Association of osteoprotegerin gene polymorphisms and osteoporosis inpostmenopausal women

Osteoporoza je česta bolest uslijed koje dolazi do smanjenja koštane mase. Nedostatak u mikroarhitekturi koštanog tkiva negativno utječe na čvrstoću kostiju te dovodi do povećanog rizika od prijeloma kostiju. Osteoprotegerin gen (OPG) vrlo je bitan u genetičkoj kontroli koštane mase te ima vrlo značajnu ulogu u nastanku osteoporoze. Najčešći tip polimorfizma pripada SNP polimorfizmu. Otkriće receptora aktivatora nuklearnog faktora kb (RANK)/RANK ligand RANKL/OPG pridonio je boljem razumijevanju načina regulacije formacije i resorpcije kosti.RANK-RANKL-OPG sustav mogao bi biti usmjeren kao nova strategija liječenja bolesti.Osteoporosis is a common disease characterized by low bone mass. Reduced microarchitecture of bone tissues affects bone strength leading to an increased risk of bone fractures .Osteoprotegerin gene (OPG) is an important candidate gene of osteoporosis and may have an important role in development of osteoporosis. SNP polymorphism is the most common type of polymorphism. Discovery of the receptor activator of nuclear factor RANK/RANK ligand RANKL/OPG contributed to understanding of bone formation and resorption. Targeting of RANK- RANKL-OPG system may represent a new strategy in the treatment of bone diseases

Health-Related Quality of Life in Antiviral-Treated Chronic Hepatitis C Patients

Chronic hepatitis C has a profound negative impact on both physical and mental well-being, thus decreasing health-related quality of life (HRQL). The most common complaints include symptoms such as fatigue, depression, and neurocognitive deficits. The burden of chronic HCV infections is multiplied by emotional and psychological issues that affect patients’ functional health and work ability. Treatment of chronic HCV infection may at the beginning cause worse HRQL rates, as a result of common adverse effects like fatigue, muscle aches, and depression. However, the relationship between sustained virologic response (SVR) and improvement in HRQL is well known. Treatment-related adverse effects may discourage patients from starting therapy and reduce their adherence to treatment. Novel agents, with improved adverse effect profiles and SVR rates, allow more patients the opportunity to achieve improvements in HRQL during and after treatment

HCV and Work Ability Assessment

Modifications to work and work ability assessment are required to prevent occupational transmission of hepatitis C virus (HCV). This is usually required in the health care setting, where exposure-prone procedures (EPPs) should not be carried out by infectious carriers of HCV. The risk of an individual surgeon acquiring HCV has been estimated at 0.001–0.032% per annum. Even in an area with a high prevalence of HCV among its population, the risk of acquiring HCV through occupational exposure is low. Rates of viral clearance with treatment of acute HCV infection are considerably higher than treatment of chronic HCV infection. Consequently, it is imperative that health care workers follow universal precautions and promptly report all exposures to blood or body fluid exposures according to their local policy. Health care workers who embark on, or transfer to, a career that requires EPP (exposure-prone procedures and dialysis work) should be assessed to ensure that they are free from infection with HCV. If the HCV antibodies are positive, the health care worker should be tested for HCV RNA PCR. If the HCV RNA PCR is negative on two separate occasions, the health care worker may be permitted to perform EPPs. If the HCV RNA PCR is positive, the health care worker should not be allowed to perform EPPs. Health care workers who already perform EPPs and who believe they may have been exposed to HCV infection should be advised to seek advice from their occupational health department for confidential advice on whether they should be tested

Approaches and Considerations for the Successful Treatment of HCV Infection

The complexity of the hepatitis C virus (HCV) infection is reflected in its therapy, and great efforts are needed from the patient and the physician to be successful in eliminating the infection. How HCV will progress depends a lot on patient characteristics and social factors, in addition to the timing of initiation, duration, and final results of the therapy. The first treatment approved for patients with chronic hepatitis C was interferon (IFN) which had a sustained viral response (SVR) rate in 20%. Due to side effects, the adherence to this treatment was limited and required a patient-tailored approach with various medical disciplines working together and intervening at the right time to minimize potential obstacles. The introduction of direct-acting antivirals (DAAs) has contributed to the advancement of HCV treatment. However, a major obstacle to wide use of DAAs is their high price which has largely limited access to treatment. Guidelines and recommendations on treatment of hepatitis C have been developed to assist physicians and other health care providers to determine priority. Despite that, the arrival of new oral therapies has been met with enthusiasm as shorter, simpler, safer treatment allows for the possibility of delivering antiviral therapy on a large scale

