青蒿素治疗弓形虫病的研究和临床治疗效果的初步观察

弓形虫病目前常用的临床治疗药物,包括磺胺类、乙胺嘧啶、螺旋霉素及氯化林可霉素等,单用或联用,均存在疗程长、毒副反应较多、疗效不太理想,且不能根治等问题[1]。为此,探寻新的抗弓形虫药物甚为迫切。我们自1994年初开始试用对疟疾治疗有较佳的杀灭疟原虫的作用且在动物     

银杏酸、阿奇霉素和大蒜素抗弓形虫增殖效果研究

目的评价银杏酸、阿奇霉素和大蒜素体外和体内抗弓形虫增殖的效果。方法体外试验,培养HFF细胞做为弓形虫宿主细胞,采用MTT法检测3种药物的安全浓度和体外抗弓形虫增殖的效果。体内试验,以腹腔注射的方式给药,观察感染弓形虫小鼠的存活时间,比较3种药物的体内抗弓形虫增殖效果。结果银杏酸和阿奇霉素可显著抑制细胞内弓形虫的增殖,两者效果相近。银杏酸和阿奇霉素均可延长小鼠存活时间。大蒜素抗弓形虫效果微弱。结论银杏酸具有抗弓形虫作用。     

青蒿素衍生物治疗AIDS合并脑弓形虫感染2例

本文报道了青蒿素衍生物(双氢青蒿素哌喹片、青蒿琥酯片)治疗AIDS合并脑弓形虫感染患者2例,详细描述了该患者诊断、治疗的过程,并做出了相应的讨论分析。     

弓形虫致鼠胚神经系统畸形中NCAM的表达及青蒿素保护作用的研究

目的探讨弓形虫感染孕早期大鼠致胚胎神经系统畸形的分子机制及青蒿素对胚胎的保护作用。方法将SD孕鼠随机分为对照组、模型组和模型治疗组,各组孕鼠于妊娠第3 d(E3)腹腔注射弓形虫RH强毒株,并分别于E12、E14、E16、E18剖腹取胎鼠,进行形态学观察;PCR法检测羊水中弓形虫B1基因表达,免疫荧光染色观察神经细胞粘附分子(NCAM)在胚胎不同发育时期的神经细胞中的表达规律。结果模型组胚胎发育状况差,活胎率低,为11.82%;PCR检测到模型组胚胎羊水B1基因的表达。对照组和模型治疗组E14、E16鼠胚神经细胞中NCAM呈阳性,模型组染色较其他4组弱。结论 NCAM低表达是神经系统畸形发生的重要因素,青蒿素对鼠胚弓形虫感染有保护作用。     

杭州市肝病患者弓形虫感染调查

目的 了解杭州市肝病患者弓形虫感染情况,为弓形虫病防治提供参考依据。方法 选择肝癌、乙型肝炎、肝纤维化和肝脂肪变性4类肝脏疾病患者各300例,以1 200例体检健康人群作为对照,检测并比较肝病患者和健康对照人群抗弓形虫IgG和IgM抗体阳性率。结果 1 200例肝病患者中,抗弓形虫IgG抗体阳性288例,阳性率为24.00%;抗弓形虫IgM抗体阳性14例,阳性率为1.17%。1 200例健康对照中,抗弓形虫IgG抗体阳性137例,阳性率为11.42%;抗弓形虫IgM抗体阳性13例,阳性率为1.08%。肝病患者和健康对照抗弓形虫IgG抗体阳性率差异有统计学意义（[χ2] = 65.19,P < 0.01）,但两者抗弓形虫IgM抗体阳性率差异无统计学意义（[χ2] = 0.04,P > 0.05）。肝癌、乙型肝炎、肝纤维化和肝脂肪变性患者抗弓形虫IgG抗体阳性率分别为26.00%、25.00%、23.33%和21.67%,差异无统计学意义（[χ2] = 1.79,P > 0.05）。 结论 杭州市肝病患者抗弓形虫IgM抗体阳性率较高,应加强肝病患者弓形虫病防治和健康教育。     

