Search PubMed⌕ Search

Biomedical subjects

E Ludwig

Publications and source records attributed to E Ludwig.

At least 19 recordsLinked to original sources
PubMed1995

Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis.

BACKGROUND: Although both genetic and nongenetic factors contribute to the pathogenesis of coronary artery disease, the identification of specific genetic lesions has lagged behind the identification of critical environmental risk factors. A reported association between myocardial infarction (MI) and the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in European men suggests a critical role for this genomic region. However, the generality of this association remains to be determined. It also is not clear at what stage in disease progression the association with the ACE I/D polymorphism becomes important. METHODS AND RESULTS: We evaluated the ACE I/D polymorphism in patients who had undergone coronary angiography (402 men and 295 women) and in 203 representative control subjects. After polymerase chain reaction amplification, genotypes were determined by agarose gel sizing and by hybridization with allele-specific oligonucleotides. After patients were categorized by the degree of coronary artery stenosis and the occurrence of an MI, the distribution of ACE I/D genotypes was evaluated by log linear analysis. Patients were genetically representative of the regional population, and patients with > 60% stenosis of their coronary arteries had the same distribution of ACE I/D genotypes as did patients with < 10% stenosis. However, among patients with stenosis, the occurrence of an MI was significantly associated with the D allele in all patients (odds ratio [OR], 1.59; P = .002) and in men alone (OR, 1.63; P = .006). The lack of significance in women (OR, 1.40; P = .263) is probably due to the fact that only 36 women in the present study had experienced an MI. Furthermore, the association between MI and the ACE I/D polymorphism was independent of blood pressure, smoking habits, and body mass index. CONCLUSIONS: Segregation of the ACE I/D polymorphism is a pervasive genetic risk factor for MI in whites but has no evident effect on the events leading to stenosis of the coronary arteries. This suggests that risk of MI is influenced by two independent processes--atherogenesis that leads to coronary stenosis followed by conversion to MI. The renin-angiotensin system appears to confer significant risk of infarction by influencing the conversion to MI but has no apparent effect on the development of atherostenosis.

Aged↗
PubMed1995

Oxidation versus addition reactions of glutathione during the interactions with quinoid thioethers of 4-(dimethylamino)phenol.

4-(Dimethylamino)phenol (DMAP) is a potent cyanide antidote which forms many equivalents of ferrihemoglobin in vivo and in vitro. During this process formation of phenoxyl radicals was observed which are reduced by ferrohemoglobin, thereby sustaining a catalytic cycle of ferrihemoglobin formation, or which disproportionate to give the quinone imine of DMAP. In the presence of thiols, e.g., glutathione (GSH), formation of 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP), 4-(dimethylamino)-2,6-bis(glutathion-S-yl)phenol (2,6-bis-GS-DMAP), and 4-(dimethylamino)-2,3,6-tris(glutathion-S-yl)phenol (2,3,6-tris-GS-DMAP) was observed. While the trisubstituted glutathione conjugate is a stable end product, 2-GS-DMAP and 2,6-bis-GS-DMAP were still reactive and produced ferrihemoglobin. It is concluded that formation of polysubstituted DMAP thioethers is a result of sequential oxidation/addition reactions with quinoid intermediates. Formation of glutathione disulfide (GSSG) was minimal during the interaction of oxidized DMAP or 2-GS-DMAP with glutathione but became significant when oxidized 2,6-bis-GS-DMAP reacted with GSH. Thus it is conceivable that the bulky glutathione substituents in 2,6-bis-GS-DMAP render the addition of a third GSH molecule to the quinone imine derivative more difficult, and other reactions may get a chance. The reaction mechanism of GSSG formation has not been fully resolved, but a radical pathway mechanism involving thiyl radicals is proposed. Oxidation and addition reactions were also observed in the absence of oxygen when ferrihemoglobin served as oxidant. In the presence of oxygen, however, GSSG formation was increased, Partly due to hydrogen peroxide formation, partly due to an additional trapping reaction of the glutathione disulfide radical anion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗
PubMed1995

Reactivity of glutathione adducts of 4-(dimethylamino)phenol. Formation of a highly reactive cyclization product.

During ferrihemoglobin formation, 4-(dimethylamino)phenol (DMAP), a potent cyanide antidote, forms a quinoid compound that is prone to sequential oxidation/addition reactions. In human red cells and hemoglobin solutions fortified with glutathione, a transient adduct has been isolated and identified as 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP). This compound still formed ferrihemoglobin but differed from parent DMAP in that the reaction rate was roughly proportional to the oxygen concentration and exhibited a lag phase, pointing to a reactive autoxidation product. The compound was isolated and tentatively identified as an intramolecular cyclization product of 2-GS-DMAP. Formation of this product includes three reaction steps: (1) formation of a quinoid intermediate, (2) addition of the alpha-amino nitrogen atom of the glutamate residue to the aromatic ring, and (3) autoxidation of the cyclization product to give a highly reactive o-quinone imine. The isolated compound existed in two isomeric states (1H-NMR) which upon reduction could be separated by HPLC. The isolated reduced isomers mutually converted into each other. A model compound which was synthesized to mimic the most important structural features, 4-(dimethylamino)-6-[S-(2'-hydroxyethyl)-thio]-N-(2"-phenylethyl)-1,2- quinone imine, had a very similar visible spectum and exhibited an even higher ferrihemoglobin activity than the cyclization product. A similar phenomenon of intramolecular cyclization of a thioether of DMAP had been observed earlier: DMAP covalently bound to the SH groups of the beta-chains in hemoglobin formed a cross-link with the C-terminal histidine residue in the presence of oxygen but not in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗
PubMed1991

