Ultraviolet irradiation and the skin antioxidant system.
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Animals↗
Biomedical subjects
J Fuchs
Publications and source records attributed to J Fuchs.
Escherichia coli thioredoxin folds into two compact forms of different stability to urea denaturation.
The urea-induced denaturation of Escherichia coli thioredoxin and thioredoxin variants has been examined by electrophoresis on urea gradient slab gels by the method of Creighton [Creighton, T. (1986) Methods Enzymol. 131, 156-172]. Thioredoxin has only two cysteine residues, and these form a redox-active disulfide at the active site. Oxidized thioredoxin-S2 and reduced thioredoxin-(SH)2 each show two folded isomers with a large difference in stability to urea denaturation. The difference in stability is greater for the isomers of oxidized than for the isomers of reduced thioredoxin. At 2 degrees C, the urea concentrations at the denaturation midpoint are approximately 8 and 4.3 M for the oxidized isomers and 4.8 and 3.7 M for the reduced isomers. The difference between the gel patterns of samples applied in native versus denaturing buffer, and at 2 and 25 degrees C, is characteristic for the involvement of a cis-proline-trans-proline isomerization. The data very strongly suggest that the two folded forms of different stabilities correspond to the cis and trans isomers of the highly conserved Pro 76 peptide bond, which is cis in the crystal structure of oxidized thioredoxin. Urea gel experiments with the mutant thioredoxin P76A, with alanine substituted for proline at position 76, corroborate this interpretation. The electrophoretic banding pattern diagnostic for an involvement of proline isomerization in urea denaturation is not observed for oxidized P76A. In broad estimates of delta G degree for the native-denatured transition, the difference in delta G degree (no urea) between the putative cis and trans isomers of the Ile 75-Pro 76 peptide bond is approximately 3 kcal/mol for oxidized thioredoxin and approximately 1.5 kcal/mol for reduced thioredoxin. Since cis oxidized thioredoxin is much more stable than trans, folded oxidized thioredoxin is essentially all cis. In folded reduced thioredoxin, cis and trans interconvert slowly, on the minute time scale at 2 and 25 degrees C. In the absence of urea, the folded reduced thioredoxin is less than a few percent trans. Three additional mutants with additions or substitutions at the active site also show electrophoresis banding patterns consistent with a difference in stability between cis and trans isomers.
Bacterial Proteins↗
Atrial fibrillation. Cause and time of onset.
To characterize groups of patients presenting at the emergency room with atrial fibrillation (AF) according to the various causes of AF and the time of its onset, 704 medical files from the Beilinson Medical Center (Petah Tikva, Israel), during an eight-year period, were reviewed. Two thirds of all patients converted to sinus rhythm (SR) within a seven-day in-hospital treatment. The most frequent causes associated with AF were atherosclerotic cardiovascular disease, 55%; rheumatic heart disease, 22.8%; chronic obstructive pulmonary disease, 2.8%; Wolf-Parkinson-White syndrome, 2.6%; and thyrotoxicosis, 2.6%. There was a relatively large group of idiopathic AF (4.5%). Best convertors to SR were patients with idiopathic AF (93.9%), then patients with Wolf-Parkinson-White syndrome (88.8%), followed by atherosclerotic cardiovascular disease (71.6%), and thyrotoxicosis (63.2%). Patients with rheumatic heart disease and chronic obstructive pulmonary disease had the lowest percentage of successful conversion to SR--46% and 55%, respectively. We conclude that there are differences regarding gender, age, and possible conversion of AF to SR according to the different causes of AF.
Aged↗
Drug-related syncope.
The records of 483 patients admitted to the emergency room because of syncope were reviewed. Forty-one patients were found to have drug-related syncope. Thirty-nine experienced syncope related to drugs administered for cardiovascular disease. The most frequently associated diseases were anginal syndrome (22 patients), hypertension (13 patients), and a history of myocardial infarction (6 patients). Thirty-eight patients experienced symptomatic orthostatic hypotension following drug taking (nitrates in 19 patients, beta blockers in 10 patients, nifedipine in 3 patients, prazosin and quinidine in 2 patients each, methyldopa and verapamil in 1 patient each). One patient developed complete heart block as a result of digoxin intoxication. Two patients developed the characteristic picture of anaphylactic reaction (1 with ampicillin, 1 with dipyrone). During one-year follow-up, without the offending medications, no further syncopal episodes were reported by these patients. We conclude that drug-related syncope was more common among our patients with syncope than had been reported previously. It is suggested that drug-related syncope should be taken into consideration in any patient with syncope who is treated by any of the above-mentioned drugs.
