Daniela Maric

Lipid and protein oxidation in female patients with chronic fatigue syndrome

Introduction Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS. Material and methods Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined. Results The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol. Conclusions The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.

Cystatin C in pre-eclampsia.

Objective: To evaluate diagnostic value of cystatin C serum levels as alternative marker of renal function in pre-eclamsia (PE) and compare it with the traditional markers of renal function, creatinine and uric acid. In order to investigate the possible influence of inflammation on biochemical markers of renal function, serum levels of high sensitive CRP were measured (hsCRP). Methods: In this prospective study markers of kidney function were investigated in two groups of pregnant women: one with PE (n = 32) and the other of healthy pregnant women (n = 60). Serum cystatin C levels were measured as well as levels of traditional renal markers creatinin and uric acid and levels of high sensitive C-reactive protein. Results: Serum levels of cystatin C, creatinine and uric acid were significantly higher in the PE group than in the control group. Serum levels of hsCRP were higher in approximately the same number of patients with PE (50%) as in normal pregnancies (40%), without significant differences in CRP values between the two groups of patients. Conclusions: Cystatin C serum level may have significant role as a marker of pre-eclampsia specially when used in combination with uric acid levels.

Multivitamin mineral supplementation in patients with chronic fatigue syndrome.

Background Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months. CFS has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Treatment is with a vitamin and mineral supplement, but this therapeutic option so far has not been properly researched. Material/Methods This prospective study included 38 women of reproductive age consecutively diagnosed by CDC definition of CFS and treated with a multivitamin mineral supplement. Before and after the 2-month supplementation, SOD activity was determined and patients self-assessed their improvement in 2 questionnaires: the Fibro Fatigue Scale (FFS) and the Quality of Life Scale (SF36). Results There was a significant improvement in SOD activity levels; and significant decreases in fatigue (p=0.0009), sleep disorders (p=0.008), autonomic nervous system symptoms (p=0.018), frequency and intensity of headaches (p=0.0001), and subjective feeling of infection (p=0.0002). No positive effect on quality of life was found. Conclusions Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS.

Fever of Unknown Origin in Elderly Patients

INTRODUCTION Causes of fever of unknown origin are different. It is considered that it can be caused with over 200 different clinical entities. Aetiological causes differ according to different categories of age. Febricity in the elderly is at most the result of autoimmune processes, malignancies, bacterial infections and vasculitis. OBJECTIVE The aim of this study was to determine the most common characteristics of fever, the most common laboratory, bacterial and viral tests and to analyze applied therapy in patients with unknown febrile state, and to affirm final diagnosis in elderly patients, as well as younger than 65 years old, and to define outcome of disease in both groups of patients. METHODS Research comprised 100 patients who had been treated at the Infectious Disease Clinic of the Clinical Centre of Vojvodina in Novi Sad, during a three-year period, and in whom fever of unknown origin had been diagnosed. Patients were divided into two homogenous groups of 50 people. The first one (S) consisted of patients older than 65 years, and the second, control group (K) was constituted of patients younger than the age of 65. All of them were chosen by random sample method. RESULTS Average results of standard laboratory parameters of infection were obtained, such as erythrocyte sedimentation rate (ESR), fibrinogen, CRP, and especially leukocyte, and those were significantly higher in the group of elderly patients. The cause had not been found in 10% of elderly patient group, and in the younger group, not even in the third of patients. Among known causative agents dominant were infections, usually of respiratory and urinary tract, in both tested groups. Even 28% of the elderly had sepsis, and 10% endocarditis. Malignant diseases were more frequent in group of the elderly patients, and immune i.e. systematic disorders were evenly noticed in both groups of patients. CONCLUSION Despite advanced studies in medicine, and existence of modern diagnostic procedures, fever of unknown origin is still today differential diagnostic problem.

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.

Antioxidant Status in Normal Pregnancy and Preeclampsia upon Multivitamin-Mineral Supplementation in the Region of Vojvodina

Normal pregnancy is associated with oxidative stress and this is even increased during preeclampsia (PE). The decrease in total antioxidant capacity is the pathophysiological basis for vitamin supplementation during pregnancy, but the beneficial effect of this approach is still unclear. Levels of creatinine, urea, cystatin, malondialdehyde (MDA), superoxide dysmutase activity (SOD), glutathione peroxidase (GSH-Px) activity and acidum ascorbicum were measured in the serums of all women. Mean MDA level in maternal plasma in normal pregnancies was significantly lower than in PE pregnancies (2,78 ±0.78 pmol/mg vs 3.20±0.91 pmol/mg, p< 0.05), as well as mean GSH-Px levels (811 ±206 U/l vs 1350±575 U/l, p< 0.05. Mean ascorbic acid values were significantly higher in normal than in PE pregnancies (9,85 ±2,43 mg/L vs 5.54±1.81 mg/L, p< 0.001), as well as mean SOD values (26.8 ±18.45% vs 12.3±10.3%, p< 0.001). There were no significant differences in normal pregnancy group with and without multivitamin supplementation. MDA levels were significantly lower in PE pregnancies with vitamin supplementation (2.99 ± 0.81 pmol/mg vs 3.42 ± 1.01 pmol/mg, p< 0.05), as well as GSC-Px levels (1200 ± 500 U/l vs 1500 ± 650 U/l, p< 0.05). Ascorbic acid values were significantly higher in the PE group with vitamin supplementation (6.16 ± 1.66 mg/L vs 4.92 ± 1.96 mg/L, p< 0.05), as well as SOD levels (13 ± 11.4 % vs 11.6 ± 9.2%, p< 0.001).

