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Biomedical subjects

R Böhm

Publications and source records attributed to R Böhm.

At least 55 records · Page 3Linked to original sources

Quantitation of R- and S-propafenone and of the main metabolite in plasma.

Several methods for the determination of racemic propafenone or its enantiomers as well of the main metabolite R,S-5-hydroxypropafenone are known from the literature. The method described here enables the simple simultaneous quantification of R- and S-propafenone and of R,S-5-hydroxypropafenone in human plasma. The method is based on an HPLC separation using a Chiralpak AD column. High recovery rates (80-95%) were achieved by means of a liquid-liquid-extraction at pH 11 with dichloromethane as solvent. The separation on the chiral carrier were carried out with n-hexane/2-propanol; the addition of diethylamine is useful. The obtained capacity factors are k' = 2.36 for R-propafenone and k' = 3.82 for S-propafenone. R,S-propanolol and R,S-metoprolol were used as internal standards. The method described can be used for pharmacokinetic trials in man with the following limits of quantitation: 10 ng/ml for R- and S-propafenone and 20 ng/ml for R,S-5-hydroxypropafenone.

Adrenergic beta-Antagonists↗

[The bioequivalence of two oral propafenone preparations].

The bioequivalence of two oral racemic propafenone (CAS 54063-53-5) preparations was tested in an open, randomised, crossover trial with administration of single doses of 300 mg on two different occasions with a washout period of 7 days. 24 healthy, male volunteers, all proved to be rapid hydroxylators of debrisoquine, were enrolled in the trial. The concentrations of R(+)-, S(-)-propafenone and 5-hydroxypropafenone (5-OH-propafenone) were measured up to 12 h after administration by means of a sensitive and specific HPLC method that allowed the simultaneous quantification of all three substances in plasma. The results of 23 volunteers were evaluated pharmacokinetically. Main target parameters were AUC0-infinity and Cmax of both enantiomers of propafenone. Secondary target parameters were AUC0-infinity and Cmax of 5-OH-propafenone as well as tmax for R(+)- and S(-)-propafenone. The 90% confidence intervals for AUC0-infinity for R(+)-, S(-)-, and 5-OH-propafenone were 0.85-1.07, 0.83-1.10 and 0.84-1.05, respectively. The confidence intervals for Cmax were 0.81-1.12, 0.82-1.17 and 0.87-1.09 for R-, S-, and 5-OH-propafenone, respectively. The concentration maxima of both enantiomers were registered on average 15 min earlier after administration of the test preparation. This difference is of no clinical relevance. Both preparations are bioequivalent according to the criteria of the Committee for Proprietary Medicinal Products (CPMP).

Administration, Oral↗

[Effect of structural changes in animal husbandry on the environment due to wastes and residues from animal production].

From the statistic data it can be taken, that especially in the old federal states of Germany, in the new future animal husbandry will be more and more concentrated in certain regions. This structural change probably is followed by a similar concentration process concerning slaughterhouses and within limitations the rendering industry too. This will result in a higher regional environmental pollution by volatile and soluble components as well as microorganism from agricultural wastes of animal origin, by offal and by products from slaughtering as well as by highly contaminated slaughterhouse wastewater and by pollutants in air and waste-water from rendering plants. Further regional environmental and epidemiological risks are connected with recycling of voluminous slaughterhouse wastes like rumen-, stomach- and gut-contents to the farms as fertilizers, unless strictly hygienic guidelines have to be followed in the future.

Abattoirs↗

Which bicarbonate concentration is adequate to lactate-buffered substitution fluids in maintenance hemofiltration?

We investigated the metabolic and hemodynamic effects of a lactate- and a bicarbonate-buffered (bicarbonate concentration 31.4 mmol/l, type I) hemofiltration substitution fluid in a prospective crossover study of 3 weeks each in 11 patients on maintenance hemofiltration. The lactate-buffered hemofiltration (lactate concentration 34-44.5 mmol/l) lead to hyperlactatemia in all patients without signs of overt lactic acidosis but showed a better control of acid-base balance (pH, base excess, standard bicarbonate) than the type I bicarbonate-buffered fluid (p < 0.01). In 6 patients a higher concentration of bicarbonate- (39.7 mmol/l, type II) buffered fluid was tested. The parameters of acid-base balance showed a better control during type II than during type I bicarbonate hemofiltration and were similar to the lactate-buffered phase. Plasma lactate levels between type I and type II bicarbonate hemofiltration were not different. Also in the steady state phase of the treatment (days 7-9 [week 3]) parameters of acid-base balance rose more to normal values during type II than during lactate-buffered hemofiltration. Hemodynamic parameters showed no differences between the three types of buffers used. Furthermore, also the type II bicarbonate fluid was well tolerated. Bicarbonate in a higher concentration (39.7 mmol/l) proved to be a safe and practical alternative to lactate-buffered hemofiltration.