东台市猪肉食品加工企业从业人员弓形虫感染血清流行病学调查

目的 了解东台市猪肉食品加工企业从业人员弓形虫感染情况。方法 以东台市某肉食品加工企业从业人员200例作为调查对象,采集其静脉血并分离血清,采用酶联免疫吸附法检测血清抗弓形虫IgG抗体。 结果 200例肉食品加工企业从业人员中,血清抗弓形虫IgG抗体阳性36例,阳性率为18.0%。不同工龄者血清抗弓形虫IgG抗体阳性率差异有统计学意义（[χ2] = 9.813,P ＜0.05）;随着工龄的增加,血清抗弓形虫IgG抗体阳性率逐渐升高。与动物直接接触频繁者血清抗弓形虫IgG抗体阳性率明显升高。结论 东台市猪肉食品加工从业人员血清抗弓形虫IgG抗体阳性率较高,对此类人群应加强弓形虫感染检测及健康教育。     

γ-干扰素和白介素抗弓形虫感染研究进展

刚地弓形虫(Toxoplasma gondii)是一种专性有核细胞内寄生虫,可以感染包括人类在内的几乎所有温血动物,能引起严重的人兽共患弓形虫病。宿主体内γ-干扰素和白介素的水平影响弓形虫的垂直传播并决定弓形虫病的发生与转归,γ-干扰素和白介素在宿主抗弓形虫感染中有着重要的作用。本文对γ-干扰素和白介素抗弓形虫感染研究进展进行了综述。     

福建地区新生儿刚地弓形虫感染血清学调查

目的调查福建地区新生儿刚地弓形虫感染血清学阳性率,为制定先天性弓形虫病防控措施提供参考依据。方法以2017—2018年福建地区出生的1 045例新生儿作为研究对象,其中早产儿387例、足月儿658例。采集新生儿脐带血,检测并比较早产儿和足月儿血清抗弓形虫IgG抗体阳性率。收集早产儿和足月儿母亲肘静脉血,检测并比较早产儿和足月儿母亲血清抗弓形虫Ig G抗体阳性率。结果福建地区1 045例新生儿血清抗弓形虫IgG抗体阳性率为9.38%。387例早产儿血清抗弓形虫IgG抗体阳性率为18.35%,男婴和女婴血清抗体阳性率差异无统计学意义(17.69%vs. 18.75%,χ~2=0.07,P 0.05)。658例足月儿血清抗弓形虫IgG抗体阳性率为4.10%,男婴和女婴血清抗弓形虫IgG抗体阳性率差异无统计学意义(4.14%vs. 4.08%,χ~2=0,P 0.05)。早产儿血清抗弓形虫Ig G抗体阳性率显著高于足月儿(χ~2=58.17,P 0.01)。1 045例新生儿母亲血清抗弓形虫IgG抗体阳性率为15.02%,早产儿母亲血清抗弓形虫IgG抗体阳性率显著高于足月儿母亲(20.93%vs. 11.55%,χ~2=16.79,P 0.01)。结论福建地区早产儿及其母亲弓形虫感染血清学阳性率显著高于足月儿及其母亲;应加强孕前弓形虫感染检测和弓形虫病防护知识健康教育,从而有效降低先天性弓形虫病发病率。     

湖北武汉地区产妇胎盘血清抗弓形虫抗体的检测

为了解武汉地区产妇体内抗弓形虫抗体的水平,提供防治先天性弓形虫病的流行病学资料,我们于1985年12月至1986年11月采用IHA法对武汉地区310例产妇的胎盘血清进行了抗弓形虫抗体的检测。     

弓形虫棒状体颈部蛋白及棒状体蛋白研究的新进展

刚地弓形虫（Toxoplasma gondii）是一种专性细胞内寄生原虫。因其复杂的生活史和致病机理,目前尚无有效的专用药物进行治疗。近年来,关于抗弓形虫免疫及疫苗的研究逐步深入,棒状体颈部蛋白（RONs）及棒状体蛋白（ROPs）作为重要的抗弓形虫疫苗的候选抗原分子,广泛应用于新型抗弓形虫疫苗的研究中。本文总结了近几年来弓形虫棒状体颈部蛋白及棒状体蛋白的研究新进展,尤其是这些RONs及ROPs作为新型DNA疫苗分子研。宽的最新进展。     

