Search PubMed⌕ Search

Biomedical subjects

B Suh

Publications and source records attributed to B Suh.

36 records · Page 2Linked to original sources
PubMed1988

In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoylglycine in newborns.

Hyperbilirubinemia is frequently observed in neonates, and serious neurological complications such as kernicterus can be precipitated when the concentration of unconjugated bilirubin is abnormally increased. The administration of drugs which bind to albumin and compete with bilirubin can increase the possibility of such a complication. To test the bilirubin-displacing activity of pharmacological agents that are used with newborns, 52 antimicrobial agents were investigated in vitro. A glycine conjugate of salicylate, 2-hydroxybenzoylglycine, which is known to be present at elevated levels in newborns and has a potent bilirubin-displacing property, was used as a positive control agent. Pooled cord serum was used as a source of hyperbilirubinemic serum. A centrifugal ultrafiltration method with semipermeable cones was employed to determine the effects of potential bilirubin-displacing agents on the levels of total bilirubin. 2-Hydroxybenzoylglycine was demonstrated to be the most potent bilirubin-displacing agent. Antibiotics could be classified into four groups: high-level displacers (sulfisoxazole, sulfamethoxazole, dicloxacillin, cefoperazone, and ceftriaxone), intermediate-level displacers (moxalactam, nafcillin, and 14 others), low-level displacers (aztreonam, carbenicillin, and 11 others), and nondisplacers (mezlocillin, cefuroxime, kanamycin, and 15 others). It is concluded that the ultrafiltration method is a rapid and readily reproducible for the determination of bilirubin displacement and that antibiotics with a tendency to displace bilirubin should be avoided in jaundiced newborns whenever appropriate alternatives are available.

Anti-Bacterial Agents↗
PubMed1987

Demonstration of 2-hydroxybenzoylglycine as a drug binding inhibitor in newborn infants.

Newborn infants have drug binding defects that share similarities to those of uremic subjects. Since 2-hydroxybenzoylglycine has been chemically defined to be a major drug binding inhibitor in uremia, a search for the presence of a similar compound in the sera of newborn infants was made. An organic substance that has the characteristics of 2-hydroxybenzoylglycine as supported by the retardation factor values on thin-layer chromatograms, retention times of high performance liquid chromatograms, fluorescence emission spectra, and mass spectrum has been demonstrated to be present in the majority of the neonatal sera studied. A strong positive correlation between the levels of the binding inhibitor and the extent of binding defects for nafcillin has been observed. The substance could effectively reduce the total bilirubin concentration when added to the cord sera specimens. It is concluded that 2-hydroxybenzoylglycine plays an important role in drug binding defects observed in the newborn, and the inhibitor may also play a part in the precipitation of bilirubin-induced neurotoxicity in neonates when the substance is abnormally elevated.

Bilirubin↗
PubMed1986

A new HPLC analytical method for o-hydroxyhippuric acid in uremic serum.

o-Hydroxyhippuric acid (HHA) is formed in liver during the process of detoxication of salicylic acid which arises from either salicylic-containing dietary vegetables or hydrolysis of aspirin. Recently, HHA has also been shown as one of the so-called 'uremic toxins'. By derivatization of HHA with o-phthaldialdehyde (OPA), the resulting fluorescent product can easily be measured with the limit of measurement somewhere below 3 pmol on high performance liquid chromatography. Using the method described, an approximately 85% recovery of added HHA in human sera was obtained. This analytical system is now being employed to determine the concentration of HHA in human sera of uremic patients. Determination of HHA content in human uremic patients is very important, since uremia is associated with defective binding of many acidic drugs to serum protein(s) and HHA replaces these drugs by tightly binding to these proteins. This could potentially affect the therapeutic effectiveness of various pharmacologic agents.

Chromatography, High Pressure Liquid↗
PubMed1985

Case report: prosthetic valve endocarditis due to a nutritionally variant streptococcus.

