Nataša Popović

The Frequency of Poststroke Infections and Their Impact on Early Stroke Outcome

INTRODUCTION Poststroke infections are the most common medical complications of stroke and can occur in up to 65% of patients. The aim of this study was to assess the rate of infectious complications during hospitalization of stroke patients and to evaluate the impact of infection in general, including each of the urinary tract infection (UTI), pneumonia, and sepsis, on fatal and poor functional outcome at discharge. METHODS This retrospective study enrolled patients who have been diagnosed with acute ischemic stroke treated in a 1-year period. Poor functional outcome at discharge was defined as severe invalidity and included patients with modified Rankin Scale score of 3-5. Univariate and multivariate analyses were performed. RESULTS We analyzed 133 patients with acute ischemic stroke. Poststroke infection occurred in 63 (47.4%) patients. The most common infection was UTI that was present in 27 (20.3%) patients. Multivariate logistic regression analysis after adjustment for confounders demonstrated that poststroke infection was an independent predictor of poor functional outcome (odds ratio [OR] 12.82, 95% confidence interval [CI] 4.09-40.0, P < .001) and death at discharge (OR 14.92, 95% CI 2.97-76.92, P = .001). When analyzing the impact of each infectious complication, multivariate logistic regression showed that UTIs were an independent predictor of poor functional outcome (OR 14.08, 95% CI 3.06-64.84, P = .001) and death (OR 9.81, 95% CI 1.46-65.68, P = .019) at discharge. CONCLUSION Infection is a frequent poststroke complication and represents an independent predictor of poor functional and fatal early stroke outcome.

Oral teicoplanin for successful treatment of severe refractory Clostridium difficile infection.

INTRODUCTION Clostridium difficile is the leading cause of hospital-acquired diarrhoea. There is no defined protocol for treating severe Clostridium difficile infection (CDI) refractory to vancomycin or vancomycin and metronidazole combination therapy. The aim of this study was to evaluate the rate of clinical cure, time to resolution of diarrhoea and recurrence rate in patients with severe refractory CDI treated with oral teicoplanin. METHODOLOGY A one-year prospective study was carried out in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia. Patients with severe and complicated CDI who failed to respond to oral vancomycin and intravenous metronidazole combination therapy were enrolled. They were given oral teicoplanin 100 mg bi-daily. Patients were followed for recurrence for eight weeks. RESULTS Nine patients with a mean age of 70.8±9.4 years were analyzed. All patients had pseudomembranous colitis, and five had complicated disease. In four patients intracolonic delivery of vancomycin was also performed in addition to oral vancomycin and intravenous metronidazole prior to initiating teicoplanin, but without improvement. After teicoplanin initiation all patients achieved clinical cure. The mean time to resolution of diarrhoea after teicoplanin introduction was 6.3±4.5 days. There was no statistically significant difference in time to resolution of diarrhoea according to initial leucocyte count, age over 65 years, the presence of ileus, complicated disease and the use of concomitant antibiotic therapy (p = 0.652, 0,652, 0.374, 0.374, and 0,548, respectively). None of the patients experienced recurrence. CONCLUSIONS Oral teicoplanin might be a potential treatment for severe and complicated refractory CDI, but further studies are required.

Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats

Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

Clostridium difficile infection: a Serbian single-center experience

INTRODUCTION Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. Severity of CDI is associated with advanced age and co-morbidities. The clinical spectrum varies from mild watery diarrhea to severe fulminant pseudomembranous colitis with complications. METHODOLOGY This study conducted over a six-year period (2008 to 2013) included 510 patients treated at the University Hospital for Infectious and Tropical Diseases in Belgrade, Serbia. In patients with a history of previous hospitalization and/or treatment with antimicrobial agents who developed diarrhea, the diagnosis was established with rapid tests for C. difficile toxin A and B and by stool culture for C. difficile (454 patients) or by endoscopic examination and histological analyses of the biopsy samples taken from the colonic mucosa (56 patients). RESULTS The mean age of patients was 67.71±13.34 years. A total of 67.8% patients were older than 65 years. Over half (58.7%) of the patients were female. 93% had been previously hospitalized and/or had surgical interventions, during which they had been treated with antibiotics. In the clinical presentation spectrum, pseudomembranous colitis occurred in 51.0%. The mean duration of illness after the introduction of specific antibiotic therapy was 7.10 ± 4.88 days. Complications developed in 14 patients. The disease relapsed in 43 (8.4%). Thirty-two (6.3%) patients died, mostly due to co-morbidities. CONCLUSIONS CDI is the most important cause of hospital-acquired diarrhea in Serbia. The disease mainly affects elderly patients with co-morbidities. The incidence of complications is low and prognosis is age dependent and related to pre-existing diseases.

Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study.