[The determination of protein hydrophobicity. 1. Determination of the hydrophobicity of selected cereal and milk proteins using their sodium dodecyl sulfate binding capacities].

The sodium dodecylsulphate (SDS) binding capacities of secalin, gliadin and gluten in the presence of a very low SDS concentration were determined and compared to the SDS binding capacities of bovine serum albumin (BSA), beta-lactoglobulin, ovalbumin und beta-casein. The SDS binding capacities of endosperm proteins determined in phosphate buffer (pH 6.0) are very low. Only 0.6 microgram .. 0.8 microgram SDS were bound to 500 micrograms of the proteins. This low SDS binding capacities do not correlate with the expected hydrophobicity of these proteins. In comparison, 500 micrograms of ovalbumin, beta-lactoglobulin and BSA each bind 0.5, 5.9 and 13.5 micrograms SDS, respectively. According to literature the SDS binding capacities of these proteins are in correlation with the surface hydrophobicity determined with cis-parinaric acid using the fluorescence probe method. The SDS binding capacities of endosperm proteins increased in the presence of 0.1 N acetic acid and consequently 6.2 micrograms .. 6.9 micrograms SDS were bound to 500 micrograms of the corresponding proteins. beta-casein described as a highly hydrophobic protein binds only 0.9 micrograms SDS to 500 micrograms of it in phosphate puffer (pH 6.0) and 1.2 micrograms SDS in 0.1 N acetic acid, respectively.

Chemical Phenomena↗
PubMed1991

[The determination of protein hydrophobicity. 2. Determination of the of protein binding of sodium dodecyl sulfate with the use of the ultracentrifuge].

The interaction between sodium dodecylsulphate (SDS) and the proteins bovine serum albumin (BSA) and ovalbumin, respectively, was studied using a synthetic boundary cell of an ultracentrifuge. A method for the determination of protein-bound SDS is described. The SDS binding capacity of BSA is found to be 250 +/- 50 micrograms SDS per 500 micrograms of BSA. The amount of SDS bound by ovalbumin is so low that the procedure cannot be recommended for this protein.

Ovalbumin↗
PubMed1989

High-frequency jet ventilation during oleic-acid induced pulmonary oedema.

In oleic acid-induced pulmonary oedema (OAPO) sequential intrapulmonary fluid accumulation occurs leading to different expiratory flow pattern in dependent lung regions. The potential effects on efficacy of high-frequency jet ventilation (HFJV, f = 3 Hz, I: E = 0.43, FiO2 = 0.4) were studied and compared with continuous positive pressure ventilation (CPPV, f = 12-18/min, I:E = 0.5, TV = 12 ml/kg, PEEP = 0.5 kPa, FiO2 = 0.4) in a dog model of OAPO. In the control state (lung-healthy dogs), 15 min after oleic acid lung injury (interstitial oedema, period I) and 60 min after onset of OAPO (alveolar oedema, period II), gas exchange, lung volumes, compliance, resistance and haemodynamics were measured. The course of lung oedema was determined indirectly by means of washout curves of helium (foreign gas bolus-test, FGB) and nitrogen (single breath-test for oxygen, SBO2). During control, there were no significant differences between the HFJV-group (n = 7) and the CPPV-group (n = 6) by virtue of gas exchange, lung volumes and haemodynamics. During period I, PaO2 decreased significantly both with HFJV (p less than 0.01) and CPPV (p less than 0.05), being lower in the HFJV-group (p less than 0.05). PaCO2, pulmonary and haemodynamic parameters were unchanged. Onset of phase IV of the alveolar plateau (closing volume CV) occurred significantly earlier (p less than 0.05) in all animals. Impaired ventilation of dependent lung regions, increased maldistribution of intrapulmonary gas and VA/Q-mismatching may be the underlying mechanisms for lower efficacy of HFJV during interstitial lung oedema. In period II, pulmonary and cardiocirculatory parameters had changed significantly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effect of ciprofloxacin on antipyrine metabolism.

