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Biomedical subjects

M Kolb

Publications and source records attributed to M Kolb.

At least 55 records · Page 3Linked to original sources
PubMed1987

Synthesis and evaluation of mono-, di-, and trifluoroethenyl-GABA derivatives as GABA-T inhibitors.

The syntheses of four derivatives of gamma-vinyl-GABA, in which vinylic hydrogen atoms were replaced by fluorine, are described. With use of 5-ethenyl-2-pyrrolidinone as starting material, the E and Z isomers of 4-amino-6-fluoro-5-hexenoic acid were prepared. The 6,6-difluoro and 5,6,6-trifluoro analogues could be synthesized from 4-oxobutanoic acid tert-butyl ester and (2,2-difluoroethenyl)- and (trifluoroethenyl)lithium correspondingly. The compounds were tested as inhibitors of GABA-T, and their in vitro and in vivo biochemistry is reported. The most active derivative was (Z)-4-amino-6-fluoro-5-hexenoic acid; the structure-activity relationship in the series is discussed.

4-Aminobutyrate Transaminase↗
PubMed1986

Marked and prolonged inhibition of mammalian ornithine decarboxylase in vivo by esters of (E)-2-(fluoromethyl)dehydroornithine.

(E)-2-(fluoromethyl)dehydroornithine, a new enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC) is no more effective than alpha-difluoromethylornithine (DFMO) at inhibiting polyamine biosynthesis in rat hepatoma tissue culture (HTC) cells and in rat organs even though its potency is over 15 times higher than that of DFMO in vitro. The methyl, ethyl, octyl and benzyl esters of (E)-2-(fluoromethyl)dehydroornithine were synthesized as potential prodrugs of the amino acid. When tested at concentration equivalent to the Ki value of the amino acid, they are devoid of ODC-inhibitory property. When measured 6 hr after its addition to the HTC cell culture medium, the absorption of methyl ester was 20 times higher than that of the parent amino acid or that of DFMO, and was accompanied by a more marked intracellular accumulation of (E)-2-(fluoromethyl)dehydroornithine than that achieved by the addition of the parent amino acid. The methyl ester used at 10 times lower concentrations is as effective as its parent amino acid or as DFMO at inhibiting polyamine biosynthesis in HTC cells. Similarly, the methyl and the ethyl esters of (E)-2-(fluoromethyl)dehydroornithine used at 10 times lower doses are as effective as the parent amino acid and as DFMO at inhibiting ODC in the ventral prostate of rat, 6 hr after oral administration. All the esters of (E)-2-(fluoromethyl)dehydroornithine produce a particularly long duration of ODC inhibition in the ventral prostate and in the testes. Repeated administration (25 mg/kg given once a day by gavage) of the methyl ester of (E)-2-(fluoromethyl)dehydroornithine for 8 days to rats results in a constant 80% inhibition of ODC over a 24-hr period, accompanied by a 90% decrease of putrescine and spermidine concentrations in the ventral prostate.

Adenosylmethionine Decarboxylase↗
PubMed1986

Facile synthesis of glycol metabolites of phenethylamine drugs.

High yields of potential glycol metabolites of p-synephrine, epinephrine, octopamine, and normacromerine can be obtained from the readily available monosubstituted and disubstituted acetophenones. The general procedure involves alpha-bromination followed by displacement with acetate ion and reduction with lithium aluminum hydride. Yields ranged from 46 to 91%. Furthermore, the procedure minimizes some problems inherent in aromatic glycol synthesis which include dimerization and pinacol-pinacolone rearrangement.

Chemical Phenomena↗
PubMed1986

[Trypan blue and alizarin red S sequential staining with subsequent fixation. A modified technic for the study of the corneal endothelium].

A sequential corneal endothelium staining technique with trypan blue (TB)--alizarin red S (ARS)--ethanol-trypan blue is described which can be performed in a few minutes. The first step permits the TB exclusion to be determined as a criterion of normal endothelial cell function. The two following steps permit intercellular staining by ARS and nuclear staining by TB. After each staining procedure, fixation can be performed by methanol or ethanol, both with full-thickness corneal preparations or endothelial flat mounts. In flat preparations, the focussing problems and optical artifacts of full-thickness mounts can be avoided. These modifications render simple sequential staining with subsequent fixation a complement and alternative to specular microscopy and to the customary complicated silver staining of corneal endothelium.

Animals↗
PubMed1986

Use of EEG digital filtering and display for HPNS diagnosis.

