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Biomedical subjects

E Junker

Publications and source records attributed to E Junker.

At least 19 recordsLinked to original sources

Upper trapezius muscle conduction velocity during fatigue in subjects with and without work-related muscular disorders: a non-invasive high spatial resolution approach.

The development of fatigue at the muscle fibre level can be assessed in terms of a decrease in conduction velocity (CV). The present study aimed to investigate if work-related muscular disorders in occupations characterised by static loads of long duration affect fatigue resistance in the painful muscle. A group of eight secretaries suffering from bilateral chronic muscle pain in the shoulder/neck region was compared to a group of healthy subjects. The upper trapezius muscle was studied under isometric contractions, holding the arm in the horizontal plane up to the endurance point. Changes in CV estimated at the motor unit level were investigated using a non-invasive high spatial resolution electromyographic (EMG) approach. In addition, the number of motor unit potentials per second (PPS), and the root mean square (RMS) of bipolar signals were assessed, and the results reported as the mean and standard error for each value. Subjects with work-related disorders showed less pronounced changes in CV with respect to healthy subjects. No differences between subjects with and without work-related disorders were encountered for the PPS and RMS. The present findings on CV indicate an increased fatigue-related recruitment of MUs in the painful muscle with respect to a healthy muscle. The fact that this recruitment is not reflected in the PPS and RMS estimates might be due to a fatigue-induced decrease in the firing rate and/or the de-recruitment of fatigued MUs. Furthermore, methodological limitations of the adopted method in the estimation of 'global' parameters such as the PPS and RMS have to be considered.

Adult↗

Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury?

OBJECTIVE: To investigate glutathione and amino acids related to glutathione metabolism in patients with anorexia nervosa in order to test the hypothesis that these patients exhibit a deficiency of glutathione and therefore might be at an increased risk of developing toxic liver injury. DESIGN: Controlled observatory study and case report. SETTING: University Hospital. SUBJECTS: Subjects included 11 female patients with anorexia nervosa and 12 healthy female controls. INTERVENTIONS: Determination of fasting free and total glutathione, homocysteine, vitamins B(6) and B(12) and folic acid in plasma. RESULTS: A 14-y-old patient with a body mass index of 12.6 kg/m(2) presented with markedly elevated transaminases (ALAT >50 x upper limit of normal), and paracetamol was detected in her blood. Patients with anorexia nervosa exhibited lower circulating concentrations of free cysteine (8.9+/-1.5 vs 12.0+/-1.4 micromol/l) and free and total glutathione (5.0+/-1.3 vs 7.1+/-1.2 and 11.2+/-3.8 vs 16.2+/-5.0 micromol/l, respectively). The plasma concentrations of homocysteine (17.5+/-4.9 vs 12.0+/-3.8 micromol/l) and also of glycine (194+/-37 vs 143+/-41 micromol/l) and glutamine (422+/-51 vs 353+/-51 micromol/l) were significantly higher in patients with anorexia nervosa who were not deficient in folic acid, vitamin B(6) and B(12). CONCLUSIONS: Lower plasma concentrations of glutathione suggest lower intracellular concentrations of the tripeptide. Higher homocysteine, glycine and glutamine concentrations point to a decreased utilization of these amino acids for glutathione synthesis and an impairment of trans-sulfuration. Consequently, the capacity of patients with anorexia nervosa to detoxify electrophilic metabolites and reactive oxygen species via glutathione may be impaired.

Acetaminophen↗

Characterization and localization of drug resistance determinants in multidrug-resistant, integron-carrying Salmonella enterica serotype Typhimurium strains.

The genetic background of the antimicrobial resistance of 10 selected multiresistant Salmonella serotype Typhimurium (S. Typhimurium) strains (including the emerging monophasic variant [4,5,12:i:- ]) was investigated. All strains shared class 1 integrons (with seven types of variable regions) and belonged to different lineages (L1-L6) according to their phage types, DNA polymorphisms by XbaI-pulsed-field gel electrophoresis (PFGE), integrons, and/or resistance patterns. The strains were screened for the presence and localization (chromosomal or plasmid) of 32 DNA sequences representing integron-, Tn21-like transposon-, resistance-, and virulence-plasmid genes. Strains belonging to lineage L1 (definitive phage type DT104) carried the 90-kb Salmonella virulence plasmid together with the complete or partial chromosomally located Salmonella Genomic Island 1 (SGI1). All strains belonging to the other five lineages carried their resistance determinants on various resistance plasmids. Two of these strains showed complex plasmid profiles, which included a 95 kb virulence plasmid together with two or four resistance plasmids. Two strains carried a resistance plasmid that lacked the virulence-plasmid-encoding sequences. The remaining two strains carried two different hybrid virulence-resistance plasmids. Twenty-three of the DNA sequences could be assigned to distinct XbaI genomic restriction patterns (PFGE profiles). In this way, the influence of the resistance and virulence plasmids on the PFGE profiles was determined, and several groups of resistance genes could be identified. The data obtained represent a useful epidemiological tool for tracing the emergence and distribution of multiresistant S. Typhimurium worldwide.

