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B Kohl

Publications and source records attributed to B Kohl.

34 records · Page 2Linked to original sources
PubMed1993

Angiotensin II enhances insulin sensitivity in healthy volunteers under euglycemic conditions.

OBJECTIVE: It has been postulated that vasoconstrictors cause insulin resistance. This effect has been documented for epinephrine but not for angiotensin II (Ang II). The aim of this study was to investigate the effect of the latter on insulin sensitivity. DESIGN: In order to study the influence of subpressor doses of Ang II on insulin-mediated glucose uptake under euglycemic conditions, eight healthy volunteers were allocated in random order to sham infusion or infusion of Ang II (first 0.75 ng/kg per min and subsequently 1.5 ng/kg per min). In addition, in seven of the subjects Ang II was infused after 3 days of indomethacin pretreatment (150 mg/day). METHODS: Insulin-mediated glucose uptake (expressed as M value) was measured with the euglycemic clamp technique. Insulin levels were measured enzymatically, plasma renin activity, Ang II, aldosterone and C-peptide levels by radioimmunoassay, blood pressure by Dinamap and muscle blood flow by plethysmography. RESULTS: The M value after sham infusion was 7.81 +/- 1.52 mg/kg per min and after 1.5 ng/kg Ang II per min was 9.76 +/- 1.26 mg/kg per min (P < 0.001). Indomethacin pretreatment did not abolish the Ang II-induced rise in the M value. Mean arterial blood pressure during the euglycemic clamp was unchanged with sham infusion and the low dose of Ang II. It increased slightly with the higher dose of Ang II. Inferior limb muscle perfusion was higher after infusion of Ang II than after sham infusion; this effect was not obliterated by indomethacin pretreatment. CONCLUSIONS: Ang II increases insulin-mediated glucose uptake: that is, it enhances insulin sensitivity by mechanisms independent of prostaglandins. The observations are of potential relevance to the changes in insulin sensitivity in some forms of hypertension.

Adult↗
PubMed1993

Inhibition of hepatic microsomal drug metabolism by atracurium administration in the rat.

The muscle relaxant atracurium is known to undergo extrahepatic degradation via Hofmann elimination and ester hydrolysis. The purpose of the present study was to evaluate the effects of atracurium on hepatic P450-dependent enzyme activities. Thirty-two male Sprague-Dawley rats were anaesthetized, mechanically ventilated, and randomly allocated to one of four study groups: group 1 received saline, group 2 atracurium, group 3 vecuronium, and group 4 pancuronium intravenously for a period of 3 hr. Equipotent doses of the muscle relaxants were applied; the doses had been obtained in a pilot study using evoked electromyography. At the end of the study period, the livers were removed and analyzed. All three muscle relaxants may lead to inhibition of hepatic drug metabolism. Atracurium influences hepatic P450, although it is predominantly degraded in extrahepatic tissues. Further studies are needed to evaluate the contribution of the major metabolite laudanosine to this inhibitory action.

Aminopyrine N-Demethylase↗
PubMed1993

Lipoprotein(a) serum levels and apolipoprotein(a) phenotypes in children with chronic renal disease.

Lipoprotein(a) [Lp(a)] has recently been characterized as a genetically determined risk factor for atherosclerosis and thrombosis. Normally, Lp(a) serum levels are closely related to the apo(a) phenotype. We studied Lp(a) serum levels and apo(a) phenotypes in 136 young subjects, aged 0.8-24.7 y, including patients with glomerular disease and normal renal function (n = 28), patients with chronic renal failure (n = 20), patients treated by hemodialysis (n = 10), peritoneal dialysis (n = 16), and renal transplantation (n = 23), and in controls (n = 39). Of all, 21 patients had proteinuria in the nephrotic range. The distribution of Lp(a) levels in normal subjects was skewed to the left with 97% having levels below 300 mg/L. A subpopulation with increased Lp(a) levels (13-42%) could be detected in all groups with renal disease, and increased mean serum Lp(a) levels were found in patients with nephrotic range proteinuria, in patients with chronic renal failure, and in patients on peritoneal dialysis. Serum Lp(a) levels were not correlated with age, gender, type of renal disease, renal function or severity of proteinuria, but were correlated with the apo(a) phenotype. For a given phenotype, Lp(a) levels tended to be higher in patients than in controls. We conclude that increased Lp(a) serum levels are frequently found in young patients with chronic renal disease, possibly predisposing them to an increased risk for atherosclerosis and thrombosis.

