Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles.

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements.

Gross morphology and adhesion-associated physical properties of Drosophila larval salivary gland glue secretion.

One of the major functions of the larval salivary glands (SGs) of many Drosophila species is to produce a massive secretion during puparium formation. This so-called proteinaceous glue is exocytosed into the centrally located lumen, and subsequently expectorated, serving as an adhesive to attach the puparial case to a solid substrate during metamorphosis. Although this was first described almost 70 years ago, a detailed description of the morphology and mechanical properties of the glue is largely missing. Its main known physical property is that it is released as a watery liquid that quickly hardens into a solid cement. Here, we provide a detailed morphological and topological analysis of the solidified glue. We demonstrated that it forms a distinctive enamel-like plaque that is composed of a central fingerprint surrounded by a cascade of laterally layered terraces. The solidifying glue rapidly produces crystals of KCl on these alluvial-like terraces. Since the properties of the glue affect the adhesion of the puparium to its substrate, and so can influence the success of metamorphosis, we evaluated over 80 different materials for their ability to adhere to the glue to determine which properties favor strong adhesion. We found that the alkaline Sgs-glue adheres strongly to wettable and positively charged surfaces but not to neutral or negatively charged and hydrophobic surfaces. Puparia formed on unfavored materials can be removed easily without leaving fingerprints or cascading terraces. For successful adhesion of the Sgs-glue, the material surface must display a specific type of triboelectric charge. Interestingly, the expectorated glue can move upwards against gravity on the surface of freshly formed puparia via specific, unique and novel anatomical structures present in the puparial's lateral abdominal segments that we have named bidentia.

Apis mellifera filamentous virus from a honey bee gut microbiome survey in Hungary.

In Hungary, as part of a nationwide, climatically balanced survey for a next-generation sequencing-based study of the honey bee (Apis mellifera) gut microbiome, repeated sampling was carried out during the honey production season (March and May 2019). Among other findings, the presence of Apis mellifera filamentous virus (AmFV) was detected in all samples, some at very high levels. AmFV-derived reads were more abundant in the March samples than in the May samples. In March, a higher abundance of AmFV-originated reads was identified in samples collected from warmer areas compared to those collected from cooler areas. A lower proportion of AmFV-derived reads were identified in samples collected in March from the wetter areas than those collected from the drier areas. AmFV-read abundance in samples collected in May showed no significant differences between groups based on either environmental temperature or precipitation. The AmFV abundance correlated negatively with Bartonella apihabitans, Bartonella choladocola, and positively with Frischella perrara, Gilliamella apicola, Gilliamella sp. ESL0443, Lactobacillus apis, Lactobacillus kullabergensis, Lactobacillus sp. IBH004. De novo metagenome assembly of four samples resulted in almost the complete AmFV genome. According to phylogenetic analysis based on DNA polymerase, the Hungarian strains are closest to the strain CH-05 isolated in Switzerland.

Ixodes ricinus tick bacteriome alterations based on a climatically representative survey in Hungary.

IMPORTANCE: Climate-sensitive disease vectors, such as ticks, respond to the environment with changes in their microbiome. These changes can affect the emergence or re-emergence of various vector-borne pathogens, such as the causative agent of Lyme borreliosis (LB) or tick-borne encephalitis. This aspect is particularly emphasized in light of climate change. The climatically representative assessment of microbiome differences in various developmental stages of the most common Central European tick species, Ixodes ricinus, deepens our understanding of the potential climatic factors behind microbial relative abundance and interaction changes. This knowledge can support the development of novel disease vector control strategies.

Field efficacy of fluralaner (Bravecto® chewable tablets) for preventing Babesia canis infection transmitted by Dermacentor reticulatus ticks to dogs.