Base Sequence↗

Effect of oral and intravenous S,N-diacetylcysteine monoethyl ester on circulating and hepatic sulfhydryls in the Rat.

The role of GSH in the detoxification of reactive metabolites of oxygen and xenobiotics, in gene expression, and as a source of cysteine is well established. Because decreased circulating and intracellular concentrations of GSH might be of pathogenetic relevance in several clinical conditions, there is a growing interest in pharmacological interventions to correct a deranged sulfhydryl status. In this study, the disposition and the effect of S,N-diacetylcysteine monoethyl ester (DACE) on sulfhydryls were investigated after i.v. and intraduodenal (i.d.) administrations to rats. DACE was rapidly hydrolyzed and deacetylated to N-acetylcysteine and cysteine in plasma. High concentrations of cysteine were attained in the circulation and in the liver after i.v. and i.d. administrations of 5 mmol/kg DACE, and physiological levels of GSH in the liver and in plasma increased by 30 and 300%, respectively, with i.v. and i.d. administrations. Incubation of peripheral blood mononuclear cells with 1 mM DACE resulted in higher intracellular concentrations of cysteine and GSH after 24 h than incubations with equimolar concentrations of cysteine, N-acetylcysteine, or oxothiazolidine carboxylic acid, respectively. It is concluded that DACE provides an efficient delivery system for cysteine that markedly increases intra- and extracellular cysteine and GSH after i.v. and i.d. administrations. Because its uptake into cells is probably not dependent on an active transport process, DACE results in higher intracellular concentrations of cysteine than those resulting from other prodrugs of cysteine and cysteine itself. The compound may thus have advantages over other compounds for the correction of a deranged sulfhydryl status.

Acetylcysteine↗

Time course of total cysteine, glutathione and homocysteine in plasma of patients with chronic hepatitis C treated with interferon-alpha with and without supplementation with N-acetylcysteine.

BACKGROUND/AIMS: Glutathione depletion might be one reason for the low rate of response of patients with chronic hepatitis C to treatment with interferon. The aim of the present study was to document the thiol status of patients with chronic hepatitis C and the effects of N-acetylcysteine, a precursor for glutathione synthesis, on the concentrations of total cysteine, glutathione and homocysteine during treatment of chronic hepatitis C with interferon. METHODS: Total cysteine, glutathione and homocysteine in plasma were measured by high performance liquid chromatography, following reduction of disulfides and derivatization of thiols with monobromobimane in a group of 36 patients with chronic hepatitis C, who participated in a multicenter, double-blind, randomized, placebo-controlled clinical trial studying the effect of supplementation with N-acetylcysteine (600 mg three times daily) on the response to treatment with interferon-a (3 MU three times per week) for 6 months. RESULTS: The concentrations of total cysteine (367.0+/-43.9 vs 360.4+/-33.5 nmol/ml, mean+/-95% confidence interval), glutathione (12.5+/-1.6 vs 14.1+/-1.3 nmol/ml) and homocysteine (21.2+/-4.5 vs 19.6+/-5.2 nmol/ml) were similar in patients with chronic hepatitis C and healthy control subjects Supplementation with N-acetylcysteine resulted in measurable concentrations of N-acetylcysteine in plasma, but did not significantly increase the concentrations of cysteine, glutathione or homocysteine. There was no difference between the two treatment groups with regard to transaminases and clearance of HCV RNA. CONCLUSIONS: Circulating concentrations of total cysteine, glutathione and homocysteine are normal in patients with chronic hepatitis C. Supplementation with N-acetylcysteine did not increase the circulating concentrations of total cysteine, glutathione and homocysteine.

Acetylcysteine↗

Chondroitin sulfate proteoglycans in the developing central nervous system. II. Immunocytochemical localization of neurocan and phosphacan.