Acid-Base Equilibrium↗

Mimosine-induced cell death and related chromatin changes.

The non-protein amino acid mimosine has recently been shown to induce an unusual mode of cell death that differs from necrosis and apoptosis, the two fundamental schemes of cell death. The drug affects primarily the cell nucleus and induces first condensation of the chromatin into a regular network of fibrils and then gradual decondensation. The present study was performed to evaluate effective mimosine concentrations, time dependency of toxicity, and mimosine-related alterations of the chromatin, DNA and histones. To this end, primarily cultured carp hepatocytes were exposed to a wide range of mimosine (10(-1) to 10(-4) M) up to 12 h and investigated by means of light microscopy, electron microscopy, and histochemistry for DNA and histones. With 10(-1) M mimosine severe cytopathological transformations were obtained already after 3 h whereas 10(-2) M was cytotoxic only after 12 h. Lower concentrations were ineffective within the experimental period. Cytopathology started with condensation of the chromatin into a homogeneous network of ca. 25 nm wide fibrils and segregation of the nucleolus. In parallel, the nuclei were depleted from histones leaving the pattern of DNA fluorescence largely unchanged. The following period of chromatin decondensation was characterized by removal of electron-dense components from the condensed chromatin fibrils and gradual loss of the DNA. The segregated nucleolus and also the nuclear pores remained well preserved until final cell lysis.

Animals↗

Mimosine, a naturally occurring drug interfering primarily with the cell nucleus.

The non-proteinogen aminoacid mimosine interfered seriously with cultured carp hepatocytes when added to the culture medium for 6 h in a concentration of 0.1 M. Cell transformation started with condensation of the chromatin into an unusual network of fibrils and segregation of the reticulate nucleolus into its fibrillar and granular components. Then chromatin condensation spread homogeneously across the entire nucleus. At the end of the condensation period the nuclear envelope extended towards the cytoplasm and the nuclear interior resulting in a very confusing nuclear boundary. Later, the nucleus expanded and the chromatin was gradually decondensed but the segregated nucleolus persisted until nuclear lysis. The DNA staining pattern did not change throughout the condensation period. DNA was even present in most decondensing nuclei. The cytoplasmic organelles were only slightly affected during chromatin condensation but significantly altered thereafter. The observed course of mimosine-induced cell transformation is very unusual. The first period covering chromatin condensation with structural intactness of the cell organelles resembles in some aspects apoptosis but additionally includes some special signs. The following phase of cellular disintegration, however, is similar to necrosis. Due to this unique course of cell death, mimosine should be further tested for its potential suitability in experimental cell research and cancer chemotherapy.

Animals↗

Diagnosis and treatment of a solitary infected hepatic cyst in two patients with adult polycystic kidney disease.

We report on two women (one 52-year-old who underwent kidney transplantation 15 months ago and the other, 71-year-old, undergoing hemodialysis) both with adult polycystic kidney disease who had to be hospitalized because of recurrent fever attacks up to 40 degrees C without any remarkable abdominal symptoms. Staphylococcus hominis and E. coli were recovered respectively from blood cultures of both patients. Evidence for the presence of a solitary infected cyst in the liver could only be obtained by computed tomography (CT) with i.v. administration of a contrast medium. In both cases the infected liver cyst was non-operatively drained with a CT-guided percutaneous catheter and therefore the necessity of laparotomy was avoided.

Aged↗

[Behavior of selected salmonellae in the environment].

In the introduction the epidemiological significance of Salmonella surviving in the environment is demonstrated. The mathematical functions describing the kinetics of inactivation in thermal destruction of microorganism known as DT values or T90-rates were mentioned, and the main factors influencing the bacterial survival on surfaces, in liquids and in the soil were indicated. Basic data concerning the tenacity of S. enteritidis and S. typhimurium on surfaces in the stable, in slurry, on pastures, in the soil, in water and waste water as well as in living vectors were collected from the literature.

Animals↗

[Toxic myopathy with kidney failure as a colchicine side effect ifn familial Mediterranean fever].