Evidence that Collagen Releases Human Platelet Constituents by Two Different Mechanisms

SUMMARY
Collagen is believed to be involved in the initial events in haemostasis and has been shown by others to cause platelet aggregation and release, and also to initiate the intrinsic pathway of coagulation. The present experiments provide evidence which suggests how these many effects of collagen may be involved in haemostasis.
It is shown here that collagen releases platelet constituents by two different pathways. Collagen causes platelets washed free of loosely adsorbed coagulation factors to release constituents. This activity is, therefore, independent of the intrinsic pathway of coagulation, and is not inhibited by heparin or hirudin. Collagen also releases platelet constituents by an alternative pathway which is inhibited by heparin and hirudin and is independent of factor XII, but is dependent on factor XI, subsequent factors in the intrinsic pathway of coagulation and calcium. These results suggest that collagen-induced release of platelet constituents is in part due to a direct effect on the platelet, and, in part, to an indirect effect involving coagulation factors and mediated by thrombin. The present results suggest that irreversible aggregation by collagen is also mediated by thrombin.
The possible significance of this dual action of collagen in the haemostatic process is shown in Fig 7.     

Ion channels gated by heat

All animals need to sense temperature to avoid hostile environments and to regulate their internal homeostasis. A particularly obvious example is that animals need to avoid damagingly hot stimuli. The mechanisms by which temperature is sensed have until recently been mysterious, but in the last couple of years, we have begun to understand how noxious thermal stimuli are detected by sensory neurons. Heat has been found to open a nonselective cation channel in primary sensory neurons, probably by a direct action. In a separate study, an ion channel gated by capsaicin, the active ingredient of chili peppers, was cloned from sensory neurons. This channel (vanilloid receptor subtype 1, VR1) is gated by heat in a manner similar to the native heat-activated channel, and our current best guess is that this channel is the molecular substrate for the detection of painful heat. Both the heat channel and VR1 are modulated in interesting ways. The response of the heat channel is potentiated by phosphorylation by protein kinase C, whereas VR1 is potentiated by externally applied protons. Protein kinase C is known to be activated by a variety of inflammatory mediators, including bradykinin, whereas extracellular acidification is characteristically produced by anoxia and inflammation. Both modulatory pathways are likely, therefore, to have important physiological correlates in terms of the enhanced pain (hyperalgesia) produced by tissue damage and inflammation. Future work should focus on establishing, in molecular terms, how a single ion channel can detect heat and how the detection threshold can be modulated by hyperalgesic stimuli.     

Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H₂S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions.     

Kidney: its impact on glucose homeostasis and hormonal regulation

According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although animal and in vitro studies have documented that the kidney is capable of gluconeogenesis, glucose production by the human kidney has been regarded as negligible. This knowledge is based on net balance measurements across the kidney. Recent studies combining isotopic and balance techniques have demonstrated that the human kidney is involved in the regulation of glucose homeostasis by making glucose via gluconeogenesis, taking up glucose from the circulation, and by reabsorbing glucose from the glomerular filtrate. The human liver and kidneys release approximately equal amounts of glucose via gluconeogenesis in the postabsorptive state. In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis actually increases by approximately 2-fold. Following meal ingestion, glucose utilization by the kidney increases. Increased glucose uptake into the kidney may be implicated in diabetic nephropathy. Normally each day, ～ 180 g of glucose is filtered by the kidneys; almost all of this is reabsorbed by means of sodium glucose cotransporter 2 (SGLT2), expressed in the proximal tubules. However, the capacity of SGLT2 to reabsorb glucose from the renal tubules is finite and when plasma glucose concentrations exceed a threshold, glucose begins to appear in the urine. Renal glucose release is stimulated by epinephrine and is inhibited by insulin. Handling of glucose by the kidney is altered in type 2 diabetes mellitus (T2DM): renal gluconeogenesis and renal glucose uptake are increased in both the postabsorptive and postprandial states, and renal glucose reabsorption is also increased Since renal glucose release is almost exclusively due to gluconeogenesis, it seems that the kidney is as important gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactae glutamine and glycerol.     

LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases

Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor. It is formed by protein arginine N-methyltransferases (PRMTs), which utilize S-adenosylmethionine as methyl group donor. ADMA plasma concentration is elevated in hypercholesterolemia, leading to endothelial dysfunction and producing proatherogenic changes of endothelial cell function. Four different isoforms of human PRMTs have been identified. Because the release of ADMA from human endothelial cells is increased in the presence of native or oxidized LDL cholesterol, we investigated the potential involvement of PRMT activity and gene expression in this effect. We found that the production of ADMA by human endothelial cells is upregulated in the presence of methionine or homocysteine and inhibited by either of the methyltransferase inhibitors S-adenosylhomocysteine, adenosine dialdehyde, or cycloleucine. This effect is specific for ADMA but not symmetrical dimethylarginine. The upregulation of ADMA release by native and oxidized LDL is abolished by S-adenosylhomocysteine and by the antioxidant pyrrollidine dithiocarbamate. Furthermore, a methyl-(14)C label is transferred from S-adenosylmethionine to ADMA but not symmetrical dimethylarginine, in human endothelial cells. The expression of PRMTs is upregulated in the presence of native or oxidized LDL. Our data suggest that the production of ADMA by human endothelial cells is regulated by S-adenosylmethionine-dependent methyltransferases. This activity is upregulated by LDL cholesterol, which may be due in part to the enhanced gene expression of PRMTs. In concentrations reached by stimulation of methyltransferases (5 to 50 micromol/L), ADMA significantly inhibited the formation of (15)N-nitrite from L-[guanidino-(15)N(2)]arginine. These findings suggest a novel mechanism by which ADMA concentration is elevated in hypercholesterolemia, leading to endothelial dysfunction and atherosclerosis.     

Factor VIII: structure and function in blood clotting

Factor VIII (antihemophilic factor) is the protein that is deficient or defective in patients with classical hemophilia and Von Willebrand syndrome. Factor VIII in plasma is thought to be associated in a complex with the highest molecular weight multimers of another glycoprotein, Von Willebrand protein. Highly purified human factor VIII appears to have an Mr of between 200,000 and 300,000 and to consist of several polypeptide chains. The concentration of factor VIII in plasma is around 100-200 ng/ml, equivalent to around 1 nM. The purified proteins retain one or more of the known properties of factor VIII, including the acceleration of factor IXa-mediated activation of factor X, ability to be activated by thrombin and factor Xa, inactivation by activated protein C, and by human antibodies to factor VIII. Among the known clotting factors, factors VIII and V are exceptional in not possessing enzymatic activity. Factors IXa and VIII and X appear to form a functional complex, all of which need to be present and active simultaneously for optimal activation of factor X. The mechanism by which factor VIII promotes activation of factor X by factor IXa is not known, but the major effect is to increase the rate of the reaction. Following treatment of factor VIII with thrombin, a new and smaller polypeptide Mr around 70,000 +/- 5,000 is produced. Factors IXa and Xa also have been reported to activate factor VIII. It is not known whether limited proteolytic cleavage is required absolutely for the expression of factor VIII activity or if it only increases an activity already expressed by the uncleaved protein. Factor VIII is inactivated by thrombin and by activated protein C. Thus, factor VIII can be modulated by at least four of the serine proteases in the clotting system. A major goal for future research is to increase our understanding of the role in blood clotting played by factor VIII, and to apply this information to clinical problems which result from inherited abnormalities of factor VIII.     

Thyrotropin releasing hormone and naloxone attenuate the antihypertensive action of central alpha 2-adrenoceptor stimulation through different mechanisms

In various forms of shock, TRH is equivalent to naloxone in reversing the hypotension and improving the survival rate. The present findings indicate that in spontaneously hypertensive rats (SHR), TRH has another naloxone-like effect in antagonizing the antihypertensive response to clonidine and alpha-methyldopa. When given during the hypotensive response to alpha-methyldopa, both naloxone and TRH produce a pressor response. While this effect of naloxone is blocked by prazosin, the effect of TRH is not influenced by prazosin or hexamethonium but is inhibited by a vasopressin pressor antagonist. This suggests that the pressor response to naloxone is mediated by the sympathetic nervous system, whereas the similar action of TRH is independent of sympatho-adrenomedullary functions and it is mediated by vasopressin.     