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.

Prediction of brain atrophy using three drug scores in neuroasymptomatic HIV-infected patients with controlled viremia

BACKGROUND Despite potent antiretroviral therapy, HIV still causes brain damage. Better penetration into the CNS and efficient elimination of monocyte/macrophages reservoirs are two main characteristics of an antiretroviral drug that could prevent brain damage. The aim of our study was to assess efficacy of three antiretroviral drug scores to predict brain atrophy in HIV-infected patients. METHODS A cross sectional study consisting of 56 HIV-infected patients with controlled viremia, who had no clinically evident neurocognitive impairment. All patients had MRI of the head. A typical T2 transversal slice was analyzed and ventricles-brain ratio (VBr) as an overall brain atrophy index was calculated. Three antiretroviral drug scores were used and correlated with VBr: 2008 and 2010 CNS penetration effectiveness scores (ΣCPE2008 and ΣCPE2010) and the recently established monocyte efficacy (ΣME) score. A p-value <0.05 was considered significant. RESULTS ΣCPE2010 was significantly associated with VBr in both univariate (r=-0.285, p=0.033) and multivariate (β=-0.299, p=0.016) regression models, while ΣCPE2008 was not (r=-0.141, p=0.300 and β=-0.156, p=0.214). ΣME was associated with VBr in multivariate model only (r=-0.297, p=0.111 and β=-0.406, p=0.029). Age and reported duration of HIV infection were also significant predictors of overall brain atrophy in multivariate regression models. CONCLUSIONS Although based on similar type of research, ΣCPE2010 is a superior drug score compared to ΣCPE2008. ΣME is an efficient drug score in determining brain damage. Both ΣCPE2010 and ΣME scores should be taken into account in preventive strategies of brain atrophy and neurocognitive impairment in HIV-infected patients.

Executive functions rating scale and neurobiochemical profile in HIV- positive individuals

The set of complex cognitive processes, that are necessary for the cognitive control of behavior, known as executive functions (EF), are traditionally associated with the prefrontal cortex and commonly assessed with laboratory based tests and conventional neuroimaging. In an effort to produce a more complete and ecologically valid understanding of executive functioning, the rating scales have been developed in order to assess the behavioral aspects of EF within an everyday real-world context. The main objective of this study was to examine the relationship between behavioral aspects of EF measured by rating scale and neurometabolic profile in neurologically asymptomatic HIV-positive individuals under cART, measured using multi-voxel magnetic resonance spectroscopy (mvMRS). The sample comprised 39 HIV-positive adult male participants, stable on cART and 39 healthy HIV-negative volunteers. Both groups completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). HIV-positive group additionally underwent long-echo three-dimensional mvMRS to determine neurobiochemical profile in the anterior cingulate gyrus (ACG) of both hemispheres. Three dominant neurometabolites were detected: N-acetyl aspartate (NAA), the neuronal marker; choline (Cho), the marker of membrane metabolism and gliosis and creatine (Cr), the reference marker. Ratios of NAA/Cr and Cho/Cr were analyzed. The initially detected significant correlations between age, current CD4, BRIEF-A subscales Inhibit, Shift, Emotional Control, Plan/Organize, Self Monitoring and ratios of NAA/Cr and Cho/Cr in the dorsal and ventral part of the ACG, were lost after the introduction of Bonferroni corrections. Also, there were no significant differences between HIV–positive and HIV–negative group on any of BRIEF-A subscales. Such results possibly imply that stable cART regimen contributes to preservation of behavioral aspects of EF in asymptomatic HIV-positive individuals. Even though a subtle deficit in some aspects of EF might exist, it would not be manifest if behavioral aspect was assessed using EF rating scale. Further explanation might be that expected HIV-related changes in neurometabolic profile of the ACG under cART are not reflected in those behavioral aspects that are measurable by EF rating scale.

Neuroendocrine disorder in chronic fatigue syndrome

Background/aim: Neuroendocrine disorders are considered a possible pathogenetic mechanism in chronic fatigue syndrome (CFS). The aim of our study was to determine the function of the hypothalamic-pituitary-adrenal axis (HPA) and thyroid function in women of reproductive age suffering from CFS. Materials and methods: The study included 40 women suffering from CFS and 40 healthy women (15-45 years old). Serum levels of cortisol (0800 and 1800 hours), ACTH, total T4, total T3, and TSH were measured in all subjects. The Fibro Fatigue Scale was used for determination of fatigue level. Results: Cortisol serum levels were normal in both groups. The distinctively positive moderate correlation of morning and afternoon cortisol levels that was observed in healthy women was absent in the CFS group. This may indicate a disturbed physiological rhythm of cortisol secretion. Although basal serum T4, T3, and TSH levels were normal in all subjects, concentrations of T3 were significantly lower in the CFS group. Conclusion: One-time hormone measurement is not sufficient to detect hormonal imbalance in women suffering from CFS. Absence of a correlation between afternoon and morning cortisol level could be a more representative factor for detecting HPA axis disturbance.