Adult↗
Does determination of serum aspartate aminotransferase contribute to the diagnosis of acute myocardial infarction?
Values for total lactate dehydrogenase (LD), LD isoenzymes, and serum aspartate aminotransferase (AST) were determined in 150 patients with acute myocardial infarction (AMI) and 130 non-AMI patients 24, 48, and 72 hours after admission. The authors assessed the diagnostic yield of a single determination of AST, LD, and three LD isoenzymes tests: LD-1 greater than LD-2; LD-1 greater than 90 U/L; LD-1/LD greater than 0.4. They also assessed the diagnostic accuracy of combined determination of AST with LD and AST with each of the above three LD isoenzymes tests. The efficiency of single determination of AST was better than that of LD (88% vs. 80%, 48 hours after admission). The most efficient single test for diagnosing AMI was the LD-1 greater than 90 U/L test (92%, 48 hours after admission). The efficiency of the combined AST/LD test was better than that of a single determination of each of the two enzymes (90% vs. 88% and 80%, 48 hours after admission). The highest efficiency was achieved, however, with combined determination of AST and any of the three LD isoenzymes tests. It was found to be more efficient than single determination of each of the LD isoenzymes tests (95.5-96% vs. 89-92.5%) and more efficient than the combined determination of the AST/LD test (95.5-96% vs. 89-90%). The authors conclude that AST should be determined in every patient with suspected AMI because its determination may contribute to the diagnostic yield of LD isoenzymes tests, especially in patients with AMI admitted 48-72 hours after onset of symptoms, when creatine kinase declined to near normal values.
Adult↗
Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation.
Antioxidants may play a significant role in ameliorating or preventing photobiologic damage in skin that could lead to cutaneous disorders such as cancer and premature aging. The objective of this study was to assess the acute cutaneous enzymic and nonenzymic antioxidant response to a single exposure of large fluence (300 mJ/cm2) ultraviolet radiation (greater than 280 nm) in hairless mice. This treatment caused an immediate and statistically significant inhibition of glutathione reductase and catalase activity. Glutathione peroxidase and superoxide dismutase were not affected. Glutathione levels decreased and, conversely glutathione disulfide concentrations increased. A slight depletion of the total glutathione was observed, while the content of total ascorbic acid did not change. The lipophilic antioxidants alpha-tocopherol, ubiquinol 9 and ubiquinone 9 also decreased significantly, and the concentration of malondialdehyde remained constant. The free radical scavenging activity of epidermis, as assessed by reduction of the stable, cationic nitroxide radical [2,2,6,6-tetramethyl-1-piperidinoxy-4-(2',4',6'-trimethyl) methylpyridinium perchlorate] was considerably inhibited. The study indicates that immediately after exposure to a large fluence of ultraviolet radiation the enzymic and nonenzymic antioxidant capacity of skin decreases significantly.
Animals↗
Free radical reduction mechanisms in mouse epidermis skin homogenates.
Scavenging mechanisms for persistent free radicals were investigated using nitroxide-type radicals as model compounds. The free radical reducing activity of a) isolated thioredoxin reductase, a flavin containing oxidoreductase, b) skin homogenates, and c) the epidermis of hairless mice was studied by electron spin resonance spectroscopy. In all three systems, reduction rates of different classes of nitroxide free radicals exhibited the following order: oxazolidinoxy greater than piperidinoxy greater than dihydropyrroloxy. The main reductant for piperidinoxy radicals in mouse skin homogenate is ascorbic acid. Other reducing activities were stimulated by NAD(P)H and could be inhibited by N-ethyl maleimide, suggesting involvement of thiol-dependent processes. Mammalian thioredoxin, a competitive inhibitor of nitroxide reduction by thioredoxin reductase, significantly stimulates nitroxide scavenging in skin homogenate. Thioredoxin reductase did not significantly participate in nitroxide reduction in skin homogenates. At the surface of mouse epidermis a cationic dihydropyrroloxy nitroxide, which was stable in the presence of mammalian thioredoxin reductase was readily reduced. The epidermal reduction was inhibited by zinc, N-ethyl maleimide, and by heat (70 degrees C, 5 min). At least for mouse epidermis, reduction of a variety of nitroxides is a complex phenomenon involving enzymatic and nonenzymatic mechanisms and cannot be used as a specific assay for an enzyme, e.g., thioredoxin reductase. The study indicates the epidermis contains an effective antioxidant system that scavenges ascorbate-sensitive piperidinoxy nitroxides as well as more reducing radicals exemplified by dihydropyrroloxy nitroxides.
