Prostaglandin F2\ g=a\ . (PGF2\g=a\) is luteolytic in the ewe when infused into the ovarian artery (Barrett, Blockey, Brown, Cumming, Goding, Mole & Obst, 1971; McCracken, Baird & Goding, 1971) or the ipsilateral uterine vein (Thorburn & Nicol, 1971). These observations, together with the identification of PGF2\g=a\ in the uterine venous plasma of anaesthetized ewes towards the end of the oestrous cycle (Bland, Horton & Poyser, 1971;McCracken et al. 1971), strongly suggest that PGF2\g=a\ is the uterine luteolytic factor in sheep. This paper describes in detail the changes in PGF concentration in utero\p=m-\ovarian venous plasma of conscious ewes during the oestrous cycle.Polyvinyl catheters (1\m=.\5 mm o.d.) were inserted into the right and left utero\p=m-\ ovarian veins via uterine vein branches in two Merino ewes 10 and 11 days after oestrus. Utero\p=m-\ovarian venous samples were collected every 2-3 h from the day after surgery.Concentrations of PGF were measured by a radioimmunoassay (Thorburn, Nicol, Bassett, Shutt & Cox, 1972) using antisera raised in rabbits. Prostaglandin F2a and PGFloe compete in an almost identical manner with [9-3H]PGF2lx over the analytical range (0-1-3-0 ng) of the assay. Prostaglandin E2 competes only weakly and no crossreaction was observed with a wide range of steroids and lipids tested. Plasma samples (0-5 ml) were extracted with chloroform, then acidified and re-extracted. The second chloroform extracts were chromatographed on silica gel columns to separate the PGF group from other prostaglandins. Method blanks were equivalent to 0-2 ng PGF and recoveries averaged 60%. Identity of the measured substances as PGF or PGF-like compounds was based on the selective extraction procedure, Chromatographie puri¬ fication and the specificity of the antibodies to PGF ; also negligible values were ob¬ tained with peripheral plasma. Data were corrected for blank values and procedural losses. Progesterone was measured by the method of Thorburn & Schneider (1972).With frequent sampling we detected a complex series of peaks in the concentration of PGF between days 13 and 17 of the oestrous cycle (Fig. 1). These peaks were of short duration and increased in frequency as oestrus approached. Very low concen¬ trations were measured at other times except on days 2 and 3 in samples from one ewe (3976). In this same ewe, which had a corpus luteum (CL) in each ovary, there was striking similarity in the concentrations of PGF on each side (Fig. 1). Ewe 4854 had a single CL in the right ovary during the first cycle.

SUMMARY Progesterone concentrations in the peripheral plasma of goats were measured by a protein-binding assay. The mean concentration was extremely low on the day of oestrus (0·2 ng/ml) and was not significantly different from that found in anoestrous or ovariectomized animals. The concentration increased to a maximum of 4 ng/ml on about day 10 of the 21-day cycle, and decreased rapidly during the last 3 days of the cycle. Plasma progesterone concentration during early pregnancy (2·5–3·5 ng/ml) was similar to the luteal phase value and remained steady from day 8 to day 60. Between days 60 and 70 there was a secondary increase in progesterone concentration which was maintained at this increased level (4·5–5·5 ng/ml) until just before parturition. In twin-bearing animals, the secondary increase was greater. Progesterone concentration decreased rapidly during the 1–2 days preceding parturition, but the concentration was still quite high on the day of parturition (1·25 ng/ml). The progesterone concentration in peripheral plasma was markedly increased during anaesthesia and the operation. After bilateral ovariectomy of the pregnant goat, peripheral progesterone concentration fell rapidly from 9 to 2·5 ng/ml during the first ½ h and then more slowly during the next 5–6 h. The animals aborted 36–48 h later. A consistent positive arterio—venous difference for progesterone was observed across the pregnant uterus in two unanaesthetized goats. These results indicate that the ovary is the main site of progesterone production in the pregnant goat and that production by the placenta is small and unlikely to influence the level of this hormone in the maternal circulation.

Cytarabine is intracellularly activated and correlations have been established between the pharmacokinetic behaviour of active metabolites and their antileukemic effect. Recently, a good response to high-dose treatment of leukemias has additionally been attributed to a so-called low deamination phenotype of cytarabine inactivation. Consequently, these findings would support plasma level monitoring of cytarabine and its metabolite uracil arabinoside in high-dose cytarabine regimens. This pharmacokinetic study presents data attempting to reevaluate these observations. Thirty-seven patients were treated by 3-h high-dose cytarabine infusions (9 patients 1000 mg/m2, 28 patients 3000 mg/m2) as part of their treatment for acute leukemia. Serial blood samples during and post infusion were analysed for cytarabine (araC) and its deamination product uracil arabinoside (araU) using HPLC with UV-detection. Considerable interindividual variation was observed in end-infusion plasma concentrations of araC (1000 mg/m2: 2.1-fold, 3000 mg/m2: 5.5-fold) and araU (1000 mg/m2: 2.7-fold, 3000 mg/m2: 2.9-fold). The median ratio of end infusion concentrations araU/araC (on a molar basis) was 5.6 (S.D. 3.0), extreme ratio values were 2 and 14. No differences of the araU/araC ratio were found between the two dosages used. Minimum plasma araC concentrations at the end of infusion were 10.5 micromol/l and 22.0 micromol/l at a dose of 1000 and 3000 mg/m2, respectively. In our European study population a "fast" deamination phenotype of cytarabine (araU/araC ratio > 14) was not be observed.

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Dose-response curves to aerosol histamine in 102 anesthetized, intubated, spontaneously breathing dogs revealed a spectrum of airway responsiveness with a greater than 40-fold difference between the most and the least sensitive animals. The frequency distribution of responses fits a log normal distribution. No correlation was found between sex, age, or control values of dynamic compliance (Cdyn) and lung resistance (RL) and the dose of histamine required to cause a response. Repetitive studies in 17 dogs observed for up to 20 mo showed that the dose at which an individual dog would respond was reproducible within a narrow range and that the differences between dogs were highly significant (P greater than 0.001). The long-term reproducibility of the response to aerosol histamine in individual dogs suggests that short-term reversible airway insults are not responsible for the range in responses noted between animals.