Pharmacogenomics: Sex Differences and Application in Pediatrics

Pharmacogenomics is a promising field which increasingly influences medicine and biomedical research in many areas. The aim of this article is to review recent advancements in the understanding of genetic polymorphisms and their influence on interindividual variability in drug response. Also, the main variabilities in drug response according to sex differences will be discussed. The translation of pharmacogenomics into the clinical routine as well as the challenges of achieving the goal of personalized medicine are also discussed. The role of pharmacogenetic tests in pediatrics has not been well defined yet, but it is clear that those tests could help in resolving some issues regarding the administration of drugs to children. At the conclusion, the foremost ethical, social and regulatory issues regarding the translation of pharmacogenomics into clinical practice and future perspectives in the field will be discussed

Occurrence of Hepatocellular Carcinoma in Patients with Chronic hepatitis C Treated with Direct-Acting Antiviral Therapy

Poznato je kako oboljeli od kronične bolesti jetre učestalije obolijevaju od hepatocelularnog karcinoma. Premda se RNA molekula hepatitis C virusa uspješno eliminira iz cirkulacije direktnodjelujućim antivirusnim lijekovima, HCV RNA može ostati i dalje prisutna u jetrenom tkivu ili perifernim mononuklearnim stanicama te je taj entitet poznat kao okultni HCV. Postoje brojne nedoumice povezane s ponovnom pojavom HCC-a nakon provedenog liječenja DAA terapijom jetrenih stanica kronično zaraženih HCV-om, a jedan od glavnih čimbenika rizika koji dovodi do de novo HCC-a je pojava kroničnosti HCV-a u stanicama jetre. Mnoge studije provedene su s ciljem istraživanja promjena jetrenih stanica inficiranih HCV-om u HCC. Međutim, još uvijek nisu u potpunosti jasni molekularni mehanizmi koji vode do progresije kronične HCV infekcije u HCC i učinak HCV-a na promjenu DNA ploidnosti, što dovodi do ponovnog povratka HCC-a nakon liječenja DAA terapijom. Stoga je cilj ovoga članka razmotriti čimbenike rizika koji bi mogli dovesti do razvoja HCC-a nakon liječenja HCV-a upotrebom DAA terapije, poput uloge ciroze jetre, promjene DNA ploidnosti, reaktivacije virusa hepatitisa B, kao i okultne HCV infekcije.Patients with chronic liver disease are known to be more likely to develop hepatocellular carcinoma (HCC). Although direct-acting antivirals have proven successful in eliminating the hepatitis C virus RNA from blood circulation, the HCV RNA can still remain present in liver tissue or peripheral blood mononuclear cells – a condition known as occult HCV infection. There have been numerous concerns related to the recurrence of HCC after DAA treatment of hepatocytes infected with chronic HCV. One of the major risk factors leading to de novo HCC is the chronicity of HCV in liver cells. Moreover, numerous studies investigated the change of HCV-infected hepatocytes into HCC. However, the molecular mechanisms leading to the progression of chronic HCV infection into HCC, as well as the effect of HCV on the alteration of DNA ploidy that leads to recurrence of HCC after DAA treatment, are still unclear. Therefore, this article examines the risk factors that could lead to the development of HCC after treatment of HCV with DAAs, such as the role of liver cirrhosis, reactivation of hepatitis B virus, alteration of DNA ploidy and occult HCV infection

Occurrence of Hepatocellular Carcinoma in Patients with Chronic hepatitis C Treated with Direct-Acting Antiviral Therapy

