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Biomedical subjects

J Fiedler

Publications and source records attributed to J Fiedler.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of peroxisome proliferator-activated receptor alpha activation on leukotriene B4 metabolism in isolated rat hepatocytes.

Leukotriene B4 (LTB4) is a potent mediator of inflammation that recruits granulocytes to the site of injury during the inflammatory response. The biological activity of LTB4 is terminated by its metabolism into inactive metabolites. Recent studies have suggested that LTB4 may have additional activity as an endogenous ligand for the transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Based on the data presented, a model was proposed in which LTB4 acts in a negative feedback manner by inducing the transcription of genes involved its own metabolism. In the present study the effect of PPARalpha activation on LTB4 metabolism was directly investigated. Primary cultures of rat hepatocytes were treated with LTB4 or the PPARalpha agonist WY-14,643, and LTB4 metabolism was assessed by measuring levels of LTB4 and the formation of LTB4 metabolites. In addition, the effect of PPARalpha activation on levels of acyl-CoA oxidase mRNA and expression of CYP4F proteins, which are specific omega-hydroxylases for LTB4, was determined. Treatment of hepatocytes with WY-14,643, but not LTB4, was found to increase acyl-CoA oxidase mRNA and enhance expression of rat hepatic CYP4F proteins and CYP4A1. Neither WY-14,643 nor LTB4 caused an increase of the basal levels of LTB4 metabolism, and no novel metabolites were observed. These results do not support the hypothesis that a pathway of negative feedback regulation of LTB4 metabolism involving PPARalpha exists in hepatocytes, because activation of PPARalpha by LTB4 or other PPARalpha agonists did not correlate with an increase in LTB4 metabolism.

Animals↗
PubMed2001

A proposed vitamin A supplementation programme for South Africa--design, coverage and cost.

BACKGROUND: A national survey of the micronutrient status of preschool children in South Africa established that vitamin A deficiency is a significant public health problem, requiring urgent attention. A number of immediate and long-term interventions were recommended, including the introduction of a vitamin A supplementation programme and a food fortification programme. OBJECTIVES: The aim of the study was to assist in the development and implementation of a national vitamin A supplementation programme at primary health care facilities for mothers and children. This was achieved by determining the design, coverage and cost of a national primary health care facility vitamin A supplementation programme. METHODS: Based on an extensive review of the literature, the main components of a primary health care facility vitamin A supplementation programme were identified. The annual, recurrent costs of each of the programme components were estimated for the nine provinces in South Africa. Immunisation coverage rates were used as a proxy for estimating the coverage of the programme. RESULTS: The main components of the programme were identified as: promotion, training, purchase of vitamin A capsules, distribution of vitamin A capsules to primary health care facilities, distribution of capsules to the programme beneficiaries, and monitoring and evaluation. The programme would operate from primary health care facilities and would target all children between 6 and 24 months of age and newly delivered mothers. It was estimated that the programme would cover 74% of children and 95% of postpartum women nationally. The total annual, recurrent cost of the national programme was estimated at R16.4 million. The bulk of the costs would include personnel costs, comprising 68% of the total costs. Other costs included promotion (27%), vitamin A capsules (4%) and training (1%). The cost of the programme would vary significantly by province, but the provinces' average total cost per beneficiary would be similar. CONCLUSION: A primary health care facility vitamin A supplementation programme has been designed and accompanied by an estimated overall cost and coverage for implementation. The findings of the study showed that the programme would be financially feasible and would reach the majority of children under 24 months of age. It is recommended that further research be undertaken to extend the programme to the more 'hard to reach' population using other strategies such as mass immunisation campaigns.

Adolescent↗
PubMed2001

[FMD and international trade relations--conditions and consequences].

The outbreak of foot-and-mouth disease in several member states of the European Union this year made the risks linked to this epidemic pretty clear to the public. In this connection, the possibility of vaccinations was controversially discussed not only among experts. Therefore it has to be taken into consideration that every kind of vaccination leads to economic consequences, which have to be taken into account when making such a decision. It is an illusion assuming that there will be a return to prophylactic vaccination. However in certain situations such emergency vaccination have to be available as an additional measure of control. Because of present decisions of the European Commission any consequences connected therewith are known. Thereby the EU regulations coincide with those of the Office International des Epizooties (OIE) and make the extent of restrictions after vaccination calculable. The assessment leads to the conclusion that preventive measures, rapid and successful eradication of FMD outbreaks as well as the option of emergency vaccination have to be followed as an overall conception.