Using immunocytochemistry, we have compared the distribution of neurocan and phosphacan in the developing central nervous system. At embryonic day 13 (E13), phosphacan surrounds the radially oriented neuroepithelial cells of the telencephalon, whereas neurocan staining of brain parenchyma is very weak. By E16-19, strong staining of both neurocan and phosphacan is seen in the marginal zone and subplate of the neocortex, and phosphacan is present in the ventricular zone and also has a diffuse distribution in other brain areas. Phosphacan is also widely distributed in embryonic spinal cord, where it is strongly expressed throughout the gray and white matter, in the dorsal and ventral nerve roots, and in the roof plate at E13, when neurocan immunoreactivity is seen only in the mesenchyme of the future spinal canal. Neurocan first begins to appear in the spinal cord at E16-19, in the region of ventral motor neurons. In early postnatal and adult cerebellum, neurocan immunoreactivity is seen in the prospective white matter and in the granule cell, Purkinje cell, and molecular layers, whereas phosphacan immunoreactivity is associated with Bergmann glial fibers in the molecular layer and their cell bodies (the Golgi epithelial cells) below the Purkinje cells. These immunocytochemical results demonstrate that the expression of neurocan and phosphacan follow different developmental time courses not only in postnatal brain (as previously demonstrated by radioimmunoassay) but also in the embryonic central nervous system. The specific localization and different temporal expression patterns of these two proteoglycans are consistent with other evidence indicating that they have overlapping or complementary roles in axon guidance, cell interactions, and neurite outgrowth during nervous tissue histogenesis.

Animals↗

Chondroitin sulfate and chondroitin/keratan sulfate proteoglycans of nervous tissue: developmental changes of neurocan and phosphacan.

We have studied developmental changes in the structure and concentration of the hyaluronic acid-binding proteoglycan, neurocan, and of phosphacan, another major chondroitin sulfate proteoglycan of nervous tissue that represents the extracellular domain of a receptor-type protein tyrosine phosphatase. A new monoclonal antibody (designated 1F6), which recognizes an epitope in the N-terminal portion of neurocan, has been used for the isolation of proteolytic processing fragments that occur together with link protein in a complex with hyaluronic acid. Both link protein and two of the neurocan fragments were identified by amino acid sequencing. The N-terminal fragments of neurocan are also recognized by monoclonal antibodies (5C4, 8A4, and 3B1) to epitopes in the G1 and G2 domains of aggrecan and/or in the hyaluronic acid-binding domain of link protein. The presence in brain of these N-terminal fragments is consistent with the developmentally regulated appearance of the C-terminal half of neurocan, which we described previously. We have also used a slot-blot radioimmunoassay to determine the concentrations of neurocan and phosphacan in developing brain. The levels of both proteoglycans increased rapidly during early brain development, but whereas neurocan reached a peak at approximately postnatal day 4 and then declined to below embryonic levels in adult brain, the concentration of phosphacan remained essentially unchanged after postnatal day 12. Keratan sulfate on phosphacan-KS (a glycoform that contains both chondroitin sulfate and keratan sulfate chains) was not detectable until just before birth, and its peak concentration (at 3 weeks postnatal) was reached approximately 1 week later than that of the phosphacan core protein. Immunocytochemical studies using monoclonal antibodies to keratan sulfate (3H1 and 5D4) together with specific glycosidases (endo-beta-galactosidase, keratanase, and keratanase II) also showed that with the exception of some very localized areas, keratan sulfate is generally not present in the embryonic rat CNS.

Aging↗

Supplementation of N-acetylcysteine fails to increase glutathione in lymphocytes and plasma of patients with AIDS.

Because glutathione (GSH) in plasma and lymphocytes of HIV-infected patients is low, adjunct therapy with N-acetylcysteine (NAC) to restore GSH homeostasis has been proposed. To investigate the effect of NAC on the GSH status we treated six patients with AIDS with 1.8 g/day of NAC for 2 weeks. During treatment the plasma concentration of cysteine, a precursor for GSH synthesis, increased significantly. Nevertheless, there was no significant increase in GSH in plasma and peripheral blood mononuclear cells. The failure of sulfhydryl supplementation to increase GSH suggests that the low concentrations of the tripeptide are not the result of an increased consumption secondary to an oxidant stress, but rather the consequence of a decreased rate of synthesis of GSH in HIV infection.

Acetylcysteine↗

Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy.