Control of adrenocortical growth in vivo

Adrenocortical growth is discussed with respect to its relation to body weight, elevated ACTH (provoked by sustained stress, adrenal enzyme deficiency, and adrenal enucleation), and unilateral adrenalectomy. It seems likely that these three conditions under which adrenal growth occurs are each controlled and mediated by different agents. Least is known about the growth of adrenals with the growth of the organism; however, because treatment with growth hormone is known to stimulate adrenal mitogenesis, and because adrenals grow in proportion to body growth by increasing cell number, it is proposed that this growth may be mediated by growth hormone (via somatomedin). ACTH causes primarily adrenocortical cellular hypertrophy which is subsequently followed by hyperplasia. It has been shown that the application of a sustained stressor, induction of adrenal enzyme deficiency and adrenal enucleation all result in persistent elevation in circulating ACTH levels and adrenal growth. It appears that the stimulus to ACTH secretion is a virtual or real decrease in corticosteroid feedback signal, and that ACTH secretion is regulated by corticosteroid levels. An additional humoral factor may be triggered by adrenal enucleation, and the possibility that a fragment of the N-terminal peptide of the ACTH precursor molecule plays this role is entertained. Finally, the evidence that the proliferative adrenal growth after unilateral adrenalectomy is mediated by afferent and crossed efferent neural pathways, and is regulated by aldosterone, pineal peptides and exposure to constant light is discussed.     

Energy transformations early in the bacteriorhodopsin photocycle revealed by DNP-enhanced solid-state NMR

By exploiting dynamic nuclear polarization (DNP) at 90 K, we observe the first NMR spectrum of the K intermediate in the ion-motive photocycle of bacteriorhodopsin. The intermediate is identified by its reversion to the resting state of the protein in red light and by its thermal decay to the L intermediate. The (15)N chemical shift of the Schiff base in K indicates that contact has been lost with its counterion. Under these circumstances, the visible absorption of K is expected to be more red-shifted than is observed and this suggests torsion around single bonds of the retinylidene chromophore. This is in contrast to the development of a strong counterion interaction and double bond torsion in L. Thus, photon energy is stored in electrostatic modes in K and is transferred to torsional modes in L. This transfer is facilitated by the reduction in bond alternation that occurs with the initial loss of the counterion interaction, and is driven by the attraction of the Schiff base to a new counterion. Nevertheless, the process appears to be difficult, as judged by the multiple L substates, with weaker counterion interactions, that are trapped at lower temperatures. The double-bond torsion ultimately developed in the first half of the photocycle is probably responsible for enforcing vectoriality in the pump by causing a decisive switch in the connectivity of the active site once the Schiff base and its counterion are neutralized by proton transfer.     

Tissue factor pathway.

Blood coagulation is initiated in response to vessel damage in order to preserve the integrity of the mammalian vascular system. The coagulation cascade can also be initiated by mediators of the inflammatory response, and fibrin deposition has been noted in a variety of pathological states. The cascade of coagulation zymogen activations which leads to clot formation is initiated by exposure of flowing blood to Tissue Factor (TF), the cellular receptor and cofactor for Factor VII (FVII). FVII binds to the receptor in a I:I stoichiometric complex and is rapidly activated. FVIIa undergoes an active site transition upon binding TF in the presence of calcium which enhances the fundamental properties of the enzyme. This results in rapid autocatalytic activation of FVII to FVIIa, thereby amplifying the response by generating more TF-FVIIa complexes. The TF-FVIIa activates both FIX and FX. Further FXa generation by the FIXa-FVIIIa-Ca2+-phospholipid complex is required to sustain the coagulation mechanism, since the TF-FVIIa complex is rapidly inactivated by Tissue Factor pathway inhibitor (TFPI). TFPI circulates in plasma, is associated with vascular cell surface and is released from platelets following stimulation by thrombin. TFPI requires the formation of an active TF-FVIIa complex and FXa generation before inhibition can occur. TFPI prevents further participation of TF in the coagulation process by forming a stable quaternary complex, TF-FVIIa-FXa-TFPI.