Animals↗
PubMed2000

Metal vs ligand reduction in complexes of 1,3-dimethylalloxazine (DMA) with copper(I), ruthenium(II), and tungsten(VI). Crystal structures of (DMA)WO2Cl2 and (bis(1-methylimidazol-2-yl)ketone)WO2Cl2.

The complexes [(DMA)Cu(PPh3)2](BF4) (1) (DMA = 1,3-dimethylalloxazine), [(DMA)Ru(bpy)2](PF6)2 (2), and (DMA)WO2Cl2 (3) were obtained as O4-N5-chelated species, as evident from an X-ray crystal structure analysis for 3 and from spectroscopy (NMR, IR, and UV-vis spectroelectrochemistry) for 1 and 2. The tungsten(VI) center in 3 has its oxide ligands in a cis/equatorial position and the chloride ligands in a trans/axial position; it also exhibits a relatively short bond to O4 (2.232(3) A) and a very long bond to N5 (2.462(3) A). Comparison with the new structurally characterized compound (BIK)WO2Cl2 (4) (BIK = bis(1-methylimidazol-2-yl)ketone), which has W-N bonds of about 2.30 A, confirms the unusual length of the W-N bond in 3, probably caused by repulsion between one of the oxo ligands and the peri-hydrogen atom (H6) of DMA. One-electron reduction of the complexes occurs reversibly at room temperature in THF (1, 2) or at 198 K in CH2Cl2 (3). EPR spectroscopy reveals that this process is ligand-centered for 1 and 2 but metal-centered for 3. Density functional methods and ab initio methodology are used to illustrate the correspondence in spin distribution between the radical anion pi systems of alloxazine and isoalloxazine ("flavosemiquinone").

Journal Article↗
PubMed2000

Electron paramagnetic resonance and spectroscopic characteristics of electrogenerated mixed-valent systems [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+ (M = Rh, Ir; L = 2,5-diiminopyrazines) in relation to the radicals [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ and [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+.

Electrochemical reduction of the dinuclear [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]2+ ions (M = Rh, Ir; L = 2,5-bis(1-phenyliminoethyl)pyrazine (bpip) and 2,5-bis[1-(2,6-dimethylphenyl)iminoethyl]pyrazine (bxip)) proceeds via the paramagnetic intermediates [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ (L = bpip) or [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+ (L = bxip) and [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+. Whereas the first is clearly a radical species with a small g anisotropy, the chloride-free cations are distinguished by structured intervalence charge transfer (IVCT) bands in the near-infrared region and by rhombic electron paramagnetic resonance features between g = 1.9 and g = 2.3, which suggests considerable metal participation at the singly occupied MO. Alternatives for the d configuration assignment and for the role of the bisbidentate-conjugated bridging ligands will be discussed. The main difference between bpip and bxip systems is the destabilization of the chloride-containing forms through the bxip ligand for reasons of steric interference.

Journal Article↗
PubMed2000

Serum leptin levels in patients with hyperlipidemias.

Leptin is a protein hormone produced by adipocytes that reflects the body fat content. The aim of our study was to compare serum leptin levels in randomly selected untreated males and females with hypercholesterolemia and combined hyperlipidemia and in healthy control subjects matched for age and body mass index and to study the relations between leptin and serum lipids and lipoproteins. No statistically significant differences in serum leptin levels were found between the male control group (5.26 +/- 2.81 ng/mL(-1)) and the male group with hypercholesterolemia (8.16 +/- 3.85 ng/mL(-1)) or combined hyperlipidemia (7.51 +/- 4.83 ng/mL(-1)) and between the female control group (13.0 +/- 8.12 ng/mL(-1)) and the female group with hypercholesterolemia (15.36 +/- 8.89 ng/mL(-1)) or combined hyperlipidemia (18.63 +/- 10.15 ng/mL(-1)). Leptin concentration in male group with hypercholesterolemia did not differ significantly from the female control group; in the other male groups, leptin levels were significantly lower than those of the other female groups. Serum leptin levels in all studied groups except for the male group with hypercholesterolemia positively correlated with body mass index. Serum leptin levels correlated negatively with high-density lipoprotein cholesterol in the female group with hypercholesterolemia (r = -0.67, P < 0.01) and the male group with combined hyperlipidemia (r = -0.56, P < 0.01). A positive correlation between serum leptin and high-density lipoprotein cholesterol (r = 0.67, P < 0.01) and between leptin and lipoprotein (a) (r = 0.71, P < 005) was found in female group with combined hyperlipidemia. No other significant relationships between leptin and serum lipids or lipoproteins were found. We conclude that serum leptin levels in patients with hyperlipidemias do not significantly differ from those healthy control subjects matched by age and body mass index.

