广龙昊膏药对大鼠腰椎间盘突出模型细胞因子IL-1、NO及组织胺的影响

为探讨IL-1、NO及组织胺在腰椎间盘突出中的作用及广龙昊膏药的治疗效果，将60只大鼠造模并随机分为正常组（A组）、造模组（B组）、广龙昊膏药组（C组）和奇正止痛膏组（D组），观察其神经根周围局部组织中IL-1、NO及组织胺的含量。结果显示，B组中的IL-1、NO及组织胺较A组显著升高（P〈0．01）。C组、D组较B组明显下降（P〈0．01）。表明大鼠腰椎间盘突出模型中细胞因子IL-1、NO及组织胺明显增加可能是腰椎间盘突出中的潜在始动或促进因素，而C组能显著降低神经根局部中IL-1、NO及组织胺的含量，说明广龙昊膏药作用部分是通过抑制炎性细胞因子的活性实现的。     

N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

Integration of new regulatory strategies into the network of an endocrine control system: limitation of androgen secretion by rat testis is achieved by substrate-dependent modulation of P450XVII enzyme concentration and catalytic efficiency.

In addition to the well-known control circuits involved in the regulation and adaptation of testicular androgen biosynthesis, it is proposed that two new control strategies are involved in the maintenance of steady-state testosterone secretion rates by testicular Leydig cells. Cytochrome P450XVII (steroid-17 alpha-monooxygenase/steroid-17,20-lyase), one key enzyme in steroid hormone biosynthesis, responds to external human choriogonadotropin stimulation with an oxygen-dependent and substrate flux-dependent inactivation and decomposition, and increased substrate availability decreases the efficiency of androgen formation in favour of abortive intermediate leakage. These results are discussed as a paradigm of substrate-dependent modulation of cytochrome P450 activities.     

啤酒酵母在工业贮存期间的变化对生物合成1，6－二磷酸果糖的影响

随着工业贮存期的延长，啤酒酵母细胞的存活率及对葡萄糖连续磷酸化的速率迅速下降，１，６－二磷酸果糖在发酵液中的浓度由贮存前的７５ｇ／Ｌ降至贮存２个星期时的３０ｇ／Ｌ。     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

Molecular basis for treating endometriosis with aromatase inhibitors

Although treatment of one unusually aggressive case of postmenopausal endometriosis with an aromatase inhibitor has been strikingly successful, large clinical trials are required to establish whether aromatase inhibitors will have a significant role in the medical management of endometriosis. Introduction of aromatase inhibitors into the treatment of endometriosis underscores the importance of basic research leading to the development of novel strategies in reproductive disorders. It was shown earlier that aromatase activity was not detectable in normal endometrium. Aromatase, however, is expressed inappropriately in endometriosis and stimulated by prostaglandin E2. Aromatase activity gives rise to local biosynthesis of oestrogen, which, in turn, stimulates prostaglandin E2 production, thus establishing a positive feedback cycle. This favours accumulation of oestrogen and prostaglandins in endometriosis, which is an inflammatory disorder dependent on oestrogen for growth.     

Synthesis of gonadotrophins and its regulation in the pituitary gland

Regulation of the synthesis of pituitary gonadotrophins LH andFSH has been studied in the rat using either cell-free translationof pituitary mRNAs, or hybridization techniques with syntheticoligodeoxynucleotides or cloned complementary DNAs. Gonadectomygreatly increases and supplementing gonadectomized rats withgonadal steroids diminishes the rate of synthesis of the gonadotrophinsubunits. Hybridization experiments suggest that gonadal steroidsregulate the expression of the genes coding for pituitary gonadotrophinsubunit precursors. Using the incorporation of labelled methionineby pituitary cells in culture, followed by specific immunoprecipitationof LH-related subunits and SDS-poly-acrylamide gel analysisof immunoprecipitated peptides, there was evidence that gonadotrophinreleasing hormone (GnRH) significantly enhances the radioactivityincorporated into both - and LH-subunits. This effect is specific,it is not a secondary effect due to the release of LH. A cyclicAMP (cAMP) analogue, 8-Br-cAMP, as well as forskolin and choleragen,which are cAMP generators and a diacylglycerol analogue, tetradecanoylphorbolacetate (TPA), mimic the stimulatory action of GnRH on the synthesisof the polypeptide chains of LH. However, no evidence has beenobtained that either cAMP or diacylglycerols mediate this GnRHeffect. These results suggest that the synthesis of pituitarygonadotrophins is under a double control of gonadal steroidsand GnRH which exert opposite effects, inhibitory for steroidsand stimulatory for GnRH. The negative control by steroids occursat the genomic level, while the positive effect of GnRH proceedsvia different mechanisms which remain to be elucidated.     

Biosynthetic and regulatory role of lys9 mutants of Saccharomyces cerevisiae

Summary Derepression of lysine biosynthetic enzymes of Saccharomyces cerevisiae was investigated in lys9 auxotrophs which lack saccharopine reductase activity. Five enzymes (homocitrate synthase, homoisocitrate dehydrogenase, -aminoadipate aminotransferase, -aminoadipate reductase and saccharopine dehydrogenase) were constitutively derepressed in all lys9 mutants with up to eight-fold higher enzyme levels than in isogenic wild-type cells. Levels of these enzymes in lys2, lys14, and lys15 S mutants were the same or lower than those in wild-type cells. The regulatory property of lys9 mutants exhibited recessiveness to the wild-type gene in heterozygous diploids. Unlike the mating type effect, homozygous diploids resulting from crosses between lys9 auxotrophs exhibited even higher levels of derepressed enzymes than the haploid mutants. Addition of a higher concentration of lysine to the growth medium resulted in reduction of enzyme levels although they were still derepressed. These results suggest that lys9 mutants represent a lesion for the saccharopine reductase and may represent a repressor mutation which in the wild-type cells simultaneously represses unlinked structural genes that encode for five of the lysine biosynthetic enzymes.