Vol 1-1 Mini Review

Vitamin C improves the health span of animal models of werner syndrome

Michel Lebel*

Centre de recherche du CHU de Québec, Faculty of Medicine, Université Laval, Quebec City Quebec, Canada

 Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a pro-oxidant/pro-inflammatory status, genomic instability, and by the premature onset of several age-associated diseases. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA replication, repair, and transcription. This review focuses on the beneficial impact of vitamin C treatment in mutant mouse and worm models of WS with an emphasis on serum metabolomic and cytokinome profiles in Wrn mutant mice. Vitamin C normalizes the health and life span of these mutant animals. More importantly, our recent results indicate that it will be possible to follow the beneficial impact of vitamin C at a systemic level by monitoring specific serum metabolites and inflammatory cytokines in a longitudinal study involving WS patients.

Read More
Vol 1-1 Mini Review

Benign multifocal stenosing ulceration, or CMUSE---A rarely diagnosed small intestinal disorder

Hugh James Freeman*

Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, BC, Canada

 A rarely diagnosed clinical and pathological disorder was historically characterized by multiple benign small intestinal ulcers, involving the mucosa and, occasionally, the submucosa of the small intestine, and histopathologically by non-specific inflammatory changes without granulomas. These early reports also noted that recurrent episodes of abdominal pain often developed due to obstructive events, sometimes associated with localized stricture formation. This usually responded to steroid treatment, intestinal resection, or both. Recent advances owing largely to emerging imaging methods have provided added criteria for separation of this entity from other disorders, including Crohn’s disease and medication-related small bowel ulceration. Most important, recent long-term follow-up studies have suggested a potential for confusion with other functional or motility-based clinical disorders and emphasize the likelihood of a much more benign clinical course.

Read More
Vol 1-1 Mini Review

Will European reference networks benefit all EU patients with rare siseases?

Sally Ann Lynch1,2* & Jillian P Casey2

1National Rare Disease Office, Mater Hospital Dublin 7, Ireland
2UCD Academic Centre of Rare Disease, School of Medicine and Medical Sciences, Belfield, Dublin 4, Ireland

 European Reference Networks are being established across the EU with the aim of improving the care of patients with rare diseases. Recognising that experts are rare, ERNs are tasked with the aim of encouraging collaboration of experts across individual member states. Membership of an ERN is dependent on fulfilling criteria to allow one to be described as a centre of expertise. ERNs will produce guidelines through consensus and the development of EU wide registries should help to facilitate clinical trials. However, the ERN entry requirements are such that some member states will struggle to fulfil the criteria. Investment in trained staff for rare diseases has been poor in some countries risking the possibility that ERN membership may be restricted to a limited number of member states.

Read More
Vol 1-1 Commentary
Vol 1-1 Commentary

Commentary: Erythema marginatum as an early symptom of hereditary angioedema: case report of 2 newborns

Inmaculada Martinez-Saguer1* and Henriette Farkas2

1Hemophilia Center Rhine Main, Germany
2Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Hungary

Read More
Vol 1-1 Mini Review

Serendipity in inborn errors of metabolism: Combining two genetic mutations in a single patient

Khalil Charafeddine and Mohammad-Zouheir Habbal*

Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon

Read More
Vol 1-1 Mini Review

Mitochondria and cystic fibrosis transmembrane conductance regulator dialogue: Some news

Maria Favia1 and Anna Atlante2*

1Department of Biosciences, Biotechnology and Biopharmaceutics - University of Bari, Via E. Orabona 4, 70126, Bari, Italy
2Institute of Biomembrane and Bioenergetics - CNR, Via G. Amendola 165/A, 70126, Bari, Italy

 Cystic fibrosis is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. It results from different possible mutations in the CFTR gene, which encodes the CFTR chloride channel, a protein that controls the movement of salt and water in and out of your body's cells. It follows that the abnormal channel function of the expressed protein on the secretory cell membrane determines the clinical phenotype in its classical form. Novel and more recent studies on mitochondrial bioenergetics - aiming to rediscover a possible role of mitochondria in this disease - provide a springboard for upcoming research to further understand the molecular mechanisms responsible for the involvement of mitochondria in CF and identify the protein/s primarily responsible for the F508del-CFTR-dependent mitochondrial alterations. Here, we review these CFTR-driven mitochondrial defects, thus revealing potential new targets for therapy.