BACKGROUND: The isoxazoline fluralaner is effective for prevention of Babesia canis transmission from infected Dermacentor reticulatus ticks to dogs for 84 days in a controlled environment. This study was designed to evaluate the effectiveness of fluralaner chewable tablets for sustained prevention of B. canis infection of dogs in endemic areas under natural conditions. METHODS: In Europe, privately owned, clinically healthy pet dogs were enrolled and randomized either to receive fluralaner at 25-56 mg/kg (Bravecto® chewable tablets) on days 0 and 84, or to remain untreated during the D. reticulatus season. Blood samples were collected to evaluate B. canis exposure: on days 0 and 21 (exposure before day 0), during the study and at the end of the tick season (dogs suspected of having become infected after day 0). Efficacy was determined by the percentage reduction in B. canis transmission risk based on the difference in B. canis-positive tests in fluralaner-treated dogs compared with untreated dogs. In addition, ticks collected at monthly intervals throughout the study were identified to species level and females tested for B. canis DNA. RESULTS: A total of 152 dogs were enrolled in the study, although nine dogs were excluded because they tested positive for B. canis DNA or antibodies within 21 days after enrollment. During the study period, no fluralaner-treated dog became positive for B. canis, resulting in calculated efficacy of 100%. However, babesiosis infection was diagnosed in five untreated control dogs (Fisher's exact test, left-sided, P = 0.0312). Tick analyses revealed that one sample collected in Hungary was infected with B. canis. CONCLUSION: Oral administration of Bravecto chewable tablets at the recommended dosage to dogs completely prevented B. canis transmission under field conditions in an endemic area for 12 weeks.

Screening of Domestic Cats from North-Eastern Hungary for Hepatozoon felis and Cytauxzoon europaeus That Cause Infections in Local Wildcat Populations.

Among vector-borne protozoa Hepatozoon felis and Cytauxzoon europaeus are considered emerging species in felids in Europe. To investigate the presence of these two protozoa 127 domestic cats and 4 wildcats were screened by PCRs targeting the 18S rRNA gene of Hepatozoon spp. and piroplasms, as well as the cytb gene of Cytauxzoon spp. The samples were collected inside and outside a region of Hungary, where both protozoan groups are endemic in wildcats. Among domestic cats, one proved to be infected with H. felis. Furthermore, spleen samples of four wildcats were also examined, among which three tested positive for H. felis, and one had co-infection with C. europaeus. Importantly, H. felis from the co-infected wildcat belonged to genogroup II, similarly to H. felis from the positive domestic cat. Based on phylogenetic evidence, this genogroup probably represents a separate species from genogroup I of H. felis, which was hitherto reported from Mediterranean countries in Europe. The two other wildcats also harbored H. felis from genogroup I. Neither Hepatozoon nor Cytauxzoon infections were detected outside the recently discovered endemic region. In conclusion, this study demonstrates for the first time in Europe that H. felis from genogroup II may emerge in free-roaming domestic cats in regions where this protozoan parasite is endemic in wildcats.

Antimicrobial resistance gene lack in tick-borne pathogenic bacteria.

Tick-borne infections, including those of bacterial origin, are significant public health issues. Antimicrobial resistance (AMR), which is one of the most pressing health challenges of our time, is driven by specific genetic determinants, primarily by the antimicrobial resistance genes (ARGs) of bacteria. In our work, we investigated the occurrence of ARGs in the genomes of tick-borne bacterial species that can cause human infections. For this purpose, we processed short/long reads of 1550 bacterial isolates of the genera Anaplasma (n = 20), Bartonella (n = 131), Borrelia (n = 311), Coxiella (n = 73), Ehrlichia (n = 13), Francisella (n = 959) and Rickettsia (n = 43) generated by second/third generation sequencing that have been freely accessible at the NCBI SRA repository. From Francisella tularensis, 98.9% of the samples contained the FTU-1 beta-lactamase gene. However, it is part of the F. tularensis representative genome as well. Furthermore, 16.3% of them contained additional ARGs. Only 2.2% of isolates from other genera (Bartonella: 2, Coxiella: 8, Ehrlichia: 1, Rickettsia: 2) contained any ARG. We found that the odds of ARG occurrence in Coxiella samples were significantly higher in isolates related to farm animals than from other sources. Our results describe a surprising lack of ARGs in these bacteria and suggest that Coxiella species in farm animal settings could play a role in the spread of AMR.