BACKGROUND The epidemiological characteristics of hepatitis C virus (HCV) infection have not yet been described in Serbia. AIMS To determine the prevalence of anti-HCV-positive individuals among first-time blood donors and the risk factors for hepatitis C transmission. METHODS A multicentre case-control study nested within a prospective cohort study was conducted at 10 main transfusion centres in Serbia in 2013 and 27,160 blood donors who gave blood for the first time were included. Blood donors with confirmed anti-HCV positivity and seronegative controls were enrolled to determine the risk factors. RESULTS Of 27,160 blood donors 52 were anti-HCV-positive; seroprevalence was 0.19%. By univariate analysis, marital status, educational level, drug use, previous transfusion, tattooing, non-use of condoms and number of sexual partners, were risk factors for hepatitis C. In the final multivariate analysis, three factors remained independently predictive: drug use, tattooing and previous blood transfusion. In total, 87.5% of cases had at least one of the risk factors for HCV transmission; 20.9% presumed that they knew when the infection occurred. CONCLUSION HCV seroprevalence in Serbia is higher than in developed European countries. Preventive measures need to be directed towards drug use and tattooing facilities. The admission questionnaire for blood donors should be improved.

Qualitative study of Mollusca communities in the Serbian Danube stretch (river km 1260–863.4)

First detailed limnological study was performed from April 2003 to June 2008 in a 396.6 km long section of the Serbian Danube (divided in three parts; from 1260 r-km to 863.4 r-km) to examine community composition and spatial distribution of Mollusca with special attention to the expansion of Ponto-Caspian species, propagation of invasive and introduced species and occurrence of endemic species. Mollusca samples were collected at 15 sites in April, June, September and November. We investigated the spatial distributions and calculated the faunistic similarity of localities with respect to the community composition using the Sørensen Quotient of Similarity. Site variation in analyzed qualitative traits was examined using correspondence analysis. Additionally, the obtained Complete Linkage City-block (Manhattan) distances among sites/parts were subjected to UPGMA (unweighted pair-group method using arithmetic averages) cluster analysis. The class Gastropoda was represented by 18 species from two subclasses (Prosobranchia — six families and Pulmonata — three families).The class Bivalvia was represented by 15 species from four families of order Eulamellibranchiata. Mollusca were represented by 33 species belonging to 17 genera and 13 families. Out of five recorded Ponto-Caspian species in the studied Danube stretch, Lithoglyphus naticoides (Pfeiffer, 1828) and Dreissena polymorpha (Pallas, 1771) are assumed to be invasive species with the highest occurrence frequency (F = 1, each). Four new species in invertebrate fauna for the Danube, denoted as the introduced species — Neozoa, were identified: Theodoxus fluviatilis (L., 1758), Corbicula fluminalis (Müller, 1774), C. fluminea (Müller, 1774), and Sinanodonta woodiana (Lea, 1834). The only endemic species of Gastropoda found in the Danube was Viviparus acerosus Bourguignat, 1862.

Antioxidant status in women with uterine leiomyoma: relation with sex hormones

Uterine leiomyomas are benign soft-tissues tumors that arise from uterine smooth muscle tissue. Etiopathogenesis of leiomyomas is not well understood. We aimed to examine whether antioxidant enzyme activities and lipid hydroperoxides level in patients with leiomyoma are influenced by changes in sex hormones and gonadotropins (estradiol (E2), progesterone, FSH, and LH) during menstrual cycle and in postmenopause. The material consisted of blood and uterine tissue specimens. Hormone concentrations were determined and assays for superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and lipid hydroperoxides concentration were performed. In blood of examined women, a significant difference in catalase, glutathione peroxidase and glutathione reductase activity was recorded among the phases. There was also a positive correlation between the estradiol/progesterone concentration and the catalase activity. Progesterone negatively correlated with lipid hydroperoxides level. In myoma tissue, we recorded a phase-related difference in lipid hydroperoxides level and activities of superoxide dismutase, glutathione peroxidase activities, and glutathione reductase. Negative correlation was observed between FSH and glutathione peroxidase. The results suggest that antioxidant status in patients with uterine leiomyoma is influenced by the changes in sex hormones during the menstrual cycle and in postmenopause, indicating a role of the observed relationship in the leiomyoma etiology.

