Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease, with chronically infected making up approximately 1% of the global population. Of those infected, 70% ...(55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death.
Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects.
We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug-drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation.
We present a comprehensive overview of specific direct-acting antiviral metabolism and drug-drug interaction issues in different settings.
Despite its complex pharmacokinetics and the possibility of drug-drug interactions, direct-acting antivirals are highly efficacious in providing viral clearance, which is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with tight control of immunosuppressive therapy.
Advanced glycation end products (AGEs) represent an endogenously produced or exogenously derived group of compounds derived from nonenzymatic glycation. Recent experimental studies are suggesting ...that AGEs could play an important role in the skin's quality and its aging process. Hence, the aim of this study was to clinically evaluate the AGEs and skin quality parameters across different age groups in the general population. The study included 237 participants. Melanin, erythema, hydration, friction and transepidermal water loss (TEWL) were evaluated using noninvasive probes, while AGEs were evaluated using a skin autofluorescence reader. There was a significant positive correlation between AGEs and the amount of melanin (
< 0.001), erythema (
< 0.001) and TEWL (
< 0.001), while there was a significant negative correlation between AGEs and hydration (
< 0.001) and friction (
< 0.001). After dividing the sample into three groups depending on their age, in all three groups, there was a significant positive correlation between AGEs and the melanin count (
< 0.001) and TEWL (
< 0.001), while there was a significant negative correlation between AGEs and skin hydration (
< 0.001). Multiple linear regression analysis showed that the level of AGEs as a dependent variable retained a significant association with age (
< 0.001), melanin (
< 0.001), erythema (
= 0.005) and TEWL (
< 0.001) as positive predictors. Moreover, AGEs retained a significant association with skin hydration (
< 0.001) and friction (
= 0.017) as negative predictors. These outcomes imply that AGEs could be linked with the complex physiology of the skin and its aging process.
Recent clinical and scientific evidence confirms the negative impact of long-term periodontitis on the clinical course and progression of various liver diseases. Periodontitis is a chronic, ...slow-progressing infectious disease of the tooth supporting tissues caused mainly by the gram-negative bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola and Tannerellaforsythia. These specific pathogens can be easily translocated from oral cavity to the intestine. Disruption of the intestine microbiota composition by orally derived periodontal pathogenic bacteria has recently been suggested to be a causal mechanism between periodontitis and liver disease. Furthermore, both diseases have the ability to induce an inflammatory response and lead to the creation of inflammatory mediators through which they may influence each other. Recent epidemiologic studies have demonstrated that individuals with liver cirrhosis have considerably poorer periodontal clinical parameters than those without cirrhosis. Periodontal therapy in cirrhosis patients favorably modulates oral and gut microbiome, the course of systemic inflammation, cirrhosis prognostic factors, and cognitive function. Therefore, future clinical researches should be focused on detailed examination of the biological mechanisms, strength and direction of the association between advanced liver disease and periodontitis. Key words: Inflammation; Liver diseases; Oral health; Periodontitis Rezultati novijih klinickih i znanstvenih istrazivanja potvrduju negativan utjecaj parodontitisa na klinicki tijek razlicitih bolesti jetre. Parodontitis je kronicna, sporo napredujuca infekcija potpornih tkiva zuba uzrokovana uglavnom gram negativnim bakterijama Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola i Tannerella forsythia. Ovi mikroorganizmi mogu vrlo lako iz usne supljine dospjeti u crijeva uzrokujuci promjenu crijevnog mikrobioma, sto se smatra jednom od mogucih poveznica izmedu parodontitisa i bolesti jetre. Nadalje, obje bolesti su upalnog karaktera i uzrokuju stvaranje razlicitih upalnih medijatora putem kojih mogu utjecati jedna na drugu. Nedavna epidemioloska istrazivanja pokazala su da bolesnici s cirozom jetre imaju znacajno losiji parodontni status u odnosu na zdrave ispitanike. Uoceno je da parodontna terapija kod bolesnika s cirozom jetre pozitivno utjece na oralnu i crijevnu mikrofloru, tijek upalnih procesa, prognosticke cimbenike i kognitivnu funkciju. Stoga se buduca klinicka ispitivanja trebaju usredotociti na proucavanje bioloskih mehanizama, jacine i smjera povezanosti uznapredovale bolesti jetre i parodontitisa. Kljucne rijeci: Upala; Bolesti jetre; Oralno zdravlje; Parodontitis
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.
