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This paper sets out to examine the facts behind the trade of long distance transportation of cattle. In particular it looks at the various welfare implications during handling and transport with examples from research work on cattle. The role of the science is explained and the methodology for assessing the welfare of animals is then presented. Finally, public concerns and legal position are presented as they play an important role to promote farm animal welfare principles during transportation.

The aim of the present study is to analyze virtual learning environments and to provide a framework for assuring quality in farm animal welfare curricula. The framework is constructed according to the experimental learning for a case study developed in the context of the Leonardo da Vinci Community Vocational Training Action Pilot Project entitled “WELFOOD-Promoting quality assurance in animal welfare-environment-food quality interaction studies through upgraded e-Learning”. WELFOOD addressed objectives such as improvement and competencies of the skills in vocational training to promote employability and facilitate integration and reintegration in terms of capabilities and knowledge, needed for improved technologies in animal husbandry and food industry.

The pikeperch (Sander lucioperca) is very important and valuable freshwater fish in Hungary. The quality of lash is very high (white, tasty and boneless) thus the gastronomically demand grows year by year. Besides the pikeperch is an attractive game fish and as a top predator, plays an important role in the maintenance of ecological balance in freshwater ecosystems. The success of pond culture of pikeperch depends on the propagation and nursing methods. Recently the technological development of artificial reproduction ensures the production of more fry and fingerlings. Present study investigates the different reproduction methods in consideration of the spawning behaviour of the pikeperch breeders. Between the hormone treatment and spawning there were observed six stagers in the behaviour of pike-perch couples- In addition to the observations on behaviour of spawning, various hormone products were examined in order to stimulate and synchronise the ovulation of pike perch breeders. Best results were recorded in case of using dried carp pituitary as a hormone treatment (170g eggs/stripped females), while the treatment with GnRH analogs resulted 145 g respectively. Moreover the price and biological advances of GnRH analogs require more research in their use in the field of artificial propagation of pikeperch. These hormones do not interfere violently the neuro-humoral regulation of the ovulation, thus contributes to maintain better conditions of animal welfare during the propagation procedure.

Abstract The low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats). As impaired dopamine D1 receptor (D1R) function might play a role in the cognitive dysfunctions observed in patients with schizophrenia, the second goal of this study was to determine the brain-region-specific D1R-mediated signaling, ligand binding, and mRNA expression. None of the treatments affected the behavior of the control animals significantly; however, the combination treatment enhanced D1R binding and activation in the cerebral cortex. The Wisket rats exhibited impaired motivation, attention, and cognitive function, as well as a lower level of cortical D1R binding, signaling, and gene expression. Clozapine caused further deterioration of the behavioral parameters, without a significant effect on the D1R system. Metformin blunted the clozapine-induced impairments, and, similarly to that observed in the control animals, increased the functional activity of D1R. This study highlights the beneficial effects of metformin (at the behavioral and cellular levels) in blunting clozapine-induced adverse effects.

The AlpArray Gravity Research Group (AAGRG), as part of the European AlpArray program, focuses on the compilation of a homogeneous surface-based gravity data set across the Alpine area. In 2017 10 European countries in the Alpine realm agreed to contribute with gravity data for a new compilation of the Alpine gravity field in an area spanning from 2 to 23∘ E and from 41 to 51∘ N. This compilation relies on existing national gravity databases and, for the Ligurian and the Adriatic seas, on shipborne data of the Service Hydrographique et Océanographique de la Marine and of the Bureau Gravimétrique International. Furthermore, for the Ivrea zone in the Western Alps, recently acquired data were added to the database. This first pan-Alpine gravity data map is homogeneous regarding input data sets, applied methods and all corrections, as well as reference frames. Here, the AAGRG presents the data set of the recalculated gravity fields on a 4 km × 4 km grid for public release and a 2 km × 2 km grid for special request. The final products also include calculated values for mass and bathymetry corrections of the measured gravity at each grid point, as well as height. This allows users to use later customized densities for their own calculations of mass corrections. Correction densities used are 2670 kg m−3 for landmasses, 1030 kg m−3 for water masses above the ellipsoid and −1640 kg m−3 for those below the ellipsoid and 1000 kg m−3 for lake water masses. The correction radius was set to the Hayford zone O2 (167 km). The new Bouguer anomaly is station completed (CBA) and compiled according to the most modern criteria and reference frames (both positioning and gravity), including atmospheric corrections. Special emphasis was put on the gravity effect of the numerous lakes in the study area, which can have an effect of up to 5 mGal for gravity stations located at shorelines with steep slopes, e.g., for the rather deep reservoirs in the Alps. The results of an error statistic based on cross validations and/or “interpolation residuals” are provided for the entire database. As an example, the interpolation residuals of the Austrian data set range between about −8 and +8 mGal and the cross-validation residuals between −14 and +10 mGal; standard deviations are well below 1 mGal. The accuracy of the newly compiled gravity database is close to ±5 mGal for most areas. A first interpretation of the new map shows that the resolution of the gravity anomalies is suited for applications ranging from intra-crustal- to crustal-scale modeling to interdisciplinary studies on the regional and continental scales, as well as applications as joint inversion with other data sets. The data are published with the DOI https://doi.org/10.5880/fidgeo.2020.045 (Zahorec et al., 2021) via GFZ Data Services.