First detection of Ixodiphagus hookeri (Hymenoptera: Encyrtidae) in Ixodes ricinus ticks (Acari: Ixodidae) from multiple locations in Hungary.

The parasitoid wasp, Ixodiphagus hookeri (Hymenoptera: Encyrtidae), is the natural enemy of a wide range of hard and soft tick species. While these encyrtid wasps are supposed to be distributed worldwide, only a few studies report on their actual distribution around the globe. Within a shotgun sequencing-based metagenome analysis, the occurrence of I. hookeri was screened at multiple Ixodes ricinus (Acari: Ixodidae) tick sampling points in Hungary to contribute to the assessment of the distribution patterns of the parasitoid wasps in Central Europe. To our knowledge, the first report of the species in Hungary and the description of the southernmost I. hookeri associated geoposition in Central Europe took place within our study. I. hookeri infested I. ricinus nymphs were detected at five sampling points in Hungary. The results show that the exact distribution range of I. hookeri is still barely studied. At the same time, unprecedented public health issues being brought about by climate change might require steps toward the exploitation of the tick biocontrol potential and as an ecological bioindicator role of the parasitoid wasp in the future.

A histochemical and morphological study of the mucus producing pedal gland system in Latia neritoides (Mollusca; Gastropoda; Hygrophila).

The freshwater gastropod Latia neritoides is endemic to the streams of New Zealand's North Island. This species has evolved a unique defence system: it exudes a luminescent mucus thought to deter predators. While the bioluminescence itself has been investigated before, the underlying gland system has remained unstudied and relevant information to understand the defence system has been missing till now. For the release of the glowing mucus of L. neritoides two places of origin were assumed: the lateral foot area or the mantel cavity. In this study the focus was on the first suggestion. To gain insight into the defence system, morphological as well as histochemical analyses were performed involving all secretory gland types in the sub-epithelial foot layer. The results were compared with the foot gland system of Neritina sp., a snail living in a comparable habitat, but using a different survival strategy. The gland types of the two gastropods were compared and their mucus types were investigated. Seven subepithelial gland cell types can be distinguished in the foot region of L. neritoides. Neritina sp., in contrast, has six gland cell types of which three laterally located ones are epithelial. Both species show a pedal gland in the anterior foot region. A striking difference between the species are two prominent subepithelial gland cell types (L1l/L2l) in the lateral foot area of L. neritoides, which are missing in Neritina sp. These gland cells are distributed throughout the entire lateral foot area of L. neritoides and make up about 85% of the mucus gland cells in this area. Defence mucus and trail mucus of L. neritoides show different specificities in lectin staining, but are not equally represented in the gland cell types. Yet, based on the huge size and high density of L1l and L2L, we envision a role for these gland types in the defence system.

Natural diversity of the honey bee (Apis mellifera) gut bacteriome in various climatic and seasonal states.

As pollinators and producers of numerous human-consumed products, honey bees have great ecological, economic and health importance. The composition of their bacteriota, for which the available knowledge is limited, is essential for their body's functioning. Based on our survey, we performed a metagenomic analysis of samples collected by repeated sampling. We used geolocations that represent the climatic types of the study area over two nutritionally extreme periods (March and May) of the collection season. Regarding bacteriome composition, a significant difference was found between the samples from March and May. The samples' bacteriome from March showed a significant composition difference between cooler and warmer regions. However, there were no significant bacteriome composition differences among the climatic classes of samples taken in May. Based on our results, one may conclude that the composition of healthy core bacteriomes in honey bees varies depending on the climatic and seasonal conditions. This is likely due to climatic factors and vegetation states determining the availability and nutrient content of flowering plants. The results of our study prove that in order to gain a thorough understanding of a microbiome's natural diversity, we need to obtain the necessary information from extreme ranges within the host's healthy state.