The sulfhydryl status of cells, particularly the intracellular concentration of glutathione, is a critical determinant of the response of tumor and normal cells to cytostatic drugs. Recent data indicate that the administration of mercaptoethane sulfonate (mesna), which is often combined with ifosfamide, markedly decreases the circulating concentration of total cysteine and could thereby influence the response of the organism to the cytotoxic effects of chemotherapy. The aim of the present study was to assess the effects of the combination of ifosfamide/mesna on sulfhydryl and disulfide homeostasis in tumor patients. Ifosfamide was infused into 14 patients with advanced sarcoma for 5 days at a dose of 2.4-3.2 g/m2 per day together with mesna. The plasma concentrations of total mesna, cysteine, glutathione, and homocysteine were measured before and on days 1 and 6 of the first course of ifosfamide/mesna therapy and prior to the next course of chemotherapy, and the urinary excretion of cysteine and mesna was monitored daily using a high-performance liquid chromatography (HPLC) method. Ifosfamide/mesna resulted in a marked depletion of circulating total cysteine, i.e., cysteine, cystine, and cysteine mixed disulfides [from 245 +/- 36 to 50 +/- 14 nmol/ml (mean +/- 95% CI) on day 6], total glutathione (from 6.9 +/- 1.1 to 2.5 +/- 1.1 nmol/ml), and total homocysteine (from 12.3 +/- 2.1 to 1.4 +/- 1.1 nmol/ml). The values returned to baseline levels prior to the next course of chemotherapy. The urinary excretion of cysteine increased significantly from 0.28 to 1.82 mmol/day on the 1st day, whereupon it returned toward baseline. An average of 62% +/- 6% of the delivered dose of mesna was recovered in urine. The combination of ifosfamide/mesna results in depletion of circulating total cysteine, glutathione, and homocysteine. This marked derangement of sulfhydryl and disulfide homeostasis could modulate the efficacy and toxicity of ifosfamide/mesna therapy.

Adult↗

Mitochondrial function reflected by the decarboxylation of [13C]ketoisocaproate is impaired in alcoholics.

Mitochondria of patients with alcoholic liver disease exhibit structural abnormalities, and mitochondria isolated from animals exposed to ethanol are functionally deficient when studied in vitro. To assess possible functional consequences of these ethanol-associated alterations in vivo, we measured mitochondrial function in alcoholics noninvasively with a breath test. A mitochondrial function, the decarboxylation of ketoisocaproate (KICA), was assessed by measuring the exhalation of 13CO2 following the administration of 1 mg/kg 2-keto[1-13C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the KICA breath test in 12 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 13CO2 and the fraction of the administered dose decarboxylated in 120 min were both significantly lower in alcoholics than in healthy controls and patients with nonalcoholic liver disease. In alcoholics, KICA decarboxylation was impaired in the presence of normal quantitative liver function tests such as the aminopyrine breath test and galactose elimination capacity, indicating that KICA decarboxylation does not simply reflect a decreased functional hepatic mass. The enrichment of circulating KICA with [13C]KICA was similar in alcoholics and controls, indicating that a decreased bioavailability or an increased dilution of labeled KICA cannot account for the decreased exhalation of 13CO2. It is concluded that mitochondrial function as reflected by KICA decarboxylation is impaired in chronic alcoholics. The functional impairment is specific for ethanol abuse and not a reflection of decreased global hepatic function. KICA decarboxylation could thus be useful as a marker for excessive ethanol consumption.

Adult↗

[Current status of tuberculosis in Vienna].

The increasing number of HIV infected persons on the one hand, and a continuously increasing number of immigrants from countries with high incidence of active tuberculosis on the other hand have an influence on the incidence of tuberculosis in Vienna in general. Nevertheless people of Austrian origin have a decreasing chance of getting tuberculosis if they are not infected with HIV. Screening of risk groups (e.g. immigrants and HIV infected persons) is a good tool to prevent a further epidemic outbreak of tuberculosis in Austria.

AIDS-Related Opportunistic Infections↗

[Guidelines for tuberculin diagnosis. Consensus paper of the Austrian Society of Lung Diseases and Tuberculosis].

Three facts made new guidelines for tuberkulin skin-testing in Austria necessary: the low incidence of tuberculosis, the stop of routinously performed BCG-vaccination in neonates and the increasing importance of infections with atypical mycobacterials. According to analogous guidelines in Germany, Switzerland, the USA, and other countries and related to the Austrian specifities in tuberculosis situation the authors present guidelines thought as a consensus-paper of the Austrian Societies for Lung Diseases and Tuberculosis and for Pediatrics. The most essential guideline include that tuberkulin skin testing as a screening method with multiple puncture tests cannot further be recommended, and that the Mendel-Mantoux-test is the gold standard test. Only this test is sensitive and specific enough for case-finding and for giving indication to start a preventive or curative chemotherapy. The cut-off size of reactive areas for positive Mendel-Mantoux tuberculin-reaction are presented in this paper and also the consequences what is to decide in relationship to the test result.

Adolescent↗

Depletion of circulating cyst(e)ine by oral and intravenous mesna.

