Vitamin D metabolism and function during pregnancy and the neonatal period

Recent evidence suggests that vitamin D plays an important role in calcium homeostasis during pregnancy and early extrauterine life. Vitamin D is metabolized by successive hydroxylations to 25-hydroxyvitamin D and then to 1,25-dihydroxyvitamin D, the most potent known metabolite of the vitamin. During pregnancy, the concentrations of this metabolite in maternal serum increase in parallel with the increased need to absorb dietary calcium. 1,25-Dihydroxyvitamin D is produced in the fetoplacental unit as well as in the maternal kidneys. Receptors for 1,25-dihydroxyvitamin D appear to be present in the placenta suggesting that the placenta may be a target for vitamin D action. Developmental changes in vitamin D metabolism and action have been documented in the neonate as well as in the mother and fetus. Clinical studies indicate that adequate vitamin D intake is important during pregnancy. Administration of vitamin D or its metabolites appears to be useful in the treatment of neonatal disorders.     

Changes in fetal acid-base chemistries following tromethamine (THAM) or bicarbonate infusions into fetal circulation of amniotic fluid

Direct infusions of equimolar quantities of bicarbonate and tromethamine into rhesus monkey fetal circulation near term resulted in roughly equivalent increases in fetal pH. However, intra-amniotic infusion of tromethamine was not followed by alkaline changes in the fetus and in most instances was followed by a progressive fetal acidosis. This sharply contrasts with previous experimental success in elevating fetal pH via amniotic fluid bicarbonate infusions.     

Quantitative Ermittlung des Fermentgehaltes und der PAS-positiven Substanzen von Knochenmarkzellen in vivo und in vitro

Zusammenfassung Histochemisch werden Fermente und PAS-färbbare Substanzen in Ausstrichen von Knochenmark-Kulturen nachgewiesen. Die Stärke der Reaktionen ist für die einzelnen Zellarten des Knochenmarkes als Index berechnet. In den Koagulumkulturen von mehr oder weniger pathologisch verändertem Knochenmark steigt der mittlere Gesamt-Index beider Phosphatasen von 0–72 Std signifikant an, der mittlere Gesamt-Index der -Naphthylacetat-Esterase bleibt konstant, und die Indices der Peroxydase und der PAS-Reaktion fallen schon bis 24 Std signifikant ab, um später auf gleicher Höhe zu bleiben. Die in vitro ausgereiften Segmentkernigen sind stärker mit saurer und alkalischer Phosphatase ausgestattet als in vivo, aber weniger mit Peroxydase-und PAS-färbbaren Substanzen.

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Summary In smears of clot cultures of human bone marrow the content of alkaline and acid phosphatase, alpha-naphthylacetate esterase, peroxydase, and PAS-positive substances is demonstrated histochemically, The intensity of the reaction is presented as an index for the different erythroid and granulocytic precursors. In the clot cultures of a certain degree pathologically affected bone marrow the average total index of both kinds of phosphatases increases significantly from 0 to 72 hours, the average total index of the -naphthyl-acetate esterase stays the same and the indices of peroxydase and of the PAS reaction decreases significantly already in 24 hours, but keep the same level up to the 72th hour. The PMNs matured in vitro have a bigger content of alkaline and acid phosphatase than those matured in vivo, but a smaller content of peroxydase and PAS-positive substances.

     

Modulatory effects of oestrogen on immunologic responsiveness. I. Inhibition of DNA synthesis in peripheral blood lymphocytes from patients with Peyronie's disease, prostatic cancer and transsexuals and a commentary.

A reduction in the phytohaemagglutinin-induced transformation of peripheral blood lymphocytes from patients with Peyronie's disease and prostate cancer and transsexuals cultured in autologous and homologous serum following the receipt of oestrogen therapy has been observed. Reduction of lymphocyte transformation in patients with prostatic cancer and without malignancy receiving oestrogen, i.e., Peyronie's disease and transsexuals, suggests that this reduction is related to the mode of therapy rather than to malignancy or a particular pathologic state. No direct evidence exists that the observed in vitro aberrations of lymphocytic responsiveness are reflective of host compromise, but these observations are of potential relevance in terms of their implications in the therapeutic management of patients with prostatic cancer and other hormonally-dependent tumours, e.g., of the breast, as well as responsive diseases, through their effect on cellular immunocompetence and suitability of hormonally treated patients as prospective candidates for adjuvant immunotherapy. The possible relevance of the present observations to the suggested association between uterine cancer and prolonged administration of diethylstilboesterol, as well as that between development of vaginal tumours in offspring and maternal ingestion during pregnancy, also remains of potential concern, pending further investigation.     

Vascular targeting in pancreatic cancer: the novel tubulin-binding agent ZD6126 reveals antitumor activity in primary and metastatic tumor models

ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic diseases, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic diseases could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.