Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

Seroepidemiology of HTLV-III (LAV) in the Federal Republic of Germany

Summary In 1984 10,281 sera were collected in the FRG and examined for antibodies to HTLV-III (LAV) with an enzyme-linked immunosorbent assay and confirmative tests. Of the German AIDS patients 81% have antibodies. Individuals belonging to AIDS risk groups, homosexuals, haemophiliacs and i.v. drug abusers, have antibody frequencies between 25%–72%. The detection of HTLV-III antibodies in blood donours indicates that the virus is being transmitted by blood transfusions.Abbreviations AIDS acquired immunodeficiency syndrome - LAS lymphadenopathy syndrome - ARC AIDS related complex - LAV lymphadenopathy associated virus - HTLV-III human T-lymphotropic virus type III - HBV hepatitis B virus     

Kainic acid receptors and neurotoxicity in adult and immature rat cerebellar slices

The neurotoxic actions of kainate were examined in incubated slices of adult and immature rat cerebellum using light- and electron-microscopy. In the adult, Purkinje cells and inhibitory interneurones became selectively necrotic at concentrations between 5 micro M and 20 micro M. At 30 micro M, granule cells also became affected. In the immature cerebellum, at an age (8 days after birth) when the parallel fibres (thought to use glutamate as transmitter) are largely yet to be developed, selective toxicity was still evident but Purkinje cells and inhibitory interneurones were about 10-fold, and granule cells about 30-fold, less sensitive to kainate than in the adult. Kainate and other excitotoxins also increased cyclic GMP levels in cerebellar slices, apparently through the activation of excitatory amino acid receptors. In the adult tissue, the dose-cyclic GMP response curve to kainate was biphasic suggesting the presence of two components. The lower concentrations of kainate eliciting the first component mirrored those inducing selective necrosis of Purkinje cells and inhibitory interneurones while the second component correlated with necrosis of granule cells. Similar correlations applied to the immature cerebellum, but here kainate neurotoxicity appeared to be associated with the activation of receptor types different from those evident in the adult. It is suggested that kainate receptors, whose activation is associated with both neurotoxic damage and elevation of cyclic GMP levels, are located on all cell types in the adult cerebellum, with Purkinje cells and inhibitory interneurones displaying a higher sensitivity to kainate than granule cells. The lower sensitivity of immature cerebellum to the neurotoxic effect of kainate is probably due to lower levels of kainate receptors.     

三甲氧桂皮酰胺类化合物的抗惊和镇静作用

观察了三个三甲氧桂皮酰胺类化合物:3,4,5-三甲氧桂皮酰异丙胺(8701)、3,4,5-三甲氧桂皮酰环戊胺(8702)和3,4,5-三甲氧桂皮酰另丁胺(8703)的抗惊和镇静作用,发现8701具有明显的影响。它能有效的对抗最大电休克发作、戊四唑和印防己毒素所引起的惊厥,但对士的宁惊厥无效。8702和8703对上述实验性癫痫均无明显影响。8701抗戊四唑惊厥作用的机制可能与其对中枢神经递质NE和5-HT的影啊有关。     

Karyotyping chromosomes by electron microscopy. Condensation-inhibition of G bands in human and Chinese hamster chromosomes by a BrdU-Hoechst 33258 treatment

A BrdU-Hoechst 33258 treatment of living cells, which selectively induced condensation-inhibition of G-band chromatin in human and Chinese hamster chromosomes, is presented. As a consequence mitotic chromosomes showed high resolution R-banding patterns when examined by light and electron microscopy. Besides each whole chromosome identification, this procedure also permitted the electron microscopic study of specific structures, such as satellites, secondary constrictions, telomeres, centromeres, as well as G and R bands, some of them not visible by light microscopy. We have also observed that the chromatin of G and R bands behave as blocks of chromatin condensation and that G-band chromatin develops condensation along G₂. Under the BrdU-Hoechst 33258 treatment, chromatin fibers seem to invert their spontaneous pattern of condensation within the chromosomes.     

丹参提取物对氧自由基引起的化学发光的抑制作用

观察了经调理的酵母多糖（ＯＺ）、Ｎ－ｆｏｒｍｙｌｍｅｔｈｉｏｎｙｌ－Ｌｅｕｃｙｌ－ｐｈｅｎｙｌａｌａｎｉｎｅ（ｆＭＬＰ）Ｃａｌｃｉｕｍ ｉｎｏｐｈｏｒｅ（Ａ２３１８７），等几种白细胞激动剂引起的大鼠腹腔中性粒细胞（ＰＭＮｓ）的化学发光和次黄嘌呤－黄嘌呤氧化酶系统（ＨＯ－ＸＯ）产生的化学发光。观察到了具有抗炎作用的中药单体７６４－３对ＰＭＮ吞噬ＯＺ引起的化学发光及ＨＯ－ＸＯ系统产生的化学发光具有明显     