Animals↗
Investigations of anthralin free radicals in model systems and in skin of hairless mice.
The antipsoriatic compound anthralin (1.8-dihydroxy-9-anthrone) is converted in skin into several oxidized products, including persistent free radicals that are not well characterized. Anthralin oxidation was investigated by electron spin resonance spectroscopy in a biological system and in a chemical system. Free radical formation in the skin of hairless mice is reduced by the antioxidant tocopherol. The data indicate that tocopherol acts by interfering with free radical formation rather than by scavenging persistent anthralin radicals directly. The skin radicals do not correspond to 10-anthranyl, the initial paramagnetic anthralin oxidation product. Similar radicals obtained in skin are formed by anthralin exposed to ultraviolet light or alkaline solution and by mitochondria and microsomes. The pertinent skin radical is attributed to products derived from anthralin dark structures, the final oxidation products of anthralin. It is suggested that resonance stabilized, paramagnetic polycyclic hydrocarbons are the compounds detected. Their stability and low reactivity indicate a low potential for cutaneous irritation and tumor promotion. Reactive oxygen species, which have been reported to be formed concomitantly during oxidation of anthralin, and the initially formed highly reactive 10-anthranyl radical are more potent candidates for mediating tumor promotion and inflammation.
Animals↗
Acute effects of near ultraviolet and visible light on the cutaneous antioxidant defense system.
Reactive oxygen species are considered to play an important role in cutaneous pathology. Enzymic and non-enzymic antioxidants can prevent oxidative damage but may be overcome by strong pro-oxidative stimuli. The acute effect of a single exposure to near ultraviolet (UVA)/visible radiation (greater than 320 nm) on various skin antioxidants was examined in hairless mice immediately after irradiation. Impairment of cutaneous catalase and glutathione reductase activity was observed. Superoxide dismutase and glutathione peroxidase were not significantly influenced. Inhibition of catalase may render skin more susceptible to the damaging effects of hydrogen peroxide and its reaction products such as the hydroxyl radical. Partially diminished glutathione reductase activity is not accompanied by a change in reduced/oxidized glutathione level immediately after irradiation. There was a tendential (not statistically significant) decrease in cutaneous tocopherol, ubiquinol + ubiquinone 9 and ascorbic acid levels, either indicating direct photodestruction or consumption by reaction products of photooxidative stress. This partial impairment of the cutaneous antioxidant defense system by near ultraviolet/visible light, showing that the most susceptible component in skin is catalase, suggests possible pharmacological interventions.
Animals↗
Glaucoma prevalence in the Nordic countries. Estimates based on glaucoma drug consumption.
Glaucoma prevalences in the 5 Nordic countries are estimated on basis of a) wholesale of glaucoma medicaments (Denmark, Iceland, Norway, and Sweden) and b) registered glaucoma patients receiving free medication (Finland). Prevalences are compared nationally and internationally. The estimated glaucoma prevalence is highest in Norway (2.19% related to the population greater than 40 years), lowest in Denmark (0.76% in the same age group). The prevalence in Iceland, Finland, and Sweden are 2.0, 1.94, and 1.55%, respectively. We suggest that the relatively large differences in glaucoma prevalence between the countries may be explained by geographical differences in occurrence of capsular glaucoma. The sources of error concerning prevalence estimates based on glaucoma drug consumption are discussed. Pre-supposing a balance numerically between undetected glaucoma cases and patients receiving glaucoma medication without really having glaucoma, the glaucoma drug sales statistics may be taken as fair indicators of glaucoma prevalence.