Divers show symptoms of a condition known as the high pressure nervous syndrome (HPNS) at depths greater than about 180 m. A symptom that possibly lends itself to an objective diagnosis is a change in the frequency content of the EEG signal with increased slow wave (theta, 4-8 Hz) and decreased fast wave (alpha, 8-13 Hz) activity. Therefore, a method was developed, first, to obtain the power in the EEG frequency bands by digital filtering and, second, to display band-indices and ratios during a dive, in a format suitable for rapid appraisal. The formulas for the cascaded 2nd order Butterworth bandpass filters are given together with the corresponding FORTRAN program. EEG signals from 3 subjects taped during the Duke University Atlantis IV dive to a depth of 650 m were analyzed and displayed by the above method as well as by a Fast Fourier Transfer signal analyzer. The results suggest the theta: alpha ratio, which is a one-parameter EEG evaluation in the frequency domain, is a valuable descriptor for the objective HPNS diagnosis.

Computers↗
PubMed1985

[Clinical specular microscopy. Technic, organization and simple calculator morphometry].

The use of specular microscopy (SM) as a routine clinical method for qualitative morphological and quantitative morphometric analysis of the corneal endothelium requires a standardized examination technique. Organizational and apparative means are necessary for the analysis, documentation and storage of the data. The results of the immediate analysis are documented on a result form. The morphological changes are classified in 4 different groups (endothelial, pre-endothelial, retro-endothelial, and non-endothelial changes). The morphometric analysis is performed immediately: the mean cell density (mcd) is estimated by comparing the endothelial mosaic in the camera viewfinder with 3 standardized specular micrographs with known cellular density. The good correlation between the results of estimation and definite counting allows this rapid method to be used as a simple clinical screening techniques. The definitive morphometric analysis is carried out directly from the photographic negative using the fixed frame principle. The mcd and mean cell area (mca), m +/- sd, are determined by a simple method which saves time and money, using a scientific pocket calculator programmed in Basic. A specially designed slide rule serves to define the frame. The calculator may also be used for statistical analyses. This is demonstrated in a group of 127 patients (aged 51-87) before IOL implantation. The mcd and mca of the examined population is 2249 +/- 290 cells/mm2 and 444 +/- 57 microns 2. There is no statistically significant difference in mcd between the right and left eye (t-test: p = 0.93). Although statistically mcd decreases significantly with advancing age (p = 0.05), there is a large range of results in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count↗
PubMed1984

The amplification of the anticonvulsant effect of vinyl GABA (4-aminohexenoic acid) by esters of glycine.

The synergistic amplification of the anticonvulsant effects of direct and indirect GABA agonists by glycine has previously been demonstrated. We show in the present report that the anticonvulsant effect of vinyl GABA, a GABA-T (4-aminobutyrate: 2-oxoglutarate aminotransferase) inhibitor with antiepileptic efficacy, can be amplified by esters of glycine. Among the compounds studied glycine tert. butylester was the most promising. It was effective at a lower dose and had a considerably longer duration of action than glycine. From the observed glycine and glycine tert. butylester levels it is evident that glycine tert. butylester is rapidly hydrolysed within brain and other tissues. It is therefore a pro-drug of glycine, capable of enhancing central glycinergic activity.

3-Mercaptopropionic Acid↗
PubMed1982

Synthesis and biochemical properties of chemically stable product analogues of the reaction catalyzed by S-adenosyl-L-methionine decarboxylase.

Structural analogues of decarboxylated S-adenosyl-L-methionine (dc-SAM), product of the reaction catalyzed by S-adenosyl-L-methionine decarboxylase (SAM-DC), with modifications in the side-chain portion of the molecule have been synthesized, and their ability to inhibit SAM-DC has been investigated. Mainly, compounds with a nitrogen atom in place of the sulfur were investigated. The data from these inhibition studies have resulted in a delineation of the structural features required for binding on SAM-DC. It was concluded that a terminal primary amino group, a terminal carboxyl group, and the sulfonium functionality are not required for binding on SAM-DC. It was also found that analogues of dc-SAM in which replacement of the sulfur by nitrogen was the only modification were still able to form an azomethine with the enzyme. As found for SAM and dc-SAM, these compounds also caused a time-dependent inactivation of SAM-DC.

Adenosylmethionine Decarboxylase↗
PubMed1980

Case reports. Intrauterine echovirus type II infection.

The case described herein represents the first laboratory-confirmed case indicating intrauterine infection due to echovirus type II. The virus was recovered from the vagina of the mother and from the blood from the umbilical cord and nasopharynx of an apathetic newborn (all cultures were taken within 60 minutes of birth in the delivery room) with a generalized maculopapular exanthem. When the infant was 15 days of age, results of all laboratory tests and physical examinations were normal.

Adult↗