Induction of lymphokine-activated killer cells with low-dose interleukin 2 and interferon-γ in oral cancer patients

Lymphokine-activated killer (LAK) cells were induced with low-dose recombinant interleukin 2 (rIL-2) and recombinant interferon- (IFN-) in 28 oral carcinoma patients. The patients received daily intravenous injections of rIL-2 (1.2×10⁵ U/m²) and rIFN- (7.0×10⁴ U/m²), and both natural killer (NK) and LAK activities were periodically examined. A significant increase in CD16⁺CD57⁺ and CD16⁺CD57^– NK subsets was observed after the induction. An increase in the T-cell population was also found, with a significant increase in CD3⁺HLA-DR⁺, CD8⁺Leu8^–, and CD4⁺Leu8^– cells. Significant increases in NK activity, from the original level of 32.0±13.7 to 49.9±15.2%, and LAK activity, from 4.8±3.5 to 11.0±6.1%, at Day 7 were observed. Both activities were maintained at high levels during the cytokine injections, but greater enhancement of the killing activities could not be obtained subsequently. When NK and LAK activities were investigated in each subpopulation of CD3^– and CD16^– cells, no remarkable cytotoxic activity could be observed before induction in any subset without NK activity in CD3^– cells (31.1±14.3%). At Day 7, NK activity of CD16^– cells increased up to 21.4±14.9%, accompanied by an increase in CD3^–-cell activity (54.5±20.6%). LAK activities of both subsets were also enhanced, with activity at Day 7 of 6.5±5.6 and 9.4±6.6% in CD16^– and CD3^– cells, respectively. These increased activities were maintained at the same level during the induction. Phorbol myristate acetate-induced polymorphonuclear leukocyte (PMNL) O ₂ ^– generation was significantly increased, from the original 81.1±28.1 to 95.6±34.9 pmol/min/10⁴ cells, after 1 week of treatment. Protein kinase C activity in the cytosol decreased, and the activity in the membrane fraction conversely increased. No remarkable adverse effects except for mild fever were observed. Together with LAK induction ability and PMNL enhancement, with scarce toxicity, a combination of low-dose rIL-2 and rIFN- is thought to be useful in cancer treatments.     

Relationship between REM sleep latency and nocturnal cortisol concentrations in depressed patients

SUMMARY  Due to conflicting reports on the possible association between shortening of rapid eye movement (REM) latency and increased cortisol secretion in patients with severe depression, this study examined the relationship between REM sleep latency and nocturnal cortisol concentration in 12 outpatients with major depression. The results showed a significant inverse correlation ( r = —0.71, P <0.01) between REM sleep latency and mean (23.00 hours-03.00 hours) plasma cortisol concentration. Age and severity of depression did not contribute to the inverse relationship. REM activity and density during the first REM period showed no significant correlations with the cortisol measures. A review of the literature suggests that this relationship might be unique to subjects with major depression, and again raises the possibility that these biological disruptions may have a common neurochemical basis.     

A new pseudo-peptide of Arg-Gly-Asp (RGD) with inhibitory effect on tumor metastasis and enzymatic degradation of extracellular matrix

A series of pseudo-peptide analogs of the Arg-Gly-Asp (RGD) sequence of fibronectin have been synthe-sized, and their anti-metastatic effects in mice and inhibitory effects on tumor cell invasion in vitro have been examined. The partially modified retro pseudo-peptide of RGD, R_rev-COCH₂CO-D (FC-63), was more effective in inhibiting tumor metastasis than the original RGDS peptide. Replacement of the malonyl moiety of FC-63 with a carboxyethylene linkage (R_rev-COCH₂CH₂-D, FC-303 ) achieved more potent inhibition of lung metastasis of melanoma cells than FC-63. Among the analogs, FC-336, a p-xylylendiamine derivative having two FC-303 moieties, showed the most potent inhibitory effect on experimental lung metastasis produced by i.v. co-injection with B16-BL6 melanoma or colon 26 M3.1 cells in a dose-dependent manner. Multiple administrations of FC-336 after tumor inoculation also showed efficient therapeutic potency against spontaneous lung metastasis of B16-BL6 melanoma in mice. Furthermore, FC-336 effectively inhibited the invasion, migration and adhesion of tumor cells in vitro, but its inhibitory effects were not more than those of RGDS peptide. Zymography analysis revealed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by tumor cells, while the RGDS peptide did not affect the enzymatic degradation. These findings indicate that the pseudo-peptides of the RGD sequence, possessing the inhibitory property of the degradation by MMPs differently from original RGD-containing peptides, may be advantageous and useful in preventing tumor metastasis. © Rapid Science 1998