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Kidney transplantation is the gold-standard therapy for end-stage renal disease. However, in the early postoperative period following allograft kidney transplantation, insufficient graft function presents a diagnostic challenge to clinicians. Ischemic damage to the graft and/or an early autoimmune rejection may cause a decrease in function. Ischemic damage is a benign and transient condition, while acute immune rejection requires immediate therapy. A kidney graft ultrasound may produce a false negative result, and graft biopsy is invasive and slow to return results. Serum lactate dehydrogenase (LDH) is under examination as a possible tool for differential diagnosis between ischemic damage and immune rejection. Herein, we analyze the continuous lab results of four patients in the early post-transplantation period, showing patterns correlating with different clinical outcomes and prognoses. In our experience, a persistent elevated LDH accompanies ischemic damage. Immune rejection was, however, associated with a decrease in LDH. Hemodialysis was not a confounding factor, while packed red blood cell transfusion caused severe diagnostic problems.

The use of genetically modified, glyphosate-resistant crops has led to the widespread application of glyphosate-based herbicides (GBHs), making them one of the most widely used herbicide formulations on the market. To enhance the efficacy of the active ingredient, GBHs used in practice often contain other ingredients marked as inert "adjuvants" or "co-formulants", the toxic properties of which are poorly understood. The objective of this study was to compare the cytotoxic effects of pure glyphosate, three GBHs (Roundup Mega, Fozat 480 and Glyfos) and two co-formulants commonly used in GBHs as assessed via CCK-8 assay, and the extent of their potential oxidative damage as assessed via superoxide dismutase (SOD) assay, in order to reveal the role of adjuvants in the toxicity of the formulations. Our results showed that glyphosate alone did not significantly affect cell viability. In contrast, GBHs and adjuvants induced a pronounced cytotoxic effect from a concentration of 100 μM. SOD activity of cells treated with GBHs or adjuvants was significantly lower compared to cells treated with glyphosate alone. This suggests that the adjuvants in GBHs are responsible for the cytotoxic effects of the formulations through the induction of oxidative stress.

Exposure to pesticides in Arab countries is a significant public health concern due to extensive agricultural activity and pesticide use. This systematic review aimed to evaluate the genotoxic effects of agricultural pesticide exposure in the region, identify research gaps, and assess methodological limitations. Following the PRISMA guidelines, a comprehensive search yielded five relevant studies conducted in Egypt, Syria, and Jordan. Various genotoxicity assays were employed, revealing a higher level of DNA damage in exposed compared to non-exposed individuals. Farmers exposed to pesticides exhibited a significantly higher occurrence of chromosomal translocation (t(14;18)), micronuclei, and chromosomal aberrations. However, only two studies assessed cytotoxicity indirectly. The studies predominantly focused on male participants, with variations in sample size and pesticide types. The lack of detailed exposure data necessitates cautious interpretation. This review underscores the need for further research on the genotoxicity of occupational pesticide exposure in the Middle East. Future studies should adopt robust study designs, collect biological and environmental samples, conduct repeated sampling, analyze seasonal variations, and encompass diverse study sites associated with specific crop groups.

Climate change has been associated with both latitudinal and elevational shifts in species' ranges. The extent, however, to which climate change has driven recent range shifts alongside other putative drivers remains uncertain. Here, we use the changing distributions of 378 European breeding bird species over 30 years to explore the putative drivers of recent range dynamics, considering the effects of climate, land cover, other environmental variables, and species' traits on the probability of local colonisation and extinction. On average, species shifted their ranges by 2.4 km/year. These shifts, however, were significantly different from expectations due to changing climate and land cover. We found that local colonisation and extinction events were influenced primarily by initial climate conditions and by species' range traits. By contrast, changes in climate suitability over the period were less important. This highlights the limitations of using only climate and land cover when projecting future changes in species' ranges and emphasises the need for integrative, multi-predictor approaches for more robust forecasting., (© 2023. The Author(s).)

Introduction: In addition to standard highly active antiretroviral therapy protocols, complementary therapies using natural compounds are widely used by human immunodeficiency virus (HIV)-infected human patients. One such compound is the fermented wheat germ extract (FWGE), named Avemar., Materials and Methods: In this study, we investigate the effects of Avemar in a feline-acquired immunodeficiency syndrome model. MBM lymphoid cells were acutely infected by the American feline immunodeficiency virus (FIV)-Petaluma (FIV-Pet) and the European FIV Pisa-M2 strains. FL-4 lymphoid cells, continuously producing FIV-Pet, served as a model for chronic infection. Crandell Rees feline kidney (CRFK) cells were infected by either FIV-Pet or feline adenovirus (FeAdV) as a model for transactivation and opportunistic viral infection. Cell cultures were treated pre- and post-infection with serial dilutions of spray-dried FWGE (Avemar pulvis, AP), a standardized active ingredient in commercial Avemar products. Residual FIV and FeAdV infectivity was quantified., Results: In a concentration-dependent manner, AP inhibited replication of FIV strains in MBM and CRFK cells by 3-5 log. Low AP concentration prevented FIV-Pet release from FL-4 cells. Higher concentrations destroyed virus-producing cells with cytopathic effects resembling apoptosis. AP strongly inhibited FeAdV production inside CRFK cells but not in HeLa cells. Adenovirus particles are then released via the disintegration of CRFK cells., Discussion: This report is the first to describe the antiviral effects of Avemar. Further studies are required to confirm its in vitro and in vivo effects and to investigate the potential for its use as a nutraceutical in FIV-infected felines or HIV-infected humans., Conclusion: Avemar, as a single nutraceutical, inhibits FIV replication and destroys retrovirus carrier cells. An important conclusion is that prolonged Avemar treatment might reduce the number of retrovirus-producing cells in the host., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Species' range shifts and local extinctions caused by climate change lead to community composition changes. At large spatial scales, ecological barriers, such as biome boundaries, coastlines, and elevation, can influence a community's ability to shift in response to climate change. Yet, ecological barriers are rarely considered in climate change studies, potentially hindering predictions of biodiversity shifts. We used data from two consecutive European breeding bird atlases to calculate the geographic distance and direction between communities in the 1980s and their compositional best match in the 2010s and modeled their response to barriers. The ecological barriers affected both the distance and direction of bird community composition shifts, with coastlines and elevation having the strongest influence. Our results underscore the relevance of combining ecological barriers and community shift projections for identifying the forces hindering community adjustments under global change. Notably, due to (macro)ecological barriers, communities are not able to track their climatic niches, which may lead to drastic changes, and potential losses, in community compositions in the future.