Adolescent↗
PubMed1993

Serum lipid changes on low salt diet. Effects of alpha 1-adrenergic blockade.

An increase of some serum lipid fractions has been documented in normotensive healthy volunteers and patients with essential hypertension during acute drastic restriction of salt intake. To clarify the potential role of vasopressor systems, particularly the sympathetic system, in the lipid changes induced by salt restriction, we compared fasting serum lipids, glucose, insulin, and C-peptide levels in 16 normotensive healthy volunteers during 7 days of high (200 mmol/day) and 7 days of low (20 mmol/day) salt intake. The individuals were examined on either placebo or on the alpha 1-adrenergic blocker doxazosin (2 mg/day). The study was carried out using a single blind parallel group random order design with two arms of treatment. In the volunteers on placebo, total cholesterol (corrected for hemoconcentration) was significantly higher (P < .01) during low salt intake. The same was true for LDL-cholesterol, whereas HDL-cholesterol and triglycerides did not change with salt intake. The lipid changes, and, in parallel, the changes of hemoconcentration indicators, were more pronounced after 2 days than after 7 days of low salt intake. The rise of total and LDL-cholesterol on low salt was blunted after alpha 1-adrenergic blockade with doxazosin. Fasting glycemia was similar on low salt and high salt, respectively, but in placebo treated volunteers, C-peptide levels were significantly (P < .01) higher on low, rather than high, salt intake. alpha 1-Adrenergic blockade with doxazosin attenuated the rise of C-peptide levels on low salt. The results confirm previous findings that levels of total cholesterol and LDL-cholesterol change inversely with salt intake in normotensive healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

(H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate.

[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Lack of accumulation of midazolam in plasma and lipoprotein fractions during intravenous lipid infusions in patients on artificial respiration.

Severely ill patients often require total parenteral nutrition including intravenous lipid emulsions concurrently administered with lipophilic drugs. Therefore we investigated whether therapeutic application of a mixed medium chain/long chain triglyceride infusion affects the disposition of midazolam necessary for sedation in patients on artificial respiration. The concentrations of midazolam were measured in unfractionated plasma, and in lipoprotein fractions isolated from ex vivo blood samples, including determination of triglycerides and cholesterol; the albumin level was also analysed. Midazolam in the VLDL fraction was only 0.246 microgram.ml-1, whereas the total plasma concentration averaged 1.101 micrograms.ml-1, and the midazolam content of the LDL plus HDL fractions amounted to 1.771 micrograms.ml-1. Albumin in these lipoprotein fractions was just as unequally distributed. A lipid infusion resulted in a significant elevation of total triglycerides from 157 to 221 mg.dl-1 and VLDL-triglycerides from 77 to 155 mg.dl-1. The triglyceride content of the LDL plus HDL fraction rose from 102 to 139 mg.dl-1. At the same time the midazolam concentration in unfractionated plasma and in the VLDL and the LDL + HDL fractions decreased to 0.899 microgram.ml-1, 0.130 micrograms.ml-1, and 1.265 micrograms.ml-1, respectively. Cholesterol and albumin concentrations were not affected. The data show for the first time that a significant increase in plasma triglycerides during an intravenous lipid infusion does not result in accumulation of midazolam in lipoproteins, probably because albumin binding of the drug is very strong. The lack of midazolam trapping is important with respect to the safety of concurrent use of lipophilic drugs and intravenous lipid infusions.