Adult↗
PubMed2000

[The spectrum of lipids in the intrauterine growth retarded fetus and in the parents].

OBJECTIVE: The aim of this study was to determine the relationship between the parameters of individual serum lipids and the degree of intrauterine growth retardation (IUGR) of the fetus. The lipid levels were compared in fetuses with IUGR and in eutrophic fetuses and it was determined in which studied variable IUGR newborns differ from healthy newborns. METHODS: The group under study consisted of 53 pregnant women in whom IUGR of the fetus was diagnosed by ultrasound during pregnancy. The control group consisted of 26 women who gave birth to eutrophic newborns. The cases in the control group were chosen by the method of matched control so that the results could be statistically evaluated in both groups at the same gestational age and at the same maternal age. In both groups blood samples from the umbilical cord were taken after delivery and the whole spectrum of lipid levels were evaluated (cholesterol-CH, triglycerides-TGA, high-density lipoprotein--HDL, low-density lipoprotein--LDL, Lp(a) lipoprotein, and apolipoproteins-ApoB, ApoAI, ApoE). The same parameters were evaluated in maternal and paternal blood samples. In several cases, intrauterine lipid levels of the fetus were determined by cordocentesis. The incidence of hyperlipoproteinemia in the families of both groups was surveyed. SETTING: Department of Obstetrics and Gynaecology, 1st medical Faculty, Charles University, Prague. RESULTS: There was a significant incidence of hyperlipoproteinemia in the families of the mothers in the group studied (chi-square test: p < 0.001). In the mothers of the groups studied, there were statistically significant higher levels of HDL, LDL, and Lp(a) in comparison to the mothers in the control group. A significant dependence was determined between the levels of ApoAI and Lp(a) of the mothers and newborns. In the regression analysis of the dependence of lipid levels on the birth weight of the newborns, a statistical correlation was determined for the values of ApoB and Lp(a). CONCLUSION: The more increased the intrauterine growth retardation of the fetus and the lower its birth weight in relation to its gestational age, the higher its lipid levels, specifically apolipoproteins. Apolipoproteins are under genetic control and present a genetic risk for changes in the metabolism of cholesterol, hemocoagulation, and cardiovascular disease in adulthood.

Adult↗
PubMed1999

Serum leptin concentrations in patients with combined hyperlipidemia: relationship to serum lipids and lipoproteins.

Leptin is a protein hormone produced predominantly by adipocytes. Serum leptin concentrations in healthy individuals positively correlate with the body fat content and body mass index, i.e. they are higher in obese than in lean subjects. The relations between serum leptin concentration and serum lipids and lipoproteins is not yet clear. The aim of our study was to compare serum leptin concentrations in 22 randomly selected patients with untreated combined hyperlipidemia and 19 healthy control subjects matched for age and the body mass index. The relationship was studied between serum leptin concentrations and serum lipids (total, HDL, LDL cholesterol and triglycerides) and lipoproteins (lipoprotein (a), apolipoprotein B). It was found that serum leptin levels in patients with combined hyperlipidemia did not significantly differ from those of control subjects (6.69+/-4.3 vs 5.78+/-3.2 ng.ml(-1)). Serum leptin concentrations in both groups correlated positively with the body mass index. The relationship between leptin concentrations and lipid or lipoprotein levels found in any of the studied groups was not statistically significant. We conclude that serum leptin concentrations in patients with combined hyperlipidemia as well as in healthy control subjects reflect the body fat content and have no significant relation to serum lipids or lipoproteins.

Adult↗
PubMed1998

Controlled multiplex PCR of enterotoxigenic Clostridium perfringens strains in food samples.

