Alexandra Prufer de Queiroz Campos Araujo1*, Igor Prufer de Queiroz Campos Araujo2, Abelardo de Queiroz Campos Araujo3
1Institute of Pediatrics, Federal University of Rio de Janeiro (UFRJ). Rua Bruno Lobo 50, Cidade Universitária, Rio de Janeiro, RJ 21941-912, Brazil
2School of Medicine, Federal University of Rio de Janeiro (UFRJ) Rua Bruno Lobo 50, Cidade Universitária, Rio de Janeiro, RJ 21044-020, Brazil
3The Institute of Neurology, Federal University of Rio de Janeiro (UFRJ). Av Venceslau Braz, 215, Botafogo, Rio de Janeiro, RJ 22290-160, Brazil
Background: Motor neuron disorders predominately result in progressive weakness. Nevertheless a wider expression of symptoms and signs point to a more multisystemic involvement. Autonomic nervous system findings have been reported in animal models, adult and child motor neuron diseases.
Objective: Review the literature on autonomic findings in motor neuron diseases.
Method: A PubMed literature search.
Results: In the present review, we will discuss the neuropathological and clinical features of dysautonomia reported in motor neuron disease in humans and animal models.
Conclusion: The literature points to considering careful autonomic evaluation and management in patients with motor neuron disorders.DOI: 10.29245/2572-9411/2018/1.1136 View / Download Pdf
1Department of Diagnostic Imaging, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland
Neurofibromatosis type one (NF1) belongs to the most frequent rare diseases, requiring various methods of diagnostic imaging at different stages of diagnostics and follow-up. Magnetic resonance imaging (MRI) is a method of choice in diagnostics of brain: unidentified neurofibromatosis objects, optic pathway gliomas and other tumours which can spontaneously regress. NF1 patients suffer from vascular abnormalities with a predominance of aortic, renal, mesenteric, and carotid-vertebral stenoses or aneurysms. These are evaluated by ultrasound, computed tomography- or MRI-angiography and by digital subtraction angiography. In our material we described twofold higher occurrence of arterial variants in brain in NF1 than in the control group. Characteristic skeletal changes include tibial pseudarthrosis, scoliosis, sphenoid wing dysplasia, rib penciling, and gracile bones, usually diagnosed with plain radiographs. Outside CNS we deal with neurofibromas and plexiform neurofibromas in any location in the body. Their malignant transformation leads to development of malignant peripheral nerve sheath tumour, or malignant triton tumour. Rhabdomyosarcoma, juvenile myelomonocytic leukemia and phaeochromocytoma are also encountered in NF1 patients with increased frequency. Regular imaging follow-up studies should not be routinely performed in NF1 patients. MRI is recommended for follow-up of clinically suspected tumours, single whole-body MR is recommended at transition to adulthood. Positron emission tomography/computed tomography is useful for the detection of malignant transformation of tumours in NF1 patients.DOI: 10.29245/2572-9411/2017/6.1140 View / Download Pdf
Myeshia V. Shelby*
Department of Genetics and Human Genetics, Howard University Graduate School, Howard University, USA
Through a combination of in silico research and reviews of previous work, mechanisms by which nonsense-mediated mRNA decay (NMD) affects the inheritance and expressivity of Waardenburg syndrome is realized. While expressivity and inheritance both relate to biochemical processes underlying a gene’s function, this research explores how alternative splicing and premature termination codons (PTC’s) within mRNAs mutated in the disease are either translated into deleterious proteins or decayed to minimize expression of altered proteins. Elucidation of splice variants coupled with NMD perpetuating the various symptoms and inheritance patterns of this disease represent novel findings. By investigating nonsense mutations that lie within and outside the NMD boundary of these transcripts we can evaluate the effects of protein truncation versus minimized protein expression on the variable expressivity found between Type I and Type III Waardenburg syndrome, PAX3, while comparatively evaluating EDN3 and SOX10’s role in inheritance of Type IV subtypes of the disease. This review will demonstrate how alternative splicing perpetuates or limits NMD activity by way of PTC positioning, thereby affecting the presentation of Waardenburg syndrome.DOI: 10.29245/2572-9411/2017/6.1118 View / Download Pdf
