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Biomedical subjects

H Simon

Publications and source records attributed to H Simon.

At least 235 records · Page 13Linked to original sources
PubMed1983

On the reduction of aliphatic and aromatic nitro compounds by Clostridia, the role of ferredoxin and its stabilization.

Crude extracts of a variety of Clostridium species reduce aromatic and aliphatic nitro compounds in the presence of hydrogen gas. Using different Clostridia, the uptake of hydrogen by p-nitrobenzoate is about 5--10 times faster than by 2-nitroethanol. Structurally rather different aliphatic nitro compounds show rates which differ by less than a factor of 3. Hydrogenase from Clostridium kluyveri and ferredoxins from Clostridium spec. La 1 and spinach have been purified. The combinations of the hydrogenase and each one of the ferredoxins catalyse the hydrogen uptake by nitro compounds. Clostridial flavodoxin also transfer electrons onto nitro compounds. Nitroaryl and nitroalkyl compounds behave differently with ferredoxin. The first reduction step (1-electron transfer) of p-nitrobenzoate leads to the nitro radical anion which can be detected by EPR measurements. Nitro alkanes seem to form a rather unstable radical which decomposes partially to form nitrite. Furthermore, 2-(N-hydroxyimino)- and 2-(N-hydroxyamino)ethanol, a nitrogen radical of 2-(N-hydroxyamino)ethanol as well as glycol and 1,4-butanediol were detected as intermediates and side products during the reduction of 2-nitro-ethanol to 2-aminoethanol. While the hydrogenase from Clostridium kluyveri seems not to be affected by any reduction intermediate, the ferredoxin from Clostridium spec. La 1 is inactivated by nitrite in a few minutes. Ferrous and sulfide ions in concentrations substoichiometric to that of nitrite stabilize and even reactivate the ferredoxin in the presence of 2-mercaptoethanol. A mechanism for the reduction of aliphatic nitro compounds catalysed by hydrogenase and ferredoxin is proposed.

Clostridium↗
PubMed1983

The treatment of angina pectoris with the new beta-receptor blocker carteolol. Results of a controlled trial in comparison with pindolol.

This trial comprised 40 patients with angina pectoris and reproducible ischaemic ST segment depression in the exercise ECG. Whenever possible the diagnosis of coronary heart disease was confirmed by coronary angiography. After a preliminary 7-day placebo period, 20 of these patients were treated for 4 weeks with 5-(3-tert-butylamino-2-hydroxy-propoxy)-3, 4-dihydro-2(1H)-quinolinone hydrochloride (carteolol hydrochloride, Endak, Endak mite), a nonselective beta-receptor blocker, having adrenergic properties (ISA) up to 30 times more powerful than those of propranolol. The trial was double-blind and randomized; standard medication (pindolol) was given to the controls. In general, the results obtained with carteolol--and also with pindolol--may be regarded as "good" or "very good". The average weekly incidence of anginal attacks fell from 6 to 4 (p less than 0.05). Carteolol produced a definite decrease in ST segment depression during exercise, at the end of exercise and in the recovery phase (p less than 0.05). The same was true for the patients treated with pindolol. There was no statistically significant difference between the treatment groups. Pulse rate and systolic blood pressure--measured before exercise and at the end of the recovery phase--did not change; however, readings made at the end of exercise showed a significant decrease (p less than 0.05). Diastolic pressure remained essentially unaltered. There were no changes in the chest radiograph or resting ECG. Laboratory results remained unchanged in both groups. In one patient of each group treatment needed to be discontinued because of dyspnoea, mainly during exercise. This reaction could probably be related to the beta-blocker therapy. The overall response to treatment, as assessed by the physician conducting the trial, was "good" or "very good" in 75% of the patients receiving carteolol and in 70% of those receiving pindolol. 70% of the patients who had received carteolol assessed the therapeutic result as "good" or "very good"; in the pindolol group 55% made the same judgment.

Adult↗
PubMed1983

Comparison of tocainide and prajmalium bitartrate for the treatment of ventricular arrhythmias.

