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Rat liver contains a distinct blood-borne population of NK cells resistant to anti-asialo-GM1 antiserum.

A high level of anti-tumoral (NK) cytotoxicity was observed in the mononuclear population washed out from the liver microvasculature in rat. The level of cytotoxicity against K562 and YAC1 cells, percentage of large granular lymphocytes (LGL) and of OX8+ cells was significantly higher than in the inflowing portal and also caval blood. A low concentration of adherent, phagocytic and OX6+(Ia) cells and a higher level of cytotoxicity after removal of adherent cells ruled out the possibility of liver macrophages to be responsible for the cytotoxicity. Surprisingly, the liver-sequestered NK population turned to be resistant to anti-asialo-GM1 antiserum. Thus, liver microvasculature contains a significant number of cells with characteristics of NK cells which constitute a functionally distinct NK population.

Pharmacokinetics of Oral Co-Trimazine and the Penetration of Its Components Sulfadiazine and Trimethoprim into Peripheral Human Lymph

Five healthy informed male volunteers received oral doses of 820 mg sulfadiazine (SDZ) plus 180 mg trimethoprim (TMP) (co-trimazine) every 24 h. Concentrations in serum, peripheral lymph from the leg and urine were determined after the first dose, and on the 4th day to reflect approximate steady-state conditions. TMP was assayed microbiologically and unchanged SDZ by high-pressure liquid chromatography. There was a rise in concentrations from the first dose to the 4th day. The rise for SDZ was by a factor of 1.6 in both serum and lymph; the rise for TMP was also 1.6 in serum, but 1.5 in lymph. The peak concentrations at steady state were 27.7 mg/l (SD) +/- 4.3 SDZ, and 1.6 +/- 0.68 mg/l TMP. The serum values at that time were 31.7 +/- 5.8 mg/l SDZ and 2.3 +/- 0.51 mg/l TMP. The simultaneous concentrations of both SDZ and TMP were always somewhat lower in lymph than in serum, also at the end of the observation periods, i.e. 12 h after the first dose and 72 h after the final one. But the serum concentrations of both SDZ and TMP were only slightly higher than in lymph. After the final dose, the ratio between the 12-hour areas under the concentration curves of lymph and serum was 0.68 +/- 0.12 for SDZ and 0.59 +/- 0.14 for TMP. The values after the first dose were similar, 0.63 +/- 0.17 and 0.57 +/- 0.05, respectively. The elimination half-life in serum during steady state was 16.5 h for SDZ, 8.6 h for acetylated SDZ and 9.4 h for TMP. In lymph the corresponding values were 19.2, 19.2 and 8.9 h.

Temocillin Penetration of Peripheral Lymph

SummaryAn intravenous dose of temocillin 1g was administered to 5 healthy human volunteers from whom peripheral lymph, serum and urine were monitored for 12 hours. The concentrations after 1 hour were 14.3 mg/L in lymph and 58.1 mg/L in serum. The mean peak concentration in lymph (appearing between 1.5 and 2 hours) was 30.6 mg/L, and the simultaneous serum level was 47.8 mg/L. The lymph concentrations were always below those in serum, and the elimination half life was 4.4 hours from lymph compared wth 4.9 hours from serum. The ratio between the total areas under the concentration curves in lymph and in serum was 0.56, which reflects the ability of temocillin to penetrate to lymph. Serum protein binding appeared to impede the rate of transport from serum to lymph, but when compared with the results of less highly bound penicillins the total penetration of temocillin was better than expected.