Poznato je kako oboljeli od kronične bolesti jetre učestalije obolijevaju od hepatocelularnog karcinoma. Premda se RNA molekula hepatitis C virusa uspješno eliminira iz cirkulacije direktnodjelujućim antivirusnim lijekovima, HCV RNA može ostati i dalje prisutna u jetrenom tkivu ili perifernim mononuklearnim stanicama te je taj entitet poznat kao okultni HCV. Postoje brojne nedoumice povezane s ponovnom pojavom HCC-a nakon provedenog liječenja DAA terapijom jetrenih stanica kronično zaraženih HCV-om, a jedan od glavnih čimbenika rizika koji dovodi do de novo HCC-a je pojava kroničnosti HCV-a u stanicama jetre. Mnoge studije provedene su s ciljem istraživanja promjena jetrenih stanica inficiranih HCV-om u HCC. Međutim, još uvijek nisu u potpunosti jasni molekularni mehanizmi koji vode do progresije kronične HCV infekcije u HCC i učinak HCV-a na promjenu DNA ploidnosti, što dovodi do ponovnog povratka HCC-a nakon liječenja DAA terapijom. Stoga je cilj ovoga članka razmotriti čimbenike rizika koji bi mogli dovesti do razvoja HCC-a nakon liječenja HCV-a upotrebom DAA terapije, poput uloge ciroze jetre, promjene DNA ploidnosti, reaktivacije virusa hepatitisa B, kao i okultne HCV infekcije.Patients with chronic liver disease are known to be more likely to develop hepatocellular carcinoma (HCC). Although direct-acting antivirals have proven successful in eliminating the hepatitis C virus RNA from blood circulation, the HCV RNA can still remain present in liver tissue or peripheral blood mononuclear cells – a condition known as occult HCV infection. There have been numerous concerns related to the recurrence of HCC after DAA treatment of hepatocytes infected with chronic HCV. One of the major risk factors leading to de novo HCC is the chronicity of HCV in liver cells. Moreover, numerous studies investigated the change of HCV-infected hepatocytes into HCC. However, the molecular mechanisms leading to the progression of chronic HCV infection into HCC, as well as the effect of HCV on the alteration of DNA ploidy that leads to recurrence of HCC after DAA treatment, are still unclear. Therefore, this article examines the risk factors that could lead to the development of HCC after treatment of HCV with DAAs, such as the role of liver cirrhosis, reactivation of hepatitis B virus, alteration of DNA ploidy and occult HCV infection

Influence of Caffeine on Crystallization and Amelioration of Oxidative Stress on in vitro Model of Urolithiasis

Urolithiasis is a disease characterized by formation of solid crystals within the urinary tract. Kidney stone formation is still not clear but it is mostly composed of calcium oxalate which can produce free radicals that are toxic to renal tubular cells. Oxidative stress is an important contributory mechanism in cell damage and is associated with a number of disorders. Several studies have shown antioxidative effects of caffeine, proposing its possible role in stopping the formation of calcium oxalate stones in urinary tract. Hence, the aim of this study was to evaluate the toxic effects of calcium oxalate monohydrate crystals (COM) on renal epithelial cell line; Madin-Darby canine kidney cells subtype I (MDCK I) and Epithelial-like pig kidney cell line (LLC-PK1), and to determine possible inhibition of COM that caused oxidative stress by antioxidant treatment with caffeine in different concentrations in a cell culture model of urolithiasis

Are kidney malformations an additional feature of MEN2B syndrome? – Case report and literature review

Sindrom multiple endokrine neoplazije 2B (MEN2B) rijetka je autosomno dominatno nasljedna bolest uzrokovana mutacijama protoonkogena RET. Karakteriziran je pojavom medularnog karcinoma štitnjače već od rane, nerijetko dojenačke dobi, feokromocitoma koji je najčešće obostran, sluzničkim neuromima te drugim ekstraendokrinim manifestacijama i specifičnim fenotipskim značajkama koje mogu pomoći u prepoznavanju ovih bolesnika. Prikazujemo pacijenta sa sindromom MEN2B, dijabetesom melitusom tipa 1, inverznim položajem organa te prirođenim malformacijama bubrega i mokraćnog sustava. Pregledom literature uočeno je da se malformacije mokraćnog sustava opisuju i u drugih bolesnika sa sindromom MEN2B. Prepoznata uloga gena RET u razvoju anomalija mokraćnog sustava čini moguću etiološku poveznicu sa sindromom MEN2B. Predlažemo da se malformacije bubrega razmotre kao jedno od obilježja sindroma MEN2B. Budući da se osobine bolesnika sa sindromom MEN2B postupno razvijaju s dobi, prepoznavanje prirođene mane, uz prve znakove ostalih fenotipskih značajki, moglo bi pomoći ranom postavljanju dijagnoze i liječenju ovih bolesnika.Multiple endocrine neoplasia type 2B (MEN2B) is a rare familial syndrome caused by autosomal dominant mutations in the RET proto-oncogene. The disease is characterized by aggressive, early-onset medullary thyroid carcinoma, pheochromocytoma, most often bilateral, and mucosal neuromas together with other distinctive extra-endocrine manifestations and phenotypic features that can help in recognizing the patients and diagnosing the disease. We present the patient with MEN2B syndrome, type 1 diabetes mellitus, situs inversus and congenital kidney and urinary tract malformation. Reviewing the literature revealed other reports on urinary tract malformations in patients suffering from MEN2B. The recognized role of RET gene in kidney development and urinary tract malformations suggests a possible etiological link with MEN2B syndrome. We suggest that urinary tract malformations might be a feature of MEN2B syndrome. As most of the phenotype characteristics of the syndrome develop with age, recognizing congenital malformation might help in early diagnosing and treating the patients