Yijie Hu1,2, Wolfgang M. Kuebler1,3,4
1Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada
2Department of Cardiovascular Surgery, Institute of Surgical Research, Daping Hospital, Third Military Medical University, Chongqing, China
3Departments of Surgery and Physiology, University of Toronto, Toronto, ON, Canada
4Institute of Physiology, Charité Universitätsmedizin Berlin, Berlin, Germany
Of recent, inflammatory responses, formation of ectopic lymphoid tissue and autoantibodies have been increasingly implicated in the pathophysiology of pulmonary hypertension (PH). One of the earliest immune cells detected in PH and implicated in its pathogenesis were mast cells based on their demonstrated abundance in the vicinity of vascular lesions in PH patients, as well as in lungs of animal models of PH. Experimental studies using mast cell stabilizers or mast cell deficient rats in classic PH models provided proof-of-principle for the functional relevance of mast cells in the initiation and/or progression of PH and lung vascular remodeling. Yet, the cellular mechanisms by which mast cells contribute to the development of PH and pulmonary vascular remodeling has so far remained largely unclear. Importantly, understanding the downstream effectors by which activated mast cells and their secretome trigger or promote vascular remodeling may lead to the development of novel therapies for PH. Notably, recent work has unveiled a novel interplay between mast cells and the adaptive immune system in PH, in that mast cell-targeted interventions attenuate the formation of tertiary lymphoid tissue in the lung and the formation of autoantibodies. This minireview will focus on the role of mast cells in PH and their possible downstream mechanism.DOI: 10.29245/2572-9411/2017/6.1137 View / Download Pdf
Raymond Benza1*, Amresh Raina2, Manreet K. Kanwar3, Steven D. Nathan4, Stephen C. Mathai5
1Advanced Heart Failure, Transplant, Mechanical Circulatory Support and Pulmonary Hypertension Section, Allegheny Health Network, Pittsburgh, PA, USA
2Pulmonary Hypertension Program, Allegheny Health Network, Pittsburgh, PA, USA
3Chronic Thromboembolic Pulmonary Hypertension Program, Allegheny Health Network, Pittsburgh, PA, USA
4Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Vienna, VA, USA
5Johns Hopkins University School of Medicine, Division of Pulmonary and Critical Care Medicine, Baltimore, MD, USA
The soluble guanylate cyclase (sGC) stimulators riociguat and vericiguat elevate intracellular cyclic guanosine monophosphate (cGMP) levels via stimulation of the nitric oxide–sGC–cGMP pathway resulting in vasodilatory, anti-inflammatory, anti-proliferative, and anti-fibrotic effects. Riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). Placebo-controlled phase 3 trials in both indications demonstrated significant improvements in exercise capacity, functional class, and pulmonary hemodynamics, with sustained efficacy and good tolerability in long-term open-label extension studies. Pilot or phase 2 studies of riociguat in pulmonary hypertension associated with heart failure (HF) or chronic obstructive pulmonary disease showed improvements in some hemodynamic parameters, although riociguat is contraindicated in pulmonary hypertension associated with idiopathic interstitial pneumonias. Riociguat is undergoing trials in other conditions including diffuse cutaneous systemic sclerosis. Vericiguat, a novel once-daily sGC stimulator, is well tolerated in patients with HF and is undergoing a phase 3 trial in HF with reduced ejection fraction. These ongoing studies will clarify the roles of sGC stimulators in indications beyond PAH and CTEPH.
