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An NMR spectroscopic method for the determination of isosorbide dinitrate, alone or together with alprenolol or propranolol, is described. Spectra are determined in dimethyl sulfoxide-d6 containing maleic acid or 1,4-dinitrobenzene as internal standards. Both synthetic mixtures and commercial formulations were assayed, and the results were compared using compendial procedures.

To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation.

Melatonin induces an apparent platelets emission by rat's megakaryocytes in vitro.

Normal rat's recent bone marrow has been suspended in an isoionic, oxygenated, warmed solution; platelets production by megakaryocytes has never been verified.

Several anatomical, physiological and behavioral factors have part in changing the values of the detection threshold, among which the reflexly secreted oral fluid. The HCl molar concentration appears to be a hyperbolic function of preference (= taste solution/water ratio); the empirical formula of the function makes the HCl molar concentration to be known, at which the same voll. of water and taste solution are drunk, i.e. the taste threshold.

Simultaneous addition of ADP plus Melatonin induces apparent emission of platelets by rat's megacariocyte in vitro.

The studies described herein were undertaken to help define the effects of certain cyclophosphamide derivatives that have been used for selective removal of leukemic cells from marrow samples used for autologous transplantation. We have tested the effect of 4-HC and another cyclophosphamide congener, ASTA-Z 7557, on pluripotent stem cells (CFU-S) and committed progenitor cells (CFU-GM) in mice. The CFU-S were evaluated by the spleen colony assay at eight days and 12 days after transplant. The eight-day colonies are transient in nature, rapidly growing, mainly erythroid, and lack pluripotential precursors. The 12-day colonies are believed to provide a measure of hemopoietic stem cells as they slowly grow and do contain primitive precursors. Our data show that at the maximum dose levels tested, both drugs caused a 100% loss of CFU-GM and about 80%-95% inhibition of early transient CFU-S. In contrast, about 70% of the pluripotent 12-day CFU-S were spared. These data appear to explain the hemopoietic recovery seen in man after transplantation with marrow cells treated with 4-HC despite their relative absence of hemopoietic progenitor cells.

ADP induces an apparent platelets protrusion by rat's megakaryocytes in vitro.

A linear inverse relation links the HCl solution molarity to both the absolute HCl solution intake, and the ratio of the HCl solution to the total fluid intake. The last algebraic relation allows the taste threshold to be estimated.

Human acute myelogenous or lymphoblastic leukemia cells of the K-562 and CCRF-SB lines were mixed with an excess of normal human bone marrow cells to simulate a leukemia remission marrow. The cell mixtures were then incubated in vitro with mafosfamide (AZ) followed by the photoreactive dye merocyanine-540 (MC). Treated cells (1 x 10(4] were seeded in microwell plates, and increasing numbers of the line used to contaminate the normal marrow were added. Treatment with AZ alone produced total elimination (i.e., 6 logs) of CCRF-SB cells, while addition of merocyanine-540 increased the cloning efficiency from 22% to 24.4%. After treatment of the K-562-contaminated cell mixtures with AZ, nearly 1.6 logs of K-562 acute myelogenous blasts were still present, whereas AZ purging followed by MC-mediated photosensitization resulted in 100% elimination of clonogenic cells. Moreover, the combined treatment caused an increase of the cloning efficiency from 37.3% to 62%, clearly indicating that cleansing by the two agents combined was more effective than treatment with one agent alone.