Snežana Brkić

Proton Chemical Shift Imaging Study of the Combined Antiretroviral Therapy Impact on Neurometabolic Parameters in Chronic HIV Infection

BACKGROUND AND PURPOSE: The introduction of combination antiretroviral therapy has failed to reduce the high prevalence of mild forms of HIV-associated neurocognitive disorders. The aim of this study was to test the effect of combined antiretroviral therapy on brain metabolite ratios in chronic HIV infection by using proton chemical shift imaging. MATERIALS AND METHODS: We performed 2D chemical shift imaging in 91 subjects (31 HIV+ patients with chronic infection on combination antiretroviral therapy, 19 combination antiretroviral therapy–naïve HIV+ subjects with chronic infection, and 41 healthy controls), covering frontal and parietal subcortical white and cingulate gyrus gray matter, analyzing ratios of NAA/Cr and Cho/Cr on long-TE and mIns/Cr on short-TE MR spectroscopy. We correlated neurometabolic parameters with immunologic, clinical, data and combined antiretroviral therapy efficacy scores. RESULTS: There was a significant decrease in NAA/Cr (P < .05) in HIV-positive patients on and without combined antiretroviral therapy, compared with healthy controls in all locations. There were significant differences in Cho/Cr (P < .05) and mIns/Cr (P < .05) ratios between HIV+ patients on and without therapy, compared with healthy controls, but these differed in distribution. There were no significant differences in brain metabolite ratios between the 2 groups of chronically HIV-infected patients. The CNS penetration efficacy score showed weak positive correlations only with Cho/Cr ratios in some locations. CONCLUSIONS: The impact of combined antiretroviral therapy on the process of neuronal loss and dysfunction in chronic HIV infection appears to be suboptimal in successful peripheral suppression of viral replication. Spectroscopic imaging might be a useful tool for monitoring the effects of different combined antiretroviral therapy regimens on brain metabolite ratios.

Viral infections and oxidative stress

Dosadasnja istraživanja na temu virusnih infekcija i oksidativnog stresa odnose se pretežno na infekcije herpes virusima (EBV), primarnim hepatotropnim virusima (virusima hepatitisa C i hepatitisa B) i HIV infekciju. Cilj i znacaj razjasnjenja uticaja oksidativnog stresa tokom ovih infekcija jeste poboljsanje terapije i potencijalna prevencija virusnih infekcija. Po pitanju antioksidantne suplementacije tokom infekcija, ne postoji zvanican medicinski konsenzus i postoji stvarna potreba za dobro kontrolisanim istraživanjima koja ce nam dati konacne odgovore na ovu temu.

Potential of selected Lamiaceae plants in anti(retro)viral therapy

Graphical abstract Figure. No Caption available. &NA; Constant search for new drugs with antiviral properties often extends to products of natural origin. Lamiaceae is one of the most important herbal families, well known for various biological and medicinal effects of a variety of aromatic spices, including thyme, mint, oregano, basil, sage, savory, rosemary, self‐heal, hyssop, lemon balm and many others. The paper provides a review of antiviral potential of previously mentioned plants which has been demonstrated so far, with special emphasis on anti‐HIV properties. Relevant articles were compiled by searching plant names combined with keywords describing antiviral activity. The antiviral effect is direct, with prominent activity against enveloped viral species. Initial stages of the viral life cycle are the most affected, as these plants appear to be targeting mainly viral structures responsible for attachment to target cells. In case of HIV, there is some activity against key enzymes in the viral life cycle. Even in the case of drug resistance, there is an equal susceptibility to applied herbal preparations. Some in vivo experiments suggest that use of Lamiaceae representatives could help in prevention and treatment of some viral diseases. A possible reduction of side effects of diseases and conventional drug therapy are also some aspects worth further investigations.