6MWD: 6-minute walking distance; cGMP: cyclic guanosine monophosphate; CTEPH: chronic thromboembolic pulmonary hypertension; dcSSc: diffuse cutaneous systemic sclerosis; HF: heart failure; LVEF: left ventricular ejection fraction; mPAP: mean pulmonary artery pressure; NO: nitric oxide; NT-proBNP: N-terminal pro-brain natriuretic peptide; PAH: pulmonary arterial hypertension; PDE5: phosphodiesterase type 5; PEA: pulmonary endarterectomy; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; RP: Raynaud's phenomenon; sGC: soluble guanylate cyclase; tid: three times daily; WHO: World Health Organization.DOI: 10.29245/2572-9411/2017/6.1133 View / Download Pdf
DOI: 10.29245/2572-9411/2017/6.1129 View / Download Pdf
Ambra Di Veroli1, Eleonora De Bellis1, Valentina Rossi1, Annalisa Biagi1, Vito Rapisarda1, Luca Maurillo1, Maria Ilaria Del Principe1, Maria Teresa Voso1, Adriano Venditti1 and Francesco Buccisano1
1Hematology, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
Junya Oguma, Soji Ozawa*, Akihito Kazuno, Miho Nitta, Yamato Ninomiya, Kentaro Yatabe
Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
Superficial Barrett’s esophageal adenocarcinoma limited to the lamina propria, like other superficial cancers, is associated with almost no risk of lymph node metastasis. However, lymph node metastasis has been observed in patients with Barrett’s esophageal adenocarcinoma invading the muscularis mucosae. The duplication of the muscularis mucosae is a pathological characteristic of Barrett’s esophagus; however, the rate of lymph node metastasis might not differ according to the depth of invasion within the muscularis mucosae. Submucosal invasion is considered to be a risk factor for lymph node metastasis; however, many reports have suggested that submucosal invasion alone is not a risk factor but that the likelihood of lymph node metastasis increases as the number of risk factors increases. Generally, lymphovascular invasion, pathological differentiation and tumor size are also considered to be risk factors for lymph node metastasis. Previous reports have suggested that patients with superficial Barrett’s esophageal adenocarcinoma limited to T1b-SM1 may have a lower risk of lymph node metastasis and might be candidates for endoscopic resection if other risk factors are negative.DOI: 10.29245/2572-9411/2017/6.1135 View / Download Pdf
Angham Nasser Al Mutair1,2,3, Yasser Ali Binafif1
1Department of Pediatrics, Endocrinology Division, King Abdulaziz Medical City -Riyadh, King Abdullah Specialist Children Hospital (KASCH).
2King Saud bin Abdulaziz University for Health Sciences.
3King Abdullah International Medical Research Center, Riyadh 11155, Kingdom of Saudi Arabia.
Rickets in pediatrics due to vitamin D deficiency is still considering a major problem even in sunny and tropical countries. The prevalence of vitamin D deficiency and insufficiency in children between 6 and 15 years of age in the Kingdom of Saudi Arabia is 95.4%. Vitamin D requires two steps of hydroxylation to be functionally active. The first hydroxylation step occur in the liver by 25-hydroxylase encoded by CYP2R1 gene (11p15.2) to produce 25(OH)D3 and the second step of hydroxylation occur in proximal convoluted tubules in kidney by 1α-hydroxylase encoded by CYP27B1 gene (12q13.1) to produce hormonally active 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3). Vitamin D-dependent rickets type 1B (VDDR1B) is a form of rickets due to mutation in CYP2R1 gene. Until today, only five mutations were found to affect CYP2R1 gene which lead to abnormal structure and function of 25-hydroxylase enzyme. Presence of symptoms of vitamin D deficiency in good dietary history with poor response or depending on regular to high dose of vitamin D2 or D3 to maintain 25(OH)D3 level should raise the suspicion of genetic causes of CYP2R1 mutations. These mutations are inherited as autosomal recessive; the severity and response to medication depend on number of allele affected. Some of the homogenous mutation patients showed some improvement in using Calcitriol. Bypassing the first step of hydroxylation (25-hydroxylase) in liver using 25-OH-D3 (Calcifediol) as treatment lead to dramatic improvement of biochemical and radiological finding in seven recent reported cases which needs further study.DOI: 10.29245/2572-9411/2017/6.1130 View / Download Pdf
Renata Kozyraki1* and Olivier Cases1
1INSERM UMRS_1138, Centre de Recherche des Cordeliers, Paris-Diderot University, France
Gp330/Megalin/Low-Density Lipoprotein Receptor-Related Protein 2 (LRP2) is an endocytic receptor that plays multiple roles in embryonic and adult tissues. It allows the cellular uptake of various bioactive molecules, morphogens, vitamins and hormones. Lack or dysfunction of the receptor affects renal protein reabsorption, lung function, brain and eye development in both man and experimental models. Mutations in LRP2 cause the polymalformative Donnai-Barrow syndrome, a rare autosomal recessive condition, combining developmental delay, facial dysmorphology, hearing defects, high myopia and low-molecular weight proteinuria.