A 24-year-old woman with familial Mediterranean fever (FMF) had for one year been treated with colchicine, 1 mg daily, for repeated bouts of fever, abdominal pain and arthritis. She was also known to have renal amyloidosis. Lately she had developed gastrointestinal symptoms, muscle pain and obvious, predominantly proximal muscular weakness in both legs. The cause of the symptoms was rhabdomyolysis with an increased creatinine activity of 1000 U/l and marked myoglobinuria (1600 micrograms/l), as well as renal failure with normal uric acid and a creatinine clearance of 3 ml/min per 1.73 m2. Serum creatinine concentration was 970 mumol/l, urea 34 mmol/l. Muscle biopsy corresponded to a subacute necrotizing myopathy with vacuole formation, signs typical of toxic damage. Renal biopsy confirmed advanced amyloidosis. The colchicine dose was reduced to 0.5 mg/d. The renal failure responded to conservative treatment. The myopathy symptoms receded within 4 weeks, creatinine clearance rising to 25 ml/min per 1.73 m2. 12 months after reduction of the colchicine dose the patient was without any FMF-related symptoms.

Acute Kidney Injury↗

[Newer information about several aspects of animal epidemic disinfection].

The amendment of the German Veterinary Legislation concerning the eradication of notifiable diseases demanded also an updating of the relevant disinfection measures and technologies. Some hints are given, based on own experimental results, for the choice of chemical disinfectants, on some special problems of disinfection in livestock buildings and of disinfection of animal slurry and farm-yard manure as well as on biotechnological disinfection methods and environment-friendly disinfectants.

Animals↗

Mutational analysis of the operon (hyc) determining hydrogenase 3 formation in Escherichia coli.

In-frame deletions were introduced into each of the eight genes of the hyc operon coding for products required for the formation of the formate hydrogenlyase (FHL) system. The deletions were transferred to the chromosome and the resulting mutants were analysed for development of formate dehydrogenase H and hydrogenase 1, 2 and 3 activity. It was found that hycA, the promoter-proximal gene, is a regulatory gene and that it codes for a product counteracting transcriptional activation by FhlA. Deletions within the hycB to hycH genes specifically affected formate dehydrogenase H activity or hydrogenase 3 activity, or both. None of the mutations affected hydrogenase 1 or 2 activity. A model is proposed for the functional interaction of the different hyc operon gene products in the formate hydrogenlyase complex, which is based on the results of the mutational analysis, on the determination of the subcellular localization of the FdhF, HycE, HycF and HycG polypeptides and on the similarity of hyc gene product sequences with those from other hydrogenase systems. HycH, the product of the most promoter-distal gene, does not seem to form part of the functional FHL complex but rather is required for the conversion of a precursor form of the large subunit of hydrogenase 3 into the mature form.

Amino Acid Sequence↗

[Research in veterinary environmental hygiene].

The course of development of the initial subject "Veterinary Hygiene" to the reduction and specialization limited to "Animal Hygiene" and the recent extension into the broad field of environmental hygiene is described. This is done with reference to books and other publications which point the way ahead for research of veterinary medicine in environmental hygiene and thus prove the increasing importance of that subject. A survey is given over current German research in that field, future demands as well as the necessary extension of environmental hygiene in graduate and post-graduate teaching of veterinary students as well as further professional training of veterinarians.

Animals↗

Molecular characterization of an operon (hyp) necessary for the activity of the three hydrogenase isoenzymes in Escherichia coli.

The 58/59 min region of the Escherichia coli chromosome contains two divergently oriented gene clusters coding for proteins with a function in hydrogenase formation. One cluster (the hyc operon), transcribed counterclockwise with respect to the E. coli chromosome, codes for gene products with a structural role in hydrogenase 3 formation (Böhm et al., 1990). The nucleotide sequence of the divergently transcribed operon (hyp) has been determined. It contains five genes, all of which are expressed in vivo in a T7 promoter/polymerase system, and the sizes of the synthesized products correspond with those predicted from the amino acid sequence. Complementation analysis of previously characterized mutants showed that the hypB, hypC and hypD genes have a function in the formation of all three hydrogenase isoenzymes, lesions in hypB being complemented by high nickel ion concentration in the medium. Prevention of hypBCDE gene expression led to an altered electrophoretic pattern of hydrogenase 1 and 2 constituent subunits, indicating increased chemical or proteolytic subunits, Under fermentative growth conditions, operon expression was governed by an NtrA-dependent promoter lying upstream of hypA working together with an fnr gene product-dependent promoter which was localized within the hypA gene. The latter (operon-internal) promoter is responsible for hypBCDE transcription under non-fermentative conditions when the -24/-12 NtrA-dependent promoter upstream of hypA is silent.

Amino Acid Sequence↗

[The possibility of the serological differentiation of Clostridium species using enzyme immunoassays].

