Human immunodeficiency virus pathogenesis

Virus ljudske imunodeficijencije (HIV) je virus koji napada imunosni sustav i uzrokuje infekciju te sindrom stečene imunodeficijencije (AIDS). AIDS ubija više ljudi od bilo koje druge infektivne bolesti, a HIV se nastavlja širiti brže od bilo kojeg perzistentnog infektivnog agensa. Stoga nije iznenađujuće što je u proteklom desetljeću bio jedna od najproučavanijih infektivnih čestica. Kada je riječ o razumijevanju patogeneze infekcije virusom HIV, važno pitanje koje se postavlja nije samo kako virus uzrokuje nastanak bolesti, već i zašto; a ti su mehanizmi pojašnjeni detaljnije u ovom radu. Unatoč maloj veličini genoma i nekolicini gena, HIV je iznimno uspješan u iskorištavanju staničnih puteva dok neutralizira i izbjegava različite komponente imunosnog sustava. Najznačajniji napredak ostvaren u tretiranju infekcije virusom HIV jest tretman pacijenata s antiviralnim lijekovima koji mogu suprimirati replikaciju virusa HIV do nedetektabilnih razina te tako odgoditi početak razvoja bolesti. Unatoč nedostatku konačnog lijeka i efikasnog cjepiva, uvidom u patogenezu infekcije virusom HIV dolazimo do važnih spoznaja koje bi mogle omogućiti razvoj terapeutika za uspješnu kontrolu virusa u budućnosti.Human immunodeficiency virus (HIV) is a virus that attacks the immune system and causes HIV infection and acquired immunodeficiency syndrome (AIDS). AIDS kills more people than any other infectious disease, and HIV continues to spread faster than any persistent infectious agent known in the last half century. Therefore, it is not surprising that it became one of the most researched infectious particle in the past decade. The important question when it comes to understanding the pathogenesis of HIV infection is not only how the virus causes disease but also why; and these mechanisms are further explained in this paper. Despite its small genome size and its few genes, HIV is extremely successful in taking advantage of cellular pathways while neutralising and hiding from different components of immune system. The most significant advance in the medical management of HIV infection has been the treatment of patients with antiviral drugs, which can suppress HIV replication to undetectable levels and therefore postpone disease progression. Despite the lack of a cure or an effective vaccine, understanding the pathogenesis of HIV infection has yielded important insights that may enable us to design more effective therapeutics for controlling the virus in the future

Human immunodeficiency virus pathogenesis

Virus ljudske imunodeficijencije (HIV) je virus koji napada imunosni sustav i uzrokuje infekciju te sindrom stečene imunodeficijencije (AIDS). AIDS ubija više ljudi od bilo koje druge infektivne bolesti, a HIV se nastavlja širiti brže od bilo kojeg perzistentnog infektivnog agensa. Stoga nije iznenađujuće što je u proteklom desetljeću bio jedna od najproučavanijih infektivnih čestica. Kada je riječ o razumijevanju patogeneze infekcije virusom HIV, važno pitanje koje se postavlja nije samo kako virus uzrokuje nastanak bolesti, već i zašto; a ti su mehanizmi pojašnjeni detaljnije u ovom radu. Unatoč maloj veličini genoma i nekolicini gena, HIV je iznimno uspješan u iskorištavanju staničnih puteva dok neutralizira i izbjegava različite komponente imunosnog sustava. Najznačajniji napredak ostvaren u tretiranju infekcije virusom HIV jest tretman pacijenata s antiviralnim lijekovima koji mogu suprimirati replikaciju virusa HIV do nedetektabilnih razina te tako odgoditi početak razvoja bolesti. Unatoč nedostatku konačnog lijeka i efikasnog cjepiva, uvidom u patogenezu infekcije virusom HIV dolazimo do važnih spoznaja koje bi mogle omogućiti razvoj terapeutika za uspješnu kontrolu virusa u budućnosti.Human immunodeficiency virus (HIV) is a virus that attacks the immune system and causes HIV infection and acquired immunodeficiency syndrome (AIDS). AIDS kills more people than any other infectious disease, and HIV continues to spread faster than any persistent infectious agent known in the last half century. Therefore, it is not surprising that it became one of the most researched infectious particle in the past decade. The important question when it comes to understanding the pathogenesis of HIV infection is not only how the virus causes disease but also why; and these mechanisms are further explained in this paper. Despite its small genome size and its few genes, HIV is extremely successful in taking advantage of cellular pathways while neutralising and hiding from different components of immune system. The most significant advance in the medical management of HIV infection has been the treatment of patients with antiviral drugs, which can suppress HIV replication to undetectable levels and therefore postpone disease progression. Despite the lack of a cure or an effective vaccine, understanding the pathogenesis of HIV infection has yielded important insights that may enable us to design more effective therapeutics for controlling the virus in the future

The Need for Systematic Monitoring and Improved Surveillance of Hepatitis C Patients in Croatia