Adult↗
PubMed1992

The clinical significance of antisperm antibodies in infertile couples.

Sera from 150 women and 162 men with unexplained infertility were examined using a commercial enzyme-linked immunosorbent assay (ELISA) kit for antisperm antibodies. The results were compared to those of the Friberg agglutination test, the post-coital test, the sperm-cervical mucus contact (SCMC) test and the pregnancy rate. We also tested follicular fluids obtained from 38 women who underwent in-vitro fertilization (IVF). These data were compared with those obtained in serum, post-coital test data and with the later development of the oocyte in IVF. Antibodies in follicular fluid were found only in women with antibodies circulating in serum. The correlation coefficient between these was 0.88 (P < 0.001). There was no correlation between antisperm antibodies in serum found with the ELISA test, and with the agglutination test, the post-coital test or the SCMC test. Neither was there any correlation between antibodies in follicular fluid and the post-coital test, the pregnancy rate or successful IVF.

Agglutination Tests↗
PubMed1992

Circulating levels of midregional parathyroid hormone-related protein in hypercalcaemia of malignancy.

OBJECTIVE: We have developed and evaluated a sensitive radioimmunoassay directed against the midregional part of parathyroid hormone-related protein (PTHrP), which is involved in the syndrome of humoral hypercalcaemia of malignancy. PATIENTS: Midregional PTHrP levels were studied in 41 consecutive inpatients with malignancy and hypercalcaemia, 32 normocalcaemic patients with malignancy, 21 patients with primary hyperparathyroidism, 34 patients with renal failure, and 87 normals. MEASUREMENTS: The assay used an antiserum against the midregional amino acid residues 53-84 of PTHrP and PTHrP(1-86) as label and standard. Midregional PTHrP was stable in serum and plasma and could be measured directly without sample extraction. RESULTS: Normal plasma concentrations ranged from undetectable (< 5 pmol/l) to 21 pmol/l. In renal failure, PTHrP was positively correlated with serum creatinine, but PTHrP elevations of up to 30 pmol/l were found only in severe renal dysfunction with creatinine > 850 mumol/l. In hypercalcaemia caused by solid tumours, midregional PTHrP was elevated in 81% (22 of 27) of patients, ranging from undetectable to 203 pmol/l (median: 40 pmol/l). In these patients serum calcium correlated positively with PTHrP (P < 0.01). Mean PTHrP levels were indistinguishable in subgroups with and without metastatic skeletal disease. The mechanism of hypercalcaemia in 14 patients with haematological malignancy was apparently different, since all but one had normal or only marginally elevated PTHrP levels. In 21 patients with primary hyperparathyroidism midregional PTHrP was normal in 20. The assay was therefore especially useful in distinguishing the latter condition from humoral hypercalcaemia of malignancy as the second major cause of hypercalcaemia. PTHrP was normal in all 32 patients with normocalcaemic malignancy. CONCLUSION: This radioimmunoassay of midregional PTHrP provides high diagnostic sensitivity in the identification of humoral hypercalcaemia of malignancy caused by solid tumours. The assay should therefore be useful in the differential diagnosis of hypercalcaemia.

Diagnosis, Differential↗
PubMed1990

[Epidemiology of hypercalcemia. Significance of the determination of intact parathyroid hormone for differential diagnosis].

Serum-calcium levels were determined in 9666 hospital inpatients during one year. Hypercalcaemia was present in 101 patients (51 women, 50 men, mean age 57 years). In 46 patients, hypercalcaemia was caused by malignancy. The second commonest cause was primary hyperparathyroidism (pHPT) in 35 cases. In the other 20 patients, hypercalcaemia was related to thiazid medication (8 patients), elevated 25-hydroxy-vitamin-D3-levels (six patients) or immobilisation (two patients). In four patients, no cause was found. Intact parathyroid hormone levels reliably distinguished patients with pHPT (values greater than 60 ng/l) from patients with hypercalcaemia of other causes (values less than 40 ng/l). Other laboratory tests were less useful. Serum-calcium levels greater than 2.9 mmol/l were found only in pHPT and hypercalcaemia of malignancy. In pHPT, the medical history frequently revealed nephrolithiasis (12 patients) and gastrointestinal ulcers (8 patients), whereas weight loss was far more common in hypercalcaemia of malignancy (28 patients).

