Evaluation of specific humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> antigens induced in mice immunized with liposomes composed of total lipids extracted from <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.     

Strategies for the use of Ginkgo biloba extract,EGb 761®, in the treatment and management of mild cognitive impairment in Asia: Expert consensus

BackgroundMild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761^®, is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits.AimsTo present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761^® in MCI.Materials & MethodsThe ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761^® as a treatment option.ResultsEGb 761^® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761^® may help delay progression from MCI to dementia in some individuals.DiscussionEGb 761^® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761^® may benefit MCI patients with underlying CVD.ConclusionAs an expert group, we suggest it is clinically appropriate to incorporate EGb 761^® as part of the multidomain intervention for MCI.     

免疫功能正常少年患早期表现为复视的隐球菌脑膜炎1例

目的:报告免疫力正常少年的隐球菌脑膜炎1例,早期表现为复视和双眼视力低下。方法:病例报告。结果:男,17岁,两眼视物模糊并复视3wk,伴随严重的搏动性头痛、恶心、呕吐及低热。经体格检查无发热及假性脑膜炎迹象。双眼视力为6/15并视野缩窄。双眼前段正常。眼外肌运动表明双侧第六神经麻痹。眼底检查显示双侧视盘充血和轻度隆起。CT扫描大脑正常,无颅内肿块或脑室异常。腰椎穿刺发现高开放压>300mmH2O。脑脊液显微镜下及培养均存在新型隐球菌。本例由神经医疗组联合处理。患者开始静脉注射两性霉素B和氟康唑,神经症状1wk后恢复,双眼视力提高到6/6,同时周边视野恢复。随着第六神经麻痹的康复双眼复视得到好转。结论:本例强调了隐球菌脑膜炎进展缓慢的性质。即使免疫功能正常,也不会存在明显的假性脑膜炎特征,复视可能是脑膜炎患者的早期表现之一。     

The utility of Guillain‐Barré syndrome prognostic models in Malaysian patients

Guillain‐Barré syndrome (GBS) is an acute immune‐mediated neuropathy that has variable disease course and outcome. The Erasmus GBS outcome score (EGOS), modified EGOS (mEGOS), and Erasmus GBS respiratory insufficiency score (EGRIS) are prognostic models designed to predict the functional outcome of GBS patients at 6 months (EGOS and mEGOS) and the need for mechanical ventilation within a week of admission (EGRIS). The models were primarily developed in the Dutch GBS population, and thus the usefulness of these models in other GBS cohorts is less clear. In the current study, we aimed to validate mEGOS, EGOS, and EGRIS in Malaysian GBS patients. A total of 107 patients with GBS and its variants were consecutively recruited. Patients with GBS and Miller Fisher syndrome (MFS) were analysed separately. In the GBS cohort, high mEGOS and EGOS scores were significantly correlated with poor outcome at 6 months (mEGOS on admission: r = .381, P = .005; mEGOS at day 7 of admission: r = .507, P < .001; EGOS: r = .484, P < .001). However, there were no significant correlations between mEGOS or EGOS and outcome in patients with MFS (mEGOS on admission: r = .152, P = .523; mEGOS at day 7 of admission: r = .008, P = .973; EGOS: r = .110; P = .644). The score of EGRIS for GBS patients with mechanical ventilation was significantly higher than those patients without mechanical ventilation (4 ± 2 vs 3 ± 1; P < .001). We conclude that mEGOS and EGOS are clinically useful and relevant to the Malaysian GBS population but not in patients with classic MFS. EGRIS could be used to predict the need for mechanical ventilation in our local GBS patients.     

Pseudo bilateral tonsilloliths: a case report and review of the literature

Tonsilloliths are very rare concretions found in the tonsillar crypt. They are usually single and unilateral, but occasionally may be multiple or bilateral. Small concretions in the tonsils are common, but well formed giant unilateral or bilateral tonsilloliths are extremely uncommon. Only two cases of bilateral tonsilloliths have so far been reported in the literature. A case of unilateral tonsillolith, mimicking bilateral tonsilloliths taken with the orthopantogram (OPT) in a 57-year-old Malaysian Indian female with squamous cell carcinoma of the oral cavity is described. Although the OPT is a reliable and standard panoramic X-ray unit used in dentistry, superimposition of a lesion involving one side of the jaw creates a pseudo or ghost image on the contralateral side leading to a misdiagnosis of bilateral lesions. This report highlights that tonsilloliths, though rare, should be considered in the differential diagnosis of radiopaque masses involving the mandibular ramus, and that investigations such as CT scan or MRI may be required to differentiate pseudo or ghost images from true bilateral pathologies.     

Structure and function of the blood–brain barrier

Neural signalling within the central nervous system (CNS) requires a highly controlled microenvironment. Cells at three key interfaces form barriers between the blood and the CNS: the blood–brain barrier (BBB), blood–CSF barrier and the arachnoid barrier. The BBB at the level of brain microvessel endothelium is the major site of blood–CNS exchange. The structure and function of the BBB is summarised, the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms. The roles of associated cells are outlined, especially the endfeet of astrocytic glial cells, and pericytes and microglia. The embryonic development of the BBB, and changes in pathology are described. The BBB is subject to short and long-term regulation, which may be disturbed in pathology. Any programme for drug discovery or delivery, to target or avoid the CNS, needs to consider the special features of the BBB.