Blood samples were removed via chronic intra-atrial cannulae every 15 min in female rats during the estrous cycle, the last week of pregnancy, parturition and suckling. Growth hormone (GH) secretion during the estrous cycle is characterized by episodic release, occurring approximately once hourly. The surges in GH increase during the last 3–4 days of gestation, and rise to high levels during delivery and with suckling. Prolactin (PRL) shows minimal fluctuations during the estrous cycle, except for a prominent pulsatile surge during proestrus. PRL rises 4–6 h prior to parturition and declines during delivery. These studies provide a basis for further studies on the dynamics of GH and PRL secretion in the female rat.

The authors determined mean day-to-day (daily over five days), mean week-to-week (weekly over five weeks) and mean hour-to-hour (800 h, 1100 h, 1400 h) physiologic intra-individual variation of concentration values of leukocyte cell types, platelet count, and erythrocyte values (hematocrit, hemoglobin) for a group of 20 healthy adult volunteers. Total leukocyte counts and concentration values of leukocyte cell types were determined in duplicate on the Hemalong-DTM Automated Leukocyte Differential Cell Counter to minimize analytic variation. The data sets were analyzed according to an analysis of variance model. The mean physiologic hour-to-hour and week-to-week intra-individual variations in terms of % coefficient of variation included: hemoglobin, 2.5, 2.2; hematocrit, 2.6, 2.7; platelets, 1.6, 6.6; total leukocyte count, 9.4, 15.7; neutrophils, 12.9, 26.0; lymphocytes, 10.3, 13.2; monocytes, 18.6, 19.3; eosinophils, 19.9, 26.9; basophils, 7.4, 15.0; large unstained cells, 13.7, 16.0; "high-peroxidase" cells, 32.7, 25.7. Hour-to-hour variation was partitioned into random diurnal variation, group-consistent diurnal variation, and subject-specific unique individual variation. Subject-specific diurnal variation contributed greatly and statistically significantly to total diurnal variation for many of the leukocyte cell types--especially in the case of eosinophils, where it represented more than half of total diurnal variation.

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The physiologic within-day (700-2200 h) variation of leukocyte-type concentrations in blood as determined for 21 healthy young adults is reported. All blood specimens were obtained in duplicate such that the within-batch analytic variation, as well as the pertinent biologic sources of variation, was able to be determined. All specimens were analyzed on each of two automated leukocyte differential systems: Hemalog-D Differential System and the Hematrak-240 Analyzer. On the basis of a comparison of the performances of the two analyzers, it was decided to report the neutrophil and the lymphocyte values as measured on both systems, the monocyte values as measured on teh Hematrak only, and the eosinophil and basophil values as measured on the Hemalog-D only. The intrasubject within-day physiologic variations for the cell on the Hemalog-D and Hematrak, respectively, in terms of coefficient of variation wee as follows: neutrophils 19.4% and 19.6%; lymphocytes, 13.8% and 17.5%. For monocytes, as measured on the Hematrak, it was 13.4%. For eosinophils and basophils, as measured on the Hemalog-D, it was 27.2% and 8.3%, respectively. There was a consistent group-specific diurnal variance that amounted to more than 40% of the total within-day variance, both for lymphocytes and for eosinophils. The within-day physiologic variation of the cell type concentrations for eight of the volunteers was compared with that of the plasma cortisol concentrations, as determined on specimens derived from the same veni-puncture sessions. The decrease in plasma cortisol values was in most instances associated with decreases in eosinophils and increases in neutrophils. For total leukocytes and neutrophils, the mean concentration for smokers was significantly higher than that for nonsmokers.

The Hemalog D system performs automated differential white cell counts utilizing principles of cytochemistry, electro-optical measurement and signal logic processing. Using 0.4 ml of anticoagulated whole blood and an automated continuous flow staining technique, the system is designed to process a new sample each minute. The decision logic classifies individual cells by size and intensity of staining as they flow through detectors designed to measure light loss and light scattering simultaneously. With this system, 10,000 cells/ sample are classified in less than 1 min. Alcian Blue identifies basophils when used in the presence of quaternary ammonium salts and other counterions. Monocytes are the only cells stained in an esterase method using α-naphthol butyrate at pH 6.1 with hexazonium pararosanilin as coupler. This unstable diazonium is produced on stream continuously from stable components. Size and peroxidase staining serve to classify the remaining cells. Lymphocytes and large mononuclear cells are unstained, neutrophils have moderate peroxidase activity, while eosinophils stain very strongly. Threshold detection logic for light scattering and absorption differentiate the neutrophils, eosinophils and lymphocytes. The distribution of peroxidase activity in neutrophils serves as an index of maturity of these cells. The clinical evaluation of this index is reported elsewhere. Results are reported as percentage and as cells per cubic millimeter. A total white blood cell count is also reported and the pattern of cell measurements for 10,000 cells is provided as a picture with diagnostic information content. Advantages of this system in rapid screening result from improved precision of automation, the processing of large numbers of cells and the saving of labor. Precision also makes the acquisition of sequential data on single patients more meaningful and diagnostically valuable.

A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at 0.03 mg/kg, in the rat moncrotaline model of pulmonary arterial hypertension. Examination of PK/PD data from the optimization effort has revealed in vitro:in vivo correlations which link duration of action in vivo with low permeability and high basicity and demonstrate that nonspecific binding to lung tissue increases with lipophilicity.

It was demonstrated that acridine orange, analogous to cetyl pyridinium chloride, precipitates acid mucopolysaccharides, and that the precipitates can be redissolved in solutions of graded sodium chloride concentration. The established fractional solution technique for acid mucopolysaccharide complexes with cetyl pyridinium chloride has been applied to histochemical staining by replacing the cetyl pyridinium chloride with acridine orange. The staining method described differentiates between the presence of hyaluronic acid, chondroitin sulfuric acid and heparin.

We report the synthesis of deuterium-labelled derivatives of phosphatidylinositol 4-phosphate and phosphatidylinositol 5-phosphate, and demonstrate their use in quantifying levels of endogenous phospholipids in cells.