Multicenter randomized, and blinded European field study evaluating the efficacy and safety of Felpreva®, a novel spot-on formulation containing emodepside, praziquantel and tigolaner, in treating cats naturally infested with fleas and/or ticks.

The present field study evaluated the safety and 3-month preventive efficacy of a novel spot-on endectocide containing emodepside 2.04% w/v, praziquantel 8.14% w/v and tigolaner 9.79% w/v (Felpreva®, Vetoquinol) when administered at the intended commercial dose of 0.15 ml/kg body weight to privately owned cats infested by fleas (Ctenocephalides felis) and/or ticks (Ixodes ricinus, Ixodes hexagonus, Rhipicephalus spp.). The efficacy of Felpreva® to reduce the clinical signs associated with flea allergy dermatitis was also evaluated. A total of 326 cats, i.e. 120 and 206 infested by ticks and fleas respectively, from 16 different sites located in Hungary and Portugal were included on Day 0 and allocated in two Groups at a ratio of 2:1 (T1:T2). Cats of T1 were treated with Felpreva®, while cats of T2 were dosed with a commercial Control Product (Bravecto®, MSD Animal Health) licensed for the same indications. Of the 120 tick-infested cats, 79 and 41 were treated with Felpreva® and Bravecto® respectively, while of the 206 flea-infested cats, 139 were treated with Felpreva® and 67 with Bravecto®. Cats were physically examined on Days 7, 28, 56, 75 and 90; when present, fleas and ticks were counted and collected. Efficacy evaluation was based on the mean percent reduction of live parasite counts for each of five visits versus the pre-treatment count. Percent reductions of live flea and tick counts over all post-baseline periods were 99.74% (T1) versus 98.56% (T2) and 97.50% (T1) versus 98.65% (T2), respectively. Non-inferiority for the Felpreva® compared with the Bravecto® treated group was statistically demonstrated for both fleas and ticks. Three adverse events were observed and considered unlikely related to the treatment. These results show that the new topical combination product Felpreva® is safe and highly efficacious in treating flea and tick infections in cats for at least three months (90 days) with a single administration. In 16 cats that were identified with flea allergy dermatitis, the clinical signs of flea allergy dermatitis improved following treatment in both groups.

Multicenter randomized, and blinded European field study evaluating the efficacy and safety of Felpreva®, a novel spot-on formulation containing tigolaner, emodepside and praziquantel, in treating cats with mixed infection with intestinal nematodes, cestodes and/or lungworms.

This paper describes a multicentric field study which has evaluated the safety and efficacy of a novel spot on formulation containing emodepside 2.04% w/v, praziquantel 8.14% w/v and tigolaner 9.79% w/v (Felpreva®, Vetoquinol) when administered at the intended commercial dose of 0.15 ml/kg body weight to privately owned cats infected with major intestinal nematodes (Toxocara cati, Toxascaris leonina, Ancylostoma tubaeforme, Uncinaria stenocephala) and/or cestodes (Dipylidium caninum, Taenia taeniaeformis) and/or lungworms (Aelurostrongylus abstrusus, Troglostrongylus brevior). A total of 219 cats from 26 veterinary clinics located in Albania, Greece, Hungary, Italy and Portugal were included in the study. Feces from the cats were examined on a single occasion between Study Day -7 and Day 0 (baseline) and post-treatment (i) twice between Day 7 and Day 14 (± 2) (for intestinal helminths) or (ii) twice between Day 21 (± 2) and Day 28 (± 2) (for lungworms). Cats were allocated into two groups at a ratio of 2:1 (Felpreva®: Profender®, i.e. a commercial control product containing emodepside and praziquantel). Cats infected with intestinal helminths were treated once on Day 0 (i) with Felpreva® (Group 1) or (ii) with Profender® (Group 2). Animals infected with lungworms received a second treatment with Profender® on Day 14 (± 2) regardless of group allocation. Faecal egg or larval count reduction for Felpreva® was 97.47% for intestinal nematodes and 96.80% for lungworms. No cats infected with cestodes at baseline resulted positive after treatment with Felpreva®. However, the low number of cats (n = 10) did not allow for a statistical analysis to be performed. Non-inferiority of Felpreva® compared to Profender® was statistically demonstrated for all target intestinal and respiratory parasites. No adverse events nor application site reactions were observed. These results show that the new topical combination product Felpreva® is highly safe and efficacious in treating infections caused by major species of feline intestinal nematodes, cestodes and lungworms under field conditions.

