恶性疟原虫RIFIN蛋白的结构和功能研究进展

恶性疟原虫感染易引起重症疟疾甚至导致死亡,在其致病机制中,变异表面抗原家族的重复散布蛋白家族(RIFIN)起了重要作用,它们能介导微静脉血管系统中感染红细胞的黏附和玫瑰花环形成,从而阻断血流,堵塞血管导致重症疟疾。RIFIN在感染红细胞的表面表达,是重要的免疫靶点之一,但由于重复散布的基因家族rif的多基因性和基因多态性,RIFIN能够逃避免疫系统的攻击。同时,RIFIN与免疫细胞表面抑制性受体白细胞免疫球蛋白样受体B1 (LILRB1)、白细胞相关免疫球蛋白样受体1 (LAIR1)等的结合能下调免疫反应而达到免疫逃避的目的。近年来,随着对恶性疟分子机制研究的日趋深入,研发能够诱导产生有效保护性免疫的疫苗成为预防疟疾、实现疟疾消除计划的关键。本文描述了恶性疟原虫RIFIN的结构,并强调了它们在重症疟疾中的作用以及相关的免疫和疫苗研究进展。     

换血可作为治疗重症恶性疟的辅助疗法

高原虫血症是引起疟疾死亡的重要因素。换血作为疟疾化疗的辅助疗法可快速降低原虫血症。因此,有人建议以该辅助疗法治疗重症疟疾。本文报道了采用奎宁和奎宁+换血两种方法治疗50例重症疟疾的情况,并对结果进行了比较。 50例疟疾病人均符合一个或多个WHO关于重症疟疾的标准。其中脑型疟15例,有意识障碍者19人,惊厥19人,黄疸21人,严重贫血6人,肾功能不全18人和低血糖6     

脑型疟病人体内奎宁药物动力学——二室模型预测快速静注后的血浆浓度

奎宁静脉注射是治疗重症疟疾病人的建议疗法,但由于其可能导致引起死亡的心血管毒性,现改用缓慢静滴。为研究快速静脉给药后奎宁在严重疟疾病人中的潜在毒性,     

南通市重症疟疾病例特征及诊治情况分析

目的 回顾性分析南通市重症疟疾病例特征和诊治情况,总结重症疟疾的成因、评价诊治效果,为制定切实可行的重症疟疾救治措施提供科学依据。方法 收集2009-2016年南通市所有疟疾病例资料,对重症疟疾病例的发病时间、临床表现、诊断过程、治疗情况进行汇总分析。结果 2009-2016年南通市共报告疟疾病例359例,其中重症病例26例,均为境外输入性恶性疟病例,其中脑型疟12例、急性肾功能衰竭11例、重度贫血3例。26例重症疟疾病例从发病至就诊的平均时间为3.1 d,平均时间最长者在发病第12天才就诊;从发病至确诊的平均时间为5.2 d,其中11例在发病5 d后得到确诊。乡（镇）医院首诊确诊率为25.00%（1/4）,县级医疗机构首诊确诊率为90.91%（10/11）。26例重症疟疾病例通过抗疟治疗和临床对症治疗均治愈,无死亡病例。结论 重症疟疾临床表现复杂、并发症多、危害严重,加大对赴疟疾高度流行区人员的疟疾宣教、提高诊治单位医务人员对疟疾的诊治能力和镜检技能,可有效减少重症恶性疟病例发生、避免疟疾病例死亡。     

在研制疟疾红内期疫苗时进行保护性预测的必要性

由于患疟疾及死亡带来的巨大损失以及疟原虫对氯喹和其他药物日益增强的抗性,研制能用于人的疫苗已十分迫切。目前研究最多的红内期候选疫苗是SPf66,已用该疫苗接种了南美洲、非洲和东南亚的数千名志愿者。迄今仍不能肯定它是否能有效地减少重症疟疾和死亡。作者认为对免疫机制的了解和掌握对加速红内期疫苗的研制是至关重要的。     

恶性疟原虫var基因家族研究进展

疟疾严重威胁人类健康，恶性疟原虫是致疟疾病例死亡的主要病因。PfEMP1蛋白由var基因家族编码在恶性疟原虫的生存和重症疟疾发病过程中起重要作用。vor基因家族基因数目多，调控机制复杂，一直是研究的热点。该文就vor基因家族的分布、结构、多态性、转录、表达及其调控机制方面近期的进展加以综述。     

恶性疟原虫Pf155/RESA抗原与红细胞带3蛋白中和细胞粘附有关的同源基序

恶性疟原虫(P.f.)引起的重症疟疾,常由受感染红细胞粘连于毛细血管后小静脉的内皮细胞所致。对此现象的分子基础至今仍不太清楚。晚近有报告称,相当于红细胞带3     

血液滤过联合青蒿琥酯治疗2例重症恶性疟疾的体会

重症恶性疟疾发病急、临床症状复杂、并发症多,如不及时抢救可因意识障碍、昏迷、偏瘫、肾衰竭、呼吸循环功能衰竭等死亡。本文介绍2例经血液滤过联合青蒿琥酯针剂治疗的重症恶性疟疾的体会。     

脑型疟疾脑脊液乳酸盐的病理生理与预后的意义

脑型疟疾是重症恶性疟疾最常见的临床表现,死亡率约20%。死亡原因包括急性肺水肿、急性肾功能衰竭、并发细菌感染及代谢性酸中毒。恶性疟疾的昏迷原因尚不清楚,作者通过测定脑型疟疾昏迷病人脑     

恶性疟疾的高胰岛素血症和重度低血糖症

一般并不认为低血糖症是恶性疟疾的重要并发症,作者报告了泰国东部恶性疟疾并发低血糖症的发生情况、临床表现和发病机制。17例恶性疟疾中轻症3例;重症14例。其中呈脑型疟疾表现者12例;并发肾功能衰竭者4例。作者观察到恶性疟疾患者并发低血糖症是一种常见和严重的临床问题,低血糖的程度常常是严重而且容易反复发作。17例恶性疟疾患者共有30次低血糖症发作,发作时均伴血浆胰岛素和C多肽浓度的升高,且患者血浆乳酸和丙氨酸浓度亦显著升高。重症患者常有高疟原虫血症、肾脏受累和高病死率,本组14例重症患者中8例死亡,病死率为57％,其中5例死于乳酸中毒,血浆乳酸浓度的升高与高疟原虫血症密切相关。 17例恶性疟疾患者中16例接受奎宁治疗,作者观察到于低血糖症发作时血浆奎宁浓度和胰岛素浓度显     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.