The impact of environmental and behavioural cofactors on the development of cervical disorders in HR-HPV-infected women in Serbia.

Persistent infection with one or more highly oncogenic human papillomaviruses (HPVs) or high-risk-HPV (HR-HPV) is necessary but not a sufficient aetiological agent for the development of cervical neoplasia. A number of viral, host, environmental and behavioural factors are suggested to be associated with the progression of cervical disorder. This study aimed to evaluate the impact of environmental and behavioural cofactors on the development of cervical disorders in HR-HPV-infected women in Serbia. A total of 541 women have been tested by PCR for the presence of HPV on the cervix. HPV genotypes were determined by direct DNA sequencing. Women identified as HR-HPV-positive were further classified into four subgroups according to their cytological status. All relevant information about demographical and behavioural factors was obtained by interviewer-based questionnaire. A number of analytical and descriptive statistical methods were used for processing the data. The cofactors found to be of significance for the progression of cervical disease were older age, body mass index >25, lower educational level, long-term smoking, previous genital infections and cervical interventions. On the other hand, condom use was found to have a protective role. Information about these cofactors might be very important for the development of more efficient cancer prevention programmes and promotion of anti-HPV vaccination.

Levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by Epstein-Barr virus.

AIM: To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)] and bone resorption regulators [receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)] compared to EBV-negative periapical lesions and healthy pulp tissues. METHODOLOGY: The experimental group consisted of 30 EBV-positive and 30 EBV-negative periapical lesions collected in conjunction with apicoectomy. The pulp tissues of 20 impacted third molars were used as healthy controls. The qualitative and quantitative analysis of EBV was performed by nested and real-time polymerase chain reaction (PCR), respectively. The levels of RANKL and OPG were analysed by reverse transcriptase real-time PCR. The levels of 8-OHdG and GSSG were determined by enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U-test and Spearman's correlation were used for statistical analysis. RESULTS: The levels of RANKL, OPG, 8-OHdG and GSSG were significantly higher in apical periodontitis lesions compared to healthy pulp controls (P = 0.001, P < 0.001, P < 0.001 and P < 0.05, respectively). RANKL and OPG mRNA expression was significantly higher in EBV-positive compared to EBV-negative periapical lesions (P < 0.05). There was no significant correlation between EBV copy numbers and levels of RANKL, OPG, 8OH-dG and GSSG in apical periodontitis. CONCLUSION: Levels of bone resorption regulators and oxidative stress biomarkers were increased in apical periodontitis compared to healthy pulp tissues. EBV-positive periapical lesions exhibited higher levels of RANKL and OPG compared to EBV-negative periapical lesions. EBV may contribute to progression of apical periodontitis via enhanced production of bone resorption regulators.

Herpesviruses viral loads and levels of proinflammatory cytokines in apical periodontitis.

OBJECTIVES: This study aimed to analyse Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of TNF-α, IL-1ß and IL-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines. MATERIALS AND METHODS: A total of 100 samples of apical periodontitis were subjected to HCMV and EBV copy numbers analysis by nested polymerase chain reaction (PCR) and TaqMan real-time PCR. The concentrations of TNF-α, IL-1ß and IL-6 were determined by ELISA method. SPSS software was used for statistical analysis. RESULTS: There were no significant differences in the occurrence of EBV and HCMV between symptomatic and asymptomatic periapical lesions (p = .686, p = .879, respectively). Only 12 of 74 EBV (16.2%) and four of 54 HCMV (13.5%) nested PCR-positive samples showed increased viral copy numbers above the limit of 125 copies/ml. There was no significant correlation between the levels of analysed proinflammatory cytokines and herpesviral copy numbers in our sample. CONCLUSION: The observed low viral loads point to a relatively rare occurrence of active EBV and HCMV infection in our sample. Latent herpesviral infection does not enhance the production of investigated proinflammatory cytokines.

Neutron skin of (208)pb from coherent pion photoproduction.

