Biomedical subjects

Thomas Andersson

Publications and source records attributed to Thomas Andersson.

5 recordsLinked to original sources

PubMed2006

Pharmaceutical and analytical characterisation of (2R)-(3-amino-2-fluoropropyl)sulphinic acid, a GABAB receptor agonist.

(2R)-(3-amino-2-fluoropropyl)sulphinic acid (AFPSiA) is a potent GABAB agonist, which makes it a possible alternative in future GERD treatment. The degradation of AFPSiA was investigated to support the drug-development effort. The compound is too polar to be compatible with regular reversed-phase LC. Moreover, the compound and the degradation products cannot be detected by UV due to low absorption. Instead, the degradation of AFPSiA was followed by two different capillary electrophoresis methods with indirect UV detection and 1H NMR and 19F NMR. AFPSiA was very unstable in basic conditions and at temperatures above room temperature. The corresponding sulphonic acid and allylamine are formed via two separate degradation routes. Both these degradation products may cause unwanted side-effects in vivo. Aqueous solutions of AFPSiA were found to be more stable at pH between 1 and 3. It was suggested that AFPSiA should be stored frozen, preferably at -70 degrees C. In solid state, the compound can be stored at ambient conditions in closed vials with low relative humidity. A solid oral dosage form should be kept in a blister package.

Administration, Oral↗

PubMed2006

NMR, cloud-point measurements and enzymatic depolymerization: complementary tools to investigate substituent patterns in modified celluloses.

The substituent patterns of some chemically modified celluloses were characterized as a function of their size distribution, using size-exclusion chromatography coupled to both nuclear magnetic resonance spectroscopy (NMR) and cloud-point measurements. Intact and enzymatically hydrolyzed methyl cellulose (MC) was fractionated according to size, and the level of substitution of the fractions was measured off-line using NMR. Clouding behavior was also measured as a function of size. Clear differences between hydrolyzed and nonhydrolyzed samples were observed using both techniques. For samples that had been selectively hydrolyzed using cellulose-degrading enzymes, NMR data showed a direct link between the degree of degradation and the level of substitution. Differences in the clouding behavior highlighted changes in substituent levels and substituent patterns across the size distribution. The techniques gave valuable and somewhat complementary information on the substituent distributions of the samples before and after enzymatic hydrolysis.

Bacillus↗

PubMed2004

Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A neurophysiological and pathological study.

We have studied a large Swedish family with a mutation in the nerve growth factor beta (NGFB) gene causing insensitivity to deep pain without anhidrosis (hereditary sensory and autonomic neuropathy, type V; HSAN V). Painfree joint destruction and fractures were common. Peripheral nerve conduction was normal, but temperature thresholds were increased. Sural nerve biopsies showed a moderate loss of A delta fibers and a severe reduction of C fibers. The three most severely affected cases were all born to consanguineous parents, and were homozygotes for the causal genetic mutation. Treatment of these patients is discussed.

Adult↗

PubMed2003

Analytical approaches to improved characterization of substitution in hydroxypropyl cellulose.

Chemical characterization of cellulose derivatives is of high importance as it provides information about the often inhomogeneous substitution that may seriously affect the properties of these polymers in various applications. A detailed mapping of the chemical structure of these derivatives requires several advanced techniques to be employed. In this study, the average substitution and the substitution heterogeneity in two hydroxypropyl cellulose (HPC) samples from different suppliers were studied by means of NMR spectroscopy, MALDI-TOF MS, and HPAEC-PAD. (1)H and (13)C NMR provided information on the molar substitution, a parameter that could be analyzed by MALDI-TOF MS as well. In addition, the latter technique was used for determination of the distribution of the number of hydroxypropyl groups per glucose unit present in the two polymers. The heterogeneity of the substitution was studied by determining the amount of unsubstituted glucose units in the HPC samples, which was accomplished by HPAEC-PAD analysis. The results obtained suggest that the two HPC samples differ in both hydroxypropoxy content and distribution of the hydroxypropyl groups. Further, the benefits and importance of employing several analytical methods when investigating the cellulose ether substitution are demonstrated, as each method provides different kinds of information on the chemical content.

Carbohydrate Sequence↗

PubMed2000

Is vascular reactivity in skin predictable?

BACKGROUND/AIMS: Cutaneous microdialysis can be used to follow the pharmacology and metabolism of an inflammatory reaction. It is assumed that an equilibration period compensates for the trauma of catheter insertion. METHODS: In the present paper, the vascular reactivity of the skin to histamine was tested using assessment by laser Doppler perfusion imaging. In a group of six subjects, the provocation was preceded by insertion of a microdialysis catheter. In a second control group, histamine provocation alone was performed (six subjects). RESULTS: The vascular response to histamine was greater in the microdialysis catheter group than the control group. The histamine provocation caused a greater response than catheter insertion. Further, there was a correlation between the response to catheter insertion and the histamine provocation. CONCLUSION: It appears that the insertion and/or presence of a microdialysis catheter increases vascular reactivity to subsequent provocation. The response to catheter insertion may predict skin reactivity in general in the individual subject.

Journal Article↗