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G Kirsch

Publications and source records attributed to G Kirsch.

At least 37 records · Page 2Linked to original sources

Control of K+ channels by G proteins.

Heterotrimeric G3 proteins are though to couple receptors to ionic channels via cytoplasmic mediators such as cGMP in the case of retinal rods, cAMP in the case of olfactory cells, and the cAMP cascade in the case of cardiac myocytes. G protein-mediated second messenger effects on K+ channels are dealt with elsewhere in this series. Recently, membrane-delimited pathways have been uncovered and an hypothesis proposed in which the alpha subunits of G proteins directly couple receptors to ionic channels, particularly K+ channels. While direct coupling has not been proven, the membrane-delimited nature has been established for specific G proteins and their specific K+ channel effectors.

Animals↗

Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid: a useful new agent to evaluate myocardial fatty acid uptake.

Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) has been prepared as a new terminal iodophenyl-substituted fatty acid containing dimethyl-branching at the beta position. For the synthesis of this new agent, chain homologation was accomplished by fabrication of a 2,5-disubstituted thiophene by successive Friedel-Crafts acylation and Wolff-Kishner reduction reactions, followed by thiophene ring opening. The dimethyl-branching was introduced using the monomethyl ester of dimethylglutaryl chloride. Radioiodination of the 15-phenyl-3,3-dimethylpentadecanoic acid substrate in the para position then gave DMIPP. Iodine-125-labeled DMIPP showed rapid, high myocardial uptake (min, mean % injected dose/g) in fasted rats (5, 4.67; 30, 5.06; 60, 4.79; 120, 4.37), and also exhibited good heart:blood ratios (min, heart:blood: 5, 3:1; 30, 12:1; 60, 12:1; 120, 13:1). To further evaluate the effects of dimethyl-branching, the biodistribution properties of DMIPP were compared with the 3-monomethyl-branched (15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid; BMIPP) and the unbranched (15-(p-iodophenyl)pentadecanoic acid; IPP) analogs. A triple-labeled [123I]DMIPP/[131I]BMIPP/[125I]IPP mixture was administered to groups of fasted rats. These results confirmed the greater myocardial retention and higher heart:blood ratios observed with DMIPP in comparison with both the 3-monomethyl-(BMIPP) and unbranched (IPP) analogs. These data suggest that [123I]DMIPP is an excellent candidate for clinical evaluation of regional energy substrates (fatty acid) uptake.

Animals↗

[Relation of uteroplacental circulation and morphologic findings in myometrial and decidual arteries in diabetic pregnancy].

Placental blood flow measurements are compared to morphologic blood vessel examinations of the placental bed and uterus. In 122 diabetic pregnant women half life time of 113m Indium labelled blood inflow curves into the placenta as measured by a gamma scintillation camera on-line recorded to a computer system. - In 57 patients histological examination of uteroplacental arteries were done. - Congruent results of placental blood flow and arterial morphology were found in 66%. - In almost all patients with normal placental blood flow extensive physiological vessel findings were recorded. In patients with reduced placental blood flow pathomorphological changes were found in 54%. - In diabetes of long duration with angiopathic complications - above all in White-classes D, F and R - the ratio of pathological findings in placental blood flow and morphology was increased. - But also in gestational diabetes and in disturbances of carbohydrate metabolism pathological results are to be found. Pathological results in placental blood flow were more often than morphological changes (70 versus 40%), so that also functional factors as uteroplacental blood flow influencing ones are to be taken into account.

Arteries↗

[Measurement of uteroplacental circulation with 113m indium in diabetic pregnancy].

In 122 diabetic pregnancies the placental blood flow has been estimated determining the half life of the activity inflow (2 MBq 113 m In labelled transferrin) into the placental bed. We used a highly sensitive detector (modified pinhole collimator) and a computer supported evaluation, free from subjective influences. 259 flow measurements were compared to the risk of complication in the course of a diabetic pregnancy. - The half life values in the diabetic group, calculated by a gamma camera computer system by means of an iterative regression analysis, were significantly different compared to a control group (12 pregnancies without risk.) - Severe diabetic angiopathic complications (White classes D, F, and R) are accompanied by higher half life values (placental blood flow reductions) and perinatal complications. - Even in pregnant women with gestational diabetes or disturbances of the carbohydrate metabolism a disturbed placental hemodynamic is to be found.

Adult↗

Synthesis and evaluation of radioiodinated terminal p-iodophenyl-substituted alpha- and beta-methyl-branched fatty acids.

Methods have been developed for the preparation of terminal p-idophenyl-substituted alpha- and beta-methyl-branched long-chain fatty acids. The syntheses and physical properties of 14-(p-iodophenyl)-2(RS)-methyltetradecanoic acid and 15-p-iodophenyl)-3(RS)-methylpentadecanoic acid are described. The radioiodinated agents are of interest as a result of the expected pronounced uptake and prolonged myocardial retention that may result from the inhibition of fatty acid metabolism. Tissue distribution studies in rats with 14-(p-[125I]iodophenyl)-2(RS)-methyltetradecanoic acid and 15-(p-[125I]iodophenyl)-3(RS)-methylpentadecanoic acid show significant heart uptake and prolonged retention accompanied by low in vivo deiodination and high blood levels. A comparison of the heart uptake of the radioiodinated methyl-branched fatty acids and their unbranched analogues has demonstrated a greater myocardial retention of the methyl-branched fatty acids than the unbranched analogues. These results suggest that the mechanism of myocardial retention results from steric or chemical inhibition of the metabolism of these fatty acids by the presence of the methyl group.

Animals↗