Information on the size and shape of the neutron skin on (208)Pb is extracted from coherent pion photoproduction cross sections measured using the Crystal Ball detector together with the Glasgow tagger at the MAMI electron beam facility. On exploitation of an interpolated fit of a theoretical model to the measured cross sections, the half-height radius and diffuseness of the neutron distribution are found to be c(n)=6.70±0.03(stat.) fm and a(n)=0.55±0.01(stat.)(-0.03)(+0.02)(sys.) fm, respectively, corresponding to a neutron skin thickness Δr(np)=0.15±0.03(stat.)(-0.03)(+0.01)(sys.) fm. The results give the first successful extraction of a neutron skin thickness with an electromagnetic probe and indicate that the skin of (208)Pb has a halo character. The measurement provides valuable new constraints on both the structure of nuclei and the equation of state for neutron-rich matter.

Carbendazim combined with imazalil or cypermethrin potentiate DNA damage in hepatocytes of mice.

Traces of pesticides imazalil, cypermethrin and carbendazim are detected in plants used for human consumption. To explore whether their application in oral combinations will induce DNA breaks in hepatocytes, a subchronic in vivo experiment was performed in Swiss mice. Doses of 10 mg kg(-1) of imazalil (im) and cypermethrin (cy), and 20 mg kg(-1) of carbendazim (car) and their combinations (im, 10 mg kg(-1) + cy, 10 mg kg(-1); im, 10 mg kg(-1) + car, 20 mg kg(-1); car, 20 mg kg(-1) + cy, 10 mg kg(-1)) were applied daily for 28 days. Afterward, DNA damage in hepatocytes was evaluated by comet assay. Individually, imazalil and cypermethrin damaged DNA at alkali-labile sites, while the tail moment (TM) of carbendazim alone was similar to control but with higher tail length. In combination with carbendazim clastogen, properties of imazalils and cypermethrins were potentiated compared to all other treatments and control. There were pronounced sex differences in pattern of fragmentation between treated groups. Higher long tail nuclei (LTN) in females indicate that certain cells in females were especially prone to total nucleus disintegration. Due to synergistic effects, low environmentally present concentrations of imazalil and cypermethrin in food, and especially their mixtures with carbendazim have genotoxic potential that could be particularly dangerous over prolonged exposure in mammalian organism.

Changing trends in mortality of thyroid cancer in Belgrade population.

PURPOSE: Thyroid cancer patients have favorable prognosis. The aim of this study was to analyze changing trends in mortality of thyroid cancer in Belgrade, during the period between 1987 and 2006. METHODS: Mortality data were obtained from the Belgrade Office of Statistics. Mortality rates per 100,000 inhabitants were standardized according to the Segi's world population. Regression analysis was used to estimate the thyroid cancer mortality trend for the period 1987-2006. RESULTS: The average percent of deaths due to thyroid cancer among all deaths was almost 2-fold higher in females (0.11%) than in males (0.6%), as well as among deaths due to all malignancies (females 0.54% and males 0.27%). During this 20-year period, the average standardized mortality rate was 1.5 times higher in females (0.74 per 100.000) than in males (0.51 per 100.000). In the observed period, the mortality rates for thyroid cancer were increased (+0.40%) in women and decreased (-0.42%) in men. In particular, in the 60-69 years age group in males, a significant trend for mortality decrease of 3.5%/year was detected. CONCLUSION: Belgrade is classified in the regions with low risk of dying due to thyroid malignancies. The increasing trend of thyroid cancer mortality in females during the examined period calls for improvement of methods for early detection of disease and differential diagnosis of thyroid nodules, so that surgical treatment of thyroid cancer could be performed at a stage when it is not life threatening.

The quality of life of patients after a lumbar microdiscectomy: a four-year monitoring study.

