Search PubMed⌕ Search

Biomedical subjects

K H Beyer

Publications and source records attributed to K H Beyer.

At least 19 recordsLinked to original sources
PubMed1994

Pyrazinoylguanidine downregulates the glucose fatty-acid cycle in hypertensive, hyperinsulinemic diabetic patients.

Eight hypertensive patients with noninsulin dependent diabetes mellitus (NIDDM) were administered the experimental drug pyrazinoylguanidine (PZG) either alone or in combination with calcium-channel or beta-blockers. This treatment appeared to "downregulate" the glucose fatty acid cycle and reduced both systolic and diastolic blood pressures and mean body weight. Patients served as their own controls in this dose-escalation study, which included placebo treatment (baseline) 3 weeks, 300 mg PZG for 3 weeks and 600 mg for 3 weeks. PZG reduced increased serum concentrations of free fatty acids (FFA), glucose, and triglycerides (TG). TG concentrations correlated inversely with serum HDL-cholesterol concentrations. The beta-blockers used by several patients increased their FFA, glucose, insulin and TG concentrations, as well as blunting their response to PZG. The calcium-channel blockers exerted these effects to a much lesser extent. PZG reduced or abolished glycosuria, related to PZG's capacity to decrease hyperglycemia. Withdrawal of PZG restored glycosuria, as blood sugar increased. PZG was well tolerated. No patient reported any adverse effect or missed a weekly clinic visit (12 weeks). PZG deserves further study as supplementary and/or replacement therapy in NIDDM patients who are hypertensive and hyperlipidemic.

Adult↗
PubMed1992

Inhibition of urea transport across renal tubules by pyrazinoylguanidine and analogs.

In addition to glomerular filtration and passive back diffusion of urea, there occurs across the renal tubule bidirectional transport of urea inhibitable in one or both directions by specific analogs of pyrazinoylguanidine (PZG). Effect of PZG on the profiles of sodium and urea concentrations along the tubule (stop flow) are consistent with their independent transport. Inhibition of urea and sodium reabsorption by PZG is dose dependent. PZG does not inhibit potassium excretion.

Amiloride↗
PubMed1992

Pharmacokinetics of pyrazinoyl-guanidine, 3-aminopyrazinoyl-guanidine and their corresponding pyrazinoic acid metabolites in humans and dogs.

Pyrazinoylguanidine (PZG), 3-aminopyrazinoylguanidine (NH2PZG) and their pyrazinoic acid metabolites were measured by a new reverse-phase HPLC method in the serum of dogs and humans after administration of PZG, NH2PZG or 2-pyrazinoic acid (PZA). Kinetic properties of PZG and its principal metabolite, PZA, were studied in normal humans and also in azotemic patients, since PZG acts on renal tubules of patients with kidney failure to increase urea elimination. In humans and dogs, PZG was rapidly hydrolyzed to PZA. The serum half-life (t1/2) of PZG was 1 h. In turn, PZA was metabolized to 5-hydroxy-PZA, but no evidence appeared for conjugation of PZA with glycine. The apparent volume of distribution of PZG and its 3-amino analog, NH2PZG, exceeded that of total body water. In the dog the serum t1/2 for NH2PZG was twice that of PZG. Compared to PZG, NH2PZG and its metabolite, 3-aminopyrazinoic acid, were much stabler in vitro in serum and water.

Animals↗
PubMed1992

Pyrazinoylguanidine: antihypertensive, hypocholesterolemic, and renin effects.

In a single-blind, placebo-controlled study of 12 subjects diagnosed as having mild to moderate hypertension and hypercholesterolemia, pyrazinoylguanidine (PZG) in a dose of 600 mg twice daily for 4 weeks reduced systolic blood pressure and heart rate. Pyrazinoylguanidine also reduced diastolic pressures, but to a lesser extent. Pyrazinoylguanidine reduced total serum cholesterol and low-density lipoprotein (LDL). Regression analysis indicated a dose-dependent reduction of both total cholesterol and LDL by PZG, i.e., the higher the presenting serum concentration, the greater the reduction by PZG. The extent of the reductions produced by PZG in elevated cholesterols and LDLs was highly correlated (r = .949). Normal high-density lipoprotein levels were unchanged by PZG. Pyrazinoylguanidine increased 24-hour urine volume and urinary excretion of sodium. Serum Na+, K+, or Cl- concentrations were unaltered. Means for plasma aldosterone and renin activities tended to decrease, but these trends did not attain statistical significance. Pyrazinoylguanidine was well tolerated. An activity profile that includes antihypertensive effects as well as reduction in hypercholesterolemia without major impact on serum renin or electrolyte balance makes PZG an attractive candidate for the management of hypertension.

Aged↗
PubMed1991

[Immunologic studies of benzodiazepine--the effect of structural characteristics on cross-reactivity].

The manufacturers' descriptions for immunoassays for the detection of benzodiazepines in urine suggest that all therapeutically used benzodiazepines are detected equally. It is unlikely that the different molecular structures do not influence the results of pertinent measurements. Therefore, the cross-reactivity of 35 benzodiazepines and benzodiazepine-metabolites was determined with the TDx-system. As compared to nordiazepam all compounds--except diazepam--had a reduced cross-reactivity. In order to get a TDx result equal to or exceeding 200 ng/ml nordiazepam-equivalents, high benzodiazepine concentrations in urine are required in some cases. These high concentrations are not obtained in the therapeutic range of application. These considerations can be applied to other immunoassays like RIA and EMIT.

Benzodiazepines↗
PubMed1990

Novel multivalent effects of pyrazinoylguanidine in patients with azotemia.

