Kenneth L. van Golen*

The laboratory for cytoskeletal physiology, Department of biological sciences, The university of delaware, The center for translational cancer research, The Helen F. Graham Cancer Center, Newark, DE, USA

DOI: 10.29245/2572-9411/2017/6.1142 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

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

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

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

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.

DOI: 10.29245/2572-9411/2017/5.1126 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

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

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

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

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.

DOI: 10.29245/2572-9411/2017/2.1048 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

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

DOI: 10.29245/2572-9411/2017/4.1105 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

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

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.

DOI: 10.29245/2572-9411/2016/3.1069 View / Download Pdf

Vaishnavi Raja, Christian A. Reynolds, and Miriam L. Greenberg

Department of Biological Sciences, Wayne State University, USA

Barth syndrome (BTHS) is a rare X-linked genetic disorder characterized by cardiomyopathy, skeletal myopathy, neutropenia, and organic aciduria. The presence and severity of clinical manifestations are highly variable in BTHS, even among patients with identical gene mutations. Currently, less than 200 patients are diagnosed worldwide, but it is estimated that the disorder may be substantially under-diagnosed due to the variable spectrum of clinical manifestations. BTHS is caused by mutations in the gene tafazzin (TAZ), resulting in defective remodeling of cardiolipin (CL), the signature phospholipid of the mitochondrial membranes. Many of the clinical sequela associated with BTHS can be directly attributed to mitochondria defects. In 2008, a definitive biochemical test was described based on detection of the abnormal CL profile characteristic of BTHS. This mini-review provides an overview of the etiology of BTHS, as well as a description of common clinical phenotypes associated with the disorder.

DOI: 10.29245/2572-9411/2017/2.1087 View / Download Pdf

Tugba Avci*, Irfan Tasoglu, Emre Aygun and Mustafa Pac

Yuksek Ihtisas Egitim ve Arastlrma Hastanesi, Ankara, Turkey Department of Cardiovascular Surgery, Turkey


Background:There are many usage areas of the PTFE patch in cardiac surgery. In this report, we present an unusual complication which should be kept in mind about PTFE membranes.

Case presentation:The 20-year-old male patient had been operated for ascending aortic aneurysm. David Procedure was carried out. After (in)the procedure, before the sternal closure, the pericardial closure was applied with PTFE membrane to avoid the sternal adhesions. The sternal wound drainage occurred two months after the operation. After further evaluations, surgery was the choice. The cure was achieved by removing the PTFE membrane. The sternum closure was applied without pericardial closure. His wound healed fastly.

Conclusions:The complications about prosthetic materials are trouble for surgeons. In many cases, the cure is achieved by removing the prosthetic materials. In most times, radiology is helpful for diagnosis, but rarely, it might be a misleading procedure.

DOI: 10.29245/2572-9411/2016/3.1022 View / Download Pdf

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

Ercole L. Cavalieri1,2* and Eleanor G. Rogan1,2

1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA
2Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198-4388, USA

Endogenous estrogens become carcinogens when excessive catechol estrogen quinone metabolites are formed. Specifically, the catechol estrogen-3,4-quinones can react with DNA to produce a large amount of specific depurinating estrogen-DNA adducts, formed at the N-3 of Ade and N-7 of Gua. Loss of these adducts leaves apurinic sites in the DNA, which can generate subsequent cancer-initiating mutations. Unbalanced estrogen metabolism yields excessive catechol estrogen-3,4-quinones, increasing formation of the depurinating estrogen-DNA adducts and the risk of initiating cancer. Evidence for this mechanism of cancer initiation comes from studies in vitro, in cell culture, in animal models and in human subjects. High levels of estrogen-DNA adducts have been observed in women with breast, ovarian or thyroid cancer, and in men with prostate cancer or non-Hodgkin lymphoma. Observation of high levels of depurinating estrogen-DNA adducts in high risk women before the presence of breast cancer indicates that adduct formation is a critical factor in breast cancer initiation. Two dietary supplements, N-acetylcysteine and resveratrol, complement each other in reducing formation of catechol estrogen-3,4-quinones and inhibiting formation of estrogen-DNA adducts in cultured human and mouse breast epithelial cells. They also inhibit malignant transformation of these epithelial cells. In addition, formation of adducts was reduced in women who followed a Healthy Breast Protocol that includes N-acetylcysteine and resveratrol. Blocking initiation of cancer prevents promotion, progression and development of the disease. These results suggest that reducing formation of depurinating estrogen-DNA adducts can reduce the risk of developing a variety of types of human cancer.

DOI: 10.29245/2572-9411/2017/3.1093 View / Download Pdf

Kristen Whitworth*, Nicholas Graff, and Christopher Trigger

Lakeland Health Emergency Medicine Residency Program, 1234 Napier Avenue, St. Joseph, MI 49085, USA

DOI: 10.29245/2572-9411/2017/3.1112 View / Download Pdf

Laura Manelyte

Biochemistry Center Regensburg, Laboratory of Chromatin Dynamics and Nuclear Architecture, University of Regensburg, Universitätstraße 31, Regensburg DE-93053, Germany

The chromatin remodeling complexes alter chromatin structures. They remodel nucleosomes in ATP-dependent manner and have essential roles in DNA damage repair, recombination, replication and transcriptional control. Increasing evidences indicate that subunits of chromatin remodelers are mutated and/or deregulated in a number of human cancers, and how they influence the cancer gene expression program during cancer initiation and progression is becomming clearer. Therefore, chromatin remodeling complexes arose as promising new targets for the treatment of human cancers. In this review, chromatin remodeling complexes, their epigenetic reader domains and available inhibitors are described. The insights into the misregulated chromatin remodelers pathways in human malignancies and the novel approach targeting deregulated chromatin remodelers to improve chemotherapy efficiency are discussed.

DOI: 10.29245/2572-9411/2017/3.1108 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

DOI: 10.29245/2572-9411/2017/3.1115 View / Download Pdf