THE ACTIVITY OF GARLIC EXTRACTS TO THE EPITHELIAL DAMAGE CAUSED BY SODIUM TAUROCHOLATE IN A CELL CULTURE MODEL OF ULCER DISEASE

Ciljevi: Peptična ulkusna bolest (PUB) je kronična bolest koja pogađa do 10% svjetske populacije. Stanični model PUB-a može se uspostaviti u staničnom modelu ljudskih gastričnih epitelnih stanica (AGS) djelovanjem žučne soli; natrijevog taurokolata (NaT). Cilj istraživanja bio je istražiti učinke predtretmana ekstrakata češnjaka (EČ) i lanzoprazola (LPZ) u staničnom modelu ulkusne bolesti ispitivanjem oksidativnog stresa, distribucije F-aktina i određivanjem morfoloških promjena u strukturi stanične membrane. Ustroj studije: Stanice su nasađene u koncentraciji 4x105 stanica/mL te su potom inkubirane 24 sata. Stanice su potom tretirane LPZ i EČ 24, 48 i 72 sata i zatim izložene NaT tijekom 1 sata. Materijal i metode: AGS stanična linija korištena je kao model PUB. Uspostava NaT modela određena je MTT testom. Procjena je učinjena određivanjem mitotičkog potencijala stanica bojenjem proliferirajućeg staničnog jezgrenog antigena (PCNA); koncentracije glutationa (GSH) i prostaglandina E2 (PGE2) pomoću ELISA; učinka EČ na stanično preživljenje brojanjem stanica Neubauerovim hemocitometrom; ekspresije SOD, ABCG2, NFKB2 i TRX1 pomoću RT PCR-a; Vizualizacijom citoskeleta F-aktina polukvantificiranjem Rhodamine Phalloidin boje; morfoloških promjena u strukturi stanične membrane bojanjem kolesterola i fosfolipida specifičnim bojama. Rezultati: Rezultati naše studije pokazali su značajno smanjenje oštećenja stanica nakon inkubacije NAT-om, kada su AGS stanice prethodno tretirane LPZ-om (p <0,001) i povećanjem koncentracija EČ (p <0,001). Predtretman različitim koncentracijama EČ povećao je PGE2 i potisnuo iscrpljivanje GSH (p <0,001). Uočena je pozitivna korelacija SOD, NFKB2 (p <0,01) i TRX 1 (p <0,001) s LPZ i predtretmanom EČ, dok ekspresija ABCG2 nije promijenjena. (p <0,001). Predtretman stanica s EČ uzrokovao je promjene u sastavu stanične membrane i razine proteina citoskeleta izazvane izloženošću stanica NaT-u (p <0,001). Zaključak: Predtretman EČ imao je gastroprotektivni učinak u staničnom modelu PUB-i. Potrebni su daljnji eksperimenti kako bi se u potpunosti razjasnio mehanizam zaštitne uloge EČ u PUB-i.Objectives: PUD is a chronic disease affecting up to 10% of the world's population. A cellular model of PUD can be established in AGS by NaT. The aim of the study was to explore effects of GE pretreatment and LPZ addition in the cell culture model of PUD by examining oxidative stress, F-actin distribution and determine morphological changes in cell membrane structure. Study design: Cells were plated at a density of 4x105 cells/mL in 6-well plates and were grown for 24 hours. Cells were pretreated with LPZ and GE for 24, 48 and 72 hours and subsequently exposed to NaT for 1 h. Material and methods: The AGS cell line was used as a model of PUD. The establishment of the NaT model was determined by the MTT test. Evaluation was done by determination of mitotic potential of the cells by by staining against (PCNA); GSH and PGE2 concentrations by ELISA; AGS proliferation by cell counting; expression of SOD, ABCG2, NFKB2 and TRX1 by RT PCR; F-actin cytoskeleton visualization by semi-quantification of Rhodamine Phalloidin stain; morphological changes in cell membrane structure by using CL and PH specific stains. Results: Our results showed significant reduction of cell damage after NaT incubation when the AGS cells were pretreated with LPZ (p<0.001) and increasing concentrations of GE (p<0.001). Pretreatment with different concentrations of GE increased PGE2 and suppressed depletion of GSH (p<0.001). Positive correlation of SOD, NFKB2 (p<0.01) and TRX 1 (p<0.001) with LPZ and GE pretreatment were seen, while ABCG2 expression was not changed. (p<0.001). Pretreatment of the cells with GE reverses changes in the cell membrane composition and cytoskeletal protein levels induced by NaT exposure (p<0.001). Conclusion: GE pretreatment had gastroprotective effect in the cell model of PUD. Further experiments are needed to fully elucidate the mechanism of the protective role of GE in PUD