The first report of prosthetic valve endocarditis due to a nutritionally variant streptococcus is presented. A 21-year-old woman developed persistent fever within one week of mitral valve replacement. Prosthetic valve dysfunction developed necessitating valve replacement. Cultures of blood and the excised prosthetic valve using routine media were negative; Streptococcus mitior grew as satellite colonies around Staphylococcus aureus and in beef heart infusion broth supplemented with 0.001% pyridoxine HCl. Treatment with penicillin G and streptomycin for six weeks was curative. Nutritionally variant streptococci should be considered in patients with prosthetic valve endocarditis and negative routine cultures.

Adolescent↗
PubMed1983

Isolation and chemical characterization of 2-hydroxybenzoylglycine as a drug binding inhibitor in uremia.

An organic compound that inhibits drug binding in uremia has been isolated from the sera of chronic renal failure patients, and its chemical structure has been determined. Addition of the compound to normal human sera in vitro resulted in drug binding defects similar to those seen in uremia. The purification of this substance was accomplished by n-butyl chloride extraction of acidified (pH 3.0) uremic sera followed by column chromatography, thin-layer chromatography, and paper electrophoresis. From analytical studies including ultraviolet and fluorescence spectroscopy, gas chromatography, chemical ionization and electron impact mass spectrometry, and proton nuclear magnetic resonance spectroscopy, the chemical structure of the uremic binding inhibitor was deduced to be 2-hydroxybenzoylglycine. This confirms the hypothesis that the drug binding defect in uremia is due to the accumulation of endogenous metabolic products rather than an intrinsic structural defect in albumin.

Chemical Phenomena↗
PubMed1982

Correction of drug binding defects in uremia in vitro by anion exchange resin treatment.

Serum protein binding of weakly acidic drugs is impaired in uremia, but that of basic drugs tends to be normal. Treatment of uremic serum with anion exchange resin (Amberlite CG-400, acetate form) corrected binding defects for three acidic drugs (nafcillin, salicylate and sulfamethoxazole) but did not affect the binding of two basic drugs (trimethoprim and quinidine). Resin treatment of normal human serum did not alter the binding of these five drugs. Extraction of the acetate buffer eluate from resin exposed to uremic serum with n-butyl chloride at acidic pH (3.0) resulted in a fraction that could induce similar binding defects in normal human serum. The factor(s) responsible for binding defects in uremia appears to be lipid soluble, weakly acidic, and dialyzable. It is believed to be tightly bound to albumin at physiologic pH, but dissociates from it at acidic pH. These findings further support the previously proposed hypothesis that drug-binding defects in uremia are due to accumulation of certain endogenous metabolic product(s).

Adult↗
PubMed1981

Effect of free fatty acids on protein binding of antimicrobial agents.

The effect of free fatty acids (FFAs) on the binding of antibiotics to human serum proteins was studied by addition of palmitic acid to albumin solutions and normal pooled serum. FFA reduced the binding of dicloxacillin, cefamandole, and sulfamethoxazole at molar ratios of FFA to albumin of greater than 2.0. In contrast, FFA enhanced the binding of benzylpenicillin, cephalothin, and cefoxitin at physiologic molar ratios of FFA to albumin. Elevated levels of FFAs induced in vivo by heparin produced similar results with dicloxacillin and benzylpenicillin. Addition of FFA to serum, but not to albumin, reduced the binding of clindamycin and trimethoprim. That the binding of these drugs was much lower in albumin than in serum suggested the presence in serum of another antibiotic-binding protein and that FFAs can modulate binding to this protein. Binding of chloramphenicol was unaffected by FFAs. The possible clinical significance of the changes in protein binding due to FFAs is discussed.

Anti-Bacterial Agents↗
PubMed1981

Cerebrospinal fluid shunt colonization and obstruction by Paecilomyces variotii. Case report.

A 57-year-old woman underwent ventriculoperitoneal shunt placement for noncommunicating hydrocephalus. She required several shunt revisions over a 2-year period for recurrent hydrocephalus. The shunt was subsequently found to be obstructed by growth of the saprophytic fungus, Paecilomyces variotii, an infrequent human pathogen. Paecilomyces infections have caused complications associated with prosthetic cardiac valves and synthetic lens implantation; this is the first reported association with a cerebrospinal fluid shunt.

