Poremećaji genskoga izražaja u bolesnika s juvenilnim seronegativnim spondiloartropatijama [Distinctive gene expression in patients with juvenile seronegative spondyloarthtopathy]

Introduction: Juvenile spondyloarthritis (jSpA) refers to spectrum of unpredictable inflammatory diseases with overlapping features in children younger than 16 years. There is a strong association of jSpA with HLA-B27 genotype, but many studies shows that other genetic factors, of which we have little or no knowledge, plays a role in the development of jSpA. ----- Patients and methods: In this study participated 45 children with obtained HLA genotype and diagnosis of jSpA according to ILAR criteria, as well as 11 children with other forms of JIA and 12 children without diagnosis of inflammatory disease. DNA microarray gene expression was preformed in 11 patients with jSpA and in 4 participants without diagnosis of inflammatory disease, along with bioinformatic analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants. ----- Results: Microarray results and bioinformatic analysis revealed 745 differentially expressed genes involved in various inflammatory processes in jSpA patients, while qRT-PCR analysis confirmed data universality and specificity. ----- Conclusion: Our findings showed that jSpA is polygenic disease with malfunction in antigen recognition and activation of immunological response, in migration of inflammatory cells and in regulation of the immune system. Results of our study can be used for further investigation of disease patophisiology and new treatment options

JUVENILE SPONDYLOARTHRITIS

Juvenilni spondiloartritis (jSpA) skupina je multifaktorskih bolesti u kojima dolazi do poremećenog međudjelovanja imunosnog sustava i čimbenika okoliša u ljudi s predisponirajućim genotipom, što dovodi do upale i strukturnih oštećenja ciljnog tkiva. Prvi simptomi jSpA rijetko su povezani s kralježnicom, a češće se javljaju nesimetrični oligoartritis zglobova donjih ekstremiteta, daktilitis i periferni entezitis. Postoje brojni kriteriji za klasifi kaciju jSpA, no većina pedijatrijskih reumatologa danas se koristi kriterijima Međunarodne lige reumatoloških udruženja (ILAR) prema kojima je najveći broj bolesnika s artritisom i entezitisom ili artritisom ili entezitisom uz još dvije ili više od karakteristika poput bolnosti sakroilijakalnih zglobova na dodir i/ili bolnosti kralježnice zbog upalnog procesa, HLA-B27-genotipa, bolesti povezane s HLA-B27-genotipom u jednog ili više rođaka u prvom ili drugom koljenu, uveitisa te muškog spola uz više od osam godina života, svrstan u podskupinu juvenilnog idiopatskog artritisa (JIA) koju nazivamo artritis pridružen entezitisu (ErA). Sukladno tomu, dijagnoza bolesti postavlja se uglavnom na temelju kliničke slike i anamnestičkih podataka; od laboratorijskih pretraga potrebno je odrediti antinuklearna antitijela (ANA), reumatoidni faktor (RF) te HLA-tipizaciju kako bi se utvrdila prisutnost HLA-B27, B7 i/ili DR4-genotipa. S obzirom na to da velik broj bolesnika ima i supkliničku upalu crijeva, preporučljivo je provjeriti i fekalni kalprotektin. Ako postoje simptomi perifernog entezitisa, potreban je pregled muskuloskeletnim ultrazvukom s osnaženim doplerom (PDUS), a pri znakovima zahvaćenosti kralježnice radiografsko snimanje te magnetska rezonancija (MR) s kontrastnim sredstvom. Najveći broj djece s jSpA-om liječi se fi zikalnom terapijom i nesteroidnim protuupalnim lijekovima (NSAIL), dok se refraktorni oblici periferne bolesti mogu liječiti sintetskim lijekovima koji utječu na tijek bolesti (DMARD), poput sulfasalazina. Kada bolest zahvati i kralježnicu, potrebno je liječenje biološkim DMARD-ovima poput adalimumaba, infl iksimaba i etanercepta. Usprkos mnogimJuvenile spondyloartrhritis is a group of multifactorial diseases in which a disturbed interplay occurs between the immune system and environmental factors on a predisposing genetic background, which leads to infl ammation and structural damage of the target tissue. First symptoms of jSpA rarely involve the spine, while asymmetrical oligoarthritis of lower extremities, dactylitis, and peripheral enthesitis are much more common. Th ere are many classifi cation criteria for jSpA, but the majority of pediatric rheumatologists currently use the International League Against Rheumatism (ILAR) criteria according to which most patients with jSpA are classifi ed into the enthesitis-related arthritis group of juvenile idiopathic arthritis. To meet these criteria, a patient should have arthritis and/or enthesitis, with two or more symptoms such as sacroiliac joint tenderness and/or infl ammatory back pain, HLAB27 genotype, HLA B27 genotype-associated disease in a fi rst- or second-degree relative, uveitis, and male sex with eight or more years of age. Th erefore, diagnosis is most oft en made only based on clinical examination and medical history. Antinuclear antibodies (ANA), rheumatoid factor (RF), and HLA testing with B27, B7, and DR4 alleles are preferred. Since subclinical gut infl ammation is present in many patients, it is recommended to check fecal calprotectin levels. In patients with signs of peripheral enthesitis it is warranted to perform power Doppler musculoskeletal ultrasound (PDUS), and in patients with signs of axial involvement radiographic and contrast-enhanced magnetic resonance imaging. Most patients are treated with nonsteroidal anti-infl ammatory drugs (NSAIDs) and physical therapy, while in refractory cases with peripheral disease synthetic disease- modifying antirheumatic drugs (DMARDs), such as sulfasalazine, are used. In patients with axial involvement, biological DMARDs such as adalimumab, infl iximab, and etanercept are obligatory. Although a number of studies gave us a good insight into the disease pathogenesis, the response to treatment and prognosis are still diffi cult to predict