A method for serotyping and diagnosis of 30 selected Clostridia strains of 12 different species by an enzyme-immuno-assay using polystyrene balls as a solid phase is described and tested for its efficiency. The reference strains and the homologous test strains could be differentiated from the heterologous in principle. A reliable detection of the several serotypes of Cl. perfringens was not perfectly to achieve with the conjugates used here, cross-reaction with Cl. chauvoei could be removed by absorption. The conjugate of Cl. bifermentans reacted with Cl. sordellii and Cl. difficile too, and must be absorbed prior any diagnostic applications with vegetative cells of the corresponding strains. Concerning the antigenic relationships between the Clostridia strains used here, the results of Ellner and Green (7, 8) as well as of Poxton and Byrne (14) could be reconfirmed. Moreover the applied technique offers the possibility to come to a more detailed result concerning the degree of antigenic relationship. The developed method is a valuable tool for the differentiation of pathogenic Clostridia and within the group Cl. bifermentans/Cl. sordellii/Cl. difficile a rapid diagnosis at the species level could be achieved. Some limitations by cross-reactions are given, but results can be improved by absorption of the conjugates.

Clostridium↗

The effect of verapamil on carotid artery distensibility and cross-sectional compliance in hypertensive patients.

The effect of chronic administration of verapamil, following a double-blind, crossover protocol, on the distensibility and cross-sectional compliance of the common carotid artery was investigated in 19 patients with essential hypertension. Distensibility was significantly increased during verapamil treatment as compared to placebo for both left and right common carotid artery (p less than 0.01 and p less than 0.05, respectively). The cross-sectional compliance was significantly increased during verapamil treatment for the right common carotid artery (p less than 0.05). For the left common carotid artery, the difference did not reach the level of significance (p = 0.16). The common carotid artery diameter and the arterial pulse pressure were not significantly different during verapamil treatment as compared with placebo. The results of this study indicate that chronic treatment with verapamil increases distensibility and cross-sectional compliance of the common carotid artery in hypertensive subjects. These improvements have to be considered as changes in arterial wall properties because no significant differences in pulse pressure and diameter could be detected between the verapamil and placebo periods. Improved arterial wall properties could result in a better management of the flow jet from the heart, and might protect the patients from atherosclerotic complications of hypertension.

Adult↗

Nucleotide sequence and expression of an operon in Escherichia coli coding for formate hydrogenlyase components.

An 8kb segment of DNA from the 58/59 min region of the E. coli chromosome, which complements the defect of a mutant devoid of hydrogenase 3 activity, has been sequenced. Eight open reading frames were identified which are arranged in a transcriptional unit; all open reading frames were transcribed and translated in vivo in a T7 promoter/polymerase system. Analysis of the amino acid sequences derived from the nucleic acid sequences revealed that one of them, open reading frame 5 (ORF5), exhibits significant sequence similarity to conserved regions of the large subunit from Ni/Fe hydrogenases. Two of the open reading frames (orf2, orf6) code for proteins apparently carrying iron-sulphur clusters of the 4Fe/4S ferredoxin type. The product of one of the open reading frames, orf7, displays extensive sequence similarity with protein G from the chloroplast electron transport chain. ORF3 and ORF4, on the other hand, are extremely hydrophobic proteins with nine and six putative transmembrane helices, respectively. Over a limited hydrophilic sequence stretch, bordered by putative transmembrane areas, ORF3 and ORF4 exhibit homology with subunits 4 and 1 of mitochondrial and plastid NADH-ubiquinol oxidoreductases, respectively. The operon described, therefore, appears to comprise genes for redox carriers linking formate oxidation to proton reduction and for a hydrogenase of hitherto unique composition.

Aldehyde Oxidoreductases↗

Characterization of divergent NtrA-dependent promoters in the anaerobically expressed gene cluster coding for hydrogenase 3 components of Escherichia coli.

The regulatory region of two divergently oriented transcriptional units involved in the formation of the gas-evolving hydrogenase (isoenzyme 3) of Escherichia coli was investigated. DNA sequence analysis revealed the existence of a 210 bp non-coding region containing two sequences showing homology to -24/-12 NtrA-dependent promoters. These sequences were arranged in a divergent orientation entirely consistent with their being involved in transcribing the divergent operons. Through S1 protection experiments it could be shown that transcription of both promoters was NtrA-dependent and that it was regulated in an identical manner: oxygen repressed expression, as did anaerobic growth in the presence of nitrate; transcription was induced in cells grown anaerobically in the absence of exogenous electron acceptors and formate was found to be obligately required for this anaerobic induction. Lying at an approximately equal distance between both promoters was a short stretch of DNA which showed similarity to the sequence previously identified (Birkmann and Böck, 1989a) as being necessary for formate induction of the fdhF gene.

Anaerobiosis↗