We here summarize current knowledge on the receptor action. We particularly focus on the LRP2-associated face and eye anomalies and discuss how the receptor and its interacting proteins, including the multiligand receptor Cubilin (CUBN) may promote health or cause disease.DOI: 10.29245/2572-9411/2017/5.1122 View / Download Pdf
Moitza Principe1,2, Simone Borgoni1,2, Francesco Novelli1,3*
1Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
2Center for Experimental Research and Medical Studies (CeRMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza di Torino, Italy
3Molecular Biotechnology Center, University of Turin, Turin, Italy
We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis formation. Silencing of ENO1 in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibodies inhibit PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts. We recently investigated the effect of ENO1 silencing on the proteome of PDA cells, and there was a significant downregulation of proteins involved in cell-cell and cell-matrix adhesion, including alphaV/beta3 integrin in ENO1-silenced PDA cells. These changes impaired the ability of ENO1-silenced cells to adhere to collagen I and IV and fibronectin, and caused an increase in RGD (tripeptide Arg-Gly-Asp)-independent adhesion to vitronectin (VN) via urokinase plasminogen activator receptor (uPAR). Binding of uPAR to VN triggers integrin-mediated signals, which results in ERK1/2 and Rac activation, accumulation of ROS (Reactive Oxygen Species) and senescence. In ENO1-silenced cancer cells, the use of an anti-uPAR antibody led to reduced ROS production and senescence, and an increase in cell apoptosis. Overall, a decrease of in vitro and in vivo cell migration and invasion of ENO1-silenced PDA cells was observed. This commentary summarizes new data demonstrating that ENO1 promotes PDA survival, migration and metastasis by cooperating with integrins and uPAR. These data represent a springboard for a novel therapeutic strategy to counteract PDA progression based on combined targeting of integrins, uPAR and ENO1.
DOI: 10.29245/2572-9411/2017/5.1131 View / Download Pdf
DOI: 10.29245/2572-9411/2017/5.1126 View / Download Pdf
Apurva Sarathy1, Andreia M. Nunes1,2, Tatiana M. Fontelonga1, Tracy Y. Ogata1 and Dean J. Burkin1*
1Department of Pharmacology, University of Nevada, Reno School of Medicine, NV 89557, USA
2Departamento de Biologia Animal, Centro de Ecologia, Evolução e Alterações Ambientais, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal.
Po-An Tu1, 2, Jen-Wen Shiau1, Fang-Yu Lai2, Shen-Shyuan Yang3, and Pei-Hwa Wang2*
1Hsinchu Branch, Livestock Research Institute, Council of Agriculture, Executive Yuan, No. 207-5, Bi-tou-mian, Wu-hoo village, Si-hoo Township, Miao-li County 36848, Taiwan.
2Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Taipei City 10617, Taiwan.
3Hualein Animal Propagation Station, Livestock Research Institute, Council of Agriculture, No. 38, Chiang Road, Sec. 6, Chiang, Hualien 97362, Taiwan.