Background: The gradual increase in the global population has led to the rising demand for agricultural products worldwide. This required the introduction of environment- and public health-friendly advanced technologies for plant protection to guard yields from pest destruction in a sustainable way. Encapsulation technology is a promising procedure to increase the effectiveness of pesticide active ingredients while reducing human exposure and environmental impact. Despite the presumed favorable properties of encapsulated pesticide formulations on human health, it is necessary to systematically assess whether they are less harmful to human health than conventional pesticide products., Objectives: We aim to systematically review the literature to answer the question of whether micro- or nano-encapsulated pesticide formulations exert different degrees of toxicity than their conventional (not-encapsulated) counterparts in in vivo animal and in vitro (human, animal, and bacterial cell) non-target models. The answer is important to estimate the possible differences in the toxicological hazards of the two different types of pesticide formulations. Because our extracted data will come from different models, we also aim to perform subgroup analyses to investigate how toxicity varies across different models. A pooled toxicity effect estimate will also be performed by meta-analysis when appropriate., Methods: The systematic review will follow the guidelines developed by the National Toxicology Program's Office of Health Assessment and Translation (NTP/OHAT). The protocol adheres to the Preferred Reporting Items for Systematic Reviews and meta-analyses Protocol (PRISMA-P) statement. PubMed (NLM), Scopus (Elsevier), Web of Science Core Collection (Clarivate), Embase (Elsevier), and Agricola (EBSCOhost) electronic databases will be comprehensively searched in September 2022 to identify eligible studies using multiple search terms of "pesticide", "encapsulation" and "toxicity" along with their synonyms and other words that are semantically related. The reference lists of all eligible articles and retrieved reviews will be manually screened to identify additional relevant papers., Eligibility Criteria: We will include peer-reviewed experimental (non-target in vivo animal model and in vitro human, animal, and bacterial cell cultures) studies published as full-text articles in English language that simultaneously investigate the effect of any micro- or nano-encapsulated pesticide formulation, applied in all ranges of concentrations, duration, and routes of exposure, and its corresponding active ingredient(s) or its conventional non-encapsulated product formulation(s) used in the same ranges of concentrations, duration, and routes of exposure on the same pathophysiological outcome. We will exclude studies that examine pesticidal activity on target organisms, cultures of cells isolated from target organisms exposed in vivo or in vitro, and those using biological materials isolated from target organisms/cells., Study Appraisal and Synthesis: Studies identified by the search will be screened and managed according to the review inclusion and exclusion criteria in the Covidence systematic review tool by two reviewers, who will also blindly extract the data and assess the risk of bias of included studies. The OHAT risk of bias tool will be applied to evaluate the quality and risk of bias in the included studies. Study findings will be synthesized narratively by important features of the study populations, design, exposure, and endpoints. If findings make it possible, a meta-analysis will be performed on identified toxicity outcomes. To rate the certainty in the body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: In the circulatory system, the vessel branching angle may have hemodynamic consequences. We hypothesized that there is a hemodynamically optimal range for the renal artery's branching angle., Methods: Data on the posttransplant kinetics of estimated glomerular filtration rate (eGFR) were analyzed according to the donor and implant sides (right-to-right and left-to-right position; n = 46). The renal artery branching angle from the aorta of a randomly selected population was measured using an X-ray angiogram (n = 44). Computational fluid dynamics simulation was used to elucidate the hemodynamic effects of angulation., Results and Discussion: Renal transplant patients receiving a right donor kidney to the right side showed faster adaptation and higher eGFR values than those receiving a left donor kidney to the right side (eGFR: 65 ± 7 vs. 56 ± 6 mL/min/1.73 m2; p < 0.01). The average branching angle on the left side was 78° and that on the right side was 66°. Simulation results showed that the pressure, volume flow, and velocity were relatively constant between 58° and 88°, indicating that this range is optimal for the kidneys. The turbulent kinetic energy does not change significantly between 58° and 78°., Conclusion: The results suggest that there is an optimal range for the renal artery's branching angle from the aorta where hemodynamic vulnerability caused by the degree of angulation is the lowest, which should be considered during kidney transplantations., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Intensive pesticide use increased concern about the potential acute and chronic health effects of pesticides in general and among applicators in particular. This study aims to explore occupational and environmental pesticide exposure and health risks among pesticide applicators and residents. A community-based cross-sectional study was conducted involving 1,073 individuals. We examined the health effects potentially attributable to pesticide exposure using regression to estimate prevalence ratios (PR). A higher proportion of good knowledge of pesticides [75 vs. 14%; APR = 1.542 (1.358-1.752), p < 0.001] and a higher mean score of perceived health risk of pesticide use [4.21 vs. 3.90; APR = 1.079 (1.004-1.159), p < 0.05] were observed among applicators than residents. A significantly higher proportion of applicators experienced health effects presumably related to pesticide exposure among themselves (36%) than residents (16%), and a higher proportion of them used prescribed drugs in the past 12 months [51 vs. 32%; APR = 1.140 (1.003-1.295), p < 0.05]. Skin irritation, shortness of breath, cough, and dizziness were more likely reported by applicators than residents. Perceived toxicity of currently applied pesticide products, mix pesticides without gloves, regularly maintain and wash sprayer tank after application, occurrence of an incidental splash during mixing and application, and using home-based care after experiencing a symptom presumably due to pesticide exposure were significantly associated with health effects among applicators. Use of face mask and visiting health facility when experiencing a symptom presumably due to pesticide exposure were significantly positively correlated with attending training on the health risks and use of pesticides. A substantial proportion of applicators reported improper use of preventive measures and methods of pesticide waste disposal. These observations point out that applicators can face high health risks of occupational pesticide exposure in Ethiopia. Even trained applicators pursued poor preventive practices; hence, comprehensive practice-oriented in-depth training focusing on safety precautions and proper use of personal protective equipment, and provision of adequate pesticide waste disposal means are crucial interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tessema, Nagy and Ádám.)

Pesticides play a very important role for ensuring food security and economic growth but their use can cause harmful effects to human health and to the environment. The study aimed to investigate the level of knowledge, health risk perceptions, and experiences on the practice of pesticide use and management among extension officers in Ethiopia and plant doctors in Hungary. A questionnaire survey among 326 officers was conducted in the two study areas and data were analyzed by ordinal logistic regression. According to the findings, Hungarian officers had much better knowledge of pesticide products (92%), and less frequently experienced pesticide poisoning among applicators (7%) than the Ethiopians (66% and 41%, respectively). Hungarian officers perceived less health risk of pesticide use (AOR = 0.46, 95%, Cl: 0.27-0.80), were ten times more likely to deem the pesticide management system effective (AOR = 10.23, 95%, Cl: 5.68-18.46) and were nine times more likely to report that applicators used personal protective equipment (AOR = 8.95, 95%, Cl: 4.94-16.28). A significant proportion of officers from both countries reported inappropriate methods of pesticide residue disposal. These observations point out that the situation of pesticide use and knowledge and management of pesticide products is definitely better in Hungary; nevertheless, the issue continues to need more attention in both settings.

During intercontinental shipping, freight containers and other closed transport devices are applied. These closed spaces can be polluted with various harmful chemicals that may accumulate in poorly ventilated environments. The major pollutants are residues of pesticides used for fumigation as well as volatile organic compounds (VOCs) released from the goods. While handling cargos at logistics companies, workers can be exposed to these pollutants, frequently without adequate occupational health and safety precautions. A cross-sectional questionnaire survey was conducted among potentially exposed warehouse workers and office workers as controls at Hungarian logistics companies (1) to investigate the health effects of chemical pollutants occurring in closed spaces of transportation and storage and (2) to collect information about the knowledge of and attitude toward workplace chemical exposures as well as the occupational health and safety precautions applied. Pre-existing medical conditions did not show any significant difference between the working groups. Numbness or heaviness in the arms and legs (AOR = 3.99; 95% CI = 1.72-9.26) and dry cough (AOR = 2.32; 95% CI = 1.09-4.93) were significantly associated with working in closed environments of transportation and storage, while forgetfulness (AOR = 0.40; 95% CI = 0.18-0.87), sleep disturbances (AOR = 0.36; 95% CI = 0.17-0.78), and tiredness after waking up (AOR = 0.40; 95% CI = 0.20-0.79) were significantly associated with employment in office. Warehouse workers who completed specific workplace health and safety training had more detailed knowledge related to this workplace chemical issue (AOR = 8.18; 95% CI = 3.47-19.27), and they were significantly more likely to use certain preventive measures. Warehouse workers involved in handling cargos at logistics companies may be exposed to different chemical pollutants, and the related health risks remain unknown if the presence of these chemicals is not recognized. Applied occupational health and safety measures at logistics companies are not adequate enough to manage this chemical safety issue, which warrants awareness raising and the introduction of effective preventive strategies to protect workers' health at logistics companies.

