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Biomedical subjects

N H Andersen

Publications and source records attributed to N H Andersen.

71 records · Page 4Linked to original sources

On the multiplicity of platelet prostaglandin receptors. I. Evaluation of competitive antagonism by aggregometry.

Methods for the evaluation of competitive interactions at receptors associated with platelet activation and inhibition using aggregometry of human PRP have been developed. The evidence supports the suggestion that PGE1 and PGI2 share a common receptor for inhibition of platelet reactivity, but only a portion (if any) of the aggregation stimulation associated with PGE2 is the result of PGE2 binding (without efficacy) to this receptor. PGE2 (at .3-20 microM) is an effective antagonist of PGE1, PGI2, and PGD2 producing a shift of about one order of magnitude in the IC50-values obtained from complete aggregation inhibition dose response curves. The antagonism of PGD2 inhibition is particularly notable, 80 nM PGE2 levels are detectable. This and other actions of PGE2 indicate another platelet receptor for PGE2. PGE1 acts at both the PGE2 and PGI2 receptor. Other substances showing PGI2-like actions only at high doses (1-30 microM), display additive responses with PGI2 indicative of decreased affinity for the I2/E1 receptor and the absence of PGE2-like aggregation stimulation activity. PGI2 methyl ester has intrinsic inhibitory action not associated with in situ ester hydrolysis. The methyl ester is dissaggregatory showing particular specificity for inhibition of release and second wave aggregation.

Adenosine Diphosphate↗

Aureobasidium pullulans metabolism of prostaglandins of the A-type.

Aureobasidium pullulans, originally introduced as an inadvertent contaminant in solutions used for evaluating the stability of prostaglandins, proved to lead to the rapid disappearance of the cyclopentenone unit of PGA2 (as monitored by circular dichroic spectroscopy). The cyclopentenone unit is converted, in various metabolites, to a 9-keto, 9 alpha or 9 beta-hydroxy group lacking the ring unsaturation. The major EtoAc-soluble 9-hydroxy metabolite (Compound-I) was shown to be 9 alpha, 15 alpha-dihydroxy-2, 3, 4, 5-tetranor-13-trans-prostenoic acid. Similar tetranor 9-hydroxy metabolites with one additional degree of unsaturation, and with a 9 beta-hydroxy group, also occur but these have not been fully characterized. Only two of the wide range of 9-keto metabolites are fully characterized by mass spectral (MS) data: 9, 15-oxo-2, 3, 4, 5-tetranorprostanoic acid and 9, 15-oxo-2, 3, 4, 5-tetranor-13-trans-prostenoic acid. The water soluble metabolites have not been characterized further. The fully characterized metabolites together with MS data from mixtures of minor metabolites indicate that A. pullulans can perform the following transformation: beta-oxidation, dehydrogenation at C-15, reduction of the enone carbon-carbon double bonds (both delta 10,11 and delta 13,14), reduction of the 9-ketone, and possibly migration of the cyclopentyl double bond (delta 10, 11 leads to delta 11, 12). A. pullulans metabolizes 15-epimeric PGA2 equally readily with the production of similar products. PGA1 affords less 9-keto metabolites with compound I constituting 33% of the product by HPLC analysis. A. pullulans displays some enantioselectivity, PGA2 and 15-epi-PGA2 are each metabolized more rapidly than their enantiomers. Other prostaglandins appear to be less readily metabolized.

Chemical Phenomena↗

Synthesis of diastereomeric bis-unsaturated prostaglandins.

With the report given herein all diastereomers of PGF2, PGE2, and PGD2 which bear the naturally recognized 15-S hydroxylated center, whether in the natural or entprostanoic acid skeleton, have been prepared by a route involving initial introduction of the carboxyl (alpha) chain (1). A major advantage of the initial alpha-ylation route is the facile reduction of the 13, 14-en-15-one system with methanolic NaBH4 which proceeds without competing 1,4-reduction. The products are thus free of 13,14-dihydro-PG2 contaminants (2). The initial pharmacological evaluation of these diastereomers will be submitted for publication in this journal (3).

Chemical Phenomena↗

Molecular basis of prostaglandin potency. II. Proton NMR studies of the conformation of prostaglandin F2alpha.

The proton nmr of PGF2alpha (dissolved in aqueous tBuOH) in the presence of PrC13 and limited amounts of base shows LIS shifts for the terminal methyl indicating an average effective chain length (C-1 to C-20) like that of octanoic acid, further evidence that the alpha and omega carbons of prostaglandins are closer in space than would be expected based on a random distribution of confermers with alternate zig-zag sections of hydrocarbon chains. Assessing the exact nature of the sidechain alignment will require further experiments.