The antiarrhythmic efficacy of tocainide, a new antiarrhythmic substance, has been compared with that of prajmalium bitartrate, a drug in clinical use for many years in the German speaking countries. The investigation was performed as a double-blind cross-over study in 20 patients with ventricular arrhythmias (VA) of various origin. The efficacy was assessed by serial Holter monitoring. Plasma levels were measured to study the dose-effect relationship. Applying to the criterion of a reduction of VA of more than 75% or an improvement according to the Lown grading 8 pts. under tocainide and 7 under prajmalium bitartrate were responders. Side effects were few and under tocainide only 2 pts. had to discontinue the therapy. From the present findings tocainide and prajmalium bitartrate have the same efficient antiarrhythmic effects in the majority of patients.

Adult↗
PubMed1982

6-Hydroxydopamine lesions of dopaminergic A10 neurons. Long-term effects on the urinary excretion of free and conjugated catecholamines and their metabolites in the rat.

Free and conjugated catecholamines (dopamine, noradrenaline, adrenaline) and their methoxylated and/or deaminated metabolites were studied in rat urine after the bilateral destruction of the A10 dopaminergic cell group. Two months after the lesion, dopamine (DA) loss reached 91% in the nucleus accumbens, and was greater than 80% in olfactory tubercles, lateral septum and frontal cortex. At the same time urinary conjugated dihydroxyphenylacetic acid (DOPAC) was decreased by 45% whilst homovanillic acid (HVA) was increased only in its sulfated form (+62%). In contrast, no changes were observed in the free and conjugated forms of urinary DA, 3-methoxytyramine noradrenaline, normetanephrine, adrenaline, vanylmandelic acid, 3-methoxy-4-hydroxyphenylglycol and in the free forms of DOPAC and HVA. The present report confirms and extends our previous findings on the relationships between central dopaminergic activity and urinary deaminated metabolites of DA in the rat. It emphasizes the interest of urinary assays which could provide in vivo information on CNS functions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

On the kinetics and mechanism of enoate reductase.

Enoate reductases from Clostridium spec. La 1 and Clostridium kluyveri show a rather broad substrate specificity i.e. many alpha,beta-unsaturated carboxylates are reduced in a NADH-dependent reaction. The relative rates for different substrates are different for both reductases. The Km value of NADH for the reductase from C. spec. La 1 is about 12 muM. The transhydrogenase activity (reduction of N-acetylpyridine adenine dinucleotide) with NADH shows a maximum at pH 8 which is about 2 units higher than that for the reduction of enoates. Results of initial rate studies can be best explained by a Bi Bi ping pong mechanism. No back reaction and no proton exchange from 2(-3)H-labelled acylates could be demonstrated. NAD+ is a mixed-type inhibitor. The product inhibition constant Ki = 0.84mM and the dissociation constant for the dead-end inhibition complex 4.8mM. Aliphatic acylates show no measurable inhibition when they are applied in concentrations at the 100-fold Km values of the corresponding enoates. Measurable inhibitions can be observed with phenyl group-containing acylates. 3-Phenylpropionate (38mM) shows about 86% inhibition. Fumarate which is not a substrate inhibits the reduction of enoates by NADH as well as by reduced methylviologen. However, the reduction of NAD+ by reduced methylviologen as well that of acetylpyridine adenine dinucleotide by NADH is not inhibited by fumarate. On the other hand inhibitors such as morin or dicoumarol which probably bind to the flavin domain do not impair the reduction of enoates by reduced methylviologen however, all reductions with NADH are inhibited. These results are indicative for three binding domains: one for NADH which can be blocked by dicoumarol or morin, another for enoates which can be occupied by fumarate and a third one for reduced methylviologen. Enoate reductase splits off exclusively the (4S)-hydrogen atom from NADH. There is no direct hydrogen transfer from NADH to the products. Depending on the substrate concentration the isotope effect of the reduction of (E)-2-methyl-2-butenoate with (4S)-[4(-3)H]NADH varies from 6.8 to 1.3. The presence of NAD+ decreases the isotope effect.