Introduction: Hungary joined Eurotransplant International (ET) to improve the chance of transplantation for Hungarian patients and patient outcomes, including access and graft and patient survival. After 5 years of full membership, the evaluation of numbers and quality indicators is possible., Method: A comparison was made between 5 years prior to a preliminary cooperation agreement (2007-2011) and 5 years after full ET membership (2014-2018). During the 2 study periods, we analyzed numbers and circumstances of deceased organ donors, multiorgan donors, donated organs, and transplantations in Hungary and development of waiting lists along with international organ exchanges., Result: The number of actual organ donors increased by 22.09% (729 vs 890), an additional 823 organ removals represents an increase of 42.71% (1927 vs 2750). There were 46.51% more transplants managed in the selected periods (1561 vs 2287). The number of new patients on the waiting list increased (2305 vs 3247; 40.87%). The mean kidney mismatch number decreased from 3.21 to 2.96., Conclusion: Joining ET has been an effective and efficient in terms of increasing access to organs and the lives of patients on the Hungarian waiting list posttransplant. It is also a benefit for patients with special needs because the number of organ transplants is greater than the increased number of donors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glyphosate is the most commonly used herbicide around the world, which led to its accumulation in the environment and consequent ubiquitous human exposure. Glyphosate is marketed in numerous glyphosate-based herbicide formulations (GBHs) that include co-formulants to enhance herbicidal effect of the active ingredient, but are declared as inert substances. However, these other ingredients can have biologic activity on their own and may interact with the glyphosate in synergistic toxicity. In this study, we focused to compare the cytogenetic effect of the active ingredient glyphosate and three marketed GBHs (Roundup Mega, Fozat 480, and Glyfos) by investigating cytotoxicity with fluorescent co-labeling and WST-1 cell viability assay as well as genotoxicity with cytokinesis block micronucleus assay in isolated human mononuclear white blood cells. Glyphosate had no notable cytotoxic activity over the tested concentration range (0-10,000 μM), whereas all the selected GBHs induced significant cell death from 1,000 μM regardless of metabolic activation (S9). Micronucleus (MN) formation induced by glyphosate and its formulations at sub-cytotoxic concentrations (0-100 μM) exhibited a diverse pattern. Glyphosate caused statistically significant increase of MN frequency at the highest concentration (100 μM) after 20-h exposure. Contrarily, Roundup Mega exerted a significant genotoxic effect at 100 μM both after 4- and 20-h exposures; moreover, Glyfos and Fozat 480 also resulted in a statistically significant increase of MN frequency from the concentration of 10 μM after 4-h and 20-h treatment, respectively. The presence of S9 had no effect on MN formation induced by either glyphosate or GBHs. The differences observed in the cytotoxic and genotoxic pattern between the active principle and formulations confirm the previous concept that the presence of co-formulants in the formulations or the interaction of them with the active ingredient is responsible for the increased toxicity of herbicide products, and draw attention to the fact that GBHs are still currently in use, the toxicity of which rivals that of POEA-containing formulations (e.g., Glyfos) already banned in Europe. Hence, it is advisable to subject them to further comprehensive toxicological screening to assess the true health risks of exposed individuals, and to reconsider their free availability to any users., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nagy, Argaw Tessema, Szász, Smeirat, Al Rajo and Ádám.)

Wildlife conservation policies directed at common and widespread, but declining, species are difficult to design and implement effectively, as multiple environmental changes are likely to contribute to population declines. Conservation actions ultimately aim to influence demographic rates, but targeting actions towards feasible improvements in these is challenging in widespread species with ranges that encompass a wide range of environmental conditions. Across Europe, sharp declines in the abundance of migratory landbirds have driven international calls for action, but actions that could feasibly contribute to population recovery have yet to be identified. Targeted actions to improve conditions on poor-quality sites could be an effective approach, but only if local conditions consistently influence local demography and hence population trends. Using long-term measures of abundance and demography of breeding birds at survey sites across Europe, we show that co-occurring species with differing migration behaviours have similar directions of local population trends and magnitudes of productivity, but not survival rates. Targeted actions to boost local productivity within Europe, alongside large-scale (non-targeted) environmental protection across non-breeding ranges, could therefore help address the urgent need to halt migrant landbird declines. Such demographic routes to recovery are likely to be increasingly needed to address global wildlife declines.

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population-the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations. With that in mind, we investigated the applicability of data on selected obesity-related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population. Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity-related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG ( N = 1783) and HR ( N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates. Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation's (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPARγ on WC as a continuous outcome. Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).

Humans are exposed to complex chemical mixtures, such as pesticides. Although the need for the assessment of health and environmental hazards deriving from the interactions between various substances found in commercial pesticide formulations is becoming increasingly recognized, the approval of pesticide products is still mostly limited to determining the toxicity of the individual ingredients ignoring the possible combined effects in mixtures. The objective of this study was to systematically review the literature of in vitro and in vivo studies that simultaneously examine the toxicity of pesticide product formulations and their declared active ingredients to compare their toxicity to human health and to the environment. Two electronic databases were searched for studies that assessed the health effects of active pesticide ingredients and their product formulations. The literature search was performed with a combination of the following terms: "pesticide", "formulation", "commercial product", "commercial pesticide" and "health". After screening by predefined inclusion and exclusion criteria, quality and reliability assessment of eligible publications was conducted by use of the ToxRTool. Two investigators independently screened the identified publications and extracted results from eligible studies. Our search yielded 36 toxicity studies; 23 studies investigated herbicides, 15 examined insecticides and 4 focused on fungicides. Twenty-four studies reported increased toxicity of the product formulations versus their active ingredients, which, in most cases, were attributed to the presence of adjuvants in the formulations. A significant number (n = 10) of studies focused on the comparative testing of glyphosate and glyphosate-based herbicides, and six of them concluded that Roundup, the dominant product formulation of glyphosate, is more toxic than the active ingredient alone. We identified only 8 studies demonstrating reduced toxicity of product formulations in relation to the active ingredient that might be due to a potential antagonistic effect between the constituents. The results of this review demonstrate the inadequacy of current EU testing requirements for assessing the health hazards of pesticide product formulations based mainly on the evaluation of the individual ingredients and of at least one representative use and formulation. Ignoring the possible risks deriving from the interaction between the active and other ingredients of various commercial pesticide product formulations might result in the misinterpretation of its toxicological profile. At EU level efforts are currently made to address this issue. In this context, we recommend that all product formulations should be fully assessed during the authorization process., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Glyphosate is the most heavily applied active compound of agricultural pesticides. It is solely used in more than 750 different glyphosate-based herbicide formulations (GBHs) that also contain other substances, mostly presumed as inert by regulatory agencies. The toxicity of formulations is currently assessed substance by substance, neglecting possible combined effects in mixtures and many of the findings regarding the toxic effects of glyphosate and GBHs to human cells are inconsistent. This is the first study to investigate and compare the cyto- and genotoxic potential of the active ingredient glyphosate and GBHs in human mononuclear white blood (HMWB) cells. HMWB cells were treated for 4 h at 37 °C with increasing concentrations (1-1000 μM) of glyphosate alone and in three GBHs (Roundup Mega, Fozat 480 and Glyfos) to test cytotoxic effect with fluorescent colabelling and genotoxic effect with comet assay. In addition, each concentration was tested with and without metabolic activation using human liver S9 fraction. We found that glyphosate alone does not induce significant cytotoxicity and genotoxicity over the tested concentration range. Contrarily, GBHs induced statistically significant cell death from 250 μM (Roundup Mega and Glyfos) and 500 μM (Fozat 480), as well as statistically significant increase of DNA damage from 500 μM (Roundup Mega and Glyfos) and 750 μM (Fozat 480); however, the latter observation may not be explained by direct DNA injuries, rather due to the high level of cell death (>70%) exerted by the formulations. Metabolic activation significantly increased the DNA damage levels induced by Glyfos, but not of the other GBHs and of glyphosate. The differences observed in the toxic pattern of formulations and the active principle may be attributed to the higher cytotoxic activity of other ingredients in the formulations or to the interaction of them with the active ingredient glyphosate. Hence, further investigation of formulations is crucial for assessing the true health risks of occupational and environmental exposures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tacrolimus is an important part of immunosuppressive therapy after solid organ transplantation. The therapeutic range of the drug from the calcineurin inhibitor group is narrow. Adjustment of the blood concentration can be very complicated but to be able to avoid the occurrence of side effects or ineffective immunosuppression it is inevitable. This article summarizes the properties of tacrolimus pharmacokinetics, pharmacogenetics and pharmacodynamics. We will focus on individual variations of cytochrome enzymes. In the following part, a new method for screening high risk patients will be introduced. We will present the publications of the determination of the concentration/dose (C/D) ratio. By determining the C/D ratio, researchers identify fast and slow metabolizing patient groups. Fast metabolizers require higher doses in general and the occurrence of complications is also more frequent in this group. Long-term results are lagging behind the slow metabolizing group. The long-term results of renal transplantation nowadays contribute to the postoperative period and the later years rather than the surgery itself. It includes the proper management of previous illnesses (e.g., hypertension, diabetes, endocrinological problems), detection of complications (e.g., infections, malignancies), and the precise regulation of immunosuppressive therapy. Orv Hetil. 2019; 160(30): 1178-1183.