Pripravci ljekovitih biljaka u liječenju prehlade i gripe

Influenza viruses represent a permanent global health threat with approximately one billion people infected each year. Although influenza is usually self-limited infection, there are specific populations in which complications are common and sometimes fatal. Therefore, antiviral therapy with neuraminidase inhibitors and less often with adamantanes is becoming preferable course of action. Nevertheless, herbal plants, reviewed in this article, and plant preparations are still a widespread option for influenza and other viral diseases both in developed and developing countries

Pripravci ljekovitih biljaka kao antireumatici

For centuries rheumatic diseases are global economic and social burden. Only in the last century modern conventional medicine has find a way to tackle these chronic inflammatory diseases, but even today many complementary and alternative therapeutic modalities are widely used. Th is article represents an overview of the most common used medicinal plants preparations in the treatment of rheumatic diseases. These plants (Salix alba, Coriandrum sativum, Mentha x piperita, Arnica montana, Zingiber officinale, Capsicum frutescens, Larix decidua, Pinus mugo, Urtica dioica, Juniperus communis, Hypericum perforatum, Arctium lappa, Chamomilla recutita, Harpagophytum procumbens and Symphytum offi cinale) contain various chemical compounds (flavonoids, phenolic acids, essential oils, tannins, iridoids, alkaloids, phenolic heterosides, vitamins, polysaccharides, coumarins etc.) that contribute to their antirheumatical activity

Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis

Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in the development of the disease. To date, only a few studies have tried to find those associated genes by obtaining expression profiles, but with inconsistent results due to various patient selection criteria and methodology. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in highly homogeneous cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA) according to ILAR criteria. For the purposes of the research, total RNA was isolated from whole blood of 45 children with jSpA and known HLA genotype, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of inflammatory disease. DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatical analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants of the study. Microarray results and bioinformatical analysis revealed 745 differentially expressed genes involved in various inflammatory processes, while qRT-PCR analysis of selected genes confirmed data universality and specificity of expression profiles in jSpA patients. The present study indicates that jSpA could be a polygenic disease with a possible malfunction in antigen recognition and activation of immunological response, migration of inflammatory cells and regulation of the immune system. Among genes involved in these processes TLR4, NLRP3, CXCR4 and PTPN12 showed almost consistent expression in study patients diagnosed with jSpA. Those genes and their products could therefore potentially be used as novel biomarkers, possibly predictive of disease prognosis and response to therapy, or even as a target for new therapeutic approaches

Typical course of cystinuria leading to untypical complications in pregnancy: A case report and review of literature

Cystinuria is a rare genetic disorder inherited by an autosomal recessive pattern which affects the transmembrane transporter for the base amino acid cystine. It has a general prevalence of 1 in 7000 with demographic variations. Patients with cystinuria have excessive urinary excretion of cystine, which can lead to the formation of stones. Up to 70% of patients will develop chronic kidney disease that can progress even to end-stage renal disease. Symptoms usually start in the first two decades of life with a typical presentation consisting of flank pain and renal colic, usually accompanied by urinary tract infection and deterioration of kidney function. Men are typically affected twice as often as women and have a more severe clinical course. Diagnosis is made by spectrophotometric analysis of the stones that are collected after spontaneous expulsion or medical intervention. Genetic testing is not mandatory but is recommended in uncertain cases or as a part of genetic counseling. Treatment consists of diet modification, alkalization of urine, and thiol-based therapies if other measures fail to prevent stone formation. In pregnancy, cystinuria with the formation of cystine stones represents a therapeutic challenge and requires a multidisciplinary approach consisting of an uro-nephrology team and a gynecologist. We present the case of a 34-year-old woman with cystinuria on whom the diagnosis was made by analysis of the expulsed stone. While her previous pregnancies were without complications, her third pregnancy was accompanied by frequent urinary tract infections, acute worsening of kidney function, and urological interventions during pregnancy due to the formation of new stones. Despite the complicated course, the pregnancy was successfully carried to term with the delivery of a healthy female child

Developing Reflection and Collaboration in Translational Medicine Toward Patients and Unmet Medical Needs

This perspective article aims to highlight the importance of values-driven personal reflection and collaboration for effective translational medicine training. We frame the dilemma in translational medicine and provide an approach for solution emphasizing collaboration and co-creation for innovative change in translational medicine. We cite the science in transition literature suggesting why personal reflection and a collaborative approach is important. We identify the problem with publication pressures and the bibliometric mindset. We focus on motivation to seek and find results that really matter for patients and individuals to maintain health in the real world. We review how the international EUREKA Institute for Translational Medicine (established in 2007) works with students, to harness their core values and develop personal growth skills to improve their leadership effectiveness, to work toward collaborative gain and potentially more meaningful results for patients and medical needs. We describe how the EUREKA Institute's unique setting, curriculum and hidden curriculum aspects effectively train program participants. The article highlights creating an immersive safe space, personal reflection, connection, structured brainstorming, group problem solving, collaboration and co-creation to facilitate innovation in translational medicine. The article relates program features to their theoretical underpinnings such as Theory U, Mediation Theory and Strategic Innovation Theory. The six authors from different global regions, ages, career stages, translational medicine contexts and years of attendance at the EUREKA Institute provide their reflections on training impact. Lessons learned and recommendations for research and application are discussed