Aim: The aim of this study was emphasizing the need for a more systematic monitoring of patients diagnosed with HCV in Croatia. Methods: From 2014 to 2018, at the University Hospital for Infectious Diseases, sera from 23,524 patients were tested for HCV. Confirmatory testing was performed by Western Blot. Adult patients with an anti-HCV positive screening test were analysed. HCV RNA was quantified by real-time PCR, while HCV genotypes and subtypes were determined by PCR and the reverse hybridization method. Results: A total of 428 anti-HCV ELISA-positive adults were analysed (68.7% males, 31.3% females, median age 43 years, range 19-88 years). Hepatitis C was confirmed by WB in 390, while 28 patients had borderline WB results. Anti-HCV was not confirmed by WB in 10 patients. HCV RNA was tested in 331 patients and viremia was detected in 218 patients. There was no data on HCV RNA in 97 patients (22.66%). HCV genotypes/subtypes were determined in 185 of 218 anti-HCV WB positive patients. Genotype 1 was detected in 97/185 (52.43%), genotype 2 was detected in 3/185 (1.62%), while subtype 3a was detected in 76/185 (41.08%) and genotype 4 in 9/185 patients (4.86%). Conclusion: In a five-year period, the HCV seroprevalence rate in subjects tested at the University Hospital for Infectious Diseases was 1.81%. According to the data analysed, almost one quarter of patients with detected anti-HCV antibodies were not treated further, which indicates the need for a systematic monitoring of patients diagnosed with HCV. It is necessary to determine viremia after a positive anti-HCV screening result in order to initiate treatment and prevent HCV-related complications. (Radmanić L, Cetinić Balent N, Šimičić P, Vince A, Židovec Lepej S, Đaković Rode O. The Need for Systematic Monitoring and Improved Surveillance of Hepatitis C Patients in Croatia. SEEMEDJ 2020; 4(2); 28-34

Mario Schiavato and Children's Literature

Rad ne sadrži sažetak

Mario Schiavato and Children's Literature

Rad ne sadrži sažetak

A Glimpse on the Evolution of RNA Viruses: Implications and Lessons from SARS-CoV-2

RNA viruses are characterised by extremely high genetic variability due to fast replication, large population size, low fidelity, and (usually) a lack of proofreading mechanisms of RNA polymerases leading to high mutation rates. Furthermore, viral recombination and reassortment may act as a significant evolutionary force among viruses contributing to greater genetic diversity than obtainable by mutation alone. The above-mentioned properties allow for the rapid evolution of RNA viruses, which may result in difficulties in viral eradication, changes in virulence and pathogenicity, and lead to events such as cross-species transmissions, which are matters of great interest in the light of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemics. In this review, we aim to explore the molecular mechanisms of the variability of viral RNA genomes, emphasising the evolutionary trajectory of SARS-CoV-2 and its variants. Furthermore, the causes and consequences of coronavirus variation are explored, along with theories on the origin of human coronaviruses and features of emergent RNA viruses in general. Finally, we summarise the current knowledge on the circulating variants of concern and highlight the many unknowns regarding SARS-CoV-2 pathogenesis

The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment

The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment

Distinct Expression Patterns of Genes Coding for Biological Response Modifiers Involved in Inflammatory Responses and Development of Fibrosis in Chronic Hepatitis C: Upregulation of SMAD-6 and MMP-8 and Downregulation of CAV-1, CTGF, CEBPB, PLG, TIMP-3, MMP-1, ITGA-1, ITGA-2 and LOX

Background and Objectives: The aim of this study was to analyze the expression of genes on transcriptomic levels involved in inflammatory immune responses and the development of fibrosis in patients with chronic hepatitis C. Materials and Methods: Expression patterns of 84 selected genes were analyzed with real-time quantitative RT PCR arrays in the peripheral blood of treatment-naive patients with chronic hepatitis C and healthy controls. The panel included pro- and anti-fibrotic genes, genes coding for extracellular matrix (EMC) structural constituents and remodeling enzymes, cell adhesion molecules, inflammatory cytokines, chemokines and growth factors, signal transduction members of the transforming growth factor- beta (TGF-ß) superfamily, transcription factors, and genes involved in epithelial to mesenchymal transition. Results: The expression of SMAD-6 coding for a signal transduction TGF-beta superfamily member as well as MMP-8 coding for an ECM protein were significantly increased in CHC patients compared with controls. Conclusions: Chronic hepatitis C was also characterized by a significant downregulation of a set of genes including CAV-1, CTGF, TIMP-3, MMP-1, ITGA-1, LOX, ITGA-2, PLG and CEBPB encoding various biological response modifiers and transcription factors. Our results suggest that chronic hepatitis C is associated with distinct patterns of gene expression modulation in pathways associated with the regulation of immune responses and development of fibrosis

Distinct Cytokine Profiles in Severe COVID-19 and Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles in patients with severe COVID-19 and NAFLD. A total of 94 patients with severe COVID-19 were included. Upon admission, clinical and laboratory data were collected, a liver ultrasound was performed to determine the presence of steatosis, and subsequently, 51 were diagnosed with NAFLD according to the current guidelines. There were no differences in age, sex, comorbidities, and baseline disease severity between the groups. Serum cytokine concentrations were analyzed using a multiplex bead-based assay by flow cytometry. Upon admission, the NAFLD group had higher C-reactive protein, procalcitonin, alanine aminotransferase, lactate dehydrogenase, and fibrinogen. Interleukins-6, -8, and -10 and CXCL10 were significantly higher, while IFN-γ was lower in NAFLD patients. Patients with NAFLD who progressed to critical illness had higher concentrations of IL-6, -8, -10, and IFN-β, and IL-8 and IL-10 appear to be effective prognostic biomarkers associated with time to recovery. In conclusion, NAFLD is associated with distinct cytokine profiles in COVID-19, possibly associated with disease severity and adverse outcomes