MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannosebinding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection

Evolution of the hepcidin gene in primates

<p>Abstract</p> <p>Background</p> <p>Hepcidin/LEAP-1 is an iron regulatory hormone originally identified as an antimicrobial peptide. As part of a systematic analysis of the evolution of host defense peptides in primates, we have sequenced the orthologous gene from 14 species of non-human primates.</p> <p>Results</p> <p>The sequence of the mature peptide is highly conserved amongst all the analyzed species, being identical to the human one in great apes and gibbons, with a single residue conservative variation in Old-World monkeys and with few substitutions in New-World monkeys.</p> <p>Conclusion</p> <p>Our analysis indicates that hepcidin's role as a regulatory hormone, which involves interaction with a conserved receptor (ferroportin), may result in conservation over most of its sequence, with the exception of the stretch between residues 15 and 18, which in New-World monkeys (as well as in other mammals) shows a significant variation, possibly indicating that this structural region is involved in other functions.</p

DEFB1 polymorphisms and HIV-1 mother-to-child transmission in Zambian population

6Human Beta Defensin-1 (hBD-1) is a component of the innate immune system, the first line of defence against pathogens, already reported as involved in the susceptibility to HIV-1 infection and HIV-1 mother-to-child transmission (MTCT) in different populations. We investigated the role of DEFB1 gene (encoding for hBD-1) functional polymorphisms in the susceptibility to HIV-1 MTCT in a population from Zambia.partially_openembargoed_20190320Zupin, Luisa; Polesello, Vania; Segat, Ludovica; Kamada, Anselmo Jiro; Kuhn, Louise; Crovella, SergioZupin, Luisa; Polesello, Vania; Segat, Ludovica; Kamada, Anselmo Jiro; Kuhn, Louise; Crovella, Sergi

Population pharmacokinetics of intravenous acyclovir in oncologic pediatric patients

Background: Acyclovir represents the first-line prophylaxis and therapy for herpes virus infections. However, its pharmacokinetics in children exposes them to the risk of ineffective or toxic concentrations. The study was aimed at investigating the population pharmacokinetics (POP/PK) of intravenous (IV) acyclovir in oncologic children. Methods: Patients (age, 8.6 ± 5.0 years, 73 males and 47 females) received IV acyclovir for prophylaxis (n = 94) and therapy (n = 26) under a therapeutic drug monitoring (i.e., minimum and maximal plasma concentrations, &gt;0.5 and &lt;25 mg/L, respectively). Plasma concentrations were fitted by nonlinear mixed effect modeling and a simulation of dosing regimens was performed. Findings were stratified according to an estimated glomerular filtration rate (eGFR) threshold of 250 ml/min/1.73m2. Results: The final 1-compartment POP/PK model showed that eGFR had a significant effect on drug clearance, while allometric body weight influenced both clearance and volume of distribution. The population clearance (14.0 ± 5.5 L/h) was consistent across occasions. Simulation of standard 1-h IV infusion showed that a 10-mg/kg dose every 6 h achieved target concentrations in children with normal eGFR (i.e., ≤250 ml/min/1.73m2). Increased eGFR values required higher doses that led to an augmented risk of toxic peak concentrations. On the contrary, simulated prolonged (i.e., 2 and 3-h) or continuous IV infusions at lower doses increased the probability of target attainment while reducing the risk of toxicities. Conclusion: Due to the variable pharmacokinetics of acyclovir, standard dosing regimens may not be effective in some patients. Prospective trials should confirm the therapeutic advantage of prolonged and continuous IV infusion

DEFB1 polymorphisms and salivary hBD-1 concentration in Oral Lichen Planus patients and healthy subjects

The aetiology of Oral Lichen Planus (OLP), a chronic inflammatory disease of oral mucosa, is not yet well understood. Since innate immunity may be hypothesized as involved in the susceptibility to OLP, we studied human beta defensin 1 (hBD-1) an antimicrobial peptide constitutively expressed in the saliva, looking at functional genetic variants possibly able to diminish hBD-1 production an consequently conferring major susceptibility to OLP

Herpes simplex virus (HSV) pneumonia in the non-ventilated immunocompromised host: Burden and predictors

Objectives: To evaluate burden and predictors of HSV pneumonia among immunocompromised patients not undergoing invasive mechanical ventilation according to a tailored diagnostic algorithm. Methods: This prospective, observational study included immunocompromised adults with pneumonia non-responding to empirical antibiotic therapy. Bronchoalveolar lavage (BAL) specimens were cultured for bacteria, mycobacteria and fungi. Real-time PCR for Herpesviruses and other microorganisms were performed on BAL and other specimens. Cytological examination of BAL samples was carried out for identification of intranuclear inclusion bodies and immunohistochemical staining for HSV. Results: We enrolled 45 patients (mean age 64.6 years) from January 2015 to June 2016. Nineteen (42.2%) cases tested positive for HSV-1 PCR on BAL. According to our definitions, 11 (24.4%) patients had HSV- 1 pneumonia with viral loads ranging between 10 3 copies/mL and 10 7 copies/mL. HSV-1 positive throat swab (OR 85.2, 95% CI 5.83\u20131245.1, P < 0.001) and solid organ transplant (SOT) (OR 53.3, 95% CI 1.37\u20132072.8, P < 0.03) as underlying condition were found to be independently associated with HSV pneumonia by multivariable analysis. Conclusions: HSV pneumonia turned out to be relatively common and should be investigated especially in individuals with HSV positive throat swab and SOT. Interventional studies are needed to assess the real clinical impact of HSV pneumonia in immunocompromised patients

Frequency of HLA B*5701 allele carriers in abacavir treated-HIV infected patients and controls from northeastern Brazil

n our study population from Northeastern Brazil, the frequency of HLA-B*5701 was between Caucasian and African ethnic groups; however, when stratifying for ethnicity, our findings show that the HLA B*5701 carriers' frequencies are more similar to those previously reported for Caucasians and Africans. Considering the clinical importance of hypersensitivity to Abacavir treatment in HIV-infected patients and the frequency of HLA B*5701 carriers reported in this study (3.1% in patients and 3.4% in the controls), we suggest the preventive use of HLA B*5701 testing in clinical practice in Abacavir treatment in Northeastern Brazil

Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration

Human \u3b2-defensin 1 (hBD-1) is an antimicrobial peptide involved in epithelial defence of various tissues, also present in the saliva. Individual genetic variations within the DEFB1 gene, encoding for hBD-1, could influence gene expression and protein production