Chemical Phenomena↗

Dehydration of prostaglandins: study by spectroscopic method.

The ultraviolet (UV) and optical rotatory dispersion (ORD) spectra of prostaglandins E(1), A(1), B(1), and their naturally derived 15-epimers are presented. The dehydration sequence E --> A --> B under acidic and basic conditions has been studied by UV and ORD. Conditions for quantitative conversion of PGE(1) to PGA(1) are described. The combination of ORD and UV affords a nondestructive assay which can determine the relative amounts of E-, A-, and B-type prostaglandins with as little as 1-2 micro g of material. The total quantity of prostaglandins can be estimated (+/-15%) in this way or, more accurately, by treatment with alkali of an aliquot (200 ng is sufficient) and determination of the change in absorbance at 278 nm.

Chemical Phenomena↗

Total shoulder replacement in rheumatoid arthritis: proximal migration and loosening.

A prospective study of 62 Neer mark II total shoulder arthroplasties performed during the period from 1981 to 1990 on 51 patients with rheumatoid arthritis was undertaken to evaluate factors associated with component loosening and proximal humeral migration. Thirty-two (51%) showed proximal migration of the humerus before surgery was performed. The mean follow-up time was 92 months (range 52 to 139 months). The results revealed proximal migration in 55% of the patients (34 shoulders), and 40% (25 shoulders) showed progressive radiographic loosening of the glenoid component. Five of 12 press-fit humeral components demonstrated progressive radiographic loosening, whereas no signs of loosening were found in 50 cemented humeral components. In spite of progressive component loosening and progressive migration, this study demonstrated good pain relief in 89% of the patients (55 shoulders) and also a significant improvement in range of movement and function. The presence of proximal humeral migration did not significantly influence the average results-neither pain relief, range of movement, abduction force, nor function. Also, component loosening did not significantly influence the average pain relief, range of movement, abduction force, or function. The risk of clinical asymptomatic loosening is a relatively late complication that is eventually followed by pronounced bone destruction related to the loose component. Long-term radiographic control of total shoulders with rheumatoid arthritis is recommended. Hemiarthroplasty with a cemented humeral prosthesis may be a better treatment in the end stage of rheumatoid arthritis of the shoulder.

Adult↗

Frozen shoulder: arthroscopy and manipulation under general anesthesia and early passive motion.

During a 15-month period, 24 patients with arthroscopically verified frozen shoulders were treated with manipulation while under general anesthesia and early passive motion. The minimum follow-up was 12 months, and the average duration from onset of the disease until treatment was 8 months. All patients had moderate to severe pain, and the average range of motion was less than 40% of the opposite shoulder. During the follow-up period, 75% of the patients obtained normal or almost full range of motion, and 79% had slight pain or no pain at all. Eighteen (75%) patients returned to work 9 weeks (mean) after treatment. There was no relationship between the end result and the initial pathologic condition. We believe that manipulation combined with arthroscopy is an effective way of shortening the course of an apparently self-limiting disease and should be considered when conservative treatment has failed.

Adult↗

Self-training versus physiotherapist-supervised rehabilitation of the shoulder in patients treated with arthroscopic subacromial decompression: a clinical randomized study.

In a controlled clinical prospective study, 43 consecutive patients (43 shoulders) with subacromial impingement resistant to conservative therapy and without full-thickness rotator cuff tears underwent arthroscopic subacromial decompression. The patients were randomized to either self-training or physiotherapist-guided rehabilitation for immediate postoperative rehabilitation. Postoperative follow-up was performed by an independent observer after 3, 6, and 12 months. With the use of the Constant score for evaluation of functional outcome, patients training themselves improved from a mean 53 points (range 26 to 81 points) to a mean 79 points (range 45 to 100) points after 12 months. Physiotherapist-supervised patients improved from a mean 54 points (range 20 to 90 points) to a mean 80 points (range 40 to 100 points). The self-training patients returned to work after a mean 8.5 weeks (range 1 to 14 weeks), whereas the physiotherapist-supervised patients returned to work after a mean 8 weeks (range 3 to 13 weeks). No statistical difference was found between the 2 rehabilitation methods. This study was unable to show any beneficial effect of physiotherapist-supervised rehabilitation after arthroscopic subacromial decompression of the shoulder.

Adult↗