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Biomedical subjects

R Flückiger

Publications and source records attributed to R Flückiger.

At least 55 records · Page 3Linked to original sources

Methoxatin (PQQ), coenzyme for copper-dependent amine and mixed-function oxidation in mammalian tissues.

The newly discovered coenzyme PQQ can now be measured at picomole levels with redox cycling methods developed in our laboratory. PQQ-peptides have been obtained from digests of the copper quinoenzymes, diamine oxidase, lysyl oxidase and dopamine-beta-hydroxylase. PQQ is present in egg yolk and milk, suggesting its immediate availability for developing embryos and newborn animals. We suggest that PQQ, when exposed in traumatized, ischemic, inflammed or pathological tissues, may catalyze the formation of large amounts of superoxide and should be considered as a source of oxidative stress when planning pharmacotherapeutic intervention. PQQ and quinoproteins play a role in the redox metabolism and structural integrity of cells and tissues.

Amines↗

[Fornix rupture. A contribution to differential acute abdomen diagnosis].

The diffuse retroperitoneal extravasation of urine most often secondary to an ureteric calculus may present as a surgical emergency with localized or general abdominal symptoms. As the clinical signs are intriguing, history and a blurred psoas shadow on the plain film of the abdomen are the best guides to the right diagnosis definitely confirmed by an intravenous urography. Management usually is conservative and the recovery most often uneventful.

Abdomen, Acute↗

The amplified detection of free and bound methoxatin (PQQ) with nitroblue tetrazolium redox reactions: insights into the PQQ-locus.

Porcine kidney diamine oxidase, a PQQ-enzyme, can be directly measured by formazan production with putrescine and nitroblue tetrazolium. This cyclic reaction in air is unaffected by superoxide dimutase, suggesting a two electron transfer between substrate-reduced PQQ-locus and nitroblue tetrazolium, without intermediate formation of superoxide. With albumin-bound PQQ and detergent-exposed PQQ-loci, glycine can be oxidized by PQQ and electrons repetitively transferred through PQQ-sites to nitroblue tetrazolium, the rate of formazan production detecting picomoles of exposed PQQ-locus. Exposed PQQ-loci are also reducible with NaCNBH3. Nitroblue tetrazolium, reoxidizes the reduced PQQ-locus with formazan production. These experiments suggest that the PQQ-locus of quinoproteins contains a [ketone-ketoimine in equilibrium with ketoamine] redox center.

Amine Oxidase (Copper-Containing)↗

Glycated haemoglobins.

The association between elevated levels of glycated haemoglobins and diabetes mellitus has been known for twenty years [92]. Since then the determination of glycated haemoglobins has become a valuable tool for the objective assessment of long-term glycaemia in diabetic patients. The marked clinical interest in reliable measurements of glycated haemoglobins has stimulated the development and perfection of the necessary methodology. Limitations of the techniques have led to investigation of the underlying causes. Some of them led to the recognition of processes that were not known to occur in vivo before, such as glycation at sites other than the amino terminus of the beta-chains, modification of haemoglobin by reactants other than glucose or the existence of labile haemoglobin adducts. With ideal methodology these features would have gone unnoticed. Furthermore, the determination of glycated haemoglobin in large populations of diabetic patients has lead to the discovery of new, clinically silent mutant haemoglobins. Today, the routine determination of glycated haemoglobins in diabetic patients probably represents the broadest screening for mutant haemoglobins. The experience with glycated haemoglobins shows that overcoming difficulties in their determination, and progress in biomedical research, are closely intertwined.

Animals↗

The interaction of aminogroups with pyrroloquinoline quinone as detected by the reduction of nitroblue tetrazolium.

The interaction of pyrroloquinoline quinone (PQQ) with amino groups was followed by measuring the capacity of adducts to reduce nitroblue tetrazolium (NBT). Of the natural amino acids only glycine, ornithine, and lysine interacted strongly with PQQ. The reducing activity of other less reactive amino acids, but not of lysine, was increased by ammonia, primary or secondary amines. Divalent cations, in contrast inhibited development of NBT-reducing activity. PQQ also developed NBT-reactivity in the presence of serotonin and albumin. A reaction scheme is proposed which explains these findings. It is suggested that the NBT-reducing activity of plasma which is not caused by glycation of plasma proteins, arises from PQQ adducts inherent to plasma. This NBT-reducing activity corresponds to approximately 10 micrograms PQQ/ml plasma.

Alanine↗

Efficacy and tolerance of a miconazole-benzoyl peroxide cream combination versus a benzoyl peroxide gel in the topical treatment of acne vulgaris.

62-65% reduction in the number of lesions was obtained in the treatment of 52 patients with acne vulgaris in this randomized single-blind study comparing a 5% benzoyl peroxide/2% miconazole cream (BPO-MCZ) with a 5% benzoyl peroxide gel (BPO). While BPO gel was equally effective in male and female patients (66 and 73% reduction of lesions), the BPO-MCZ cream was significantly more effective in the latter (50 vs. 74% mean reduction of lesions). Tolerance was significantly better with the BPO/MCZ cream preparation, particularly in females.

Acne Vulgaris↗

[HbA1c determination in capillary blood].

A practical procedure is described for the determination of HbA1c in capillary blood collected in micro-hematocrit-capillaries. These blood samples can be mailed to the analytical laboratory prior to consultation with the physician. The results of such determinations in 23 juvenile diabetic patients obtained during a two-year observation period are presented.

