Sodium oxacillin in the horse: serum, synovial fluid, peritoneal fluid, and urine concentrations after single-dose intramuscular administration

Six healthy adult mares were given a single dose (25 mg/kg of body weight) of sodium oxacillin IM. Oxacillin concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The mean peak serum oxacillin concentration was 9.75 microgram/ml at 0.5 hour after injection. Mean peak oxacillin concentrations in synovial and peritoneal fluids were 1.45 microgram/ml and 2.60 microgram/ml at 1 hour and 2 hours, respectively. These concentrations decreased in parallel with serum values and were not measurable at 48 hours. Urine concentrations of oxacillin were high, with a mean peak concentration of 2,790.2 microgram/ml at 0.5 hour.     

Immunoglobulin A antibodies to Helicobacter pylori

Serological testing for immunoglobulin G (IgG) antibodies to Helicobacter pylori has proven useful in supporting the diagnosis of infection with this organism, but the clinical value of IgA antibodies in H. pylori-related gastritis remains controversial. The purpose of our study was to determine the frequency of IgA-positive IgG-negative patients with symptoms of gastrointestinal (GI) disorders, thus assessing the clinical utility of IgA testing for H. pylori-related gastritis. It was found previously that the frequency of infected individuals in this category (IgA positive and IgG negative) is about 2%, but a large number of IgG-negative patients with GI disorders suggestive of H. pylori infection have not been investigated until now.     

Characterization of binding properties to human P-glycoprotein: development of a [3H]verapamil radioligand-binding assay

Interaction with the exsorptive transporter P-glycoprotein (P-gp) is a possible source of peculiarities in drug pharmacokinetics, including dose-dependent absorption, drug-drug interactions, intestinal secretion, and limited permeability of the blood-brain barrier. Among the established in vitro methods of the analysis of drug interactions with P-gp, none directly quantifies the affinity of ligands with P-gp. Instead, they measure the result of a membrane permeation and a receptor-binding process; this may lead to difficulties in the interpretation of results. An assay for quantification of drug affinity to the transporter is presented on the basis of the radioligand-binding assay principle. This has the advantage of directly quantifying the interaction between drugs and P-gp. Because of the reversible and competitive interaction of numerous substrates with P-gp, a radioligand-binding assay was developed by taking [3H]verapamil and [3H]vinblastine as radioligands and the human intestinal Caco-2 cells, overexpressed with P-gp by culturing in the presence of vinblastine or transfecting with multidrug resistance gene MDR-1 as receptor preparation. The assay was performed in 96-well plates and has the potential to be used as a high-throughput method. A clear induction of the expression of P-gp was demonstrated in the Caco-2 cells grown in the presence of vinblastine, as well as in the transfected cells, although to a lesser extent. Both radioligands were shown to bind to P-gp. Verapamil was the radioligand of choice for further investigations due to its lower nonspecific binding to the transporter preparation. Kinetics as well as specificity of the binding of verapamil to the P-gp preparation were demonstrated. A two-affinity model was found to adequately describe the data derived from saturation as well as from competition experiments, in accordance with previous findings on two exsorption sites for P-gp. The binding properties of [3H]verapamil and [3H]vinblastine to a P-gp preparation derived from induced Caco-2 cells are described. The concentration-dependent displacement of the radioligand by nonlabeled substrates for P-gp should be a suitable principle for the determination of drug affinity to the respective binding sites at the human intestinal multidrug transporter P-gp.     

The imprinted domain in mouse distal Chromosome 7: reagents for mutagenesis and sequencing

BACKGROUND: Right lower quadrant abdominal pain may pose a diagnostic problem in patients with cystic fibrosis. Abdominal ultrasound examination, used commonly in the diagnostic work-up, may reveal abnormalities of the appendix. However, interpretation of such findings is problematic, because the appearance of the gastrointestinal system during routine examination has not been documented in patients with cystic fibrosis. The purpose of this study was to investigate the findings during routine abdominal ultrasound scans in our cohort of patients with cystic fibrosis and in control subjects. METHODS: Abdominal ultrasound scans were performed prospectively during routine clinic visits in a cohort of patients with cystic fibrosis. RESULTS: Fifty patients aged 10+/-6 years, (range, 0.5-28 years) were examined; 45 had pancreatic insufficiency. Four patients (3 with pancreatic insufficiency) reported right lower quadrant pain at the time of the scan. According to standard ultrasound criteria, the appearance of the appendix was abnormal in 8 patients (16%), 6 had a mucoid appendix, and 2 had a pathologically thickened appendiceal wall. Only 1 of these 8 patients mentioned abdominal pain at the time of the study. Other incidental findings included gallstones (3 patients), intussusception (2 patients), and pancreatic cyst (1 patient). CONCLUSIONS: Abnormalities can be observed during routine abdominal ultrasonographic studies in cystic fibrosis. These findings may not be associated with abdominal pain; their clinical relevance needs further investigation.