Neurocognitive profile of HIV-positive adults on combined antiretroviral therapy: A single-centre study in Serbia

ABSTRACT The advent of combined antiretroviral therapy (cART) has prolonged the life expectancy of HIV + individuals and decreased the incidence of HIV-associated dementia. However, milder forms of neurocognitive impairment remain common and are often associated with poor daily functioning and lower medication adherence. This paper presents a research aimed at exploring the cognitive status differences between HIV + subjects (N = 39) on cART therapy and a group of demographically comparable healthy subjects (N = 39) in Serbia. The significance of differences between the HIV + group and the healthy control group in performance in six cognitive domains was tested using the multivariate analysis of variance. Results showed a lower performance of the HIV + group in the domains of attention/working memory, and learning. HIV-related clinical variables were not significantly associated with cognitive performance. An older age in HIV + patients was significantly related to a lower performance in all six cognitive domains, as opposed to healthy subjects, implying a synergistic interaction between HIV and aging, resulting in accentuated cognitive difficulties. Our findings suggest that even with the absence of a subjective experience of cognitive deficits and with a good basic control of the illness, a certain degree of cognitive deficit can be observed in the tested group.

Serbia: Courts Struggle with a New Categorical Statutory Exclusionary Rule

In 2001, independent Serbia kept on using the code which existed before the break-up of Yugoslavia, albeit with many amendments that have altered the approach to the use of evidence gathered in violation of the law. Like most continental European countries, Serbia had a system of nullities, but Serbian courts interpreted them fairly strictly, and ruled that any evidence gathered in violation of statutory prohibitions could not be placed in the file at trial and was therefore inadmissible. The Serbian Code of Criminal Procedure now has many specific exclusionary rules related to violations in the issuance of wiretap warrants, and warrants to use undercover informants, but not, yet, in relation to searches and seizures. However, a general exclusionary rule added in 2009 has required exclusion of any evidence gathered in violation of the constitution, international law, or explicit evidentiary prohibitions. A new Code of Criminal Procedure was enacted in 2011 and will go into force in 2013, and it will contain an even broader exclusionary rule, extending exclusion to the fruits of the poisonous tree of even statutory violations.

APRIL and sTACI could be predictors of multiorgan dysfunction syndrome in sepsis

ABSTRACT Although the role of B cells in sepsis immunoregulation has become an interesting topic, there is lack of data on the role of B cell function regulators in prediction of multiorgan dysfunction syndrome (MODS). The aim of this study was to evaluate the prognostic value of A Proliferation Inducing Ligand (APRIL) and soluble Transmembrane Activator and CAML Interactor Protein (sTACI), the main B cell function regulators, in prediction of MODS development within the first 48 h after admission to intensive care unit, among septic patients. We included 112 patients with sepsis, treated at Clinic for Infectious Diseases and Emergency Center, Clinical Center of Vojvodina, Novi Sad, Serbia. Plasma concentrations of APRIL and sTACI were determined at the admission and potential development of MODS was confirmed in the first 48 h. Concentrations of APRIL (p = 0.003) and sTACI (p<0.001) were higher in patients who developed MODS (n = 30). ROC curve analysis showed that AUC for sTACI (AUC = 0.764) was greater than that for procalcitonin (AUC = 0.719) and APRIL (AUC = 0.673) in MODS development prediction. Multivariate regression analysis showed that sTACI, as an anti-inflammatory biomarker stimulating the apoptosis of B cells, was the only independent predictor of MODS, beside SOFA score. Elevated level of sTACI could be the alarm for the increased B cell apoptosis and development of immune paralysis. Including these biomarkers into predictive scores specific for septic patients may potentially improve their sensitivity and specificity. Measurement of their concentrations dynamics could contribute to better assessment of sepsis evolution and timely introduction of immunomodulatory therapy.

Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers

INTRODUCTION The aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis. METHODS One-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05. RESULTS A significant depletion of the complement was observed in non-survivors (AUCROCC3 = 0.692, pC3 < 0.001,AUCROCC4 = 0.672, pC4 = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = -0.364, p = 0.011, C3-SOFA ρ = -0.460, p < 0.001), aPTT (ρ = -0.407, p < 0.001), PT (ρ = -0.408, p < 0.001), and D-dimer (ρ = -0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 0.207, p = 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients. CONCLUSION In septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers.

