Poly(ADP-ribose) polymerase inhibitors in the prevention of neuronal cell death

Poly(ADP-ribose) polymerase is a nucleic enzyme that promotes energy-dependent repair of DNA, thus helping to protect against DNA fragmentation. Overactivation of PARP, for example in the context of apoptosis, may contribute to neuronal cell death. This article briefly reviews claims for PARP inhibitors as agents for the prevention of neuronal cell death, registered in the period 1998 – December 2001. Biological data are sparse in these patents, few claims are backed by in vitro biochemical data and fewer still with in vivo animal model data. The latter have used animal models of ischaemia rather than of neurodegeneration. The place of PARP inhibitors as a clinical therapy to prevent neuronal cell death remains to be determined.     

Solubilization of flurbiprofen into aptamer-modified PEG–PLA micelles for targeted delivery to brain-derived endothelial cells in vitro

Abstract

Novel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients.     

Rethinking children’s public health: the development of an assets model

It has been suggested that asset-based strategies could provide an opportunity to rethink the approach to public health; however, this may not be a viable option unless there is clear recognition of specific individual assets. Although there has been some consideration of assets within a child health context, this is limited and previous studies have not sought to identify assets from the perspective of the child. This paper reports on a study that drew on an ethnographic approach, using a photo-elicitation method, to facilitate the mapping of children’s internal and external assets from the viewpoint of children themselves. Two primary schools in the South-East of England were used to recruit 20 year five children (aged 9–11 years of age). The participants, 10 boys and 10 girls, were given disposable cameras and asked to take photographs of the activities that they enjoyed. The children’s photographs were used as prompts during individual semi-structured interviews. A constant comparative analysis facilitated the mapping of the children’s assets as the children described them; this process revealed one overall stabilising asset (‘My Family’) as well as eight internal and three external assets. All of the assets are presented within an original model, ‘I’m good’: the children’s asset wheel [CAW], which was developed from the findings. It is suggested that the CAW could complement previous asset-based work to facilitate the rethinking of approaches to the enhancement of children’s public health.     

原发性干燥综合征合并肺动脉高压的临床研究

目的探讨原发性干燥综合征(pSS)并发肺动脉高压(PAH)的发生率、临床特点及筛查方法。方法对61例临床确诊为pSS的患者行彩色多普勒超声心动检查,应用三尖瓣反流速度来估测肺动脉收缩压(PASP),依据PAH诊断标准将其分为PAH组(10例)和非PAH组(51例),收集2组的临床资料、实验室检查、胸CT扫描和超声心动的检测结果并进行比较。结果 (1)61例pSS患者中并发PAH者占16.4%,PAH组中PASP为31~64mmHg,平均(40±9)mmHg,其中4例无任何与PAH相关的临床表现,PAH的发生与患者年龄、性别、病程无关。(2)患者的主要症状为发热、干咳、胸闷或胸痛、心悸、进行性呼吸困难、雷诺现象、胸腔积液和肺间质病变,PAH组雷诺现象、心悸、肺间质病变的发生率高于非PAH组(P<0.05),PAH组的补体C3水平低于非PAH组(P<0.05)。(3)PAH组瓣膜受累达100%,其中2例仅伴有右心系统扩大,3例同时出现左心和右心系统扩大,PAH组左房内径、右房内径、右室内径、肺动脉内径高于非PAH组(P<0.05或P<0.01)。结论 pSS并发PAH并不少见,患者即使无相应临床症状,也应行超声心动筛查,这对PAH的临床早期诊断和治疗十分重要。     

Huperzine alkaloids from Australasian and southeast Asian Huperzia

Context: The pharmaceutical alkaloid huperzine A (HupA), currently used in herbal supplements and medicines worldwide, is predominantly sourced from the Chinese lycopod Huperzia serrata (Thunb. ex Murray) Trev. (Lycopodiaceae), which on average contains only 0.08?mg HupA g^?1 dry weight, and is experiencing a rapid decline in China due to over-harvesting.

Objective: To find a high-yielding, natural source of HupA and/or the related huperzine B (HupB) that could potentially be used as the starting material in a commercial propagation program.