Pharmacogenomics is a promising field which increasingly influences medicine and biomedical research in many areas. Aim of this article is to provide a comprehensive review of recent progress in the ...understanding of the genetic polymorphisms and their influence on interindividual variability in drug response. Also, main variabilites in drug response according to sex gender differences will be discussed. Translation of pharmacogenomics into clinical practice and the challenges of reaching the goal of individualized 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 administration of drugs to children. At the end, main ethical, social and regulatory issues regarding translation of pharmacogenomics into clinical practice and future perspectives in the field will be shown.
Koštani morfogenetski proteini (BMP) čine grupu čimbenika rasta i diferencijacije unutar TGFβ nado- bitelji. Oni induciraju stvaranje ektopične i ortotopične endohondralne kosti te su uključeni u ...regulaciju stanične proliferacije, diferencijacije, apoptoze i mezenhimalno-epitelne interakcije u važnim tkivnim morfogenetskim procesima izvan koštanog sustava. Koštane naprave koje sadrže BMP2 i BMP7 pro- tein odobrene su za poboljšanje koštanog cijeljenja kod pacijenata s defektima dugih cjevastih kostiju i kod prednje spinalne fuzije kralježnice. Međutim, zbog visoke cijene i mnogobrojnih nuspojava koje su uključivale pojavu heterotopičnih osifikacija, retrogradnu ejakulaciju i bol, njihova je klinička prim-
jena ograničena. U ovom smo preglednom radu raspravili otkriće BMP molekula, njihovu biologiju i primjenu u kliničkim studijama s posebnim osvrtom na nedavno otkrivenu novu autolognu koštanu napravu (ABGS) koja sadrži BMP6. Novi ABGS sastoji se od nosača autolognog koaguluma (ABC) s otopljenim BMP6 koji je ključan za pokretanje diferencijacije mezenhimalnih stanica u smjeru stvaranja endohondralne kosti. ABC je ispunio sve potrebne uvjete za formulaciju optimalnog nosača za BMP6 isključivo zbog jednostavnosti priprave i primjene te odsustva imunogenog i upalnog odgovora na mjestu implantacije. Uz dodatak alografta ili sintetičke keramike što je potvrđeno na životinjskim modelima došlo je do značajnog povećanja volumena te poboljšanja mikroarhitekture novonastale kosti. Prvo kliničko ispitivanje provedeno je na pacijentima s distalnim prijelomima radijusa (faza I studije), a drugo na pacijentima koji su podvrgnuti visokoj osteotomiji tibije (faza I/II studije) bez uočenih ozbiljnih nuspojava. Trenutno je u tijeku studija OSTEOproSPINE u kojoj se testira učinkovitost ABGS u kom- binaciji s koštanim alograftom u bolesnika s kroničnim bolovima u leđima uzrokovanim degenerativnim promjenama intervertebralnog diska. Nova ABGS koštana naprava značajna je prekretnica i napredak u području koštane biologije te regenerativne medicine koštanog sustava.
Redox potentials of two reducing (sodium dithionite and glucose) and two oxidizing (hydrogen
peroxide and sodium hypochlorite) agents were monitored at various concentrations and at different
...temperatures for 30–75 minutes after the exposure of their water solutions (glucose and
hypochlorite solutions once; sodium dithionite and hydrogen peroxide solutions one, two
and/or three-times) to the static magnetic field of flux density of 0.9 V s m–2. The aim of the investigation
was to suggest improvements, i.e., intensification and stability, of the reduction-oxidation
ability of selected agents applicable in textile fibre processing, primarily bleaching and
vat dyeing. Results of the experiments show that magnetic treatment (of solutions) raises both
the reducing ability of glucose and the oxidation ability of hydrogen peroxide and sodium
hypochlorite, promising some technological and economical benefits for the textile industry as
well as for other fields of chemistry.
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