INTRODUCTION/AIM: Health-conditioned quality of patients' life is equally a result of their subjective perception of the disease and their objective condition. The aim of this paper is to evaluate the quality of life of surgically treated lumbar radiculopathy patients by using a generic and a lumbar disease-specific questionnaire. METHODOLOGY: 50 patients were evaluated (average age: 44.9 years; 52 male and 48 female). Two questionnaires were used for this purpose: the SF36 generic questionnaire, measuring eight quality of life domains divided into two sub-domains (overall physical and overall mental health), and the NASS LBP lumbar disease-specific questionnaire measuring four domains (pain and disability, motor and sensory neurogenic symptoms, expectations from the treatment and satisfaction with it). The results of the physical domain (SF36-PHYS) are low at the beginning of monitoring (25.7); they increase over the following 6 months (46.4) and drop insignificantly after 4 years (45.9). The mental health value (40.4) remained unchanged as compared to that of the general population. Values of the physical functioning domain reach that of the general population (80.0) after 6 months. Neurogenic symptoms domain results (NASS LBP-NS) do not correlate with other scales and domains. The conclusion is that the quality of life of patients after a lumbar microdiscectomy deteriorates significantly from a physical point of view immediately after it. It normalizes over the following 6 months, though a certain degree of physical damage still remains. Mental health alteration is not specific for lumbar radiculopathy. The neurogenic symptoms domain is the least improved dimension of their quality of life: it is very specific and to be evaluated with a special test set.

DNA damage and repair after exposure to sevoflurane in vivo, evaluated in Swiss albino mice by the alkaline comet assay and micronucleus test.

The relationship between DNA damage and repair of peripheral blood leukocytes, liver, kidney and brain cells was investigated in Swiss albino mice (Mus musculus L.) after exposure to sevoflurane (2.4 vol% for 2 h daily, for 3 days). Genetic damage of mouse cells was investigated by the comet assay and micronucleus test. To perform the comet assay, mice were divided into a control group and 4 groups of exposed mice sacrificed on day 3 of the experiment, at 0, 2, 6 or 24 h after the last exposure to sevoflurane. Mean tail length (TL), tail moment (TM), and tail intensity (TI) values were significantly higher in exposed mice (all examined organs) than in the control group. Significant DNA damage immediately after exposure to sevoflurane was observed in leukocytes. Damage induction in the liver, kidney, and brain occurred 6 h later than in leukocytes, as expected according to the toxicokinetics of the drug, where blood is the first compartment to absorb sevoflurane. However, none of the tested tissues revealed signs of repair until 24 h after the exposure. To distinguish the unrepaired genome damage in vivo, the micronucleus test was applied. Number of micronuclei in reticulocytes showed a statistically significant increase, as compared with the control group at all observed times after the treatment.

Beam-helicity asymmetries in double-pion photoproduction off the proton.

Beam-helicity asymmetries have been measured at the MAMI accelerator in Mainz in the three isospin channels gamma[over -->]p-->pi(+)pi(0)n, gamma[over -->]p-->pi(0)pi(0)p, and gamma[over -->]p-->pi(+)pi(-)p. The circularly polarized photons, produced from bremsstrahlung of longitudinally polarized electrons, were tagged with the Glasgow magnetic spectrometer. Charged pions and the decay photons of pi(0) mesons were detected in a 4pi electromagnetic calorimeter which combined the Crystal Ball detector with the TAPS detector. The precisely measured asymmetries are very sensitive to details of the production processes and are thus key observables in the modeling of the reaction dynamics.

Perfect angiographic patency of the arterial coronary-coronary conduit five years following surgery.

Five years ago, the left internal thoracic artery free segment was used as a coronary-coronary bypass over a single, distal lesion of the large left anterior descending coronary artery in a patient with triple vessel disease. The patient has recently been readmitted, complaining of chest discomfort. Although he was scheduled for percutaneous coronary intervention due to disease progression on the circumflex coronary artery, the perfect angiographic patency of the arterial coronary-coronary conduit has been confirmed.

[Cardiac surgery in patients with heparin-induced thrombocytopenia (HIT II)].