Materials and methods: We surveyed 17 Huperzia species (15 indigenous to Australia and southeast Asia) for their foliar HupA and HupB concentrations. We also studied intra-specific variation for the huperzines in four species that were available in sufficient numbers, and determined tissue-specific accumulation in larger specimens.

Results: HupA was detected in 11 Australasian and southeast Asian species, with eight also containing HupB, albeit at much lower concentrations. A H. elmeri (Herter) Holub plant from the Philippines had one of the highest HupA concentrations recorded (1.01?mg g^?1 dry wt) and it also had the highest HupB content of all plants surveyed (0.34?mg g^?1 dry wt). Intra-specific HupA and HupB concentrations were extremely variable, and at the intra-plant level, reproductive strobili were found to accumulate the highest HupA concentrations.

Discussion and conclusion: Select Huperzia species from Australia and southeast Asia have potential as the starting material for establishing commercial HupA plantations, but the high intra-specific variability observed suggests that detailed screening is needed to isolate high huperzine-yielding individuals.     

A rare case of a strangulated Littre’s hernia with Meckel’s diverticulum duplication. Case report and literature review

IntroductionThe Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract present in approximately 1–4% of the population; the MD duplication is exceedingly rare with only a few reports of it. Here we present the firs case of a strangulated Littre’s hernia with MD duplication.Presentation of caseA 30-year-old male presented to the emergency room with clinical signs of small bowel obstruction, at physical examination, a right incarcerated inguinal hernia with erythema was found. We did a laparotomy, and two MD were found, one in the sac with ischemia, and the other 90 cm from the Bahuińs valve. A diverticulectomy of the ischemic diverticulum was done, and the other MD was left in place; the inguinal region was repaired with a Lichtenstein technique.DiscussionThe complications of the MD are 3–4 times more frequent in men, been an intestinal obstruction, hemorrhage, diverticulitis, ulceration, and perforation. A Littrés hernia is when the MD is found in the sac; this is seen in the inguinal region in 50% of the cases. The management of a Littre’s hernia is the resection of the MD; it could be done by an intestinal resection or by a diverticulectomy accordingly to the Park criteria.ConclusionAs to our knowledge, this is the first case of an incarcerated Littre’s hernia with duplication of a Meckel’s diverticulum.     

Development of anti-neutrophil cytoplasmic antibody-associated vasculitis in a patient with Graves’ disease independent of anti-thyroid drug therapy

Abstract

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients with Graves’ disease (GD) is linked with the use of anti-thyroid drugs (ATDs). We report the co-occurrence of AAV and GD in a patient that was independent of ATD therapy. A 38-year-old white male presented with systemic symptoms, palpitations, tremors, purpuric skin lesions, and digital pain. Physical examination and biological tests confirmed GD. He quickly developed multiple digital gangrenes and testicular pain/mass. Skin and testicular biopsies showed granulomatous vasculitis of the small- and medium-sized vessels, while his serum contained anti-proteinase-3 antibody.     

Autoantibodies against complement C1q in patients with Behcet’s disease: association with vascular involvement

Abstract

Aim. The aim of our study was to determine the prevalence of anti-C1q antibodies and their possible association with clinical presentation in Behcet’s disease (BD) patients with special emphasis for patients with vascular involvement.

Methods. Plasma anti-C1q Abs levels were measured using an enzyme-linked immunosorbent assay in 51 BD patients and 25 age- and gender-matched healthy controls.

Results. We found elevated concentrations of anti-C1q more frequently in patients with BD (18 %) than in healthy controls (8 %). The highest prevalence was found in patients with vascular BD (42 %) which was significantly higher than patients without vascular BD and healthy controls (p = 0.025). Furthermore, patients with vascular BD had the highest mean anti-C1q levels when compared to BD patients without vascular involvement or healthy control subjects (p = 0.015). We did not find significant differences in the prevalence of any other organ involvement between BD patients with elevated vs. normal anti-C1q ab levels. Anti-C1q ab levels positively correlated with ESR (r = 0.383, p = 0.006) and negatively with C4 (r = ?0.304, p = 0.030).

Conclusion. In conclusion, we found an increased prevalence of anti-C1q autoantibodies in BD patients with vascular involvement. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies in BD and other autoimmune diseases in which vasculitis is a component.