODS: All subjects received a single 50mg oral dose of ximelagatran in solution. Blood and urine samples for pharmacokinetic evaluation were collected up to 12 and 24 hours after administration, respectively. Blood samples were also collected to determine the activated partial thromboplastin time (APTT), an ex vivo coagulation time measurement used to demonstrate inhibition of thrombin, up to 24 hours after administration. RESULTS: The absorption of ximelagatran, and its bioconversion to melagatran, was rapid in all three ethnic groups. The metabolite pattern in plasma and urine was similar in all groups, with melagatran being the dominant compound. For ximelagatran, the mean area under the plasma concentration-time curve (AUC) was similar in the three groups, suggesting that there was no difference in the extent to which ximelagatran was absorbed. Melagatran AUC was higher in the Asian subjects, with a mean Asian/Caucasian ratio (95% CI) of 1.23 (1.04, 1.45). This was presumably because of their lower bodyweight, which is correlated to lower renal function. Following normalisation for bodyweight, there were no statistically significant differences between the three ethnic groups. This finding suggests that renal elimination was lower for Asian subjects, whereas there were no differences in the conversion of ximelagatran to melagatran. The interindividual variability of melagatran AUC was low (coefficient of variation 19-26%), and the mean bioavailability of melagatran, estimated using a mean value for melagatran clearance obtained from Caucasian subjects in a previous study, was approximately 20% in all groups (range of mean values 19-23%). APTT increased nonlinearly with increasing melagatran plasma concentration, and no difference in the concentration-response relationship was observed between the groups. CONCLUSIONS: After oral administration of ximelagatran, the pharmacokinetic and pharmacodynamic properties of melagatran are independent of ethnic origin. The elimination of melagatran is correlated with renal function.

Administration, Oral↗

PubMed2002

Prior poliomyelitis-evidence of cytokine production in the central nervous system.

In order to study the role of a possible inflammatory reaction in the post-polio syndrome (PPS) four key cytokines were determined by means of mRNA expression in mononuclear cells from cerebrospinal fluid (CSF) and peripheral blood of 13 patients. Data were compared with those of samples from eight non-inflammatory control persons. The PPS-patients displayed increased numbers of CSF cells expressing mRNA for TNF-alpha (p<0.02), IFN-gamma (p<0.02), IL-4 (p<0.001) and IL-10 (p<0.05), in comparison to the non-inflammatory controls. As positive controls, samples from patients with Multiple Sclerosis (MS) were examined. We conclude that there is a chronic intra CNS expression of inflammatory cytokines in PPS, in the range of that in MS, a well known neuroinflammatory disease. However, the pathogenic significance of this is unclear.

Aged↗

PubMed2002

Mapping of an immotile short tail sperm defect in the Finnish Yorkshire on porcine Chromosome 16.

An immotile short tail sperm defect has recently been identified as a hereditary disorder present within the Finnish Yorkshire pig population. The syndrome is inherited as an autosomal recessive disease exclusively expressed in male individuals as shorter sperm tail length and immotile spermatozoa. Based on the assumption of a recent common origin of the disease-causing mutation, a genome-wide search was performed with 228 evenly spaced microsatellites by homozygosity mapping of affected and unaffected DNA pools. One locus, SW2411 on Chr 16, demonstrated a significantly skewed allele distribution between the two pools. Linkage analysis of five markers in this region mapped the disease-causing gene within a 6-cM confidence interval region with a highest LOD score of 7.7 at marker SW419. It appears that three-marker haplotypes can be used for marker-assisted selection within analyzed pedigrees. Furthermore, future fine mapping may reveal a more precise population-wide associated haplotype and facilitate identification of a new gene affecting sperm tail development.

Animals↗

PubMed2002

Hereditary sterilizing short-tail sperm defect in Finnish Yorkshire boars.

A new infertility syndrome has recently been described in Finnish Yorkshire boars. Typical for the syndrome is total akinesia and severe tail malformation of the spermatozoa. Morphometric analysis was performed on semen smears from 20 affected and 18 control boars and on testicular tissue sections from 5 affected and 4 control boars. Semen morphometry revealed that, in affected boars, the length of the sperm tails was only 33% of that of the controls (15.4 microm vs. 47.0 microm, P < 0.0001). Typical for the spermatozoa of affected boars was also an abundant frequency of proximal cytoplasmic droplets (72.4% vs. 6.9%, P < 0.0001), whereas no major sperm-head abnormalities were recorded. In the testicular tissue samples, viewed at light microscopic level, the volume densities of seminiferous tubules or interstitium did not differ. The most characteristic change in the seminiferous epithelium of the affected boars was a reduced number of elongated spermatids. Densities of Sertoli cells and Leydig cells between affected and control boars did not differ. The ultrastructure of testicular tissue from affected boars showed severe alterations in the assembly of the midpiece and tail of the spermatozoa. As well, a typical finding in the seminiferous epithelium of affected boars was conspicuous deposition of lipid droplets. The pathogenesis of this syndrome severely affects spermiogenesis and motility. Spermatozoa have malformed, short tails, which never become motile. This syndrome is not manifested in the structure or function of other ciliated cells in the affected animals.

Animals↗