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Biomedical subjects

J Fuchs

Publications and source records attributed to J Fuchs.

At least 199 records · Page 11Linked to original sources

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↗

Elevated serum creatine kinase levels. An early diagnostic sign of acute dissection of the aorta.

Twenty-two patients suffering from acute dissection of the aorta were analyzed for their serum creatine kinase levels within six hours of onset of acute chest pain. Elevated serum levels were found in 14 patients (64%). In five patients, creatine kinase isoenzyme analysis was performed. These five patients showed more than 95% creatine phosphokinase MM isoenzyme of the total creatine kinase level. The finding of elevated levels of total creatine kinase in patients presenting with acute chest pain does not exclude acute dissection of the aorta. Determination of creatine kinase isoenzymes may be helpful in the differential diagnosis of acute chest pain.

Adult↗

Mitochondrial sulfhydryl groups under oligomycin-inhibited, aging, and uncoupling conditions: beneficial influence of cardioprotective drugs.

Uncoupling, oligomycin-inhibited, and aging/swelling conditions comprise three models for mitochondrial dysfunction. In these models, the effects of cardioprotective agents on rat heart mitochondrial membrane -SH reactivity have been studied. For -SH detection two different chromophores were used: dithionitrobenzoate (NbS2) and monobromobimane (MB). The objective of this study is to reveal the influence of three cardioprotective substances against the loss of membrane -SH reactivity: (i) The thiol reagent 2-mercaptopropionylglycine (MPG) prevents the decrease of thiols caused by carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), aging, and oligomycin measured with MB and NbS2, and the diminution by oleate detected with MB. The small amount of MPG (6 nmol/mg protein), necessary for the protection, agrees with oligomycin sensitivity of the -SH groups concerned. (ii) The active metabolite of molsidomine, 3-morpholinosydnonimine (SIN-1), protects against the decrease of thiols by FCCP, oleate, and aging monitored with MB. In the case of oligomycin -SH groups accessible to NbS2 are protected. (iii) Another antianginal drug, isosorbidedinitrate (ISDN) does not protect membrane thiol groups. In contrast to SIN-1, ISDN probably requires enzymatic activation. It is suggested that MPG as well as SIN-1 may help to restitute the original -SH status of the mitochondrial membrane.

Aging↗

Reactivity of mitochondrial sulfhydryl groups toward dithionitrobenzoic acid and bromobimanes under oligomycin-inhibited and uncoupling conditions.

Thiol reactivity was determined in rat heart mitochondria using chromophores of differing polarities: monobromobimane (MB), dithionitrobenzoate (NbS2), and bromobimane-q (MQ). The purpose of this study is to correlate reaction rates of protein thiols in the mitochondrial membrane with the oligomycin-inhibited and uncoupled states: In all cases investigated the reactivity of -SH groups toward MB decreases under the above conditions. In parallel with an increase of their uncoupling activities the uncouplers reduce the reaction rate of thiol groups toward NbS2 and, progressively, toward MQ, indicating differences in sensitivity of thiol groups to uncouplers depending on the polarity of the environment. The pattern of -SH reactivity under inhibition by oligomycin resembles that of carbonylcyanide-p-trifluoromethoxyphenylhydrazone. Functional changes of the mitochondrial membrane probably correlate with reactivity/polarity changes of membrane -SH groups. Masking of membrane thiol groups thus is not specific for uncouplers but is also observed under inhibition with oligomycin.

Animals↗

Isolation and partial characterization of insulin of the honeybee (Apis mellifica).

In the honeybee (Apis mellifica), insulin-like material was partially purified with acid ethanol extractions by a classic method for recovering insulin and following gel filtration on a Sephadex G-50 column. The preparations were characterized by their ability to cross-react with porcine insulin antibodies. Insulin-like biological activity was demonstrated using the insulin bioassay. Stimulation of glucose oxidation or lipogenesis was measured by isolated rat adipocytes. Insulin seems to be more widespread in invertebrates than was previously assumed.

Adipose Tissue↗