Adult↗
PubMed1987

Mechanism of action of monoclonal antibodies that block the light activation of the guanyl nucleotide-binding protein, transducin.

Seven monoclonal antibodies to the alpha subunit (G alpha) of the frog photoreceptor guanyl nucleotide-binding protein (transducin or G-protein) have been characterized as to their effect on G-protein function, and this has been correlated in the accompanying paper (Deretic, D., and Hamm, H. E. (1987) J. Biol. Chem. 262, 10839-10847) with the antibody-binding sites on G alpha tryptic fragments. Antibodies 4A, 7A, 7B, 7C, and 7D are members of a class of antibodies that block G-protein activation by light and therefore also block activation of the cGMP phosphodiesterase. All these blocking antibodies also block the interaction of G-protein with rhodopsin as measured by the light-scattering "binding signal," and as measured by the stabilization of meta-rhodopsin II by bound G-protein (extra-meta-rhodopsin II). The antibodies (or Fab fragments) also solubilize G alpha beta gamma from the membrane in the dark under isosmotic conditions and thus interfere with G alpha interaction with the membrane. Antibody 4A also blocks the extra-meta-rhodopsin II generated by G-protein-rhodopsin interaction in detergent solubilized membranes. Thus, even in the absence of phospholipids, antibody 4A blocks G-protein-rhodopsin interaction. Therefore, we suggest that the antibodies recognize a region of G alpha involved with binding to rhodopsin. An alternative hypothesis is that this antigenic site is a region of interaction between the alpha and beta gamma subunits, disruption of this interaction leading to removal of both the alpha and beta gamma subunits from the membrane and blocking interaction with rhodopsin. This does not seem to be the case because the antibodies immunoprecipitate the alpha beta gamma complex, and not just the alpha subunit. Other antibodies, 4C and 4H, do not block phosphodiesterase activation, the light-scattering signal, extra-meta-rhodopsin II formation, or interaction with the membrane in the dark and therefore recognize other sites on G alpha.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1987

Temperature dependence of G-protein activation in photoreceptor membranes. Transient extra metarhodopsin II on bovine disk membranes.

The thermal activation barrier of guanosine triphosphate dependent dissociation of the light-induced rhodopsin-G-protein complex has been determined using a spectroscopic technique (enhanced formation of metarhodopsin II). The dissociation rate has been measured in the range - 2 degrees C less than or equal to t less than or equal to 12 degrees C. The Arrhenius plot yields apparent activation energies: 166 +/- 10 kJmol-1 with 5'-guanylylimidodiphosphate (GMPPNP) and 175 +/- 15 kJmol-1 with GTP. The rhodopsin-G-protein dissociation rate is linearly related to the concentration of GMPPNP in the measurable range (less than or equal to 200 microM). The data show that, at low temperature (1 degree C), the rate limiting step of G-protein activation is the bimolecular reaction between the protein and the nucleotide. This also seems to hold true for more physiological conditions as suggested by extrapolation and comparison with nucleotide exchange rates in the literature. The high activation barrier of the nucleotide exchange reaction is explained in terms of rapid endothermic preequilibrium between an inactive and an exchanging state of the rhodopsin-G-protein complex.

Animals↗
PubMed1984

Determination of total and free phenytoin in serum by non-isotopic immunoassays and gas chromatography.