Varicella zoster virus transmission dynamics in Vojvodina, Serbia

This study aimed at establishing baseline key epidemiological parameters for varicella zoster virus (VZV) infection in Vojvodina, Serbia, with the ultimate goal to quantify the VZV transmission potential in the population. Seroprevalence data generated during the first large cross-sectional VZV serosurvey were modelled, using a two-tiered modelling approach to calculate age-specific forces of infection (FOI), the basic reproduction number (R0) and herd immunity threshold (H). Seroprevalence and modelling data were compared with corresponding pre-vaccination epidemiological parameters from 11 countries participating in the European Sero-Epidemiology Network 2 (ESEN2) project. Serbia fits into the general dynamic VZV transmission patterns in Europe in the pre-vaccine era, with estimated R0 = 4.12, (95% CI: 2.69–7.07) and H = 0.76 (95% CI: 0.63–0.86). The highest VZV transmission occurs among preschool children, as evidenced by the estimation of the highest FOI (0.22, 95% CI: 0.11–0.34) in the 0.5–4 age group, with a peak FOI of 0.25 at 2.23 years. Seroprevalence was consistently lower in 5–14 year-olds, resulting in considerable shares of VZV-susceptible adolescents (7.3%), and young adults (6%), resembling the situation in a minority of European countries. The obtained key epidemiological parameters showed most intense VZV transmission in preschool children aged <4 years, justifying the consideration of universal childhood immunization in the future. National immunization strategy should consider programs for VZV serologic screening and immunization of susceptible groups, including adolescents and women of reproductive age. This work is an important milestone towards the evaluation of varicella immunization policy options in Serbia.

The role of TNF-α superfamily members in immunopathogenesis of sepsis

Background Members of TNF&agr; superfamily, A proliferation inducing ligand (APRIL), B‐cell activating factor (BAFF) and Transmembrane activator and calcium cyclophylin interactor (TACI) are main regulators of B‐cell function. The aim of this study was to evaluate concentrations of APRIL, BAFF and soluble TACI (sTACI) receptor in septic patients compared to healthy controls and compare concentrations of these biomarkers depending on sepsis severity and outcome. Materials and methods A total of 115 septic patients and 30 healthy volunteers were included and concentrations of APRIL, BAFF and sTACI were determined in all subjects at the admission (ELISA R&D Systems tests). Concentrations of these biomarkers in function of sepsis severity (sepsis n = 94 and septic shock n = 21) and outcome (lethal n = 40, recovery n = 75) were tested, as well as correlations with APACHE II and SOFA scores, immunoglobulins, complement, PCT and CRP concentrations. Results Concentrations of all three biomarkers were significantly increased in septic patients compared to controls (AUCAPRIL = 0.982, AUCBAFF = 0.873, AUCsTACI = 0.683). Higher concentrations of APRIL and sTACI (p = 0.033, p = 0.037), and lower concentrations of BAFF (p = 0.005) were observed in patients with septic shock compared to sepsis. BAFF concentrations correlated positively with IgM, C3 and C4 levels. sTACI and APRIL were shown to be predictors of lethal outcome (p = 0.003, p = 0.049). Conclusions Concentrations of observed TNF&agr; superfamily members are significantly increased in septic patients, confirming their role in sepsis pathogenesis. Higher concentrations of anti‐inflammatory sTACI receptor correlated with severity of sepsis and poorer prognosis, thus potentially indicating domination of anti‐inflammatory response in septic patients with worse outcome. HighlightsHigh concentrations of TNF‐&agr; superfamily members point to prompt activation of B cells in sepsis.APRIL, BAFF and sTACI are good predictors of septic shock and lethal outcome in sepsis.Their concentrations correlate well with SOFA, but do not correlate with PCT.Lower BAFF and higher sTACI concentrations suggest increased apoptosis of B cells in septic shock.sTACI is an anti‐inflamatory cytokine that had the highest AUC in outcome prediction.

Garlic clove applied as vaginal suppository – A case report

OBJECTIVE Besides conventional drugs, various vaginal disorders are often treated with complementary and alternative medicines. Different natural products are often used in treatment of genital infections. The aim is to present a case of treatment of vaginal infection with a garlic clove. METHODS A detailed interview was conducted with the subject whose condition was described in this case. RESULTS Young woman was diagnosed with vaginal Ureaplasma sp. infection. After failed local treatment with antibiotics and antifungals, subject obtained advice to treat the disorder with incised clove of garlic. Control examination by her gynecologist confirmed that infection was successfully cured. Subject experienced no adverse effects. CONCLUSIONS Garlic clove successfully cured vaginal infection presented in this case. However, application to genital organs should be reserved for dosage forms, in order to prevent potential toxicity and to obtain reproducibility of active compounds concentrations.