An adenovirus (AdV) has been isolated from the rectal swab of a domestic cat ( Felis catus ) and named feline adenovirus (FeAdV) isolate. It replicates and causes cytopathological effects in many human, feline, other mammalian cell lines that have both Coxsackie-adenovirus-receptor and integrins. Its antigens cross-react with anti-human adenovirus antibodies in immunofluorescence and immunocytochemistry assays. Electron microscopy revealed typical extracellular icosahedral particles and pseudo arrays inside cells. Sequence analysis of hexon and fiber genes indicates that this virus might belong to human adenovirus (HAdV) C species and might be a variant of type 1. In the fiber protein, three altered amino acids occur in the shaft; four altered residues are found in the knob region as compared to a European HAdV might be type 1 isolate (strain 1038, D11). One alteration affects amino acid 442 forming an RGS motif in an alanine rich region that might be an alternative way to bind integrins with subsequent internalization. Substitutions in the hexon sequence are silent. As compared to published HAdV sequences, the fiber is related to the original American prototype and recently described Taiwanese HAdV 1 isolates, but the hexon sequences are related to adenovirus isolates from France, Germany, Japan, and Taiwan. Serology carried out on FeAdV infected M426 cells indicates a prevalence of IgG in 80% of domestic cats in Delaware, United States. FeAdV isolate seems to be a recently recognized virus with possible pathogenic effects and, simultaneous human and feline infections are possible. Further molecular and biological characterization of this feline adenovirus isolate, as well as studies on both human and feline epidemiology and pathomechanisms, especially in endangered big cats, are warranted. FeAdV might have further practical advantages. Namely, it could be utilized in both human and feline AIDS research, developed into diagnostic tools, and gene therapy vectors in the near future.

The first kidney transplantation was performed in Hungary by András Németh in 1962. It was a living donor procedure. After many years of silence, organized cadaveric programs were established in Budapest (1973), Szeged (1979), Debrecen (1991), and Pécs (1993). The heart program was initiated by Professor Zoltán Szabó in 1992 and the liver transplant program by Professor Ferenc Perner in 1993. The pancreas transplantation program was started in Pécs in 1998 by Károly Kalmár-Nagy, followed another in Budapest by Robert Langer in 2004. The lung transplant program was started in cooperation with Vienna in 1996. This fruitful collaboration continues today, even though that the national Hungarian program was established by Ferenc Rényi-Vámos and Professor György Lang in 2015, as it is detailed in this special issue. As a framework, the Hungarian Society of Organ Transplantation was founded in 1997 to give a scientific background for the transplant professionals. The coordination and organ allocation from deceased donors is carried out in collaboration with Eurotransplant. Usually more than 200 potential cadaveric donors are reported yearly, and 168 actual donation after brain death (DBD) donors (17.17 pmp) were utilized in 2018. The multiorgan donor rate was 65.5% among all DBDs in 2018; 505 organs were donated for transplant purposes. To date, more than 10,000 organ transplantations have been performed. The living related kidney transplant program was established in all transplant centers, led by Budapest. In this paper the authors summarize the activity of the Hungarian transplant community and of the Society over the last few decades., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pencycuron, a phenylurea-type antifungal agent, is used in agriculture worldwide for inhibiting the growth of various fungal pathogens of crops. Pencycuron residues were found in vegetables, soil and drinking water. Accordingly, both occupational and consumer exposure can be expected and may be significant. However, human toxicity studies on its genotoxic, mutagenic or carcinogenic potential are lacking. Therefore, a collaborative study was performed in two laboratories to investigate whether pencycuron exposure can induce DNA damage. The genotoxic effect of 0-100 μg/ml pencycuron in in vitro cultures of human mononuclear white blood cells (MWBCs) and human hepatocytes (HepG2) was detected by cytokinesis-block micronucleus assay and comet assay. The combined results of the two labs showed a dose-dependent DNA damage detected by micronucleus frequency, which reached statistical significance at 100 μg/ml concentration after 21-h exposure in HepG2 cells (p = 0.048). Significant genotoxic effect could also be observed in the comet assay from 50 μg/ml concentration in MWBCs, and at 100 μg/ml concentration in HepG2 cells in one lab. Nevertheless, this finding was not confirmed by the other lab in HepG2 cells, where Fpg-dependent oxidative DNA damage could also not be detected. The results indicate that pencycuron may have DNA-damaging potential as well as point out inter-laboratory variability that calls for further studies to confirm the genotoxicity of this fungicide., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Antibody-mediated rejection (ABMR) is one of the factors affecting the long-term graft survival after kidney transplantation (KT). Two kidney transplant centres (University of Debrecen and University of Pécs) followed up their data of cadaveric KTs that had been performed between 2013 and 2017, and reviewed the literature. There were 454 KTs in the mentioned period, 18 cases (4%) were recognised as ABMRs. Biopsy has been performed in all cases. 22% were primary, and 78% retransplanted patients. The average age was 51.2 ± 6 years. ABMR occurred 15.4 ± 22.1 months after KT. Histology showed C4d positivity in 39% of the cases. The treatment was steroid bolus + intravenous immunoglobulin (IVIG) + plasma exchange (PE) in 16 cases, rituximab was additionally given in 5 cases. 47.4% of the patients are alive with a functioning graft, four (21%) died, and 31% of the patients had a graft loss due to ABMR. ABMR is a dangerous complication after KT. Diagnostic criteria has been unclear for years. Gold standard is the histology, however, accelerated ABMR may occur even in C4d negative cases. The exposed group includes young, retransplanted patients, having a preformed donor-specific antibody (DSA), and receiving a graft from an EC donor. The occurrence of de novo DSA and the kinetics of mean fluorescence intensity (MFI) of existing ones can be a signal for the risk of an ABMR. The effectiveness of rituximab is not proven, there is a lack of long-term controlled trials for new drugs. Our results of over 40% recovery is an extensively good result. Orv Hetil. 2018; 159(46): 1913-1929.

