Vol 1-3 Mini Review

Aberrant neural crest development causes craniofacial and other malformations in an animal model of Musculocontractural Ehlers-Danlos syndrome

Edgar M. Pera1*, Nadège Gouignard1 and Marco Maccarana2

1Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
2Dept. Experimental Medical Science, Lund University, 221 84 Lund, Sweden

Musculocontractural Ehlers-Danlos syndrome (MC-EDS) is a rare recessive disorder that is characterized by connective tissue fragility, distinct craniofacial features and congenital malformations. MC-EDS patients have defects in the enzymes dermatan sulfate epimerase-1 and dermatan 4-O-sulfotransferase-1, which are involved in the biosynthesis of iduronic acid in the chondroitin sulfate/dermatan sulfate (CS/DS) chains of proteoglycans (PGs). While the connective tissue defect is a result of disturbed collagen fibril assembly based on a decreased iduronic acid content of interacting CS/DS-PGs, the cause of the developmental malformations in MC-EDS is not well understood. This review focuses on a new role of CS/DS-PGs in the development of multipotent and highly migratory neural crest (NC) cells in the Xenopus embryo model of MC-EDS. Single iduronic acid residues in CS/DS-PGs are involved in the formation of NC-derived craniofacial structures by facilitating the migration and adhesion of NC cells to fibronectin. Our results suggest a defect in NC development as cause of the craniofacial and other congenital anomalies in MC-EDS patients, which might contribute to an improved diagnosis and etiology-based therapy.

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Vol 2-4 Mini Review

Treatment with intravenous iloprost in patients with systemic sclerosis: A short review

Elisa Visalli1, Giorgio Amato1, Marcella Di Gangi1, Alessia Benenati1, Nicolò Cino1, Caterina Gagliano2, Raffaele Falsaperla3, Alberto Farina4, Rosario Foti1

1Rheumatology Unit, A.O.U. Policlinico Vittorio Emanuele, Catania, Italy
2General Pediatrics and Pediatric Acute and Emergeny Unit, A.O.U. Policlinico Vittorio Emanuele, Catania, Italy
3Ophthalmology, NEST (Neurovisual Science Technology) and Rare Disease Center (Ra.Di.Ce.), Santa Marta Hospital, Catania, Italy
4Medical Affairs Department, Italfarmaco S.p.A., Milano, Italy

Systemic sclerosis (SSc) is a severe, chronic disease characterised by small vessel vasculopathy, autoantibodies production, and ?broblast dysfunction leading to an excessive deposition of collagen in the skin and internal organs. The beneficial effects of iloprost in improving symptoms of ischemia such as Raynaud‘s phenomenon (RP) and digital ulcers (DUs) in patients with SSc are largely due to modulating the disordered microcirculation. Literature data show that the long-term IV iloprost administration maintains efficacy in the treatment of vasculopathy, representing a rational therapeutic approach, since Raynaud’s phenomenon and digital ulcers are two of the major causes of pain and disability in scleroderma patients. Intravenous iloprost may also play a role in promoting a favourable disease course, as a stabilization of cardio-pulmonary were observed in long-term studies. Current evidences are encouraging, but further randomized and controlled trials are needed to confirm these results.

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Vol 2-4 Mini Review

Iron in erythropoietic protoporphyrias: Dr. Jekyll or Mr. Hyde?

Jasmin Barman-Aksoezen1, Xiaoye Schneider-Yin1, Elisabeth I. Minder2*

1Stadtspital Triemli, Institute of Laboratory medicine, Zurich, Switzerland
2Stadtspital Triemli, Porphyria outpatient clinics, Zurich, Switzerland

Erythropoietic protoporphyria consists of two different genetic diseases, erythropoietic protoporphyria (EPP) and X-linked erythropoietic protoporphyria (XLEPP). Both of them are often accompanied by iron deficiency. Iron supplementation appears to be beneficial in XLEPP, although the clinical experience until to date is limited. In EPP, iron supplementation is discussed ambiguously and may cause harm in the majority of cases.

This minireview summarizes the limited knowledge on the connections of iron metabolism to regulation of porphyrin and heme synthesis and the influence these regulations may have on disease severity in the protoporphyrias. Further, we propose clinical guidelines, how to manage iron deficiency in both XLEPP and EPP.

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Vol 2-4 Mini Review

The genetics of hereditary angioedema: A review

Macarena Piñero-Saavedra1 and Teresa González-Quevedo2*

1Research Coordinator, Allergy Department, Algarve Hospital Complex, Faro, Portugal
2Coordinator of the Andalusian Reference Unit for Angioedema, Allergy Department, Virgen del Rocio University Hospital, Seville, Spain

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Vol 2-4 Mini Review

PEDF: An essential stem cell regulator in models of Osteogenesis Imperfecta Type VI

Vikram Lyall1, Vivian Shih2*, and Chuhan Chung1,3*

1Department of Medicine, Yale University School of Medicine, Connecticut, USA
2Department of Orthopedics & Rehabilitation, Yale University School of Medicine, Connecticut, USA
3VA Connecticut Healthcare System, West Haven, CT, USA

The rare bone disease Osteogenesis Imperfecta (OI) type VI is caused by mutations in the gene coding for PEDF, Serpinf1. Individuals with OI type VI have an accumulation of unmineralized bone matrix and multiple fractures. Our lab group has previously shown that PEDF restoration in the mouse model of OI type VI increases bone mass and mineralization. Further, we demonstrated that PEDF directs mesenchymal stem cells to the osteoblast lineage. One mechanism appears to involve modulation of canonical Wnt/β-catenin signaling in a temporally-defined manner. We have also induced pluripotent stem cells from a patient with OI type VI and differentiated the cells into osteoblasts to investigate how PEDF regulates the expression of various bone matrix proteins such as IBSP. In this brief review, we provide an overview of PEDF biology and highlight how PEDF’s role as a stem cell regulator lends support to its causative role in OI type VI.

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Vol 2-2 Review

Takayasu's arteritis - a comprehensive review

H.S. Natraj Setty*, J.R. Vijaykumar, C.M Nagesh, Shivanand S Patil, Santhosh Jadav, T.R. Raghu, C.N. Manjunath

Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India

Takayasu’s arteritis (TA) is a chronic inflammatory disease of unknown aetiology. The mechanism of this disease is not exactly defined. The inflammatory process is generally (but not exclusively) initiated in the second or third decade of life through the actions of non-specific inflammatory cells. As the disease progresses, fibrotic stenosis occurs in aorta and its main branches. The consequence of this inflammatory process can be stenosis, thrombosis, dilatation or aneurysm formation in aorta and/ or its branches. Majority of cases have been observed in Asia, Africa, and Latin America. In Asia, its incidence (2.69 in a million per year) has been reported to be 100 times higher than in Europe and North America. Because of the delay in diagnosing the disease, patients often experience claudication, absence of pulses, hypertension, myocardial infarction (MI), and cerebrovascular accidents (CVAs). Accurate and early diagnosis of TA can reduce the economic, social, and psychological burdens. Considering the fact that classical TA has mainly been described in Asia.

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