Cerebrospinal Fluid Shunts↗
PubMed1981

Partial purification and characterization of the drug-binding-defect inducer in uremia.

The chemical basis of drug-binding defects in uremia was investigated by studying the effects of extraction of uremic sera with an organic solvent (n-butyl chloride). Extraction of uremic sera at acidic pH (3.0) with n-Butyl chloride fully corrected the binding defects for three acidic drugs (nafcillin, sulfamethoxazole, and salicylate), whereas binding of two basic drugs (trimethoprim and quinidine) was unaffected by similar treatment. When added to normal human serum or purified human serum albumin, the organic solvent layer was capable of inducing binding defects similar to those seen in uremia. Further fractionation of the organic solvent layer with purified human serum albumin at physiologic pH (7.4), followed by reacidification and extraction of the acidified albumin layer with the same solvent, gave a homogeneous fraction on thin-layer chromatography. This homogeneous fraction could induce the binding defects observed in uremia when added to normal human sera. This factor(s) is apparently a dialyzable and weakly acidic compound. It is lipid-soluble and tightly bound to albumin at physiologic pH, but extractable at acidic pH. Its molecular weight is approximately 500 or less. These findings strongly support the hypothesis that the drug-binding defect in uremia is due to accumulation of endogenous metabolic products rather than to an intrinsic structural abnormality in serum albumin.

Biological Products↗
PubMed1979

New rapid assay for nafcillin in serum by spectrofluorometry.

A new, rapid method for measuring serum levels of nafcillin by spectrofluorometry is described. The method involves extraction of 2 ml of acidified serum with n-butyl chloride, subjecting the organic solvent layer to excitation at 340 nm, and measuring the relative intensity of emission fluorescence at 380 nm. An excellent linear correlation exists between serum levels of nafcillin and the relative intensity in a drug concentration range of 0.25 to 150 mug/ml. The results obtained by this spectrofluorometric technique are in complete accord with those obtained by the conventional microbiological assay using Staphylococcus aureus ATCC 6538P. The method is not interfered with by elevated levels of endogenous metabolic products or the presence of other drugs, including a number of antimicrobial agents. The assay is interfered with, however, by the presence of salicylates, for which appropriate correction can easily be made. A salicylate assay employing a spectrofluorometric technique is also described.

Biological Assay↗
PubMed1979

Oral neomycin dosage schedules for suppression of ammonia production by bowel flora.

To better define a minimal but optimal dose of oral neomycin to suppress ammonia production by bowel flora, several dosage regimens were examined in normal healthy volunteers. Fecal urease activity was quantitatively determined and was used as an indirect measure of intrinsic ammonia production by bowel flora. Large doses of neomycin were found to exert inhibition of fecal urease for many days. There was considerable variation in enzymatic activity among subjects even after adjustments were made for protein content of the stool. Depending on the dose, there was a 1- to 3-day lag in neomycin effect on stool urease activity and several days of continued effect. The most effective regimen of those studied was a loading dose of 6 g of neomycin given in three divided doses on day 1, followed by 1 g twice daily.

Adult↗
PubMed1979

Rapid assay for determination of trimethoprim and sulfamethoxazole levels in serum by spectrofluorometry.

A rapid spectrofluorometric method for determining the levels of both trimethoprim and sulfamethoxazole from the same specimen of serum is described. The method involves stepwise extraction of the specimen first with chloroform at an alkaline pH (pH 9.0) for trimethoprim followed by n-butyl chloride at an acidic pH (pH 2.0) for sulfamethoxazole. To quantitate trimethoprim, the chloroform layer was subjected to fluorometry by exciting the specimen at 295 nm and measuring the relative intensity at 330 nm. To determine sulfamethoxazole levels, the n-butyl chloride layer was subjected to fluorometry by exciting the specimen at 285 nm and measuring the relative intensity at 330 nm. Relative intensities were linear (r greater than 0.99) over the concentration ranges of 0.5 to 40 microgram/ml for trimethoprim and 1 to 400 microgram/ml for sulfamethoxazole. Values obtained by this spectrofluorometric procedure were in excellent agreement with those obtained by a conventional fluorometric assay for trimethoprim and a colorimetric assay for sulfamethoxazole. Elevated levels of endogenous metabolic products and numerous other drugs, including a number of antimicrobial agents, did not interfere with the method. Although salicylates interfere with the determination of sulfamethoxazole, an appropriate correction can be made. This method can also be used to determine the drug levels in cerebrospinal fluid.