Heparin-induced thrombocytopenia (HIT) might be life-threatening in patients undergoing open heart surgery, due to thromboembolic events, thrombocytopenia and bleeding. If cardiac surgery with cardiopulmonary bypass (CPB) is necessary, anticoagulation therapy will be based on usage of danaparoid or direct thrombin inhibitors. Female patient was switched from per oral anticoagulant therapy to low molecular heparin therapy preparing for reredo mitral valve replacement due to endocarditis and artificial valve thrombosis. In next 10 days, thrombocytopenia was obvious (Tr 302,000 mm3 to 11,000 mm3) , and diagnoses of HIT were done. Anticoagulant therapy was continued with danaparoid, 750 IU/12 h sc. During the surgery, reredo mitral valve replacement and aortocoronary bypass on anterior descending coronary artery, blood salvage technique with rhirudin (intravenous bolus 0.4 mg/kg, in CPB prajming solution 0.4 mg/kg and continuous infusion during CPB 0.15 mg/kg/h) during cardiopulmonary bypass was used. Active coagulation time and +++ were monitored, without any sign of micro thrombosis in circuit. Postoperatively, per oral anticoagulation therapy was initiated with prolonged postoperative treatment due to basic disease, endocarditis. Patient was discharged from hospital on 21st postoperative day without any complication.

Telmisartan in daily clinical practice: factors affecting efficacy in treatment of primary arterial hypertension.

BACKGROUND: Telmisartan provides effective treatment of hypertension in a broad spectrum of patients. AIMS: To evaluate factors affecting the efficacy of telmisartan in daily clinical practice. SETTING AND DESIGN: Prospective practice-based 12-week uncontrolled cohort study. MATERIALS AND METHODS: Consecutive incident/prevalent outpatients with mild to moderate essential hypertension were started on telmisartan 40 mg/day with optional up-titration to 80 mg/day in order to achieve seated systolic (SSBP) and diastolic (SDBP) blood pressure < 140/90 mm Hg. Intent-to-treat (ITT, N=282) and per protocol (PP, N=275) efficacy assessment was based on SSBP/SDBP reduction and delivered doses. RESULTS: SSBP/SDBP decreased (165.2+/-13.1 / 98.3+/-6.7 mm Hg to 137.9+/-13.2 / 82.6+/-7.3 mm Hg), whilst telmisartan was up-titrated in 40.5% of patients during the study. Multivariate (practically identical ITT and PP) analysis indicated poorer response in obese vs. non-obese patients: lesser SDBP reduction (by around 2.2-2.3 mm Hg, P < 0.05) with higher odds of dose up-titration (odds ratio, OR around 1.90, P < 0.05); and better response in: a) patients started on telmisartan monotherapy than when added to a preexisting treatment: greater SSBP/SDBP reduction (by around 4.0 and 3.0 mm Hg, respectively, P < 0.05) with comparable odds of up-titration; b) diabetics vs. non-diabetics: greater SDBP reduction (by around 3.6-3.7 mm Hg, P < 0.05) with comparable odds of up-titration; c) men vs. women: slightly greater SDBP reduction (by around 1.2 mm Hg, 0.05 P < 0.1) with lower odds of up-titration (OR around 0.51, P < 0.05). CONCLUSION: Previous unsuccessful treatment, obesity, diabetes and gender should be considered in order to optimize the use of telmisartan for mild to moderate essential hypertension in daily clinical practice.

[Correlation between results of PCR and specific serological tests in diagnosis of Epstein-Barr virus in patients with mononucleosis syndrome].