Adult↗
Diagnosis and characteristics of lone atrial fibrillation.
Thirty-two patients with LAF were studied. Nineteen (59 percent) were male subjects. Mean age was 46.8 years. They were followed up for 2 to 16 years. On admission, most patients (94 percent) were symptomatic and had palpitations, nine had nonspecific chest pain, and five had syncope or near syncope. Left atrial size measured by echocardiography was less than 40 mm in all patients. During the follow-up period, only one patient had a complication, ie, cerebral embolism. We conclude that LAF may be regarded as a relatively benign form of AF. According to our study, one of its features is left atrial size not larger than 40 mm in echocardiography.
Adult↗
Myocardial protection by 2-mercaptopropionylglycine during global ischemia in dogs.
The hypothesis was tested, if the addition of 2-mercaptopropionylglycine (MPG, Thiola) to a crystalloid cardioplegic solution provides superior myocardial protection as assessed by biochemical and morphological parameters. Five mongrel dogs underwent a 60-min hypothermic cardioplegic arrest (untreated group). In six dogs, MPG (1.5 mmol/l) was added to the crystalloid cardioplegic solution (treated group). Thereafter a reperfusion phase of 60 min was established. At the end of the reperfusion phase samples for mitochondrial respiration parameters and for mitochondrial energization were collected. Samples for ultrastructure and negative staining were taken at the end of ischemia, and after 15, 30 and 60 min of reperfusion. Hearts which were treated with the MPG-enriched cardioplegic solution showed a better ultrastructure (1 (1/1) vs 2 (2/2), p less than 0.001) and superior preservation of the mitochondrial ATPases (2.4 +/- 2.0 versus 8.4 +/- 2.7, p less than 0.05) as compared to the untreated group at the end of ischemia. At the end of reperfusion, mitochondrial respiration, and energization of the mitochondria was improved significantly with the addition of MPG as compared to the untreated group.
Adenosine Triphosphatases↗
[Determination of gastric bicarbonate secretion in the human without acid suppression].
Gastric CO2/HCO3 was determined in absence of simultaneous inhibition of acid secretion by intra- and extragastric pCO2/pH measurements in 23 persons and calculated using the equation of Henderson-Hasselbalch. pCO2 was measured with use of a new electrode. The characteristics of the CO2 selective electrode membrane were tested in vitro. The CO2 selective membrane proved to be stable against 0.1 n HCl, gastric fluid with a pH of 1, and bile as well as mechanical irritations. 96.8 +/- 0.52% of given amounts of bicarbonate were detected in test fluids ranging in pH from 2.5-7.1. In gas and fluid, a linear relationship between given and measured bicarbonate of y = 0.97 x +1.03 with a correlation coefficient of 0.99 was observed. In vivo at pH less than 6, the intragastric pCO2 was significantly higher than that in venous blood. CO2 diffusion could be prevented by equilibration of intragastric pCO2 with venous pCO2. pCO2 was then measured in fluid as well as in reaspirated gas. Thus 94.6 +/- 8.8%, HCO3- that had been instilled intragastrically, could be detected. Without equilibration and resultant volume increase of the gas phase, bicarbonate secretion was 296.4 +/- 41.9 mumol/h under basal conditions and 520.8 +/- 252.8 mumol/h after acid stimulation. With equilibration, a bicarbonate secretion of 574.4 +/- 66.7 and 754.4 +/- 81.2 mumol/h was observed during basal and stimulated acid secretion. Our results indicate that bicarbonate measurements in absence of acid suppression require determination of CO2 in the fluid as well as in the gas phase.
Bicarbonates↗
Lactate dehydrogenase isoenzyme patterns in serum of patients with metastatic liver disease.