Humans↗
PubMed1978

Changes in protein binding during disease.

Disease states can alter protein binding of antimicrobials by either a reduction in the concentration of serum proteins or the accumulation of endogenous compounds, such as bilirubin and free fatty acids (FFA), that affect drug-protein interactions. In terms of protein concentration, extremely low levels of albumin (less than 2.5 m/100 ml) are required to markedly reduce binding of antimicrobials. In vitro addition of high concentrations of bilirubin and FFA to normal serum reduces binding of most antimicrobials. However, binding of some antibiotics appears to be enhanced at lower concentrations of FFA probably by an allosteric mechanism. These in vitro observations have been confirmed in sera from patients during heparin administration and patients with hyperbilirubinemia. Reduced protein binding of acidic antimicrobials in uremia appears to be associated with the accumulation of another, as yet unknown, endogenous binding inhibitor. Significant reduction in protein binding can affect the distribution of drugs and results of microbiologic assays.

Anti-Bacterial Agents↗
PubMed1978

Theory and practical impact of binding of antimicrobials to serum proteins and tissue.

Binding of antimicrobials to serum proteins and tissue affects their distribution, elimination and antimicrobial activity. Penetration of drugs into most tissues and interstitial and inflammatory fluids correlates with level of free drug in serum. Serum protein binding can increase or decrease the rate of drug elimination depending on whether total or free drug is available to the excretory or metabolic routes of elimination. Binding to soluble intracellular proteins (ligandin and fatty acid binding protein) appears to be important in the cellular transport and elimination of antimicrobials by renal tubular secretion and hepatic extraction. Although only free, unbound drug is antimicrobially active, the lack of well designed studies has prevented precise quantitation of the influence of binding on therapeutic efficacy in vivo. Pharmacokinetic considerations predict that serum binding greater than 80% would be necessary to significantly reduce free levels of drug in the body. However, extensive protein binding is often compensated for by greater intrinsic activity of lipophilic antimicrobials.

Animals↗
PubMed1969

Formation of thiosulfate from sulfite by Desulfovibrio vulgaris.

Crude extracts of Desulfovibrio vulgaris reduced sulfite to sulfide. Ammonium sulfate fractionation of crude extracts separated a thiosulfate-forming system from sulfite- and thiosulfate-reductase activities. Further purification by sucrose density centrifugation separated the thiosulfate-forming system into two components, both of which were required for the reaction. In addition to these two components, cytochrome c(3), ferredoxin, and hydrogenase were required to form thiosulfate from sulfite. By absorption spectra and from the effect of pH and substrate concentration, the ionic species acting as the substrate for thiosulfate-formation was concluded to be bisulfite.

Cell-Free System↗
PubMed1966

Pyruvate-carbon dioxide exchange reaction of Desulfovibrio desulfuricans.

Suh, Byungse (University of Kansas, Lawrence), and J. M. Akagi. Pyruvate-carbon dioxide exchange reaction of Desulfovibrio desulfuricans. J. Bacteriol. 91:2281-2285. 1966.-The pyruvate-CO(2) exchange reaction, catalyzed by Desulfovibrio desulfuricans, required the presence of phosphate and coenzyme A. However, the requirement for phosphate disappeared when the concentration of coenzyme A was increased to a level of 3.8 x 10(-3)m. Passing crude extracts through a diethylaminoethyl-cellulose column and an Amberlite CG-50 ion-exchange column, to remove ferredoxin and cytochrome c(3), resulted in a marked decrease in exchange activity; full activity was restored by the addition of ferredoxin or cytochrome c(3). Fe(++) or Co(++) stimulated the exchange of CO(2) into pyruvate.

Carbon Dioxide↗