Caprine arthritis and encephalitis (CAE) is an economically important viral disease that causes chronic inflammatory disease in goats. At present, the diagnosis of caprine arthritis-encephalitis virus (CAEV) infection is usually obtained through serological testing or molecular techniques, while the serological agar gel immunodiffusion test (AGID) and enzyme-linked immunosorbent assay (ELISA) testing focus on the detection of CAEV antibodies, the PCR and isothermal amplification methods directly detect the proviral sequence of CAEV. The use of Western blot is still considered a “gold standard” in CAEV serology. The delayed seroconversion or intermittent antibodies and the genetic heterogeneity of regional virus strains affect the effectiveness of diagnosis by the serological and molecular methods, respectively. Here, we review some of the most recent developments in diagnostic methods and their use in both laboratory and field diagnosis.DOI: 10.29245/2572-9411/2017/5.1125 View / Download Pdf
Laxminarayan Bhat1* and Dany Salvail2
1Reviva Pharmaceuticals, Inc., Santa Clara, CA, USA
2IPS Therapeutique Inc., Sherbrooke, Quebec, Canada
Pulmonary arterial hypertension (PAH) is a chronic, debilitating condition with a 5- to 7-year survival rate of approximately 50% following diagnosis. It is defined by pulmonary vasculature constriction and remodeling, and its pathobiology involves dysfunctional signaling of the serotonin (5-HT) receptors, 5-HT2A/2B/7 in the pulmonary arteries. RP5063 is a novel, multimodal dopamine (D)–serotonin (5-HT) stabilizer with partial agonist activity for D2/3/4 and 5-HT1A/2A antagonist activity for 5-HT2B/2C/6/7, and moderate affinity for the serotonin transporter (SERT). It received orphan status by the US Food and Drug Administration in 2016 to treat PAH. Two recent preclinical studies evaluated the effectiveness of RP5063 in PAH-induced rat models. The monocrotaline (MCT)-induced PAH model involved treatment with RP5063 (1, 3, and 10 mg/kg twice daily [BID]) over 28 days. The Sugen-hypoxia (SuHx)-induced PAH model involved treatment with RP5063 (10 and 20 mg/kg BID) over 21 days starting at Day 14 following induction. Both models demonstrated that RP5063 promoted significant functional improvements and structural changes in the pulmonary vasculature. RP5063 limited induced increases of proinflammatory cytokines in the MCT model, and limited leukotriene B4 levels, arterial obliteration, and prevented plexiform lesion formation in the SuHx model. A follow on MCT study examining the effectiveness of RP5063 alone and in combination with standard treatments corroborated these single-agent data and helped to define the framework for the clinical development of this compound. This review explores these studies, their underlying nuances, and the underlying pharmacologic rationale for the effects produced by RP5063.DOI: 10.29245/2572-9411/2017/5.1123 View / Download Pdf
Angela B. Snyder, Peter A. Lane, Mei Zhou, Susan T. Paulukonis, Mary M. Hulihan
Georgia State University, Department of Public Management and Policy, Atlanta, GA and Georgia State University, Georgia Health Policy Center, Atlanta, GA
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
Georgia State University, Georgia Health Policy Center, Atlanta, GA
Public Health Institute, Richmond, CA, Atlanta, GA
Centers for Disease Control and Prevention, Division of Blood Disorders, Atlanta, GA
Sickle cell disease affects more than 100,000 individuals in the United States, among whom disease severity varies considerably. One factor that influences disease severity is the sickle cell disease genotype. For this reason, clinical prevention and treatment guidelines tend to differentiate between genotypes. However, previous research suggests caution when using a claims-based determination of sickle cell disease genotype in healthcare quality studies.