Total lactate dehydrogenase (LD, EC 1.1.1.27) and LD isoenzymes were determined in serum of 170 patients with metastatic liver disease, 35 of whom had multiple metastatic sites. Overall, values of LD were above normal for 78% of the 170 patients. Half of the patients had an isomorphic pattern of LD isoenzymes (i.e., relative increase in all five isoenzymes); the other half had an increased LD-4,5 pattern, mostly a solitary increase in LD-5 only. Of those patients with normal LD values, 92% had the increased LD-4,5 pattern, whereas 70% of patients with LD values greater than 350 U/L had an isomorphic pattern of LD isoenzymes. All 35 patients with multiple metastatic sites had LD activity greater than 350 U/L; in the majority of them (74%) it was greater than 500 U/L; in 31 (89%), the increase was isomorphic. The diagnostic efficiency of the combined LD greater than 225 U/L (upper limit of normal) and increased LD-4,5 test results was much better than that of LD greater than 225 U/L alone (93% vs 74%). We conclude that serum LD and LD isoenzymes should be determined in every patient with suspected liver metastatic disease. The isomorphic pattern of LD isoenzymes is apparently associated with higher values for total LD and was common among the patients with multiple metastatic sites.
Aged↗
Patterns of lactate dehydrogenase isoenzymes 1 and 2 in serum of patients performing an exercise test.
Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity and LD isoenzymes were determined in serum from 56 patients and 40 healthy subjects before and 24, 48, and 72 h after they performed an exercise test. The mean (for all four times) total LD activity concentration and proportion of LD-2 were within the normal range for all 96 subjects. Mean LD-1 values for serum, although within the normal range in all subjects, were significantly higher in patients with positive exercise test results than in subjects with negative results: 75 (SD 12) U/L in 35 patients with ST depression greater than 2 mm; 63 (SD 14) U/L in 16 patients with ST depression of 1-2 mm; 43 (SD 11) U/L in subjects with negative test results, by 48 h after the test. The LD 1:2 ratio was also markedly higher in the group of patients with positive test exercise results, especially in those with ST depression greater than 2 mm (1.02, SD 0.06), compared with those subjects with negative results (0.60, SD 0.04). A similar trend was also found 24 and 72 h after the exercise test. We conclude that exercise-myocardial ischemia may lead to an increased LD 1:2 ratio in serum, and demonstrate a correlation between the degree of ischemia and the LD 1:2 ratio. Determination of the LD 1:2 ratio, even in the presence of normal total LD activity, may assist in the clinical evaluation of patients performing an exercise test.
Adult↗
Changes in creatine kinase activity in the course of acute myocardial infarction.
Peak activity of creatine kinase (CK; EC 2.7.3.2) and its decline were determined in 380 patients with acute myocardial infarction (AMI) whose CK values had peaked after admission to the hospital. During hospitalization, 26 patients either died (14 patients) or experienced nonfatal re-infarction (12 patients). In 22 of these 26 patients CK activity decreased by less than 50% within 48 h after the peak value was measured. In all patients who did not die or develop re-infarction, CK activity decreased by greater than 50% during the 48 h after the peak. Evidently the rate of decline of CK (i.e., whether more than or less than 50%) from its peak value during the 48 h after AMI may be helpful in assessing which patients are at high risk for developing re-infarction or dying.
Adult↗
Degree of myopia in relation to intelligence and educational level.
Intelligence test scores and educational levels were compared for 5943 myopic and 9891 non-myopic 18-year-old men being drafted for military service in Denmark. The former were grouped by degree of myopia, in the range -0.25 diopters (D) to -7.75 D, according to the power of correcting lenses required. Myopes of all degrees had significantly higher test scores and educational levels than non-myopes. However, the relation of these two variables to degree of myopia was not linear; for both variables there were no significant differences among myopia groups in the range -2.0 to -7.75 D. Whereas factors associated with intelligence and education seem to be important in triggering the onset of myopia, they seem to be much less important in determining the degree to which myopia progresses.
Adolescent↗
Pyruvate carboxylase from Pseudomonas citronellolis: shape of the enzyme, and localization of its prosthetic biotin group by electron microscopic affinity labeling.
Pseudomonas citronellolis is known to contain a pyruvate carboxylase with an alpha 4 beta 4 composition. All the other pyruvate carboxylases investigated so far are made up of four seemingly identical subunits. Nevertheless, this exceptional pyruvate carboxylase exhibits a size and overall shape similar to other pyruvate carboxylases. Electron microscopic affinity labeling with avidin revealed that the prosthetic biotin groups (one per alpha beta unit, i.e. four per enzyme particle) are located close to the inter-unit junctions of pairs of alpha beta units making up the enzyme. This position of the prosthetic biotin groups is very similar to the location of the biotin in the other carboxylases.
Biotin↗