The sulfhydryl status of normal and tumour cells is critically important in determining their susceptibility to various cytostatic agents. As a sulfhydryl compound, mesna (sodium 2-mercaptoethane-sulfonate) which is used in large doses to prevent haemorrhagic cystitis associated with certain chemotherapeutic regimens might derange cellular thiol homeostasis. In order to investigate the effects of mesna on the concentrations of thiols in plasma, cysteine, glutathione and their disulfides were measured by HPLC following the oral and intravenous administration of mesna to healthy volunteers. After 7.3 mmol mesna i.v. free cysteine rose from 8.2 (95% CI 7.0-9.4) nmol ml-1 to 53.6 (47.4-59.8) nmol ml-1 at 5 min, most likely due to reduction of circulating cystine by the sulfhydryl drug. This initial rise was followed by a marked decrease of total cyst(e)ine in plasma from 276 (215-337) nmol ml-1 to a nadir of 102 (89-115) nmol ml-1 between 30-120 min after infusion, most likely due to an increased uptake of cysteine into cells and an increased urinary excretion of cyst(e)ine. Qualitatively similar changes were seen after oral mesna. The present data indicate that mesna depletes circulating cyst(e)ine and may thereby markedly alter the sulfhydryl status of cells in vivo although the drug itself is not taken up by most cells.

Administration, Oral↗

Increased concentrations of omega-3 fatty acids in milk and platelet rich plasma of grass-fed cows.

Epidemiological data indicate that omega-3 fatty acids protect from cardiovascular diseases and hyperlipidemia. Cold water fish is the major recognized source of omega-3 fatty acids but fish is not a staple food in many countries. Since terrestrial green plants may also represent a source of omega-3 fatty acids we tested the hypothesis that platelet rich plasma and milk from cows feeding exclusively on green grass contains more omega-3 fatty acids than milk from cows fed conserved grass. The relative concentrations of linolenic acid (18:3) and eicosapentaenoic acid (20:5) and the ratio of eicosapentaenoic acid to arachidonic acid (20:4) which is critical for the formation of omega-3 derived eicosanoids were significantly higher in milk from grass fed cows. Similar changes were seen in the fatty acid composition of platelets. Half a liter of milk from grass-fed cows provides approximately 191 mg 18:3 and 14 mg 20:5. In this regard milk from grass fed cows may be nutritionally superior to milk from cows eating conserved grass.

Analysis of Variance↗

[Molybdenum as an air pollutant].

Investigations into the reasons for the retarded growth and discolouration of a small area of a field of rape situated on the outskirts of Vienna revealed higher than normal levels of molybdenum in the soil (up to 430 micrograms/l) and in the water (up to 9.7 mg/l). The source of the pollution was traced to a neighbouring industrial plant that was emitting the metal via the chimney stack. A review of the literature on the toxic effects of molybdenum in general and as an air pollutant in particular is provided. This shows that, in contrast to animals, this effect is relatively small in humans and plants. Nevertheless, the occupation-related inhalation of the metal has been shown to be associated with pneumoconiosis and gout-like symptoms.

Air Pollutants↗

[Total cholesterol findings in Austria--an overview of epidemiologic studies].

Hyperlipoproteinaemia is the most important public health risk factor for ischaemic heart disease. This publication gives a review of six Austrian epidemiological studies covering more than 87,000 people in all. The results are not representative for Austria, but give a picture of the epidemiology in Austria. Mean values were calculated age-standardized (age-adjusted when ten-year age groups are registered) to the Austrian population of 1985, for the age group 20 to 79 years. This age range covers 99.77% of the adult male population aged 20 or more, and 95.70% of the women. Mean total cholesterol level for the six studies is 224.2 mg/dl in men and 227.3 mg/dl in women. These results are similar to those of a representative study in the province of Vorarlberg in western Austria (220.0 mg/dl, and 227.4 mg/dl respectively). Variation range is 20.4 mg/dl in men, and 22.5 mg/dl in women; the coefficient of variation is 3.9% in both, men and women.

Adult↗

[Incidence of bronchitis in Vienna. Studies on the detection of the incidence of chronic bronchitis in Vienna].

Exact epidemiological studies about the frequency of respiratory tract disease are difficult to perform. Vague definitions and inhomogeneous examination modalities render a comparison of results difficult. Some statements can be made. Chronic bronchitis occurs more often in males. The significance increases with advancing age. Smoking habits are of utmost importance. Indoor and outdoor air pollution is without doubt a significant agent in the etiology of chronic respiratory disease.

Adult↗

[Incidence of respiratory tract diseases in children].

Children living in areas with increased levels of air pollution seem to suffer more frequently from respiratory tract disease. In preexisting respiratory tract disease air pollution may serve as an additional aggravating factor.

Air Pollution↗