Aerobiosis↗
PubMed1982

Rhein as an electron acceptor for various flavoproteins and for electron transport particles.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) which has been previously employed as an inhibitor for electron transport particles, NADH dehydrogenase, and other flavoproteins is reducible under physiological conditions. Soluble hydrogenase from Alcaligenes eutrophus H 16, several flavoproteins, and electron transport particles from baker's yeast and from beef heart were found to catalyse NADH oxidation with 9 micrometers to 2mM rhein as the electron acceptor. Dithionite or enzymatically reduced rhein (lambda max = 408 nm) is immediately reoxidized to rhein lambda max = 437 nm) by oxygen. Cyclovoltagrams reveal the midpoint redox potentials --0.240 V, -0.270 V, -0.280 V, -0.335 V at pH 6.0, 7.0, 7.7, 9.2, respectively. Due to its redox behaviour, caution should be exercised using rhein as a flavin-site-directed inhibitor for biological electron transfer systems.

Alcaligenes↗
PubMed1982

The stereochemical course of the water elimination from (2R)-phenyllactate in the amino acid fermentation of Clostridium sporogenes.

(2R,3R)-[3-3H]- and (2R,3S)-[3-3H]- phenyllactate were synthesized from phenylpyruvate with the help of phenylpyruvate tautomerase and an NADH-dependent 2-oxo-acid reductase from Clostridium sporogenes. With whole cells of C. sporogenes both (2R)-phenyllactates are mainly transformed to phenylpropionate and, to a minor extent to phenylalanine. According to recently published results, the former transformation leads from phenyllactate, or an activated derivative of it, to (E)-cinnamate which is reduced to phenylpropionate in a fast consecutive reaction. The 3H/14C-ratio of phenylpropionate deriving from (2R,3R)-[3-3H,U-14C]phenyllactate was about 85% of that of the phenyllactate and the corresponding ratio for phenylpropionate deriving from the (2R,3S)-[3-3H,U-14C]phenyllactate about 7%, respectively. Assuming that the E-configuration of cinnamate is formed directly from (2R)-phenyllactate, the water elimination occurs in a syn fashion.

Amino Acids↗
PubMed1981

Opposite changes in dopamine utilization in the nucleus accumbens and the frontal cortex after electrolytic lesion of the median raphe in the rat.

As revealed by the changes in dihydroxyphenylacetic acid (DOPAC) levels and in the DOPAC/Dopamine (DA) ratio, DA utilization was markedly enhanced in the nucleus accumbens and reduced in the prefrontal cortex of rats five days after the electrolytic lesions of the median raphe. These opposite effects were not seen any more seventeen days after the injection. These results suggest that neurones originating from the median raphe and projecting to the ventral tegmental area exert an opposite effect on the activity of DA cells innervating the nucleus accumbens and on those projecting to the prefrontal cortex.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Stereospecific reductions of 2-en-1-ols catalyzed by Clostridium kluyveri.

With ethanol as electron donor, resting cells of Clostridium kluyveri reduced (E)-2-methyl-2-buten-1-ol, (E)-3-methyl-2-penten-1-ol and (E)-2-methyl-3-phenyl-2-propen-1-ol to (R)-2-methyl-1-butanol, (R)-3-methyl-1-1-pentanol and (R)-2-methyl-3-phenyl-1-propanol, respectively. Within the experimental errors of ORD measurements the products were optically pure. That means that only one of the two possible trans additions to the carbon-carbon double bond of these derivatives of allyl alcohol took place. The reduction of (E)-2-methyl-3-phenyl-2-propen-1-ol was carried out in 2H2O buffer. Assuming tha all 3 substrates bind in an identical manner to the enzyme, the product should be (2R,3S)-2-methyl-3-phenyl-[2,3-2H2]-1-propanol. The optimal pH and ethanol concentration for the reduction have been determined. Under an atmosphere of hydrogen the reduction of the unsaturated alcohols proceeded incompletely and slower than in the presence of ethanol under an atmosphere of nitrogen.

Alcohols↗