The effect of multiple-dose ciprofloxacin on antipyrine metabolism was studied in patients suffering from bacterial infections. The patients were given antipyrine 15 mg/kg intravenously before and after ciprofloxacin treatment. The dosage of ciprofloxacin was 500 mg bd by mouth for 8-10 days. Blood samples were taken at 0, 2, 4, 6, 10 h. Antipyrine total clearance was significantly decreased after ciprofloxacin treatment (0.85 +/- 0.45 vs. 0.52 +/- 0.24 ml/min/kg): elimination rate constants for antipyrine were decreased in all patients after ciprofloxacin, whereas no change in volume of distribution was observed. The average half-life of antipyrine was increased from 9.45 +/- 3.74 h to 14.92 +/- 3.32 h. In two males with advanced chronic hepatic failure the antipyrine half-lives were extremely prolonged. Our results support the hypothesis that ciprofloxacin inhibits intrinsic hepatic drug-metabolizing capacity and may be a source of clinically important drug interactions, particularly in patients with liver disease.

Adult↗
PubMed1988

Pharmacokinetics of cefotaxime and desacetylcefotaxime in elderly patients.

This study was undertaken to determine the effect of age on the pharmacokinetics of cefotaxime and desacetylcefotaxime after intravenous administration of 1 g cefotaxime. 30 elderly patients suffering from acute infection were enrolled in the study. They were divided into 3 subgroups (group I aged 60 to 70 years, group II aged 71 to 80 years, group III aged over 80 years) with 5 men and 5 women in each. The elimination of cefotaxime in patients aged between 60 and 80 years was slightly slower than that in young people: elimination half-lives (in men and women, respectively) in group I were 1.2 and 1.58 hours, in group II, 1.45 and 1.57 hours and in group III, 2.56 and 2.59 hours. The change in elimination of desacetylcefotaxime was similar to that of cefotaxime, but less marked. The slower elimination of cefotaxime in patients over 80 years of age may allow reduction in the dose without jeopardizing the efficacy of therapy, whereas in patients under 80 years of age the normal dosage is required.

Age Factors↗
PubMed1987

[Pili canaliculi, a form of uncombable hair].

Two further cases of the hair abnormality described in 1973 by Dupré et al. as "cheveux incoiffables" and later (1978) termed pili trianguli and canaliculi are reported. This hair abnormality--a distinct anomaly without the associated physical or mental abnormalities encountered in other cases of uncombable hair--starts in the first year of life, tending to improve or to become entirely normal with age. The morphological characteristics of such hairs are grooves along the hairshaft (demonstrable only by scanning electron microscopy), resulting in triangular, reniform, or irregular cross-sections. Of the various terms used to designate the condition, that proposed by Ferrando et al. (1980) pili canaliculi, appears to be the most appropriate.

Child, Preschool↗
PubMed1985

Long-term intermittent netilmicin therapy of chronic pyelonephritis: a pharmacokinetic and clinical study.

A trial was conducted with long-term intermittent netilmicin therapy in six patients suffering from chronic pyelonephritis. Netilmicin was given in full dose for a period of 3-10 days (2-6 mg/kg/day), followed by 2 mg/kg doses once or twice weekly for 3-6 months. Individual doses were determined by computer based on the age, sex, lean body weight and serum creatinine concentrations of the patients. During the full-dose period of treatment netilmicin concentrations in serum were between 2 and 16 mg/l in serum and between 50 and 200 mg/l in urine. During intermittent treatment serum levels remained below 2 mg/l (except for 8-12 hours after dosing); in the urine concentrations were permanently in therapeutic ranges (150-4 mg/l). Renal tissue levels were simulated. Six to 12 months after long-term netilmicin treatment all patients are abacteriuric and free from symptoms. No auditory or renal toxic effects occurred.

Adult↗
PubMed1984

[The effect of enzymatic modification on lysinoalanine formation in field-bean protein isolate and beta-casein].

Lysinoalanine (LAL) was determined in alkali-treated partial hydrolysates (PH) of casein, peptides isolated from these PH and in PH of field-bean protein to clarify whether intermolecular or intramolecular LAL bridges are preferentially formed. Furthermore, the formation of LAS in plasteins was studied as a contribution to plastein research. The formation of LAL in the peptide mixtures of beta-casein and the decrease of the LAL content in the PH (as compared to intact proteins) indicates that the formation of LAL favours the intramolecular cross-linking of polypeptide chains. The LAL content decreases as the degree of hydrolysis of the PH of the field-bean protein isolate increases, and depends upon the protease used in the production of the hydrolysates. The LAL contents of the alkali-treated plasteins are less than those of the initial hydrolysates. The decrease of the LAL content is directly proportional to the hydrolysis proceeding during the plastein reaction.

Amino Acids↗
PubMed1984

[In vitro digestibility of original and modified protein isolate from faba beans].

Protein isolate from Vicia faba (API) and 18 different partial hydrolysates of API as well as plasteins produced from them were submitted to an in vitro digestion with pepsin and pancreatic proteases at their specific pH-optimum. By means of this technique a final value of hydrolysis (49,8 +/- 3,0)% was obtained with all investigated samples, in spite of the different intensity of the preliminary hydrolysis. Two samples with a degree of preliminary hydrolysis of 35% showed with 55% and 56%, respectively, a significantly higher final value. From the results may be assumed that by means of partial hydrolysis and plastein formation only such peptides will be formed which are again hydrolyzable in vitro.

Fabaceae↗