The objective of this study was to describe the extent of miscoding for the major sickle cell disease genotypes in hospital discharge data. Individuals with sickle cell disease were identified through newborn screening results or hemoglobinopathy specialty care centers, along with their sickle cell disease genotypes. These genotypes were compared to the diagnosis codes listed in hospital discharge data to assess the accuracy of the hospital codes in determining sickle cell disease genotype. Eighty-three percent (sickle cell anemia), 23% (Hemoglobin SC), and 31% (Hemoglobin Sβ+ thalassemia) of hospitalizations contained a diagnosis code that correctly reflected the individual’s true sickle cell disease genotype. The accuracy of the sickle cell disease genotype coding was indeterminate in 11% (sickle cell anemia), 12% (Hemoglobin SC), and 7% (Hemoglobin Sβ+ thalassemia) and incorrect in 3% (sickle cell anemia), 61% (Hemoglobin SC), and 52% (Hemoglobin Sβ+ thalassemia) of the hospitalizations. The use of ICD-9-CM codes from hospital discharge data for determining specific sickle cell disease genotypes is problematic. Research based solely on these or other types of administrative data could lead to incorrect understanding of the disease.DOI: 10.29245/2572-9411/2017/4.1124 View / Download Pdf
Liz Toapanta-Yanchapaxia, Juan Francisco Sánchez-Ávilaa, Nielzer Rodríguez-Almendrosb, José de Jesús Rodríguez-Andoneyc, José L. Hernández-Oropezac, Víctor Manuel Páez-Zayasa, Ignacio García-Juáreza*
aGastroenterology Department and Liver Transplant Unit, National Institute of Medical Science and Nutrition Salvador Zubirán, Mexico City, Mexico.
bPulmonary hypertension and Right Ventricular Function Department. UMAE Cardiología. Centro Médico Nacional Siglo XXI. Instituto Mexicano del Seguro Social. Mexico City, Mexico.
cPulmonary Hypertension Clinic, National Institute of Medical Science and Nutrition Salvador Zubirán, Mexico City, Mexico.
Portopulmonary hypertension (POPH) is a rare and life-threatening complication in patients with portal hypertension, with a prevalence of 3 – 8%. It is characterized by pulmonary arterial hypertension (PAH) and results from obstruction to arterial flow in the pulmonary arterial bed, leading to the progressive deterioration of both the pulmonary circulation due to arterial remodeling and of the heart, as a result of right ventricular failure. Its diagnosis is based on hemodynamic findings based on a mean pulmonary arterial pressure (mPAP) ≥ 25mmHg, an increase in pulmonary vascular resistance (PVR) > 3 Wood Units or > 240 dynes/s/cm-5, a pulmonary artery occlusion pressure (PAOP) ≤ 15mmHg or an elevated transpulmonary gradient (mPAP - PAOP: > 12 mmHg). Right heart catheterization (RHC) should be appropriately interpreted since management and MELD exception criteria depend on it. Although most therapeutic modalities have been inferred from patients with PAH, currently, new treatments are available and also various POPH clinical trials are ongoing, so further research data will soon be available. LT is a pivotal therapeutic option, but LT candidates require careful monitoring before, during and after the procedure.DOI: 10.29245/2572-9411/2017/4.1111 View / Download Pdf
Joana Silva1, 2, Rafael Fernandes1, 2, Luísa Romão1, 2, *
1Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
2Gene Expression and Regulation Group, Biosystems & Integrative Sciences Institute (BioISI), Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
Upstream open reading frames (uORFs) constitute a class of cis-acting elements that regulate translation initiation. Mutations or polymorphisms that alter, create or disrupt a uORF have been widely associated with several human disorders, including rare diseases. In this mini-review, we intend to highlight the mechanisms associated with the uORF-mediated translational regulation and describe recent examples of their deregulation in the etiology of human rare diseases. Additionally, we discuss new insights arising from ribosome profiling studies and reporter assays regarding uORF features and their intrinsic role in translational regulation. This type of knowledge is of most importance to design and implement new or improved diagnostic and/or treatment strategies for uORF-related human disorders.DOI: 10.29245/2572-9411/2017/4.1121 View / Download Pdf
Mia Aagaard Doherty1,2*, Niels Thomas Hertel3, Hanne Buciek Hove4 and Annette Haagerup1,2,5*
1NIDO Danmark, Hospitalsenheden Vest RM, Denmark
2Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital, Denmark
3Department of Paediatrics, H.C. Andersen Children’s Hospital, Odense University Hospital, Denmark
4Centre for Rare Diseases, Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Denmark
5Institute of Clinical Medicine, Health, Aarhus University, Denmark
Aim: To investigate the prevalence of neurological symptoms and the types of complications in a cohort of Danish patients with mutation verified achondroplasia and hypochondroplasia and compare the results with previously reported findings.