The authors present a case of a 67-year-old male patient, who previously had been diagnosed with a malignant liver tumor localized in segment II. He underwent bisegmentectomy (II and III) and partial IV segmentectomy. After the primary surgery jaundice developed, the level of bilirubin increased and after several imaging modalities reoperation was indicated. During the surgery a rare bile duct anatomy variant was found. The right hepatic duct joined the left duct in the parenchyma of the left lobe, and was ligated at the resection. As the liver hilum was not explored, the absence of the right duct was not discovered. Reconstruction of the biliary system was accomplished by a Roux-en-Y loop.

Introduction: The Acute Cystitis Symptom Score (ACSS) is a new self-reporting tool to evaluate the symptoms of uncomplicated acute cystitis (AC) in women. The linguistic and clinical validation process of the Hungarian version used in this study may serve as a guide for the validation of the ACSS in other languages., Material and Methods: In this prospective cohort study, women with AC (Patients) and those without (Controls) filled in the Hungarian ACSS version, during their visits to physician's office. Statistical analysis included ordinary descriptive values, calculation of reliability, validity, discriminative ability, responsiveness (sensitivity, specificity) and comparative analysis., Results: Thirty-one patients were recruited for validation along with 37 controls. Statistical analyses resulted in excellent values of internal consistency, discriminative ability and validity for diagnosis of AC. At the cut-off at a score of 6 in the 'typical' domain, positive and negative predictive values were 97% and 92%, sensitivity and specificity were 90% and 97%, respectively., Conclusions: The ACSS has demonstrated benefits for diagnosis and patient-reported outcome assessment. It is objective, fast, and cost-effective, and may help to easily confirm the accurate diagnosis of AC. Therefore, it may be especially important for clinical and epidemiological studies on AC in women.

Background: Before 2014 (the year of closure of the two largest needle exchange programs in Hungary, which halved the number of available syringes in the country despite increased injecting risk practices) no HIV was reportedly acquired in Hungary among people who inject drugs (PWIDs) who were not also men who had sex with other men (MSM). In 2014, one and in 2015 two non-MSM PWIDs were newly diagnosed with HIV who supposedly became infected in Hungary, and both incident HIV cases in 2015 were diagnosed in the AIDS stage. In addition, two new (albeit supposedly imported) non-MSM PWID cases were also registered in the first three quarters of 2016, one of which subsequently was diagnosed with and then died of AIDS. At the same time, the prevalence of HCV doubled among PWIDs (from 24% to 49% in Hungary and from 34% to 61% in Budapest)., Case Presentation: The case that we discuss in this paper is a male PWID, who was diagnosed with HIV and AIDS in May of 2015 and then died of AIDS the next month. His HIV infection status was detected with delay, and then appeared in the official statistics as an incident PWID HIV case and an incident PWID AIDS case, but not as an incident PWID AIDS death. No contact tracing followed, even though it would have been relatively easy considering the circumstances. To our knowledge, no HIV post-exposure protocol exists in hospitals, in case of HIV exposure due to an eventual needle-stick injury., Conclusions: Our paper draws attention to recently published HIV and AIDS surveillance data, and shows the failure of the system. While sounding the alarm based on three newly detected PWID HIV cases in the past 2 years may be premature, there are definitely serious problems in the HIV detection and tracing system among PWIDs in Hungary.

Purpose: Surveillance of the bacterial spectrum and antibiotic-resistance patterns of locally occurring uropathogens is essential to serve as a basis for empirical treatment of urinary tract infections (UTIs), as antibiotic-resistance rates may vary geographically with significant differences between countries and regions, and with time., Methodology: We retrospectively analysed all urine samples taken in the department of urology in a tertiary care hospital in Hungary from January 2004 to December 2015.Results/Key findings. The five most commonly occurring bacteria were Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. Resistance of Escherichia coli to ciprofloxacin increased significantly from 19 to 25 %. Although the resistance of Escherichia coli against cephalosporins showed an increasing trend, it still remained generally low. However, resistance rates of K. pneumoniae to cephalosporins were very high, reaching 60 %, due to the high rate of extended-spectrum-β-lactamase-positive Klebsiella strains. We observed a significant increase in the rate of carbapenem-resistant Pseudomonas aeruginosa., Conclusion: Fluoroquinolones cannot be recommended for empirical treatment in our region. Cephalosporins can be a good empirical choice for treating Gram-negative UTIs, but should be avoided when multi-drug resistant (MDR) bacteria are suspected. Increases in the rate of carbapenem-resistant Pseudomonas aeruginosa, and in the general rate of MDR bacteria, are both a very alarming trend. We recommend practising prudent antibiotic policy, preferably using antibiotics with the narrowest possible spectrum.

Aims: The aim of our study was to explore differences in genetic predisposition to obesity between the Hungarian general and Roma populations., Methods: A total of 1,152 samples from the Hungarian Roma population and 1,743 samples from the Hungarian general population were genotyped for 20 single nucleotide polymorphisms (SNPs) associated with the risk of obesity. Two types of multilocus genetic risk scores were constructed to estimate the combined effect of selected SNPs., Results: Risk allele frequencies differed significantly between the two populations for 11 SNPs, with no enrichment in any of the two study groups. Variants (rs1558902, rs1121980, rs9939609, and rs9941349) in the fat mass and obesity-associated (FTO) gene exhibited strong but ethnicity-independent association with obesity. Genetic risk scores showed stronger associations with obesity in the Roma population compared with the Hungarian general population; however, without significant gene-population interaction., Conclusion: Differences in obesity prevalence between the Hungarian general and Hungarian Roma populations could not be explained by their distinct genetic susceptibility, rather by ethnicity-related environmental and behavioral factors. Nonetheless, particular gene-environment interactions might contribute to the distinct penetrance of the obesity-associated genetic factors in populations of different ethnic backgrounds., (© 2017 The Author(s) Published by S. Karger GmbH, Freiburg.)

Thiolated pyrimidine derivatives have been synthetized and their antiretroviral effect against human immunodeficiency virus type 1 (HIV-1IIIB) and HIV-1 chimeric pseudovirions have been quantitatively determined in cell-based viral infectivity assays including syncytium inhibition assay as well as a single-cycle viral infection assay on HeLaCD4-LTR/ß-gal cells. Pseudotype virions prepared bearing HIV-1 envelope preference for CCR5 coreceptor, CXCR4 coreceptor or for both, respectively, with a HIV-1 core containing luciferase reporter gene were able to infect susceptible cells but are replication defective so unable to replicate in the cells . Data indicate that thiolated pyrimidine derivatives inhibited effectively virally induced cell fusion in vitro as well as infectivity of primary HIV-1IIIB strain and HIV-1 pseudovirions using chemokine receptors CCR5 or CXCR4 or both for virus entry a dose dependent manner. Inhibition was selective, depended on the pseudovirus coreceptor preference. Our results suggest that some of these sulfur containing pyrimidines interact with redoxactive -SH groups required for successful HIV entry, including a redox active disulfide in the CD4 molecule as well as -SH groups in HIV viral envelope gp120. This mode of action is unique representing a new class of potential HIV entry inhibitors.

