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A study of the pharmacokinetics of 14C-labeled acetaminophen (AAP) was performed in healthy Japanese subjects receiving an oral microdose of the drug. After separation by high-performance liquid chromatography (HPLC), the levels of AAP and its metabolites in the pooled plasma specimens were quantified using accelerator mass spectrometry (AMS). The total body clearance (CLtot)/bioavailability (F) of AAP was within the variation in the reported values at therapeutic doses, indicating the linearity of AAP pharmacokinetics. AAP-glucuronide (Glu) and AAP-4-O-sulfate satisfied the criteria of safety testing of drug metabolites. AMS could detect AAP-Cys, the active metabolite of AAP conjugated with cysteine, in the urine. Probenecid prolonged the systemic elimination of total radioactivity and caused a marked decrease in AAP-Glu levels in plasma. Probenecid likely inhibited the glucuronidation of AAP and the renal elimination of AAP-4-O-sulfate. Microdosing of 14C-labeled drug followed by AMS is a powerful tool that can be used in the early phase of drug development for pharmacokinetic analysis of drugs and their metabolites and for detecting the formation of active metabolites in humans. [ABSTRACT FROM AUTHOR]

Summary. Feline immunodeficiency virus (FIV) isolates from domestic cats have been classified into five subtypes, designated A, B, C, D and E. Although many FIV-infected cats may have frequent contact with multiple strains of FIV, they usually become infected with a single FIV subtype. In the present study, we demonstrate that peripheral blood mononuclear cells (PBMC) of FIV infected cats were resistant to exogenous FIV (second virus) replication in vitro and that the resistance of these PBMC was mediated by CD8+ T cells. In cats with a low anti-FIV activity of CD8+ T cells, the proviral DNA of the second virus inoculated into PBMC was detected intracellularly, and both the second and the originally infecting strain (original virus) were produced in the culture supernatant. In contrast, in cats with a high anti-FIV activity of CD8+ T cells, both the proviral DNA of the second virus and the original virus were detected in PBMC intracellularly, but neither virus was produced in the culture supernatant. However, when PBMCs from these cats were depleted of CD8+ T cells, the RNA of both viruses was detected in the culture supernatant. These results suggest that CD8+ T cells inhibit the late phase of FIV replication after viral integration. Moreover, the inhibition was also effective against FIV strains of different subtypes from that of the original strain. It appears that the CD8+ T cell-mediated immune response plays important roles in the maintenance of an asymptomatic state in FIV-infected cats and their resistance to superinfection. [ABSTRACT FROM AUTHOR]

A cylindrical position-sensitive x-ray gas detector has been designed, which allows a complete powder pattern to be recorded simultaneously from a specimen placed at the center of the detector circle. It covers an angular range 2θ of 120° at a 25-cm radius and works in the self-quenching streamer mode of gas ionization to provide 0.06° resolution in 2θ. Powder line positions can be determined with an accuracy of ± 0.05°. The quality of detected patterns is well suited to profile analysis. Tests made at a classical x-ray source showed that recorded line profiles are describable by asymmetric Pearson VII functions. The designed instruments have successfully been applied to in situ powder data collection from a BaBiO[sub 3-x] specimen at high temperatures and subsequent structure refinement by profile-fitting techniques. These features make the detector most suitable to the studies of fast structure changes like phase transitions with synchrotron radiation. [ABSTRACT FROM AUTHOR]

Mongolian gerbils are a laboratory host for gastric colonization with Helicobacter pylori, showing gastritis followed by typical gastric ulcer after infection with H. pylori. In such gerbils, we evaluated combined therapies of amoxicillin (AMPC) and clarithromycin (CAM) as antibiotics, and omeprazole (OPZ) as a H+/K+ adenosine triphosphatase (ATPase) inhibitor. The gerbils were orally inoculated with 2 x 10(8) bacilli of H. pylori ATCC 43504. Four weeks after inoculation, the infected gerbils were orally treated singly with OPZ, AMPC, and CAM, and their insufficient efficacy on bacterial clearance was confirmed by a polymerase chain reaction technique, and by a culture method. In contrast, combined therapy of OPZ plus either AMPC or CAM showed significant bacterial clearance, demonstrating the efficacy of this combined therapy in the gerbil model. Mongolian gerbils are suggested to be useful for the pharmacological evaluation of anti-H. pylori compounds. [ABSTRACT FROM AUTHOR]