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Biomedical subjects

S K Lin

Publications and source records attributed to S K Lin.

96 records · Page 6Linked to original sources

Observation on the metabolism of iopanoyl (Telepaque) glucuronide in dogs treated with antibiotics.

The purpose of our investigation was to determine whether iopanoyl glucuronide, the major metabolite of iopanoic acid (Telepaque), undergoes hydrolysis by bacterial beta-glucuronidase in dogs. The conjugated compound was identified and quantitated by elemental analysis, fluorescent excitation analysis, thin-layer chromatography, and high pressure liquid chromatography. The experiments were performed before and after combined antibiotic treatment with neomycin and vancomycin. It was first determined that reabsorption and excretion of sodium iopanoate was only minimally diminished during antibiotic treatment. Known amounts of iopanoyl glucuronide were infused into the small bowel of 4 awake dogs with chronic bile fistula, and bile was collected for 5--8 hours. The excretion of the recirculated conjugated compound was 4--5 times lower during antibiotic treatment. Incubation of ileal fluid with bile containing iopanoyl glucuronide suggested that beta-glucuronidase hydrolyzes the conjugated compound. Hydrolysis was markedly decreased after pretreatment with antibiotics. These findings suggest that the beta-glucuronidase produced by bacteria may be a major mechanism in enterohepatic recirculation of iopanoyl glucuronide. Mechanisms and possible implications are discussed.

Animals↗

Pharmacokinetics of iopanoic acid in the rhesus monkey: biliary excretion, plasma protein binding and biotransformation.

A dynamic infusion method, originally developed for the pharmacokinetic studies of Iodoxamic acid, was applied to the kinetic studies of the biliary excretion of another cholecystographic agent, iopanoic acid. This dynamic method has an important advantage in that the pharmacokinetic parameters involved in the hepatic uptake or biliary excretion can be evaluated from a single infusion experiment. Using the equilibrium dialysis technique, iopanoic acid was found to be highly bound to the plasma proteins. A linear relationship was found when the logarithm of unbound plasma concentration of iopanoic acid was plotted vs. the logarithm of its blood concentration. When the biliary excretion rates of iopanoic acid were fitted by a computer to the Michaelis-Menten equation against its unbound plasma concentration, the average Vm value was found to be 0.85 micron/kg/min and the average Km value was found to be 0.253 micron. Iopanoic acid was found to exist in monkey blood as unchanged species and in the bile mainly as the ester glucuronide.

Animals↗

Gastrointestinal radiology. Pharmacokinetics of iopanoate and iodoxamate in rhesus monkeys.

The pharmacokinetics, biliary excretion, plasma protein binding, enterohepatic circulation, and biotransformation of iopanoic acid and iodoxamic acid in the rhesus monkey were evaluated by a dynamic infusion method. The dynamic method has the advantage that the pharmacokinetic parameters involved in the hepatic uptake and biliary excretion can be evaluated from a single infusion experiment. The percentage of iodoxamic acid not bound to plasma protein varied from 6.1-41.2% as iodoxamic acid plasma levels were from 42 microM to 912 microM. Using the Freundlich isotherm approach, more than one class of binding site for iodoxamic acid was found. A saturable biliary excretion mechanism or hepatic uptake mechanism was determined with a Vmax of 1.03 microM/kg/min. Less than 1% of iodoxamic acid injected into the duodenum was recovered in the bile in 12 hours. Iodoxamic acid was found to exist in blood as an unchanged species. Iopanoic acid was extremely highly bound to monkey plasma protein. As blood concentration increased from 18.9 to 464 microM, the percentage unbound in plasma protein varied from 0.1-2.8%. Biliary excretion rates of iopanoic acid were fitted by a computer to the Michaelis-Menten equation against unbound plasma concentration and the average Vmax value was found to be 0.85 microM/kg/min with an average Kmax value of 0.253. Iopanoic acid was found to exist in monkey blood as unchanged species and in the bile mainly as an ester glucuronide. Coadministration experiments revealed that the interaction of iodoxamic acid and iopanoic acid in the monkey is complex. The compounds appear to compete for plasma protein binding sites as well as for binding sites on intrahepatic protein. The biliary excretion data seem to fit the ligant exclusion model, in which iopanoic acid acts as an inhibitor and competes with iodoxamic acid for binding to either of two identical sites in the liver, which, presumably, is the rate-limiting step in the liver's overall elimination of these radiographic agents.

Animals↗

A comparison of diagnostic tests to determine Helicobacter pylori infection.

Twenty-five Helicobacter pylori positive and 25 H. pylori negative subjects as defined by culture and phase contrast microscopy of antral biopsy specimens obtained from routine upper endoscopy were studied. Antral biopsies were examined by rapid urease test, phase contrast microscopy, culture and histology. Venous blood was tested for H. pylori specific IgG antibodies by an ELISA technique. Within 7 days of endoscopy the patients also had a [14C]-urea breath test. The sensitivity and specificity of the rapid urease test was 92%, the breath test 96% and 100%, histopathology 96% and 91% and serology 96% and 88%, respectively. The [14C]-urea breath test performed over 1 h with sampling of subjects at 0, 0.5 and 1 h was an accurate and reliable method. Results expressed as counts per minute of the expired 14CO2 proved to be a simple method of assessing H. pylori status. A significant correlation between severity of histological antral gastritis and the amount of 14CO2 expired was observed. This study has shown that the non-invasive 14C-urea breath test and serology are highly sensitive and specific for the diagnosis of H. pylori infection.

Breath Tests↗

Helicobacter pylori prevalence in endoscopy and medical staff.

The epidemiology and mode of transmission of Helicobacter pylori is currently unclear; it is postulated that the human stomach is the natural reservoir and that spread occurs by faecal-oral or oral-oral transmission. The aim of this study was to assess the prevalence of H. pylori in gastroenterologists and gastroenterology nurses compared with internists, general nurses and the normal population. An enzyme-linked immunosorbent assay technique (sensitivity 96%, specificity 88%) was used to detect circulating H. pylori immunoglobulin G antibodies in 39 gastroenterologists, 107 gastroenterology nurses, 25 internists and 42 general nurses. These subjects were compared to an age- and sex-matched Caucasian population obtained by random sampling of an urban population area. The overall prevalence of H. pylori in gastroenterologists was 69% compared to 40% of internists (P < 0.01), 17% of gastroenterology nurses (P < 0.001), 19% of general nurses (P < 0.01) and 32% of controls (P < 0.01). There was no significant difference in H. pylori prevalence between the gastroenterology nurses and controls, general nurses and controls. The prevalence in gastroenterologists increased with years of practice to levels greater than age-matched controls. The prevalence in gastroenterology nurses increased with age and years of working and was similar to age-matched control subjects. These findings of an increased prevalence of H. pylori infection in gastroenterologists performing endoscopy support human-to-human transmission possibly from patients to medical staff.

Adult↗

Cerebral arteritis associated with oral use of phenylpropanolamine: report of a case.

Phenylpropanolamine (PPA) is the major ingredient of many over-the-counter cold remedies and diet pills. Use or abuse of PPA may cause hemorrhagic stroke or cerebral vasculitis similar to the clinical and angiographic picture associated with amphetamine use or abuse. We report a 32-year-old Taiwanese women who developed sudden onset of severe headache, nausea and vomiting on the seventh day of oral ingestion of 75 mg PPA per day. Cerebral angiograms showed multiple areas of alternating focal constriction and dilatation ("beading" appearance) in the anterior and posterior cerebral arteries consistent with cerebral arteritis. This case should alert medical practitioners to the potential hazards of over-the-counter drugs like PPA.

Administration, Oral↗