In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins

It has been shown recently in China that arsenic trioxide (As2O3) is a very effective treatment for acute promyelocytic leukemia (APL). APL patients resistant to all-trans retinoic acid (ATRA) and conventional chemotherapy can still respond to AS2O3. In this study, we addressed the possible cellular and molecular mechanisms of this treatment by using NB4 cells as a model. The results show that: (1) As2O3 triggers relatively specific NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis. (2) As2O3 does not influence bax, bcl-x, c-myc, and p53 gene expression, but downregulates bcl-2 gene expression at both mRNA and protein levels. (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. In addition, a low percentage of untreated NB4 cells exhibits an accumulation of PML positive particles in a compartment of cytoplasm. The percentage of these cells can be significantly increased after As2O3 treatment. A similar PML staining pattern is observed in apoptotic cells. (4) ATRA pretreatment does not influence As2O3-induced apoptosis. These results suggest that induction of cell apoptosis can be one of the mechanisms of the therapeutic effect of As2O3. Moreover, this apoptosis induction occurs independently of the retinoid pathway and may be mediated, at least partly, through the modulation of bcl-2, as well as PML-RAR alpha and/ or PML proteins.     

Neuronal and synaptic arrangement in the lateralis posterior-pulvinar complex of the thalamus in the cat

Golgi and electron microscope studies on the cat's LP-pulvinar formation of the thalamus reveal the presence of two characteristically different cell populations: principal (or relay) cells and Golgi type II interneurons. These two cell types show little if any difference, both at the light and electron microscope level, from the characteristics of the similar cell types and the ultrastructural arrangement found in the sensory relay nuclei. Characteristic synaptic glomeruli (or encapsulated zones) are found in abundance in the LP-pulvianr complex. Four different types of terminal profiles containing synaptic vesicles can be identified in these glomeruli:RL = large axonal terminals with spheroid vesicles;RL = small axonal terminals with similar vesicles (relatively rare in the glomeruli and abundant in the general extraglomerular neuropil);F₁ = probably axonal profiles with flattened vesicles (present both in the glomeruli and in the general neuropil); andF₂ = profiles interpreted as of dendritic nature and belonging to Golgi type II interneurons. The numbers, percentages of different types of terminal profiles and of various combinations of interprofile contacts have been determined.     

Effect of Selective Inhibition of Potassium Channels on Vasorelaxing Response to Cromakalim,Nitroglycerin and Nitric Oxide of Canine Coronary Arteries

A comparative study was performed on the sensitivity of in-vitro vasorelaxation by nitroglycerin and cromakalim to block glibenclamide, a blocker of ATP-sensitive potassium channels, and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channels. In isolated canine coronary arteries preconstricted with 25 μM prostaglandin F_2α, nitroglycerin (0.005–1.8 μM) and cromakalim (0.15–9.6 μM) produced dose-dependent vasodilations. Glibenclamide (30 μM) had no significant effect on relaxation of the dose-response curve to nitroglycerin and almost completely abolished the relaxation by cromakalim, a known opener of ATP-sensitive potassium channels. Iberiotoxin (90 nM) decreased the maximal response to nitroglycerin and had no effect on the vasodilation induced by cromakalim. The effect of iberiotoxin on the vasorelaxing action of nitric oxide, the active metabolite of nitroglycerin, was also examined. In a low potassium chloride (14.4–20.4 mM) medium, as a contractile stimulus, iberiotoxin inhibited relaxations by exogenous nitric oxide (100–200 nM). Enhancement of potassium concentrations to 35.4–40.4 mM significantly decreased relaxation by nitric oxide and under these conditions the inhibitory action of iberiotoxin disappeared. The present study demonstrated that in canine coronary arteries, the functional role of two potassium channels can be separated by pharmacological means. Nitroglycerin-induced vasorelaxation may be mediated, at least in part, by its enzymatic breakdown product, nitric oxide that activates large-conductance calcium-activated potassium channels.     

西陵知母中新芒果甙的分离与结构鉴定

西陵知母中新芒果甙的分离与结构鉴定洪永福韩公羽郭学敏（第二军医大学药学院中西药研究室，上海２００４３３）知母（ＡｎｅｍａｒｈｅｎａａｓｐｈｏｄｅｌｏｉｄｅｓＢｇｅ．）为常用中药，以根茎入药。文献［１］记载，我国河北易县西陵出产的为最佳品，以“西陵知母...     

血管紧张素转化酶抑制剂——卡托普利酯类衍生物的合成和药理作用

卡托普利(巯甲丙脯酸)为一新型的血管紧张素转化酶抑制剂,临床用于治疗高血压和充血性心力衰竭,但半衰期短。为延长药物作用时间和提高药效,本文合成了它的酯类衍生物。初步药理试验结果表明,某些酯类化合物呈现明显降压恬性和延长作用时间。     

A comparison between previous and present histologic assessments of chronic hepatitis C viral infections in humans

ＭＥＴＨＯＤＳＬｉｖｅｒｂｉｏｐｓｉｅｓｆｒｏｍ７９ｕｎｔｒｅａｔｅｄｐａｔｉｅｎｔｓｗｅｒｅｒｅｖｉｅｗｅｄ．ＡｎｔｉＨＣＶｔｅｓｔｉｎｇｈａｄｂｅｅｎｐｅｒｆｏｒｍｅｄｂｙＥＬＩＳＡａｎｄｃｏｎｆｉｒｍｅｄｂｙａｒｅｃｏｍｂｉｎａｎｔｉｍｍ...     

Acid-Base and Electrolyte Changes during Exchange Transfusion

In connection with blood exchange transfusions carried out on forty newborn infants it has been found that the majority of the newborns requiring exchange transfusion have metabolic acidosis increasing to possibly critical severity by the end the exchange transfusion. The acidosis, however, is soon normalized spontaneously. Pretreatment with sodium bicarbonate infusion normalizes the pretrans fusion shift in acid-base balance and vents the development of a severe acidosis following the exchange transfusion without risking a subsequent alkalosis. Before exchange transfusion a slight hypernatraemia has often been observed and this increases transiently after blood exchange. Pretreatment with infusion did not modify this phenomenon. In our material no hyperpotassaemia has been encountered by the end of ex- change transfusion. I n response to pre-treatment with sodium bicarbonate infusion the plasma K⁺ level decreased slightly. By promoting the conjugation of bilirubin to proteins, pretreatment with sodium bicarbonate may presumably improve also the efficiency of the exchange transfusion; this, however, requires further proof.     

复方蚁酒的薄层鉴别研究

目的：制订复方蚁酒中蚂蚁、枸杞子的薄层鉴别方法。方法：用薄层色谱法,经溶剂提取制备样品,分别以正丁醇－冰醋酸－水（３：２：１）、甲苯－乙酸乙酯－甲醇－甲酸（４：３：０．８：０．２）为展开剂。结果：供试品色谱中,在与对照品色谱相应位置上,显相同颜色的斑点。结论：斑点清晰、重现性好,可作为该制剂的质量控制方法之一。