Assessment of Antibiotic Pharmacokinetics, Molecular Biomarkers and Clinical Status in Critically Ill Adults Diagnosed with Community-Acquired Pneumonia and Receiving Intravenous Piperacillin/Tazobactam and Hydrocortisone over the First Five Days of Intensive Care: An Observational Study (STROBE Compliant).

Severe community-acquired pneumonia (CAP) is a condition that frequently requires intensive care and, eventually, can cause to death. Piperacillin/tazobactam antibiotic therapy is employed as an empiric intravenous regimen, in many cases supplemented with intravenous bolus hydrocortisone treatment. The individual and condition-dependent pharmacokinetic properties of these drugs may lead to therapeutic failure. The impact of systemic inflammation, as well as of hydrocortisone on the altered pharmacokinetics of piperacillin is largely unknown. The protocol of a clinical study aimed at the characterization of the pharmacokinetics of piperacillin and tazobactam and its association with the concentrations of inflammatory markers and adrenal steroids during CAP therapy will be investigated in up to 40 critically ill patients. The serum concentrations of piperacillin and tazobactam, cortisol, cortisone, corticosterone and 11-deoxycortisol and interleukin-6 levels, as well as routine clinical chemistry and hematology parameters will be monitored from the beginning of treatment for up to five days. Nonparametric population pharmacokinetic modeling and Monte-Carlo simulations will be performed to make estimates of the pharmacokinetics of piperacillin and tazobactam and the probability of pharmacokinetic-pharmacodynamic target attainment. The observed individual characteristics and changes will be correlated with clinical and laboratory findings. The protocol of the observational study will be designed following the STROBE guideline.

Application of Moxidectin and Ultrasound-Aided Injection of Melarsomine During the American Heartworm Society Recommended Treatment Protocol in Dirofilaria immitis Infected Dogs.

The American Heartworm Society (AHS) recommends the three-dose alternate melarsomine therapeutic regimen, together with a macrocyclic lactone (ML) to reduce new infections and eliminate susceptible larvae and doxycycline against Wolbachia bacteria. Till now, only reports on ivermectin as an ML exist in the frame of this protocol. Between 2014 and 2020, the AHS protocol was used in 44 heartworm-positive dogs. Microfilaremic dogs were pretreated with prednisolone and clopidogrel for 1 week before the first moxidectin application. Moxidectin was applied on the 1st, 30th, 60th, and 90th therapeutic days. On the first day, dexamethasone and chloropyramine were used to avoid potential adverse effects caused by the destroyed microfilariae. During the 1st-28th days, doxycycline 10 mg/kg BID was given with probiotics. Adult heartworms were destroyed with melarsomine on the 60th, 90th, and 91st days. Butorphanol and dexamethasone were given just before melarsomine injections. The depth of the intramuscular injection site was determined by ultrasound examination of the lumbar muscles. From the 60th day, dalteparin was applied for 10 days to decrease the chance of pulmonary thromboembolism. Moxidectin did not cause adverse reactions, even in microfilaremic dogs. Gastrointestinal side effects of doxycycline were observed in three (6%) dogs, they recovered after symptomatic therapy and by lowering the initial dose to 5 mg/kg BID. Transient anorexia and diarrhea were found in one (2%), and coughing and mild dyspnea in one (2%) animal as systemic post-therapeutic complications of melarsomine. No local side effects were observed in 13 (30%) dogs, mild local side effects occurred in 29 (66%) patients, and severe local swelling in 2 (4%) cases. All dogs recovered clinically by the 120th day and no microfilaremia was seen that time. An antigen test performed in 37/44 animals on the 271st day was also negative in all cases.