Adolescent↗

Evaluation of the fructosamine test for the measurement of plasma protein glycation.

Repeated estimation of plasma protein glycation by the fructosamine assay gave more variable results than expected from analytical variability (coefficient of variation approximately 2%). Fructosamine results obtained on plasma samples drawn at different times of the day differed by up to 1 mmol/l, corresponding to a coefficient of variation of greater than 10%. As a consequence, the information concerning averaged glycaemia of a fructosamine determination is subject to an uncertainty of 7.8 mmol/l. Fructosamine concentrations were linearly related to the protein concentration. Correction for the protein concentration decreased this variability; however, factors other than protein concentration, such as lipid content, also influence results of fructosamine determinations.

Adult↗

Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites.

Nonenzymatic glycosylation of albumin in vivo occurs at multiple sites. Glucose gets attached to Lys-199, Lys-281, Lys-439, and Lys-525 as well as to some other lysine residues. The principal glycosylated site is Lys-525. Approximately 33% of the overall glycosylation occurs at this site. This site specificity is remarkable and is postulated to be a consequence of local catalysis of the nonenzymatic glycosylation reaction. It appears that positively charged amino groups in the protein catalyze the Amadori rearrangement at specific sites. The principal glycosylated site, Lys-525, lies in a Lys-Lys sequence; other glycosylated sites lie in a Lys-Lys, Lys-His, and Lys-His-Lys sequence or are near disulfide bridges, which are likely to place amino groups of more remote parts of the protein closer to these sites. The occurrence of nonenzymatic glycosylation at most of the identified sites in albumin from diabetic patients is explained by the concept of local acid-base catalysis of the Amadori rearrangement.

Amino Acid Sequence↗

[HbA1c and HbA1 determination in diabetes control].

Objective assessment of the time-averaged blood glucose concentration of the preceding weeks in diabetic patients by means of glycosylated hemoglobin measurements has proved to be of value in the management of this disease. The present article summarizes the principle of this determination and information which is important for the interpretation of results.

Blood Glucose↗

Albumin-directed antibodies in diabetes: demonstration of human serum albumin-directed IgM autoantibodies.

Sera of 406 individuals, 174 Type 1 (insulin-dependent) diabetic patients, 125 non-diabetic family members and 107 unrelated control subjects, were screened for the presence of antibodies against glycated albumin. In none of these sera could such antibodies be detected. However, antibodies directed towards monomeric, unmodified human serum albumin were detected in 13 sera. These albumin autoantibodies were of the IgM class, and occurred in sera from nondiabetic persons (0.9-1.6%) and with a five-fold higher frequency in sera from diabetic patients (5.2%). The presence of albumin antibodies was neither related to the presence of diabetic late complications, islet cell antibodies, HLA-status nor duration of diabetes. The albumin antibodies were also found in sera from persons carrying antibodies against mumps (17%) or Epstein-Barr virus.

Autoantibodies↗

Real and artefactual erythrocyte swelling in hyperglycaemia.

The mean erythrocyte volume of patients with acute diabetic decompensation was determined by Coulter measurement and found to be elevated above normal (mean increase 5.5 mu3). Experiments in vitro revealed this to be an artefact associated with Coulter determination. A more reliable estimate of in vivo erythrocyte volume can be obtained from centrifugated haematocrit and erythrocyte count. With this method, true erythrocyte swelling parallel to glucose concentration was observed when erythrocytes were exposed to isotonic glucose-NaCl solutions. This volume increase resulted from decreased sodium concentration and was in the order of 0.5-1.0 mu3 per mmol/l of sodium. Glucose was osmotically ineffective. Similar volume changes were documented in a diabetic patient parallel to his daily variations of blood glucose. In severe diabetic decompensation, dehydration usually prevents an increase in erythrocyte volume. We conclude that hyperglycaemia is associated with erythrocyte swelling if total serum tonicity remains within the normal range.

Adult↗

Effect of temperature on quantifying glycated (glycosylated) hemoglobin by cation-exchange chromatography.

As a consequence of nonideal chromatographic conditions, values for stable glycated hemoglobin (HbA1c) determined by cation-exchange chromatography in a commercial minicolumn system (y) or by "high-performance" liquid chromatography (x) differ markedly, yielding the regression line y = 0.82x + 0.6. With use of the protocol specified by the manufacturer, 20% of the HbA1c peak is not collected in the HbA1c fraction. Increasing the ionic strength of the eluting buffer by increasing the operating temperature to 28 degrees C increases the rate of elution from the minicolumn, making results of the two methods more closely comparable (y = 0.98x - 0.22). Because at a given pH the elution volume is determined primarily by the ionic strength, close limits on the composition of the eluting buffer are set by the temperature-dependence of its ionic strength. At a specified temperature and pH the position of a peak can be judged to within a volume of 1 mL if the conductivity of the eluent does not vary by more than +/- 0.05 mS.

Buffers↗

Mass spectral and HPLC analysis of biological compounds with diphenylborinic acid.

Diphenylborinic acid is shown to react with a variety of polyfunctional molecules of biological interest to give products which are easily identifiable by mass spectrometry. The diphenylborinate adducts of amino acids possess extraordinary stability and are separable by reverse phase chromatography. The stability of products is discussed with regard to the nature and stereochemical arrangement of the functional groups involved in complex formation.

Amino Acids↗