Unlabelled: Streptococcus pneumoniae is responsible for a significant amount of morbidity and mortality worldwide. Healthy carriers, mainly young children, are the most important sources of infections. In the current study, we aimed to determine the changes that have occurred since the introduction of PCV-7 in Hungary. Nasal specimens were collected from 1,022 healthy children aged 3-6 years attending day-care centres. After thorough identification, pneumococcal isolates were serotyped, and their antibiotic sensitivity was determined. The carriage rate was found to be 34.9%. A huge serotype rearrangement was detected compared to earlier results, with the previously leading serotype 14 having completely disappeared. Serotypes 11A, 35F, 19A, 6B, 15B, 3 and 38 were most prevalent, and 29 different types were identified in total. The PCV-7 types were responsible for 16.5% of all serotypes, and 36.0% are not covered by any pneumococcal vaccines. The isolates were sensitive to most tested antibiotics, except erythromycin (resistance was 21.6%). Only one penicillin-resistant strain was found. The newly and rapidly emerging non-vaccine serotypes are much more sensitive, except serotype 19A., Conclusion: Due to PCV vaccination, a complete serotype arrangement occurred also in Hungary. The old "paediatric" serotypes were replaced by serotypes 11A, 35F, 19A, 6B, 15B, 3 and 38.

Primary high-grade non-Hodgkin lymphoma of the female genital tract is extremely rare. Vaginal bleeding, abdominal pain or urinary complaints might be its most frequent symptoms. We report a 27-year-old multipara who underwent large loop excision of the transformation zone because of the repeated finding of a low-grade squamous intraepithelial lesion identified during routine cancer screening. Incidentally, CD20-positive, primary, diffuse large B-cell lymphoma infiltrating the mucosa of the endocervix was also diagnosed from this specimen. The case is unusual because the patient had no symptoms, specific colposcopic signs or visible mass. R-CHOP 21 immunochemotherapy was introduced and resulted in complete remission without hysterectomy. The patient is without any evidence of disease after 49 months of follow-up. Primary cervical lymphomas are mainly subepithelial initially, and therefore they may be under-recognized due to the inefficiency of smears to diagnose such lesions. Early diagnosis and available targeted treatment allowed a cure in the reported example., (© 2015 S. Karger AG, Basel.)

Upon HIV infection, cells become activated and cell surface thiols are present in increased number. Earlier we demonstrated in vitro anti-HIV effect of thiolated pyrimidine nucleotide UD29, which interferes thiol function. To further analyse the redox processes required for HIV-1 entry and infection, toxicity assays were performed using HIV-1 infected monolayer HeLaCD4-LTR/ β-gal cells and suspension H9 T cells treated with several thiolated nucleotide derivatives of UD29. Selective cytotoxicity of thiolated pyrimidines on HIV-1 infected cells were observed. Results indicate that thiolated pyrimidine derivates may interfere with -SH (thiol) groups concentrated in lipid rafts of cell membrane and interacts HIV-1 infected (activated) cells resulting in a selective cytotoxicity of HIV-1 infected cells, and reducing HIV-1 entry.

Phenothrin, a synthetic pyrethroid compound, is widely used to control agricultural and household insects, as well as to eliminate human louse infestation. Toxicity studies on the direct DNA-damaging effect of phenothrin are lacking. We therefore investigated whether phenothrin exposure can lead to increased DNA damage in vitro in human peripheral blood lymphocytes and in human hepatocytes. Genotoxicity was evaluated by means of the comet assay modified with formamidopyrimidine DNA-glycosylase post-treatment for the detection of oxidative base-damage in DNA. We also assessed the cytotoxic potential of this compound by use of combined fluorescence viability staining. Our results show that phenothrin induces statistically significant, dose-dependent DNA damage in the absence of marked cytotoxicity at concentrations higher than 20 μM and 50 μM in human blood peripheral lymphocytes and hepatocytes, respectively. Oxidative DNA damage could also be detected in the two cell types, although this did not reach statistical significance. These findings provide evidence of the DNA-damaging potential of phenothrin and call for additional studies to reveal the genotoxic properties of this pyrethroid. The observations also point at the importance of using caution when considering the use of phenothrin., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The role of myeloperoxidase (MPO) is essential in the killing of phagocytosed bacteria. Certain steroid hormones increase MPO plasma concentration. Our aim was to test the effect of MPO, its inhibitor indomethacin, and certain steroid hormones on bactericidal activity., Methods: Human polymorphonuclear leukocytes (PMN) were incubated with opsonised Escherichia coli and either MPO, indomethacin, estradiol, or hydrocortisone. Intracellular killing capacity was evaluated with UV microscopy after treatment with fluorescent dye. Next, an in vivo experiment was performed with nine groups of rats: in the first phase of the study indomethacin treatment and Pasteurella multocida infection (Ii), indomethacin treatment without infection (I0), untreated control with infection (Mi) and untreated control without infection (M0); in the second phase of the study rats with infection and testosterone treatment (NT), castration, infection and testosterone treatment (CT), castration, infection and estradiol treatment (CE), non-castrated infected control (N0), and castrated infected control (C0). After treatment bacteria were reisolated from the liver and heart blood on agar plates, and laboratory parameters were analyzed. For the comparison of laboratory results ANOVA or Kruskal-Wallis test and LSD post hoc test was used., Results: Indomethacin did not have a remarkable effect on the bacterial killing of PMNs, while the other compounds increased bacterial killing to various degrees. In the animal model indomethacin and infection caused a poor clinical state, a great number of reisolated bacteria, elevated white blood cell (WBC) count, decreased C-reactive protein (CRP) and serum albumin levels. Testosterone treatment resulted in less bacterial colony numbers in group NT, but not in group CT compared to respective controls (N0, C0). Estradiol treatment (CE) decreased colony numbers compared to control (C0). Hormone administration resulted in lower WBC counts, and in group CE, a decreased CRP., Conclusions: MPO, estradiol, and hydrocortisone improve bacterial killing activity of PMNs. Indomethacin treatment and castration weaken immune responses and clinical state of infected rats, while testosterone and estradiol have a beneficial effect.

The incidence and number of species involved in the spectrum of sexually transmitted infections continue to increase. Laboratories have to be prepared for identification of unusual microbes. In our practice, a male patient had recurring urethritis and balanitis after having repeated unprotected insertive sexual intercourse with female piglets. He also had allergy to scents and some metals, otherwise he showed no general symptoms. Specimens were swabbed from the urethra, inflamed glans, rectum, mouth onto several culture media, subsequently isolates were tested for their morphology, biochemical activity. Kurthia gibsonii was isolated from urethra and glans. No concomitant infection with other microbes was detected, haemoculture was negative. Relying upon antibiotic sensitivity test, he was cured with 2 × 500 mg oral cefuroxime for 15 days, and topical gentamycin cream for 2 months. This is the first reported sexually transmitted, zoonotic infection without generalization by Kurthia spp. We report first the antibiogram of K. gibsonii. Slight differences in the antibiotic sensitivity suggest independent infection and sensitivity of urethral and mucous membrane tissues to distinct K. gibsonii strains. Allergy of the patient might predispose to opportunistic infection. Such aspects ought to be tested in details in further cases.

Biofilm-forming Staphylococcus epidermidis strains are common cause of the periprosthetic infection. The treatment of the periprosthetic infection is very problematic, so the prevention of these infections by an antibiotic containing prothesis could be an option for prevention.The purpose of the present study was to examine the in vitro effects of drug delivery systems (DDSs), namely Wax 1 and Wax 2 with different vancomycin content: 0.5, 1, 2 and 4 mg. In order to control the antibacterial activity of DDSs killing curve study was performed and in order to determine the antibiotic release and the antibiotic peak concentration from the DDSs biological assay was carried out.The time kill curve studies showed, that both DDSs with all vancomycin concentration decreased significantly the bacterial counts, however, Wax 2 with 4 mg vancomycin significantly decreased the bacterial count than all the other groups.The vancomycin release was the best with the highest peak concentration from DDSs with 4 mg vancomycin contain; it was significantly better than in the other groups, however, no significant difference was observed between Wax 1 and Wax 2 in this respect.These findings suggest that Wax 2 with 4 mg vancomycin content could be a potential agent for clinical use.