A controlled multiplex polymerase chain reaction (PCR) for the detection of Clostridium(C.) perfringens enterotoxin gene (cpe) was established and compared with an in vitro antigenic detection method. Thecpe PCR and the classical method of electric immunodiffusion gave identical results. The predicted specific amplicon of the cpe gene was generated from all of the tested enterotoxigenic C. perfringens strains. In contrast, cultures of any other Clostridium species tested by PCR were negative (100% sensitivity, 100% specificity). Addition of an alphatoxin (plc) gene specific PCR as an in process control reaction was performed in order to prevent false negative PCR results. The PCR detection limit was 0.5 ng of genomic C. perfringens DNA per ml of bouillon culture. By contaminating minced meat with C. perfringens reference strains, the multiplex PCR was established as a tool for routine diagnostic laboratories. The detection limit was approximately 3.0x10(5)C. perfringens cells per gram meat. The results demonstrate the multiplex PCR as an easy, specific, sensitive and time saving diagnostic procedure. Application of this improved method should enhance the knowledge concerning epidemiological aspects of food borne diseases caused by enterotoxigenic C. perfringens.

Clostridium perfringens↗
PubMed1998

Exogenous leukotriene B4 (LTB4) inhibits human neutrophil generation of LTB4 from endogenous arachidonic acid during opsonized zymosan phagocytosis.

The effect of exogenous leukotriene B4 (LTB4) on opsonized zymosan-stimulated human neutrophil formation of 5-lipoxygenase products and arachidonic acid release was directly assessed using reverse-phase HPLC/tandem mass spectrometric methods for quantitation. Stable isotopically labeled LTB4, [1,2-13C2]LTB4, caused a dose-dependent inhibition of LTB4 production in isolated human neutrophils with significant inhibition (60 +/- 7% of control levels) when 0.12 nM [13C2]LTB4 was present. Production of 5-hydroxy-6,8,11,14-eicosatetraenoic acid and release of free arachidonic acid were also dose-dependently inhibited by exogenous LTB4. Metabolites of LTB4, 20-hydroxy-LTB4 and 3(S)-hydroxy-LTB4, also significantly reduced LTB4 production to levels as low as 10 +/- 6% and 10 +/- 7% of control levels, respectively, when present exogenously at 10 nM. Exogenous 5-hydroxy-6,8,11,14-eicosatetraenoic acid at concentrations as high as 10 nM produced no significant reduction in LTB4 biosynthesis during zymosan-stimulated human neutrophil production of LTB4. The inhibitory effect of LTB4 could be partially reversed by the LTB4 receptor antagonist U 75302. Furthermore, an alternative stimulus, N-formyl-methionyl-leucyl-phenylalanine (100 nM), did not inhibit the production of LTB4 in opsonized zymosan-stimulated human neutrophils. These results suggest that activation of the LTB4 receptor on the human neutrophil during phagocytosis limits the ultimate biosynthesis of LTB4. This autocrine effect is opposite to that observed when neutrophils have much of the signal transduction pathways bypassed when stimulated with calcium ionophore A23187 or treated with exogenous free arachidonic acid.

Arachidonic Acid↗
PubMed1996

Electron Transfer in Donor-Acceptor Molecules of Substituted Naphtoquinones: Spectral and Redox Properties of Internal Charge Transfer Complexes

The investigated compounds were substituted naphtoquinones containing aniline moiety separated from the quinoid system by a methylene bridge. The nature of substituents on both donor and acceptor parts influenced the degree of formation of an internal charge transfer complex. Properties of the internal charge transfer interactions were investigated by voltammetry, spectroscopy, and in situ spectroelectrochemistry. Quantum chemical interpretation of experiments is given.

Journal Article↗
PubMed1996

The costs and effectiveness of three vitamin A interventions in Guatemala.

The purpose of the study presented in this paper was to estimate, using secondary sources of data, the cost and effectiveness of three programs to combat vitamin A deficiency in Guatemala-the national sugar fortification program, a targeted capsules distribution program and the promotion of home food production combined with nutrition education and to draw conclusions concerning priorities for Guatemala. Data on the costs and coverage were collected from implementing agencies in Guatemala. Coverage data were converted into a common set of impact indicators. Sensitivity analyses were conducted on variables whose precise value was uncertain. Potential impacts of improvements in program performance operations were also explored. The analysis found the cost per high-risk person achieving adequate vitamin A to be US $0.98 for fortification, US $1.68-1.86 for capsule distribution and US $3.10-4.16 for food production/education. Fortification is the most efficient option if vitamin A levels in sugar are maintained at reasonable levels. Where fortified sugar is not consumed and vitamin A deficiency is highly prevalent, small-scale, targeted, complementary interventions such as capsules and food production education may be appropriate for sustained broader impacts.

