Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases

Zinc is an essential micronutrient in human body and a vital cofactor for the function of numerous proteins encoded by the human genome. Zinc has a critical role in maintaining many biochemical and physiological processes at the molecular, cellular, and multiple organ and systemic levels. The alteration of zinc homeostasis causes dysfunction of many organs and systems.In the immune system, zinc regulates the differentiation, proliferation and function of inflammatory cells, including T cells, eosinophils, and B cells, by modifying several signaling pathways such as NFκB signaling pathways and TCR signals. An adequate zinc level is essential for proper immune responses and decreased zinc levels were reported in many allergic inflammatory diseases, including atopic dermatitis, bronchial asthma, and chronic rhinosinusitis. Decreased zinc levels often enhance inflammatory activation. On the other hand, the inflammatory conditions alter the intracellular homeostasis of zinc, often decreasing zinc levels. These findings implied that there could be a vicious cycle between zinc deficiency and inflammatory conditions.In this review, we present recent evidence on the involvement of zinc in atopic dermatitis, bronchial asthma, and chronic rhinosinusitis, with insights into the involvement of zinc in the underlying molecular and cellular mechanisms related to these allergic inflammatory diseases.     

AdipoRs- a potential therapeutic target for fibrotic disorders

Introduction: Fibrotic disorders are a leading cause of morbidity and mortality; hence effective treatments are still vigorously sought. AdipoRs (AdipoR1 and Adipo2) are responsible for the antifibrotic effects of adiponectin (APN). APN exerts antifibrotic effects by binding to its receptors. APN concentration and AdipoR expression are closely associated with fibrotic disorders. Decreased AdipoR expression may reduce APN-AdipoR signaling, while the upregulation of AdipoR expression may restore the anti-fibrotic effects of APN. Loss of APN signaling exacerbates fibrosis in vivo and in vitro.

Areas covered: We assess the relationship between APN and fibrotic disorders, the structure of receptors for APN and the pathways accounting for APN or its analogs blocking fibrotic disorders. This article also discusses designed APN products and their therapeutic prospects for fibrotic disorders.

Expert opinion: AdipoRs have a critical role in blocking fibrosis. The development of small-molecule agonists toward this target represents a valid drug development pathway.     

Pyoderma gangrenosum and chronic granulomatous disease treated with adalimumab: Case-based review

BackgroundChronic granulomatous disease (CGD) is a rare immunodeficiency disorder that manifested by recurrent severe bacterial and fungal infection. It may be associated with non-infectious inflammatory complications that affect gastrointestinal tract, lung and skin. Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterizes by painful cutaneous ulceration. The coexistence of PG and CGD is very rare and the treatment is challenging; only few cases have been reported.Aim of the workTo describe the features and management of a challenging case of PG associated with CGD.Case reportA 20-year old male with a long history of recurrent bacterial and fungal infections due to CGD presented to the Rheumatology and Immunology outpatient clinic at Mansoura University hospital with an ulcerative cutaneous lesion with exudation and crusting on the left lateral malleolus. There were elevated inflammatory markers: erythrocyte sedimentation rate (ESR) 130 mm/1^st h and C-reactive protein (CRP) 52 mg/dl. Histological examination of the lesion revealed diffuse dermal infiltrate of neutrophils and nuclear dust admixed with some histiocytes, lymphocytes and plasma cells, a picture suggestive of PG. Systemic and musculoskeletal examination were unremarkable except for low grade fever (37.7 °C). Conventional immunosuppressives were not satisfactory and adalimumab (40 mg/2 weeks) was added showing significant improvement of the lesion (ESR 7 mm/h, CRP 3 mg/dl).ConclusionCGD is a rare primary immunodeficiency disorders that can be associated with PG. The coexistence of these two conditions requires judicious use of immunosuppressive agents. However; adalimumab may be an effective and safe treatment option.     

Midterm Results with the Open Chimney Technique during Endovascular Aneurysm Repair

Purpose

To report the midterm experience with chimney-endovascular aneurysm repair (Ch-EVAR) with the use of open self-expending stents for branch vessel preservation.