Limnological study of Serbian oxbow shaped Lake Srebrno, with special emphasis on the benthic community composition and structure

Abstract Detailed limnological study of the Lake Srebrno (Serbia) bottom fauna was performed in March 2007. Investigations included qualitative, quantitative, and saprobiological analysis of bottom fauna communities, physical and chemical analysis of sediments and determination of chlorophyll a concentration, as well as saprobic and trophic status analyses. Samples were collected at eighteen sites distributed along a shoreline and in deeper sections of the lake. Twenty taxa from nine macroinvertebrate groups were recorded. Family Chironomidae had the biggest index of participation, the highest species diversity and the largest density of populations in benthocenoses of Lake Srebrno. Faunistic similarity between sites was estimated according to Sorensen’s Quotient of Similarity (QS). The majority of benthocenoses - 56% showed a medium level of faunistic similarity (QS = 21-60%), and 42% of benthocenoses showed a high level of faunistic similarity (QS = 61-100%). The classification of Lake Srebrno based on saprobic and trophic levels was assessed. Saprobic level was in the range from alpha-meso- to poly-alpha-mesosaprobity. The water quality of the lake ranged from class III and between IV and III class. Generally, Lake Srebrno had eutrophic status with the gradation to hypertrophy.

SUPEROXIDE DISMUTASE AND LIPID PEROXIDATION IN CHILDREN AFFECTED BY CELIAC DISEASE

Celiac disease (CD) is an autoimmune disorder provoked by the wheat gluten and related proteins from other grains. The only treatment for the patients is a lifelong gluten free diet (GFD). Oxidative stress has been implicated in the pathogenesis of CD. The aim of this study was to examine the modulation of the biochemical response to oxidative stress in children affected by CD. The study involved peripheral blood samples and small intestinal biopsies from 69 children diagnosed with CD. According to the histological findings, patients were divided into following groups: Marsh 0: normal mucosa with no signs of inflammation (n=31); Marsh 1: mucosa was characterized by intraepithelial lymphocytosis (n=5); Marsh 2: intraepithelial lymphocytosis was accompanied by crypt hyperplasia (n=4); Marsh 3a: mucosa showed partial villous atrophy (n=20); Marsh 3b: subtotal villous atrophy was present (n=9). For the statistical purposes groups Marsh 1 and Marsh 2 were treated as one (Marsh 1+2, n=9). The activities and protein levels of copper, zinc superoxide dismutase (CuZnSOD) and manganese SOD (MnSOD), as well as the concentrations of lipid hydroperoxides (LOOH) were determined in intestinal biopsies, while in the peripheral blood, MnSOD activity was not measured, due to the methodological obstacles. CuZnSOD activity in the blood varied significantly between the analyzed groups. Marsh 3a and Marsh 3b had increased CuZnSOD activity comparing to the Marsh 0 (P < 0.05). LOOH concentration also varied significantly. LOOH level was higher in the blood of Marsh 3a (P < 0.001) and Marsh 3b (P < 0.05), than in Marsh 0. In the biopsy samples, MnSOD activity and LOOH concentration showed significant differences between the groups, while no significant difference was found for CuZnSOD activity. In comparison to Marsh 0, MnSOD activity was significantly elevated in Marsh 3a (P < 0.01). Significant increase in LOOH concentration was found in Marsh 3a (P < 0.001) and Marsh 3b (P < 0.01), comparing to Marsh 0. In addition, Marsh 3a group had higher LOOH concentration than Marsh 1+2. Relative MnSOD and CuZnSOD protein level in the peripheral blood and intestinal mucosa did not vary significantly between the analyzed groups. Positive correlations were found between the severity of mucosal lesion and CuZnSOD activity (P < 0.001), as well as LOOH concentration (P < 0.001) in the peripheral blood. Similar correlations were found also in intestinal mucosa: MnSOD: P < 0.05; CuZnSOD: P < 0.05; LOOH: P < 0.001. Our results show that oxidant/antioxidant balance is disturbed in CD patients with mucosal lesions. An increase in SOD activity as a consequence of oxidant pressure is not enough to maintain the normal level of free radicals, which leads to enhanced lipid peroxidation. These processes persist even in some patients on a long-term GFD.

Increased Activity of Hippocampal Antioxidant Enzymes as an Important Adaptive Phenomenon of the Antioxidant Defense System in Chronically Stressed Rats

Abstract This study examined the effects of chronic restraint stress (CRS: 2 hours × 14 days) on gene expression of three antioxidant enzymes, copper, zinc superoxide dismutase (SOD 1), manganese superoxide dismutase (SOD 2) and catalase (CAT) in the rat hippocampus. Also, we examined changes in the activities of SOD 1, SOD 2 and CAT in the hippocampus of chronically stressed rats. Investigated parameters were quantifi ed by using real-time RT-PCR, Western blot analysis and assay of enzymatic activity. We found that CRS did not change mRNA and protein levels of SOD 1 and CAT, but increased mRNA and protein levels of SOD 2. However, CRS treatment increased the enzyme activities of SOD 1, SOD 2 and CAT. Our fi ndings indicate that the increased activity of antioxidant enzymes (SOD 1, SOD 2 and CAT) in the hippocampus may be an important adaptive phenomenon of the antioxidant defense system in chronically stressed rats.