Serodiagnostic difficulties and possibilities of heartworm disease in regions where both Dirofilaria immitis and Dirofilaria repens infections occur.

This retrospective study was performed on 71 dogs which had been admitted for heartworm screening or with clinical suspicion of heartworm disease. The examination methods included polymerase chain reaction (PCR) to identify Dirofilaria immitis and/or Dirofilaria repens infections and a heartworm antigen (Ag) test (VetScan). By using PCR, 26 dogs were found positive only for Dirofilaria immitis (Group 1), while 21 dogs for both D. immitis and D. repens (Group 2). Group 3 included 24 dogs with D. repens infection only according to the PCR results. The sensitivity of the VetScan Ag test for the Group 1 and 2 animals proved to be 97.7% (95% Blaker confidence interval; CI 89.0%-99.9%). The specificity of the VetScan Ag test, calculated from the results of Group 3, was found to be 66.7% (95% CI 45.6%-83.1%), which was lower than that reported from the USA, where D. repens does not occur. In cases when PCR results were positive for D. repens but negative for D. immitis, the occult dirofilariosis was the likely explanation for the positive D. immitis Ag tests. These observations highlight the importance of performing more Ag tests simultaneously in those areas where both Dirofilaria species are present.

Babesiosis in Southeastern, Central and Northeastern Europe: An Emerging and Re-Emerging Tick-Borne Disease of Humans and Animals.

There is now considerable evidence that in Europe, babesiosis is an emerging infectious disease, with some of the causative species spreading as a consequence of the increasing range of their tick vector hosts. In this review, we summarize both the historic records and recent findings on the occurrence and incidence of babesiosis in 20 European countries located in southeastern Europe (Bosnia and Herzegovina, Croatia, and Serbia), central Europe (Austria, the Czech Republic, Germany, Hungary, Luxembourg, Poland, Slovakia, Slovenia, and Switzerland), and northern and northeastern Europe (Lithuania, Latvia, Estonia, Iceland, Denmark, Finland, Sweden, and Norway), identified in humans and selected species of domesticated animals (cats, dogs, horses, and cattle). Recorded cases of human babesiosis are still rare, but their number is expected to rise in the coming years. This is because of the widespread and longer seasonal activity of Ixodes ricinus as a result of climate change and because of the more extensive use of better molecular diagnostic methods. Bovine babesiosis has a re-emerging potential because of the likely loss of herd immunity, while canine babesiosis is rapidly expanding in central and northeastern Europe, its occurrence correlating with the rapid, successful expansion of the ornate dog tick (Dermacentor reticulatus) populations in Europe. Taken together, our analysis of the available reports shows clear evidence of an increasing annual incidence of babesiosis across Europe in both humans and animals that is changing in line with similar increases in the incidence of other tick-borne diseases. This situation is of major concern, and we recommend more extensive and frequent, standardized monitoring using a "One Health" approach.

Clinical and diagnostic relevance of asymmetric and symmetric dimethyl arginine (ADMA/SDMA). / Az aszimmetrikus és a szimmetrikus dimetilált arginin (ADMA/SDMA) klinikai és diagnosztikai jelentosége.