Cost-Benefit Analysis↗
PubMed1996

Breastfeeding promotion and priority setting in health.

An increase in exclusive breastfeeding prevalence can substantially reduce mortality and morbidity among infants. In this paper, estimates of the costs and impacts of three breastfeeding promotion programmes, implemented through maternity services in Brazil, Honduras and Mexico, are used to develop cost-effectiveness measures and these are compared with other health interventions. The results show that breastfeeding promotion can be one of the most cost-effective health interventions for preventing cases of diarrhoea, preventing deaths from diarrhoea, and gaining disability-adjusted life years (DALYs). The benefits are substantial over a broad range of programme types. Programmes starting with the removal of formula and medications during delivery are likely to derive a high level of impact per unit of net incremental cost. Cost-effectiveness is lower (but still attractive relative to other interventions) if hospitals already have rooming-in and no bottle-feeds; and the cost-effectiveness improves as programmes become well-established. At an annual cost of about 30 to 40 US cents per birth, programmes starting with formula feeding in nurseries and maternity wards can reduce diarrhoea cases for approximately $0.65 to $1.10 per case prevented, diarrhoea deaths for $100 to $200 per death averted, and reduce the burden of disease for approximately $2 to $4 per DALY. Maternity services that have already eliminated formula can, by investing from $2 to $3 per birth, prevent diarrhoea cases and deaths for $3.50 to $6.75 per case, and $550 to $800 per death respectively, with DALYs gained at $12 to $19 each.

Adult↗
PubMed1995

Quality of life: radical prostatectomy versus radiation therapy for prostate cancer.

PURPOSE: The impact of radical prostatectomy and external beam radiotherapy on the quality of life of patients was compared. MATERIALS AND METHODS: A total of 136 patients underwent radical prostatectomy and 60 underwent external beam radiotherapy for clinically localized prostate cancer. Patients were asked to complete a questionnaire containing The Functional Living Index: Cancer, the Profile of Moods States, and a series of questions evaluating bladder, bowel and sexual function. RESULTS: The radical prostatectomy group had worse sexual function and urinary incontinence, while the external beam radiotherapy group had worse bowel function. Of the patients 90% from both groups stated that they would undergo the treatment again. CONCLUSIONS: Radical prostatectomy and external beam radiotherapy have comparable impact upon quality of life.

Adult↗
PubMed1992

Cloning and sequence analysis of genes for dehalogenation of 4-chlorobenzoate from Arthrobacter sp. strain SU.

Strains of Arthrobacter catalyze a hydrolytic dehalogenation of 4-chlorobenzoate (4-CBA) to p-hydroxybenzoate. The reaction requires ATP and coenzyme A (CoA), indicating activation of the substrate via a thioester, like that reported for Pseudomonas sp. strain CBS3 (J. D. Scholten, K.-H. Chang, P. C. Babbit, H. Charest, M. Sylvestre, and D. Dunaway-Mariano, Science 253:182-185, 1991). The dehalogenase genes of Arthrobacter sp. strain SU were cloned and expressed in Escherichia coli. Analyses of deletions indicate that dehalogenation depends on three open reading frames (ORFs) which are organized in an operon. There is extensive sequence homology to corresponding gene products in Pseudomonas sp. strain CBS3, suggesting that ORF1 and ORF2 encode a 4-CBA-CoA-ligase and a 4-CBA-CoA dehalogenase, respectively. ORF3 possibly represents a thioesterase, although no homology to the enzyme from Pseudomonas sp. strain CBS3 exists.

Amino Acid Sequence↗
PubMed1991

Cortical ablation reduces veratridine evoked release of endogenous glutamate from superfused substantia nigra slices.

A brain slice superfusion system and HPLC coupled to fluorometric detection were used to study depolarization-evoked release of endogenous glutamate (Glu) and aspartate (Asp) from substantia nigra (SN) slices. Veratridine (15-25 microM) and K+ (50 mM) evoked both a Ca2(+)-dependent and Ca2(+)-dependent release of Glu and Asp. However, the pattern of Glu release was different from that of Asp. In addition, cortical ablation significantly reduced the evoked release of Glu but not that of Asp. There results indicate the existence in SN of functional Glu- and Asp-releasing nerve terminals. Some of the Glu-enriched nerve terminals might belong to a cortico-nigral neuronal pathway.

Animals↗