Adenoviruses have increasingly been recognized as significant viral pathogens causing high morbidity and mortality especially among immunocompromised individuals such as transplant recipients and AIDS patients. Through the infection process, after the adenovirus fiber and penton are bonded to cell surface receptors through special amino acid moieties, secondary messengers activate protein kinases, pro-inflammatory cytokines and chemokines. Serotype and species specific antibodies also are induced. Recombinant human adenoviruses have been pivotal in the development of gene therapy strategies and have shown a great promise for the treatment of genetic disorders and malignancies. Recent studies have enlightened their harmful immunological effects dependent on fiber and hexon polypeptide structure and receptor binding. Pre-existing antibodies or those elicited by vectors neutralize input recombinant adenovirus particles rendering them ineffective. Mediators induce serious even lethal side effects and cytotoxic reactions which extinguish transgene expression. To overcome these difficulties new strategies are required in the application of recombinant adenoviruses to redirect vector entry from the natural receptors to alternative binding sites or using rare human or animal adenovirus fiber molecules to modify the native fiber structure by altering amino acid structure and creating chimeric fibers. This requires searching for, isolating and characterizing new serotypes, mutants or variants for new generation vectors. Human adenovirus 1 feline isolate (feline adenovirus) might fulfil these criteria.

Alkylation is one of the most common types of DNA damage that can lead to mutations and cancer. Lung is the primary target organ of airborne alkylators such as ethylene oxide (EO). However, the ability of EO to cause lung cancer has not been clearly demonstrated yet. The aim of this study was to investigate the susceptibility of lung cells to alkylating DNA insult by detecting EO-mediated DNA damage with the alkaline comet assay in human lung epithelial cells, peripheral blood lymphocytes, and keratinocytes. The susceptibility of these cell types toward the alkylating insult induced by EO was compared against the oxidative DNA insult induced by hydrogen peroxide (H2 O2 ). Due to the volatility of EO, its active concentrations were monitored by gas chromatography during exposure and were found to decrease significantly in a time-dependent manner. EO induced a statistically significant genotoxic effect at the lowest concentration used (16.4 µM) in lung epithelial cells and in lymphocytes, while in keratinocytes, a genotoxic effect was not detected until 55.5 µM EO. However, lung epithelial cells demonstrated increased resistance to oxidative insult. In fact, oxidative DNA damage detectable by endonuclease treatment was minimal in lung cells compared with the other cell types. These results suggest an increased sensitivity of lung epithelial cells toward the alkylating effects of EO, which was not observed for oxidative DNA damage. Our findings point out the importance of DNA alkylation and the possible role of EO on the induction of lung cancer., (Copyright © 2013 Wiley Periodicals, Inc.)

In the decade prior to the turn of the millennium, great interest was raised, and rightly so, by the STD (syphilis and HIV/AIDS) epidemic that developed in the Eastern-Central European Region. Its coincidence with the far-reaching political and economic changes that took place at that time suggested a link between the two events.Hungary, where these infections had had low incidence before the period investigated, also experienced an increase in STD incidence. The trend in syphilis infection during the 20 years between 1985-2004, that preceded the turn of the millennium and when finally Hungary joined the European Union, have been analyzed. Due to the nature of venereological epidemiological surveillance in Hungary, syphilis prevalence data are appropriate for further analysis from socio-demographic aspects. Behavioural changes underlying the specific features of the epidemics in Hungary had developed several years earlier and cannot be linked to the political and economic changes that started in the early 90s. The only exception is the phenomenon of growing migration that appeared simultaneously with the political changes and had a decisive impact on the spread and level of infection in some areas in the country. As shown by our data, trends seen in specific demographic groups (females, rural population) preceded the suddenly occurring political changes by about 15 years.

The life expectancy of patients with type 1 diabetes mellitus is inferior to that of patients with some malignancies. Simultaneous pancreas-kidney transplantation is the procedure providing the best survival results among all options of renal replacement therapy. The operative techniques and immunosuppresion have been standardized in the last decade. Although the number of transplantable organs falls behind the need, simultaneous pancreas-kidney transplantation is the method of choice for the eligible patients. The results of the two Hungarian simultaneous pancreas-kidney transplantation programs are in accordance with data published in the international literature.

The first Hungarian kidney transplantation was performed by András Németh in Szeged in 1962, approximately 50 years ago. A preliminary agreement with Eurotransplant was signed in 2011, and special patient groups gained benefit from this cooperation in 2012, wnich lead to a full membership to Eurotransplant. This event inspired the authors to review the history of Hungarian kidney transplantation of the past 50 years, from the first operation to recent via the specific cornerstones of the transplant program. The donor of the first Hungarian kidney transplantation was the brother of the recipient. The operation itself was technically successful, but the lack of immunosuppression caused graft rejection, and the patient died after 79 days. His brother, the donor, is still healthy, after 50 years, and he encourages everybody to donate organs. Organized kidney transplant program started more than 10 years later, such as 1973, in Budapest. The program was supported by the Ministry of Health. New centers joined the program later, Szeged in 1979, Debrecen in 1991 and Pécs in 1993. These four transplant centers work currently in Hungary, and 6611 kidney transplantation has been performed up to the end of year 2012.

In this study antibiotic combinations for multidrug-resistant Klebsiella pneumoniae strains were investigated. The study included a colistin-susceptible and a colistin-resistant KPC-2 producing K. pneumoniae ST258 strains isolated in 2008 and 2009 during an outbreak in Hungary. Antibiotic combinations were analyzed by checkerboard technique and fractional inhibitory concentration indices were calculated. The following antibiotics were tested: ceftazidime, cefotaxime, ceftriaxone, ampicillin, imipenem, ertapenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, polymyxin B and colistin. Combinations including 0.25 μg/ml colistin plus 1 μg/ml rifampicin, 0.25 μg/ml polymyxin B plus 1 μg/ml rifampicin, 1 μg/ml imipenem plus 2 μg/ml tobramycin, were found synergistic.These in vitro synergistic combinations suggest potential therapeutical options against infections caused by KPC-2 producing, multidrug-resistant K. pneumoniae ST258.

Human adenoviruses function as genetic models and vectors for gene therapy. Upper respiratory, gastrointestinal or ocular infections usually have mild course without any major complication in immunocompetent individuals. However, reactivation from latency in immunocompromised patients may lead to death. Depending on the underlying diseases, different adenovirus serotypes damage different organs. In children with severe combined immunodeficiency syndrome, serotypes of species A and C induce lung, liver or bladder inflammation. Paediatric hematopoietic stem cell transplantation is frequently followed by serotype 31-induced pneumonia, enteritis, cystitis. B serotypes can destroy transplanted organs. In AIDS patients, D and novel F serotypes cause enteritis. Recombinants of B serotypes induce urinary tract infections. Progression of lymphomas, tumours, and systemic lupus erythematosus might be facilitated by immunosuppressive effects of adenoviruses. As far as the diagnostic work-up of adenoviruses, detection of viral DNA and virus copy number is predictive, while serology testing is quite unreliable. For treatment, cidofovir derivates, ribavirin, ganciclovir, vidarabine and microRNA have been used.

