Evaluation of prime and prime-boost immunization strategies in BALB/c mice inoculated with Leishmania infantum transfected with toxic plasmids

The etiologic agents of visceral leishmaniasis are Leishmania infantum and Leishmania donovani. Despite the variety of drugs available to treat leishmaniasis, most lead to serious adverse effects, and resistance to these drugs has been reported. Currently, no leishmaniasis vaccine is available for humans. That is why the group developed transgenic L. infantum promastigote lines, which express toxic proteins after differentiation into amastigotes. That is why group developed the pFL-AMA plasmid and transfected it into L. Infantum promastigotes. This plasmid was expressed only in the amastigote form of the parasite. Sequences encoding toxic proteins (active bovine trypsin and egg avidin) were inserted in this plasmid, and the transfected parasites died after the differentiation process. In this study, two immunization protocols were performed in BALB/c mice: prime and prime-boost immunization prior to challenge with the wild-type L. infantum (WT). The parasite burdens in the spleen, liver, and bone marrow were evaluated to verify immunological protection. Histopathological analysis of the spleen and liver and the humoral immune response were also performed. The data showed that the parasite burden was reduced in prime-boosted mice in the spleen, liver, and bone marrow, indicating that mice immunized with two doses of the transfected parasites were satisfactorily protected. High levels of IgG, IgG1, and IgG2a antibodies were observed, as well as the presence of anti-inflammatory cytokine Interleukine-10 and pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN – γ) suggesting a Th1/Th2 mix response, in addition to the presence of multinucleated giant cells in the spleen and lymphocyte infiltration in the liver. Therefore, L. infantum transfected with a toxic plasmid is an excellent vaccine candidate against visceral leishmaniasis and the application of a boost before the challenge promotes greater protection against WT L. infantum infection.     

Successful treatment of diffuse cutaneous leishmaniasis caused by Leishmania amazonensis

Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.     

Arginase and its mechanisms in Leishmania persistence

Leishmaniasis is a neglected infectious disease with clinical presentations ranging from asymptomatic or mild symptoms to chronic infection and eventual death. The mechanisms of disease susceptibility and pathology have been extensively studied, but there are no steadfast rules regarding leishmaniasis. A Th1 response is usually associated with infection control, while a predominant Th2 response is detrimental to the patient. In this scenario, the enzymes arginase and inducible nitric oxide synthase represent two possible pathways of immune response. While the former contributes to parasite replication, the latter is crucial for its control. In the present review, we collected study results that associate arginase expression in patients and in experimental models with disease susceptibility/chronicity and show some proposed mechanisms that explain the role of arginase in maintaining Leishmania infection, including polyamine and thiol synthesis, tissue-resident macrophage (TRM) proliferation and activation and T-cell suppression and exhaustion.     

有氧运动联合抗阻训练对男性肥胖青少年心血管危险因素的影响

目的 观察12周有氧运动联合抗阻训练对男性肥胖青少年心血管危险因素的影响。 方法 选取36例男性肥胖青少年（纳入肥胖组）以及36例年龄、性别相匹配的正常体重青少年（纳入对照组）作为研究对象。2组受试者均保持规律饮食习惯，肥胖组在此基础上进行12周有氧运动联合抗阻训练。于实验前、实验进行12周后分别检测2组受试者炎症因子、血脂、胰岛素敏感性、血管内皮功能以及身体成分等指标；并根据实验结束后内脏脂肪含量（VFM）变化值将肥胖组受试者进一步细分为VFM升高组和VFM降低组共2个亚组。 结果 实验前与对照组比较，发现肥胖组血清白细胞介素-1受体拮抗剂（IL-1Ra）、肿瘤坏死因子-α（TNF-α）、瘦素、胰岛素（Ins）和胰岛素抵抗指数（HOMA-IRI）、高敏C-反应蛋白（hs-CRP）及甘油三酯（TG）水平均明显升高（P<0.05），脂联素和高密度脂蛋白胆固醇（HDL-C）均明显降低（P<0.05）。实验后与实验前比较，发现肥胖组受试者体重无显著变化（P>0.05），血清IL-1Ra、干扰素-γ-诱导蛋白10（IP-10）、Ins及HOMA-IRI均明显降低（P<0.05）。亚组分析结果显示，实验后VFM降低组TG及HOMA-IRI下调幅度均较VFM升高组显著，组间差异均具有统计学意义（P<0.05）。 结论 12周有氧运动联合抗阻训练能减轻肥胖男性青少年体内炎症反应及胰岛素抵抗水平；并以运动后VFM减少者其血脂水平及胰岛素敏感性改善幅度较显著。     

内脏利什曼病合并HIV感染患者诊断和治疗研究进展

内脏利什曼病是全球被忽视的传染病之一,危害严重。而利什曼原虫-人类免疫缺陷病毒(human immunodeficiency virus,HIV)合并感染对流行地区造成的威胁更甚。利什曼原虫与HIV存在相互作用,合并感染者在临床表现、诊断及治疗方面具有一定特殊性,其病死率及复发率均高于HIV阴性的内脏利什曼病患者。本文对利什曼原虫-HIV合并感染患者的临床表现、诊断和治疗进展进行综述。     

经阴道骶棘韧带悬吊治疗盆腔器官脱垂的疗效观察

【目的】探讨经阴道骶棘韧带悬吊治疗盆腔器官脱垂(POP)的临床疗效。【方法】选取2016年1月至2018年11月在本院治疗的POP患者47例,根据选取的手术方案分为观察组(n=27)和对照组(n=20),观察组给予阴道骶棘韦刃带悬吊术,对照组给予骨盆漏斗韧带悬吊术,比较两组患者手术时间、术中出血量等;所有患者均于术后3个月进行POP-Q测量,其中Ba指阴道前壁中线距处女膜缘3cm处,C指阴道残端和Bp指阴道穹窿的反摺及阴道残端距阴道处女膜中线点最远处。术后1年采用盆底功能障碍问卷-20(PFDI-20)和性生活问卷-12(PISQ-12)评估两组患者生活质量和性生活质量并比较。【结果】观察组手术时间、术中出血量和留置尿管时间分别为(64.02±13.22)min、(87.20±12.23)mL和(87.92±12.21)h,明显少于对照组(P<0.05);观察组和对照组术后3个月Ba、C和Bp较术前改善(P<0.05),但两组术后3个月Ba、C和Bp比较差异无统计学意义(P>0.05);观察组术后1年PDFI-20评分为(20.03±2.19)分,明显低于对照组(P<0.05),而PISQ-12评分为(43.30±5.10)分,明显高于对照组(P<0.05);两组术后并发症发生率比较差异无统计学意义(P>0.05);两组随访期间无复发病例发生。【结论】经阴道骶棘韧带悬吊术治疗POP疗效显著,减少手术时间和术中出血量,提高患者生活及性生活质量,值得临床推广应用。