Kynurenic acid distribution into brain and peripheral tissues of mice

Kynurenic acid (KYN), an antagonist of excitatory amino acid receptors, is a putative antidote against neuroexcitatory amino acid toxicity. We studied various doses (0.05-3.17 mmol/kg, i.p.) and the effects of probenecid coadministration (0.70 mmol/kg, i.p.) on tissue distribution of KYN in male and female Swiss-Webster mice. After injection of [3H]KYN, samples of brain, heart, liver, kidney, skeletal muscle, and gut were collected at selected times and assayed for KYN by liquid scintillation counting. The substance was absorbed rapidly and distributed into all tissues. Its content (nmol/g, mean +/- SE) at 60 min was 0.26 +/- 0.05, 1.80 +/- 0.05, and 40.4 +/- 8.1 in brain (for 0.05, 0.53, and 3.17 mmol/kg), 1.43 +/- 0.11, 14.3 +/- 3.7, and 212 +/- 32 in heart, 1.16 +/- 0.21, 10.6 +/- 2.6, and 254 +/- 21 in liver, and 7.41 +/- 2.65, 180 +/- 63, and 1899 +/- 254 in kidney. Net accumulation of KYN in brain was much lower than in other tissues. Probenecid increased KYN concentration in brain 2.5-fold. Peak brain:blood concentration ratio occurred between 60 and 180 min, was inversely associated with dose, and was not affected by probenecid. Although brain content was similar, female mice had an earlier peak brain:blood ratio (120 min) than males (180 min) for the 0.05 mmol/kg dose. Our results suggest the presence of a restricted transfer process for KYN with delayed egress from brain.     

Human papillomavirus in laryngeal and hypopharyngeal carcinomas. Relationship to survival

OBJECTIVE: To determine the relationship between human papillomavirus (HPV) DNA detection in upper aerodigestive tract malignancies and patient outcome. DESIGN: Archival paraffin-embedded specimens from 78 previously untreated patients with squamous carcinomas of the larynx and hypopharynx were pathologically verified and analyzed by polymerase chain reaction for detection of HPV DNA. Charts were independently reviewed and coded until final analysis. SETTING: The University of Texas M. D. Anderson Cancer Center, Houston, a tertiary cancer referral center. RESULTS: DNA was successfully extracted from 65 archival patient samples (83%). The mean (+/- SEM) duration of follow-up for these patients was 42 +/- 21 months. Thirty specimens (46%) exhibited detectable HPV DNA. Detection of HPV was significantly related to decreased survival, independent of disease stage. Log rank testing revealed that HPV detection, pathologic vascular invasion, and nodal status were the most significant predictors of death of disease. CONCLUSIONS: Laryngeal and hypopharyngeal carcinomas with detectable HPV may represent a biologically distinct subset of tumors that carry a poorer prognosis than do cancers with no detectable HPV.     

Measurement of plasma oxytocinase. Comparison with urinary excretion of estrogens

Plasma cystinylaminopeptidase (CAP) activity and 24 h urinary excretion of oestrogens were measured simultaneously in 102 pathological pregnancies. The correlation between the two chemical assays is weak (p = 0,13, to 0,47). Plasma CAP levels were significantly (p less than 0,01) lowered in cases of fetal death; but urinary oestrogen assays were within the normal limits (p greater than 0,1) in this group. Each assay suggested an equal number of correct or incorrect prognoses. Their association resulted in 9 correct prognoses in 12 pregnancies with unfavourable outcome, but led to 12 unduly bad prognoses in a group of 40 normal births. The association of the two assays allows a more adequate diagnosis of high-risk pregnancies, but has the disadvantage of offering an unduly bad prognosis in a greater number of normal cases.