Antiretroviral effect of thiolated nucleotide 4-thio-uridylate (S4UMP, designated as UD29) against human immunodeficiency virus type 1 (HIV-1) have been quantitatively determined in cell-based viral infectivity assays. In syntitium inhibition assay on MT-2 human T-cell line UD29 prevented cell fusion and formation of syntitia induced by HIV-1IIIB with IC50 values of 11.7 μg/ml. In a single-cycle viral infection assay (MAGI assay) UD29 proved to have a potent inhibitory effect against HIV-1IIIB on HeLaCD4-LTR/β-gal cells, which was dose dependent with IC50 values of 4.75 μg/ml and IC90 of 39.7 μg/ml. UD29 showed a most prominent antiviral effect when administered 30 min prior HIV-1 infection. As HIV entry requires thiol/disulfide exchange process, results suggest that reactive -SH group of enol-form of the thiolated nucleotide may interfere with the function of cell surface proteins. UD29 cannot penetrate into cells and may have an interactive role in redox processes active in viral entry.

Streptococcus pneumoniae is responsible for a high level of morbidity and mortality, especially among children. For a long time, only the polysaccharide vaccine was available against pneumococcal infections, but in the last decade special conjugate vaccines were developed for paediatric use. These vaccines have made a deep impact on serotype distribution all over the world, by suppressing those serotypes included in the vaccines, while new, previously rare types emerged. These changes have been monitored closely in numerous publications all over the world. Nevertheless, data on pneumococcal serotypes in Hungary were mostly published in Hungarian, therefore not available in the international literature. In this meta-analysis, our aim was to collect and summarise all available data, and try to follow the changes observed after the introduction of the conjugate vaccines.

Frequencies of genetic polymorphisms of the three most frequent HIV-1 resistance-conferring alleles playing an important role in HIV-1 pathogenesis were analysed in Vlach Gypsy populations living in Hungary, as the largest minority. Mutations in the encoding genes, such as CCR5-∆32, CCR2-64I and SDF1-3'A are shown to result in protective effects against HIV-1 infection and disease progression. 560 samples collected from Vlach Gypsy individuals living in 6 North-East Hungarian settlements were genotyped by PCR-RFLP method. Overall allele frequencies of CCR5-∆32, CCR2-64I and SDF1-3'A were found as 0.122, 0.186 and 0.115 respectively. All the observed genotype frequencies were in accordance with Hardy-Weinberg equilibrium . In regions, however, Vlach Gypsies live in majority and in ethnically homogenous communities, a higher CCR5-∆32 mutations were found, with allele frequencies of 0.148 and 0.140 respectively, which are remarkably higher than those in general Hungarian people, and ten times higher than in regions of North-Western India from where present day Hungarian Gypsies originated in the Middle Ages. In the background of this higher CCR5-∆32 allele frequency in the population analysed in our study a genetic founder effect could be assumed. Allele frequency of CCR2-64I was found to be among the highest in Europe. SDF1-3'A allele frequency in Vlach Gypsies was significantly lower than in ethnic Hungarians. 63% of the total 560 individuals tested carried at least one of the mutations studied. These results could partially explain the low incidence of HIV/AIDS among Vlach Gypsies in Hungary.

Streptococcus pneumoniae is responsible for a significant amount of morbidity and mortality worldwide, especially among children <5 years. Healthy carriers are the most important sources of infections and the carriage also peaks in the first years of life, especially among children attending communities. In this study, for the first time in Hungary, we surveyed the nasal carriage of healthy children, just before the use of the conjugate vaccine started increasing.Nasal specimens of 358 children were cultured and pneumococci isolated. The strains were serotyped with antisera and PCR, genotyped by PFGE and their antibiotic sensitivity determined by agar dilution method.The carriage rate was 37.71%. The isolates were sensitive to most tested antibiotics, except for macrolides. In this cohort of specimens still the widespread, so-called "pediatric serotypes" dominated (14, 19F, 23F, 6A, 6B in ranking order), but three of the previously rare types: 15B, 11A and 13 were represented already by 21.5% of all strains and also a few other rare non-vaccine types (e.g. 10A or 37) were detected.The calculated vaccine coverage was 55.6% for PCV-7, 69.6% for PCV-13 and 86.7% for Pneumovax. In this cohort, only 15.9% of the children (n = 57) were vaccinated. The carriage rate of PCV-7 vaccinated children was significantly lower (30.4%) than that of the non-vaccinated group (39.2%). The clonality of the isolates was significant within each group, revealing the extensive bacterium exchange among children.

Purpose: Biofilm infections have a major role in implants or devices placed in the human body. As part of the endourological development, a great variety of foreign bodies have been designed, and with the increasing number of biomaterial devices used in urology, biofilm formation and device infection is an issue of growing importance., Methods: A literature search was performed in the Medline database regarding biofilm formation and the role of biofilms in urogenital infections using the following items in different combinations: "biofilm," "urinary tract infection," "bacteriuria," "catheter," "stent," and "encrustation." The studies were graded using the Oxford Centre for Evidence-based Medicine classification., Results: The authors present an update on the mechanism of biofilm formation in the urinary tract with special emphasis on the role of biofilms in lower and upper urinary tract infections, as well as on biofilm formation on foreign bodies, such as catheters, ureteral stents, stones, implants, and artificial urinary sphincters. The authors also summarize the different methods developed to prevent biofilm formation on urinary foreign bodies., Conclusions: Several different approaches are being investigated for preventing biofilm formation, and some promising results have been obtained. However, an ideal method has not been developed. Future researches have to aim at identifying effective mechanisms for controlling biofilm formation and to develop antimicrobial agents effective against bacteria in biofilms.

The concentration of kynurenic acid (KYNA) in the cerebrospinal fluid, which is in the nanomolar range, is known to decrease in epilepsy. The experimental data suggest that treatment with L: -KYN dose dependently increases the concentration of the neuroprotective KYNA in the brain, which itself hardly crosses the blood-brain barrier. However, it is suggested that new synthetic KYNA analogs may readily cross the blood-brain barrier. In this study, we tested the hypothesis that a new KYNA analog administered systemically in a sufficient dose results in a decreased population spike activity recorded from the pyramidal layer of area CA1 of the hippocampus, and also provides protection against pentylenetetrazole-induced epileptiform seizures.

Vancomycin-resistant enterococci (VRE) are common nosocomial pathogens; however, until now they have been rarely encountered in Hungary. In the present study, we investigated the prevalence of VRE in the teaching hospitals of the University of Debrecen. Of 7,271 Enterococcus-containing clinical samples collected between 2004 and 2009, we identified 16 VRE. Species-specific polymerase chain reaction was used to detect Enterococcus faecalis, Enterococcus faecium, Enterococcus casseliflavus, and Enterococcus gallinarum. Multiplex polymerase chain reaction was performed to identify the vancomycin resistance genes: vanA, vanB, vanC1/C2, vanD, vanE, and vanG. Restriction digestion with SalI and HindIII was introduced to differentiate the vanC1 and vanC2 genes from each other. Genetic relationships between the strains were investigated by pulsed-field gel electrophoresis. Overall, we identified the vanC1 resistance gene in 14 E. gallinarum and the vanC2 resistance gene in two E. casseliflavus strains. Except for two samples, the isolates had different pulsed-field gel electrophoresis types, suggesting sporadic emergence of the resistant bacteria. In addition, antibiotic resistance profile was determined by E-test. Three E. gallinarum strains proved to be resistant to gentamicin because of the presence of the aacA-aphD gene. Although the prevalence of VRE in Debrecen is rather low, the appearance of multiple resistances is of concern.