Methods: Retrospective descriptive study by chart review of patients followed in three outpatients clinics in the period 1997-2014. Forty-eight patients with achondroplasia and a median age of 9,5 years old and 20 patients with hypochondroplasia and a median age of 12 years old were enrolled. Neurological manifestations, epidemiological variables and clinical data were collected.
Results: Data on neurological symptoms and surgical interventions were extracted and compared with existing knowledge. Description of phenotypes revealed frequent headaches, pain in back, neck and lower limbs, sleep apnoea and conductive hearing loss. No sub-phenotype was predictive for referral to an MRI scan or neurosurgery.
Conclusion: Through investigation of phenotypes and genotypes in patients with achondroplasia and hypochondroplasia we report the frequencies of neurological symptoms, foramen magnum stenosis, spinal cord compression and neurosurgery in Danish patients. Variation in the evaluation of patients among the three clinics is found and discussed. To further standardise the management of patients, national guidelines for follow-up on children with ACH and HCH are recommended.DOI: 10.29245/2572-9411/2017/4.1113 View / Download Pdf
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.DOI: 10.29245/2572-9411/2017/4.1120 View / Download Pdf
DOI: 10.29245/2572-9411/2017/4.1105 View / Download Pdf
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
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.DOI: 10.29245/2572-9411/2017/4.1114 View / Download Pdf
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.DOI: 10.29245/2572-9411/2017/4.1110 View / Download Pdf
DOI: 10.29245/2572-9411/2017/3.1115 View / Download Pdf
Mara Sanches Guaragna1*, Anna Cristina GB Lutaif2, Vera MS Belangero2 Andréa T. Maciel-Guerra3,4, Gil Guerra-Junior4,5 and Maricilda P. De Mello1
1Center for molecular biology and Genetic engineering – CBMEG, State university of campinas, UNICAMP, Campinas, Brazil
2Integrated center of pediatric nephrology – CIN - School of medical sciences – FCM, State university of campinas, UNICAMP, Campinas, Brazil
3Department of medical genetics - School of medical sciences – FCM, State university of campinas, UNICAMP, Campinas, Brazil
4Interdisciplinary group for the Study of sex determination and differentiation – GIEDDS - State university of campinas, UNICAMP, Campinas, Brazil
5Pediatrics endocrinology, Department of pediatrics, School of medical sciences – FCM, State university of campinas, UNICAMP, Campinas, Brazil
Sarah Plucinsky1, and Kerney J. Glover1*
1Department of chemistry, Lehigh university, 6 E. Packer ave., Bethlehem, Pennsylvania, 18015, USA
Pulmonary Arterial Hypertension (PAH) is a rare disease that affects the vasculature in the lungs. Currently, there is no cure for PAH, and there appears to be no clear causal factors for the disease. Recently, through whole exome sequencing, caveolin-1, a critical component of cell surface invaginations called caveolae, has been identified as a key protein in the progression of PAH. Specifically, the mutations associated with PAH have been localized to the C-terminal domain of the protein. Since it is known that the C-terminus of caveolin-1 directly interacts with endothelial nitric oxide synthase (eNOS), the link between caveolin-1 and PAH may reside in disrupted nitric oxide (NO) levels, which ultimately triggers the disease state. Recent biophysical studies have now allowed for this relationship to be viewed in a structural context. In this mini-review, we will put the recent structural insights into the C-terminal domain of caveolin-1 into the context of PAH disease progression.DOI: 10.29245/2572-9411/2017/3.1116 View / Download Pdf