Hemophagocytic syndrome due to Epstein-Barr virus and cytomegalovirus coinfection in a patient on adalimumab

IntroductionHemophagocytic syndrome (HPS) is a rare but potentially fatal complication of viral infections. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) often infect patients receiving TNF-alpha inhibitors (TNF-α inhibitors). While EBV and CMV are well established infections for the development of infectious mononucleosis, coinfection with EBV and CMV is common among immunosuppressed patients and can result in a fatal course. In addition, such viral infections can cause HPS. To the best of our knowledge, we present here the first report of HPS induced by EBV and CMV coinfection during anti-TNFα inhibitor use.Case reportA 23-year-old man hospitalized with fever, elevated liver enzymes, lymphadenopathy, and hepatosplenomegaly was diagnosed with HPS associated with EBV and CMV coinfection while using adalimumab. No clinical improvement was observed after discontinuation of adalimumab. HPS complicated by EBV and CMV coinfection was finally diagnosed, and immediate administration of ganciclovir and prednisone was considered to have prevented a lethal clinical outcome.ConclusionFor cases showing unexplained fever, elevated liver enzymes, and lymphadenopathy while using anti-TNFα inhibitors, screening for EBV and CMV coinfection should be encouraged. In addition, HPS should be considered in patients with EBV and/or CMV infection receiving anti-TNFα inhibitors to facilitate early definitive therapy.     

基于钕铁硼磁粉的α表面污染模拟方法研究

目的 针对核应急医学救援实战化训练需求，研制安全可靠的α表面污染模拟源应用于实际训练。方法 使用便携式α表面污染检测仪测量α面源，总结变化规律；运用磁场模拟α辐射场，使用钕铁硼磁粉作为磁源，通过磁粉与胶体混合在磁场中充磁制备成磁粉胶体，再将磁粉胶体涂抹于物体表面作为模拟源，使用特定的检测电路检测，按照一定转换公式，将电压值转换为计数率或活度值，实现α表面污染的模拟。结果 使用便携式α表面污染检测仪测量α面源的计数率在α射线射程范围与测量距离呈线性关系；使用钕铁硼磁粉和胶体制备的模拟源磁感应强度在0.5～3 cm范围能够模拟α表面污染计数率的变化规律；同时能够模拟洗消的变化过程。结论 基于钕铁硼磁粉的α表面污染模拟方法安全可靠、无辐射危害，能够应用于α表面污染检测、洗消的模拟训练，对提高训练水平，提升核应急救援队伍的实际救援能力具有一定应用价值。     

Consenso Delphi de las recomendaciones para el tratamiento de los pacientes con atrofia muscular espinal en España (consenso RET-AME)

IntroductionSpinal muscular atrophy (SMA) is a neurodegenerative disease caused by a biallelic mutation of the SMN1 gene, located on the long arm of chromosome 5, and predominantly affects the motor neurons of the anterior horn of the spinal cord, causing progressive muscle weakness and atrophy. The development of disease-modifying treatments is significantly changing the natural history of SMA, but uncertainty remains about which patients can benefit from these treatments and how that benefit should be measured.MethodologyA group of experts specialised in neurology, neuropediatrics, and rehabilitation and representatives of the Spanish association of patients with SMA followed the Delphi method to reach a consensus on 5 issues related to the use of these new treatments: general aspects, treatment objectives, outcome assessment tools, requirements of the treating centres, and regulation of their use. Consensus was considered to be achieved when a response received at least 80% of votes.ResultsTreatment protocols are useful for regulating the use of high-impact medications and should guide treatment, but should be updated regularly to take into account the most recent evidence available, and their implementation should be assessed on an individual basis. Age, baseline functional status, and, in the case of children, the type of SMA and the number of copies of SMN2 are characteristics that should be considered when establishing therapeutic objectives, assessment tools, and the use of such treatments. The cost-effectiveness of these treatments in paediatric patients is mainly influenced by early treatment onset; therefore, the implementation of neonatal screening is recommended.ConclusionsThe RET-AME consensus recommendations provide a frame of reference for the appropriate use of disease-modifying treatments in patients with SMA.     

Use of the Octopus Technique for Endovascular Treatment of Complex Aortic Lesions

Purpose

To evaluate feasibility and effectiveness using the octopus endograft technique to treat complex aortic aneurysms (CAAs).