In patients with azotemia, urea excretion, urea clearance, and urea/creatinine clearance ratio were increased by pyrazinoylguanidine in a dose-related manner. Urine volume and excretion of sodium greater than chloride greater than potassium tended to increase during administration of pyrazinoylguanidine. Systemic arterial pressure declined while pyrazinoylguanidine was given at 300 or 600 mg b.i.d. for 3 days. At both doses pyrazinoylguanidine reduced plasma renin activity during the first 2 hours. Between days 1 and 3 only the high dose of pyrazinoylguanidine decreased plasma renin activity and plasma aldosterone levels. These findings with pyrazinoylguanidine are consistent with those of secretion of urea in human subjects across the renal tubules and indicate that this process is susceptible to pharmacologic alteration, even in the presence of severe renal insufficiency.

Adult↗
PubMed1988

[Fatal diltiazem poisoning].

The diagnosis at postmortem examination and the results of the chemical analysis in a case of a diltiazem intoxication are presented. Two metabolites were identified as desacetyldiltiazem and N-desmethyldiltiazem.

Alcoholism↗
PubMed1988

Active transport of urea by mammalian kidney.

With the aid of three basic organic compounds, 2-pyrazinoylguanidine, 3-amino-2-pyrazinoylguanidine, and 3,5-diamino-6-fluoro-2-pyrazinoylguanidine, urea was shown to be secreted by the renal tubules of the dog both from the lumen and into the lumen independent of urine flow.

Amiloride↗
PubMed1986

Fatal poisoning with selenium dioxide.

Two hours after suicidal ingestion of an unknown amount of selenium dioxide, a 17-year-old male was admitted to hospital with asystolia and apnea. Attempts at resuscitation failed and the patient was pronounced dead. Findings at autopsy included congestion of lungs and kidneys, diffuse swelling of the heart, and brain edema. The most impressive finding was an orange-brown discoloration of the skin and all viscera, probably due to hemolysis and/or pigmentation related to ingestion of selenium dioxide. Selenium blood and tissue levels were increased by a factor of 100-1000 as compared to normal. The highest concentrations were found in pancreas, spleen, liver, and adipose tissue. For elucidation of the chemical nature of selenium in tissues, a new analytical method which was based on carbon disulfide extraction was developed. Carbon disulfide is a good solvent for non-polar selenium compounds like elemental selenium and selenium disulfide, but not for polar compounds like selenite and selenoproteins. A major fraction of selenium in tissues was extractable by carbon disulfide, which seems to indicate the presence of elemental selenium and/or selenium disulfide. The color of these substances is red and orange, respectively. This might explain at least part of the discoloration of skin and tissues. In vitro experiments suggested that trace amounts of hydrogen selenide, which is an intermediate of selenite metabolism, probably induced hemolysis. For evaluation of the therapeutic value of hemoperfusion in selenium poisoning in vitro hemoperfusion experiments were performed, which revealed only a moderate effect on selenium blood levels.

Adolescent↗
PubMed1985

Sodium balance and blood pressure during high sodium ingestion in spontaneously hypertensive and Wistar Kyoto normotensive rats.

Objectives of this study were to compare natriuretic capability and arterial pressure elevation at high Na+ ingestion in male spontaneously hypertensive (SH) and normotensive Wistar Kyoto (WKY) rats at the young adult age of 16-19 weeks. 10 SH and 10 WKY male rats at this age were surgically implanted with arterial catheters. After a period of 10 days on low nutritionally adequate Na+ intake they were fed a high Na+ diet for a period of 1 week. Na+ retention (intake-output) on the high Na+ diet was substantial, but similar in both groups of rats. None of the animals displayed meaningful elevation of arterial pressure. Thus, the functional capacity of the young SH rat to excrete Na+ during excessive ingestion without elevation of blood pressure seems adequate as compared to normotensive rats, at least within the age range of 16-19 weeks.

Animals↗
PubMed1985

Metabolism of propallylonal.

Urinary metabolism of 5-beta-bromoallyl-5-isopropylbarbituric acid (propallylonal, Noctal), was studied in humans after an oral dose of 400 mg. About 25% of the dose was eliminated via kidneys within 48 h. Besides the unchanged drug, six metabolites could be detected. The main metabolic pathway is the hydrolysis of the beta-bromoallyl side chain to an acetonyl function (approximately 15%). The acetonyl function is subsequently reduced to the corresponding alcohol. Loss of water leads to aprobarbital which is partially oxidized to aprobarbital epoxide. Two further metabolites are formed by partial and complete oxidative degradation of the beta-bromoallyl side chain. In contrast to previously published results, no N-methylpropyllalonal could be detected. The plasma protein binding was determined by ultrafiltration (63%). Analysis of propallylonal in plasma and whole blood gave evidence for equal distribution between plasma and erythrocytes.

Barbiturates↗
PubMed1983

Sustained concurrent blood pressure and salt/water balance in unrestrained rats.

Methodology is detailed that provides sustained concurrent measurement of fluid volume and electrolyte intake and output with direct measurement of arterial pressure in unrestrained, unanesthetized spontaneously hypertensive rats (SHR). This method employs an all-Teflon arterial pressure conduction system, an air-pressurized infusion system, and standard rat metabolism cages. Blood pressure-salt/water balance studies comparing SHR unoperated, sham operated, and infused at several infusion rates and saline normalities indicated that infusion of 0.25 N saline at 0.5 ml/h sustained a patent system for high-fidelity recording of systolic and diastolic blood pressure without distortion of homeostasis over a 3-week period. Studies of basal SHR blood pressure and salt/water balance suggested that the SHR primarily used renal water-conserving mechanisms to dilute net acquired salt over an 11-day period. This methodology for sustained blood pressure measurement appears to represent a significant improvement for direct blood pressure measurement in unrestrained, unanesthetized rats.

Animals↗
PubMed1982

Chlorothiazide.

Explore the source record for details and available documents.

Animals↗