Routine laboratory diagnosis of infectious mononucleosis is based on EBV serological testing, but due to problems in interpretation of results, molecular methods, especially PCR, are often necessary. The aim of the present study was to investigate correlation between results of PCR and specific serological tests in diagnosis of Epstein-Barr virus in patients with mononucleosis syndrome. The study comprised 68 patients with mononucleosis syndrome. Their blood samples were tested using ELISA for detection of 4 EBV specific antibodies (anti-VCA IgM and IgG, anti-EA-D IgG and anti-EBNA-1 IgG) and PCR for detection of EBV DNA. According to results of serology 42 patients had acute primary infection, 2 reactivation, 1 chronic active infection, 19 past infection, and 4 have been EBV seronegative. EBV DNA was detected in 17 patients (25%) and all of them were serologically defined as acutely infected. PCR was useful for resolving unclear serology results. Specific serology is the first step in diagnosis of IM, but PCR may serve as a useful additional diagnostic tool for clarifying serological dilemmas, reaching final diagnosis and defining status of the infection.

Incoherent neutral pion photoproduction on 12C.

We present the first detailed measurement of incoherent photoproduction of neutral pions to a discrete state of a residual nucleus. The 12C(gamma,pi(0))(12)C*(4.4 MeV) reaction has been studied with the Glasgow photon tagger at MAMI employing a new technique which uses the large solid angle Crystal Ball detector both as a pi(0) spectrometer and to detect decay photons from the excited residual nucleus. The technique has potential applications to a broad range of future nuclear measurements with the Crystal Ball and similar detector systems elsewhere. Such data are sensitive to the propagation of the Delta in the nuclear medium and will give the first information on matter transition form factors from measurements with an electromagnetic probe. The incoherent cross sections are compared to two theoretical predictions including a Delta-hole model.

Evaluation of DNA damage in vivo induced by combined application of cisplatin and sevoflurane.

BACKGROUND AND OBJECTIVE: The influence of the combined application of cisplatin and sevoflurane on a variety of cell types of healthy mice or mice bearing Ehrlich ascites tumour has been investigated in an in vivo study. METHODS: The alkaline comet assay method was carried out on peripheral blood leucocytes, brain, liver, kidney and tumour cells of healthy mice or mice bearing Ehrlich ascites tumour. Groups of mice were treated intraperitoneally with cisplatin, exposed to sevoflurane or by combined treatment of sevoflurane after treatment with cisplatin for 3 consecutive days. RESULTS: The in vivo exposure to sevoflurane induced genotoxicity to all assayed cells. A strong synergistic genotoxic effect to peripheral blood leucocytes, liver and kidney cells was found in mice receiving both cisplatin and sevoflurane. In contrast, a decrease of the comet tail lengths of brain cells in the combined treatments was found as compared to cisplatin alone in both healthy (P < 0.001) and Ehrlich ascites tumour-bearing mice (P < 0.05), respectively. In addition, Ehrlich ascites tumour cells of mice treated with combined treatments showed a decrease in tail lengths (P < 0.001). These findings indicate an antagonistic effect of combined treatments. CONCLUSION: Treatment of mice with cisplatin and sevoflurane induced genotoxic effect in peripheral blood leucocytes, liver, kidney, brain and Ehrlich ascites tumour cells; synergistic effect of combined treatments was expressed in all cells but brain and Ehrlich ascites tumour cells.

Radioprotective effects of propolis and quercetin in gamma-irradiated mice evaluated by the alkaline comet assay.

The radioprotective effects of ethanolic extract of propolis (EEP) and quercetin on the white blood cells of the whole-body irradiated CBA mice were investigated. Irradiation was performed using a gamma-ray source ((60)Co), and absorbed dose was 9 Gy. The efficiency of test components was evaluated when given intraperitoneally (ip) at a dose of 100 mg kg(-1) for 3 consecutive days before and/or after irradiation. Moreover, possible genotoxic effects of test components were also assessed on non-irradiated animals. For each experimental group leukocyte count was determined and the primary DNA damage in leukocytes was assessed using the alkaline comet assay. The higher efficiency of EEP and quercetin was observed when given preventively. The results suggest that propolis and quercetin given to mice before irradiation protect their white blood cells from lethal effects of irradiation and diminish primary DNA damage as confirmed by the alkaline comet assay. Positive results obtained on gamma-irradiated mice given EEP and quercetin, complementary with our earlier observations on survival of irradiated mice, indicate that these compounds could be considered effective non-toxic radioprotectors. The exact mechanisms of radioprotection by these compounds and their effects on DNA repair processes are still to be elucidated.