Read More
Vol 1-1 Mini Review

Genomic and genetic studies in autism spectrum disorders

Moyra Smith*

University of California, Irvine, CA, USA

Read More
Vol 1-1 Commentary

Commentary: Cranberries and urinary tract infections: How can the same evidence lead to conflicting advice?

Eunice Mah1 and DeAnn J Liska1*

1Biofortis Innovation Services, 211 E. Lake Street, Addison, IL 60101, USA

 Cranberries have long been associated with the prevention of urinary tract infection (UTI); however, meta-analyses of clinical trials on the effect of cranberry for UTI have provided conflicting results. Liska and colleagues recently examined these meta-analyses to better understand the reasons behind their disparate findings and found several methodological differences. Most notably, the populations influencing conclusions varied. For example, one analysis, which concluded cranberry was not effective for UTI (RR: 0.86; 95% CI: 0.71, 1.04), had the largest contribution of results from studies in patients with complicated UTI. In contrast, another review, which included many of the same studies but weighted the evidence relatively equally across populations with complicated and uncomplicated UTI, concluded cranberry was effective (RR: 0.62; 95% CI: 0.49, 0.80). In both reviews, a significant benefit was noted in healthy women with recurrent UTI, particularly when two or three small trials in this population were analyzed; but, inclusion of a larger study that used a lower bacterial cut-off threshold for UTI outcome definition led to significant heterogeneity and non-significant results. These findings not only impact how we design meta-analyses, but also indicate the importance in considering the patient characteristics when generalizing findings across populations. In addition, the findings suggest additional research on cranberries in healthy women with recurrent UTI may be warranted.

Read More
Vol 1-1 Short Communication

Decreasing HMGB1 levels improves outcome of Pseudomonas aeruginosa keratitis in mice

Linda D. Hazlett1,2*, Sharon A. McClellan1 and Sandamali A. Ekanayaka1

1Department of Anatomy and Cell Biology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA
2Department of Ophthalmology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA

 Pseudomonas (P.) aeruginosa is a Gram negative bacterium widely dispersed in the environment which can cause acute and chronic infections in humans. According to the Centers for Disease Control and Prevention (CDC), the overall incidence of P. aeruginosa infections in USA hospitals averages about 0.4% (4/1000 discharges), and the bacterium is the fourth most commonly-isolated nosocomial pathogen accounting for 10.1% of all hospital-acquired infections. P. aeruginosa keratitis is a severe infection of the eye, progresses rapidly and remains a leading cause of corneal ulcers worldwide. Use of contact lenses is the major risk factor in the USA, while in less industrialized countries, trauma from agricultural accidents are of importance. Animal models of bacterial keratitis are of value in the study of this disease and suggest potential alternative therapeutic targets that are needed urgently due to increasing antibiotic resistance. Recently we have shown success and improved disease outcome after down-regulation of one promising target, high mobility group box(HMGB1) using small interfering RNA (siRNA). Testing more clinically relevant approaches are underway to reduce HMGB1 levels in P. aeruginosa keratitis which may hold promise for its treatment.

Read More
Vol 1-1 Commentary

Post ER Quality Control: A Role for UDP-Glucose:Glycoprotein Glucosyl Transferase and p97

Ilaria Fregno1,2,3*, Maurizio Molinari1,2,4*

1Università della Svizzera italiana, CH-6900 Lugano, Switzerland
2Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland
3Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland
4Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, CH-1015 Lausanne, Switzerland

Read More
Vol 1-1 Commentary

Commentary: Activin and TGF? use diverging mitogenic signaling in advanced colon cancer

Jessica Bauer*, Jonas J Staudacher, Nancy L Krett and Barbara Jung

Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, Illinois, USA

Read More