Összefoglaló. Régóta folynak kutatások olyan újabb biomarkerek azonosítására, amelyek segítik a krónikusan progrediáló, úgynevezett civilizációs betegségek - például cardiovascularis kórképek, vesefunkció-beszukülés - korai felismerését. Az aszimmetrikus és a szimmetrikus dimetil-arginin (ADMA és SDMA) ketto azon paraméterek közül, amelyek biológiai hatásai évtizedek óta ismertek ugyan, ám biomarkerként egyelore nem terjedtek el a humán orvosi-diagnosztikai gyakorlatban. A fehérjearginin-metiltranszferázok katalizálta folyamatban L-argininbol keletkezo vegyületek a nitrogén-monoxid-szintáz aktivitásának gátlói. Mivel a nitrogén-monoxid számos biológiai folyamat kulcsszereploje - gátolja az érpálya simaizomsejtjeinek relaxációját, csökkenti a thrombocytaaggregációt, és gyulladáscsökkento hatást fejt ki -, termelodésének zavarai megnövelik a magas vérnyomás és cardiovascularis betegségek kialakulásának kockázatát. Áttekinto közleményünkben az ADMA és az SDMA mint lehetséges új diagnosztikai markerek, valamint a társadalmi és orvosszakmai szempontból is kihívást jelento betegségek kapcsolatának bemutatását tuztük ki célul. Orv Hetil. 2022; 163(13): 500-505. Summary. Research has long been underway to identify additional biomarkers that will help in the early detection of chronic diseases of civilization, such as cardiovascular disease and renal impairment. Asymmetric and symmetric dimethyl arginine (ADMA and SDMA), two of the parameters whose biological effects have been known for decades, have not yet been widely used as biomarkers in human medical-diagnostic practice. In a process catalyzed by protein arginine methyltransferases, compounds derived from L-arginine are inhibitors of nitric oxide synthase activity. Because nitric oxide is a key player in many biological processes - for instance, inhibiting the relaxation of vascular smooth muscle cells, reducing platelet aggregation, and having anti-inflammatory effect -, disturbances in its production increase the risk of developing high blood pressure and cardiovascular disease. Therefore, in our review paper, we aimed to present the relationship between ADMA and SDMA as possible new diagnostic markers and socially and physically challenging diseases. Orv Hetil. 2022; 163(13): 500-505.

Diversity of tick species and associated pathogens on peri-urban wild boars - First report of the zoonotic Babesia cf. crassa from Hungary.

Wild boars show increasing numbers and population densities throughout Europe, including Hungary. While their presence is appreciated as game animals, they are also responsible for significant agricultural damage, habitat degradation and water quality issues. In addition, wild boars may harbor ticks and can act as reservoirs of tick-borne pathogens, thus posing a risk of transmission towards humans and domestic animals. This latter aspect of their veterinary-medical and epidemiological significance has become especially important in recent years, because increasing numbers of wild boars are reported to enter urban areas. Despite of this, reports on tick infestations of wild boars are scarce in Europe. For this study, 333 ixodid ticks were collected from 51 wild boars at 32 peri-urban locations in 14 counties of Hungary, during 2005-2008 (older samples) and 2019-2020 (new samples). Five species of ticks were identified: Dermacentor reticulatus (n = 165), Ixodes ricinus (n = 90) and Haemaphysalis concinna (n = 29) in both sample groups, while H. inermis (n = 29) and D. marginatus (n = 20) were only found among the old samples. The seasonality of collected ticks corresponded to their known activities. After DNA extraction, ticks were screened for three groups of tick-borne pathogens. All samples were negative for brucellae, recently reported to be carried and transmitted transovarially by D. marginatus. Four D. reticulatus contained Babesia canis DNA, while in one H. concinna nymph the recently discovered zoonotic B. cf. crassa (reported in Slovenia within 80 km of our sampling site) was detected. In addition, Anaplasma phagocytophilum was identified in D. reticulatus (n = 1), H. concinna (n = 3) and in its known vector, I. ricinus (n = 15). Phylogenetically, three out of four A. phagocytophilum genotypes clustered with zoonotic ones. In conclusion, despite of the high prevalence of Brucella suis in wild boars in Hungary, no evidence was found in support of the epidemiological role of ticks in transmitting brucellae. On the other hand, wild boars might introduce B. canis-carrier D. reticulatus into urban areas, unlike birds (which are not known to carry this tick species in the country). Most importantly, tick-infested wild boars can contribute to the spread of a novel zoonotic Babesia sp. and of the zoonotic variants of A. phagocytophilum.