Four different homogeneous non-isotopic immunoassays for the determination of total phenytoin in serum were evaluated and compared with a gaschromatographic method (GC) described by W. R. Külpmann & M. Oellerich [1981), J. Clin. Chem. Clin. Biochem. 19, 249-258) enzyme multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA), nephelometric inhibition immunoassay (NIIA) and substrate labeled fluorescent immunoassay (SLFIA). The between-days coefficients of variation in the medium therapeutic range were 4.0% (n = 29) with EMIT, 4.6% (n = 15) with FPIA, 7.8% (n = 10) with NIIA, 2.8% (n = 12) with SLFIA and 5.7% (n = 15) with GC. The recovery in spiked serum samples (phenytoin concentration: 11.9-99.1 mumol/l) was 98-101% with EMIT, 97-107% with FPIA, 102-110% with NIIA, 94-97% with SLFIA and 97-104% with GC. All of the tested immunoassays and GC yielded comparable results. The NIIA showed a somewhat lower correlation. In samples from an uraemic patient, however, great deviations from GC values were obtained with EMIT (bias: +22 to +85%) NIIA (+68 to +114%) and SLFIA (+48 to +52%). Only the results of FPIA were in good agreement with those of GC (bias: +1 to -7%). All the immunoassays showed a cross-reaction with 5-(4-hydroxyphenyl)-5-phenylhydantoin, which was most expressed with SLFIA and NIIA. The detectability of the immunoassays was adequate to allow precise measurements within the therapeutic range. After ultrafiltration of the serum, free phenytoin was measured by EMIT, FPIA and capillary gas chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gas↗
PubMed1983

False-positive EMIT indication of opiates and methadone in a doxylamine intoxication.

The EMIT-dau for methadone and the EMIT-ST for opiates (both EMITs from Syva-Merck) gave false-positive results when applied to urine samples of a patient suffering from a moderate doxylamine monointoxication. The error was not detected in routine TLC. Gas chromatography and mass spectrometry unequivocally indicated the presence in urine and plasma of doxylamine and its metabolites and the definite absence of methadone. Opiates could not be detected with the Abuscreen RIA (Roche), which is a more sensitive method than EMIT-ST.

Adult↗
PubMedDate not supplied

High-performance liquid chromatography improves diagnostic efficiency of carbohydrate-deficient transferrin.

Carbohydrate-deficient transferrin (CDT) is considered a useful biochemical marker of regular high alcohol intake. CDT was measured in the sera of 51 alcohol abusers, 20 patients with non-alcoholic liver disease and 30 healthy controls with an alcohol intake of < 30 g/day. The mean CDT levels of these three groups respectively were determined with high-performance liquid chromatography (HPLC; 4.6 +/- 5.2%; 0.7 +/- 0.2%; 0.7 +/- 0.2%) and with a radioimmunoassay after microcolumn anion-exchange chromatography (MAEC/RIA; 34.2 +/- 26.9 U/l; 16.9 +/- 3.8 U/l; 18.0 +/- 5.7 U/l). CDT levels in patients with severe alcohol abuse (161.6 +/- 96.4 g/day) were significantly higher than in the two other groups under investigation (P < 0.0001). In heavily drinking subjects, the mean daily alcohol intake correlated with aspartate aminotransferase levels (ASAT) but not with the CDT levels determined either with HPLC or MAEC/RIA. With both methods, the CDT levels were slightly higher in patients with an ASAT concentration > 30 U/l, which may indicate an advanced liver damage (P < 0.05). Analysis of receiver-operating characteristic (ROC) plots demonstrated that the diagnostic accuracy of the HPLC method, which determines the relative amount of CDT, was significantly higher than the established MAEC/RIA method, which measures the absolute amount of CDT (area under the ROC curve: 0.95 +/- 0.02 vs 0.73 +/- 0.05; P < 0.0001). At a specificity of > 95%, the sensitivity of CDT determined with HPLC and MAEC/RIA was 80 and 47%, respectively. In addition, HPLC may be a useful and reliable method for the determination of this important biochemical marker, since the HPLC chromatogram is a visible document of the successful isotransferrin separation and measurement.

Adolescent↗