Study on therapeutic mechanism of Neiyifang in treating endometriosis

Objective: To observe the clinical effect of Neiyifang (NYF) in treating endometriosis and to explore its therapeutic mechanism through observing its influence on plasma β-endorphin (β-EP) in different menstrual stages and levels of prostaglandins (PGs) in menstruation.Methods:NYF was administered to 104 patients with endometriosis one dose daily with 3 successive menstrual cycles as one therapeutic course. Peripheral blood β-EP level in follicular, luteal and menstrual stages, as well as PGF_2α, PGE2, thromboxane B₂ and 6-keto-PGFl α levels in menstrual stage were detected by RIA, and controlled with those in 15 healthy persons.Results: (1) The total effective rate of NYF was 81.3% and it showed significant effect in improving patients’ clinical symptoms and physical signs; (2) In menstrual stage, the levels of β-EP, 6-keto-PGF_α/ TXB₂ were lower(P <0.05) and levels of PGF_2α, PGE₂, TXB₂ and 6-keto-PGF_1α were higher (P< 0. 05) in patients than those in control, and the higher the level of PGE₂, the severer the menalgia, (3) NYF could increase levels of β-EP, 6-keto-PGF_1α, and reduce levels of PGF_2α, PGE_2α in menstrual stage of patients (all P<0.05).Conclusion: (1) NYF has good clinical effect in treating endometriosis; (2) Patients’ symptom of menalgia is closely related with the excessive high levels of PGF_2α and PGE₂, PGI₂/TXA₂ ratio disturbance, and excessive low level of β-EP; (3) NYF could significantly decrease the PGE₂, PGF_1α levels, increase the 6-keto-PGF_1α/TXB₂ ratio and the level of β-EP, so as to alleviate the menalgia in patients with endometriosis. This item was supported by National Funds of Natural Sciences(No. 30070942)     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264

The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca²⁺-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca²⁺-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC₅₀ of Ca²⁺ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to 113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component I_Kr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define I_Kr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca²⁺-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the I_Kr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions are clearly independent of sterical configuration. The combination of Ca²⁺-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic use. Received: 7 January 1997 / Accepted: 25 February 1997     

棕榈油对成人血脂和血小板功能的影响

报道了棕榈油（ＰＡ），花生油（ＰＥ）对血清总胆固醇水平（ＴＣ）在５．５～７．０ｍｍｏｌ／Ｌ的受试者血脂和血小板功能的影响。５１名受试者（男３１人，女２０人，年龄３０～６６岁之间）分为两组，一组男１５人，女１１人，称ＰＥ组；另一组男１６人女９人，称ＰＡ组，预备期３周，膳食以当地日常食用的花生油烹调，实验期６周。ＰＡ组受试者食用以棕榈油烹调的实验膳；ＰＥ组受试者仍食花生油烹调的膳食。脂肪约占膳食能量的３０％，其中６０％～６５％来自实验油。实验结果表明：与起始值相比，６周末ＰＡ组受试者血清ＴＣ，低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）和总胆固醇与高密度脂蛋白胆固醇比值（ＴＣ／ＨＤＬ－Ｃ）显著下降，血浆血栓素Ｂ２（ＴＸＢ２）／６－酮前列环素Ｆ１α、（６－ｋｅｔｏ－ＰＧＦ１α）比值显著下降，全血血小板聚集率未见显著变化。ＰＥ组受试者的血脂、血浆ＴＸＢ２、６－ｋｅｔｏ－ＰＧＦ１α及全血血小板聚集率等指标均未出现显著变化。提示，棕榈油作为我国居民家庭烹调用油并不会增加发生心血管疾病的危险。     

老年充血性心衰患者地高辛药代动力学研究

目的 :探讨老年心衰患者地高辛维持量的合理应用。　 方法 :用荧光偏振免疫分析法测定了 14例老年心衰患者血清地高辛浓度 ,并计算出药代动力学参数。　 结果 :14例老年心衰患者地高辛 t1/ 2 β,β和 Vd分别为 72 .769± 2 9.768h、0 .0 11± 0 .0 0 6h-1和 3.190± 3.30 0 L/ kg,与非老年心衰患者 ( t1/ 2 β 36.1± 2 .0 h,56.3± 12 h,β 0 .0 19± 0 .0 0 1h-1,Vd 7.37± 1.65L / kg)相比差异显著。　 结论 :老年心衰患者地高辛维持量以小量分次给药为宜 ,且更应注意个体化     

Investigation of Role of Nitric Oxide in Protection from Bordetella pertussis Respiratory Challenge

The mechanism whereby whole-cell pertussis vaccines (WCV) confer protection against Bordetella pertussis is still not fully understood. We have previously reported that macrophage activation produced by vaccination with WCV is associated with induction of NO synthesis by macrophages in response to in vitro stimulation with B. pertussis antigens. To determine whether NO production is an effector of protection or simply a marker of activation, the susceptibility of inducible nitric oxide synthase (type II, iNOS) knockout mice to infection with B. pertussis was examined. We showed that iNOS knockout mice were more susceptible to B. pertussis respiratory challenge than wild-type mice. iNOS-deficient mice also developed a less effective protective response than wild-type mice after the same immunization with WCV. This suggests that NO plays an important role in effecting protection against B. pertussis challenge.     

Spermidine synthase of Escherichia coli: localization of the speE gene.

We have obtained Escherichia coli mutants lacking spermidine synthase (putrescine aminopropyltransferase) and have found that the mutated gene (speE) is located immediately upstream from the gene coding for S-adenosylmethionine decarboxylase (speD); these genes are located at 2.7 minutes on the E. coli chromosome. Both genes are present in a 1795-base-pair fragment of E. coli DNA that was cloned into pBR322. Deletion of 105 bases upstream of speE caused a coordinate loss of both activities, indicating that speE and speD constitute a single operon. speE and speD have also been cloned separately in a high-expression vector; strains carrying these plasmids overproduce the respective enzymes.     

Effect of gradual rise in plasma calcium concentration on the impairment of atrioventricular nodal conduction due to verapamil

The possible reversal by calcium of the inhibitory action of verapamil on the atrioventricular (AV) node was investigated in anesthetized, atropinized dogs, with cardiac pacing. The His bundle potentials were recorded by endocavitory electrode and the AV node effective refractory period measured by the extrastimulus method. Calcium infusion was effective against the impairment of AV nodal conduction induced by verapamil, provided it remained moderate: the gradual rise in the plasma calcium concentration counteracted the effects of an infusion of verapamil on conduction time and effective refractory period in the AV node, as long as it did not exceed 5 mmol/L. However, beyond this level, calcium appeared less and less capable of reversing the effects of verapamil. Thus, the protective action of calcium had a bell-shaped dose-response curve, with the optimum at 5 mmol/L. This biphasic influence is consistent with the opposite opinions previously given concerning the antagonism between calcium and calcium blockers, depending on whether hypercalcemia brought into play was mild or major. In any case, the prominent role played by calcium in the slow inward current in the AV node accounts for the antagonism, observed in vivo, between calcium and verapamil. The pacemaker activity of the sinoatrial (SA) node was less influenced by both calcium blocker and calcium.