Enhanced antitumor activity of irinotecan combined with propolis and its polyphenolic compounds on Ehrlich ascites tumor in mice.

The effects of the anticancer drug irinotecan combined with ethanolic extract of propolis (EEP), a water-soluble derivate of propolis (WSDP), quercetin and naringin on the growth of Ehrlich ascites tumor (EAT) and the life span of tumor-bearing Swiss albino mice were studied. Test components were given to mice intraperitoneally (i.p.) at doses of 100mg kg(-1) for three consecutive days before the i.p. injection of EAT cells (1x10(6)). Irinotecan was administered i.p. at dose of 50mg kg(-1) on days 1, 13, and 19 after tumor cell inoculation. The results clearly demonstrate the synergistic action of irinotecan and EEP on survival time. These results suggest that clinical trials using a propolis preparation EEP combined with irinotecan may be beneficial in maximizing antitumor activity and minimizing post-chemotherapeutic reactions to the cytostatic drug.

Reduced quantity and hydrogen-peroxide production of vaginal lactobacilli in HIV positive women.

It has been suggested that vaginal lactobacilli may influence heterosexual transmission of HIV infection. The aim of this study was to compare the vaginal flora on Gram's stained and isolation rate, quantity and H2O2 production of lactobacilli between HIV positive and HIV negative women. Although, the prevalence of abnormal vaginal flora was increased in HIV infected women, there was no significant difference in isolation rate of vaginal lactobacilli between the two groups (71.87 vs. 83.33%; P>0.05). However, the results of this study showed significantly reduced quantity of lactobacilli in HIV infected women (P<0.01). In particular, the prevalence of H2O2-producing lactobacilli was lower in HIV positive as compared to HIV negative women (80 vs. 56.52%), with borderline significance (P=0.057). Taken together, our findings showed altered vaginal microflora with reduced quantity and hydrogen-peroxide production of vaginal lactobacilli in HIV positive women, but further studies are needed to assess its actual significance and potential benefit from the use of probiotic therapy.

Transaortic double valve replacement in difficult mitral valve exposure.

Adequate open exposure of the mitral valve is necessary to accomplish reconstruction or replacement of the diseased mitral valve apparatus. The technique employed by most cardiac surgeons for mitral valve access involves median sternotomy and vertical left atriotomy posterior to the interatrial sulcus. However, certain conditions can somethimes make this approach very difficult. Different approaches are discussed with particular emphasis on our case in which the transaortic double valve replacement have been performed.

Influence of light intensity from different curing units upon composite temperature rise.

The unavoidable consequence of composite resin photopolymerization is temperature rise in tooth tissue. The temperature rise depends not only on the illumination time, but also on light intensity, distance of light guide tip from composite resin surface, composition and shade of composite resin and composite thickness. The most commonly used units for polymerization today are halogen curing units, which emit a large spectrum of wavelengths. A proportion of the spectrum has no influence on degree of conversion and therefore causes unnecessary temperature rise. Units based on light source - blue light emitting diodes (LED), as an alternative for halogen curing units, have been introduced in clinical practice. The aim of this study was to show the influence of the light intensity of curing units Elipar Trilight, Astralis 7 and Lux-o-Max unit on temperature rise in composite resin sample of Tetric Ceram. The temperature was measurement with Metex M-3850 D multimeter with the tip of temperature probe put into unpolymerized composite resin sample 1 mm depth. The highest temperature rise was recorded with standard curing mode for Elipar Trilight halogen curing unit (13.3 +/- 1.21 degrees C after 40 s illumination), while the lowest temperature rise was recorded for the Lux-o-Max unit based on LED technology (5.2 +/- 1.92 degrees C after 40 s illumination).