Rock salt has remarkable mechanical properties and high economic importance; however, the strength of salt compared to other rocks makes it a rather vulnerable material. Human activities could lead to acceleration of the dissolution of soluble rock salt and collapse of subsurface caverns. Although sinkhole development can be considered a local geological disaster regarding the characteristic size of surface depressions, the deformations can result in catastrophic events. In this study we report the spatiotemporal evolution of surface deformation in the Solotvyno salt mine area in Ukraine based on Sentinel-1 interferometric synthetic aperture radar measurements. Although the mining operations were finished in 2010, several sinkholes have been opened up since then. Our results show that despite the enormous risk management efforts, the sinkholes continue to expand with a maximum line-of-sight deformation rate of 5 cm/yr. The deformation time series show a rather linear feature, and unfortunately no slowdown of the processes can be recognized based on the investigated 4.5-year-long data set. We utilized both ascending and descending satellite passes to discriminate the horizontal and vertical deformations, and our results revealed that vertical deformation is much more pronounced in the area. Analytical source modeling confirmed that the complex deformation pattern observed by Sentinel-1 radar interferometry has a direct connection to the former mining activity and is confined to the mining territory. With the 6 d repetition time of Sentinel-1 observations, the evolution of surface changes can be detected in quasi real time, which can facilitate disaster response and recovery.

Animal welfare has become a growing concern affecting acceptability of agricultural systems in many countries around the world. An earlier Judeo-Christian interpretation of the Bible (1982) that dominion over animals meant that any degree of exploitation was acceptable has changed for most people to mean that each person has responsibility for animal welfare. This view was evident in some ancient Greek writings and has parallels in Islamic teaching. A minority view of Christians, which is a widespread view of Jains, Buddhists and many Hindus, is that animals should not be used by humans as food or for other purposes. The commonest philosophical positions now, concerning how animals should be treated, are a blend of deontological and utilitarian approaches. Most people think that extremes of poor welfare in animals are unacceptable and that those who keep animals should strive for good welfare. Hence animal welfare science, which allows the evaluation of welfare, has developed rapidly.

In this study the change in amino acid profile in cow's colostrum and transient milk during the first week after parturition was examined in a Hungarian Charolais herd. Experiments were carried out with n = 37 Charolais cows in the same herd in the spring (March-April) of two consecutive years (Experiment 1: 2002, n = 15; and Experiment 2: 2003, n = 22). Colostrum and milk samples were taken by hand milking immediately after delivery, and in 24, 48, 72, and 168 hours post partum. Amino acid contents (%) in samples were measured in milk protein with an automatic amino acid analyser. Data were processed by the software of SPSS.10 statistical program package. In the postpartal period, among essential amino acids significant increases were recorded in methionine, isoleucine, lysine, and phenylalanine, and among non-essential amino acids glutamic acid and proline increased significantly. Simultaneous decreases were recorded in valine, cysteine, aspartic acid, serine, glycine, and arginine. Inconsistent figures were determined for histidine, leucine, tyrosine, and alanine content between Experiment 1 and Experiment 2.

Long term fertilisation trials were combined with storage experiments with 'Jonathan' apple trees and fruits to study influence of tree nutrition on quantity and quality of crop. The site of experiments is a typical Carpathian-basin environment with loamy silt soil, high lime content and arid summers. Conclusions has been drown from six years' set of data. Augmented levels of soil fertilisation increased cropping capacity of apple trees, however, the fruit load has not met with cropping capacity in every year. More the def cit came into view in crop load, less the fruit quality resulted in. The deficit in cropping capacity, however, could not have been determined with simple rates as fruit weight per trunk circumference or similar. Better determination was obtained where foliar nutrient contents were correlated to crop per tree figures. In general terms, the N and Ca content in leaves increased with yields when K and P content formulated reciprocally. When storage quality of 'Jonathan' apple fruits were related to crop load (kg/tree), influence of crop deficit became visible. As the crop load and foliar nutrient levels interacted, the fruit quality (number of disordered apples after 6 month of storage) subjected of both physiological phenomena. Higher determination degree were obtained when crop load was assessed together with single or multiple foliar analysis data.

Effects of nitrogen, phosphorus and potassium fertilization were investigated on the change of nutrient content, vegetative and generative production of apricot, peach and sour cherry trees, as well as on frost hardiness in long term experiments. Nitrogen and phosphorus fertilization increased only the concentration of these elements in cherry leaves without effect on growth and yield. Consequent potassium effect was proved on these stone fruit species. Effect on yield appeared following the first higher crop load. Potassium supply has positive effect on frost hardiness of apricot and sour cherry flowers and peach flower buds. In peach, the lime content of soil decreased the yield but it could be compensated by potassium dressing to some extent. Favourable nutrient boundary values were determined for soil and foliage.

Authors present synthesis of experimental work, performed in the last decades, for better understanding nutritional behaviour of apple trees and related problems in fruit quality. There were evidences supporting possible deteriorating role of potassium in feeble physiological status of apples, if applied in excess. More intensive studies proved that higher potassium uptake into leaves and fruits might be also the result of increased sink power of individual fruits. Nevertheless early senescence of apples during storage and also sensibility to bitter pit were successfully related to the increased sink power of fruits, casual relations in excessive NPK fertilization, although increase in sink power need further investigations. Impaired weather conditions during early development of fruits, hostile orchard practices in pruning, thinning, irrigation and also unskilled application of growth regulators may also contribute in the enhancement of sink power and in weakened physiological status of apple fruits.

Some experience or details are introduced in connection with the nutrient uptake of micropropagated fruit trees in the different phase of the in vitro or ex vitro development. It can be stated, that the plants during the micropropagation procedure are overfed. Special careful nutrient supply is necessary during the acclimatization.

The aim of this study was to evaluate growth and development of heifers from birth to 24 months of age and the effects on milk yield in first lactation. Body weight and height at withers of female calves (N=4167) were taken at monthly intervals. At 3 months of age the average height at withers of calves, live weight and wither index was 80.9 kg, 86.1 cm and 1.0, respectively. Figures taken at 6 months of age the height at withers, live weight and wither index increased by 17.6 cm, 92.3 kg and 1.7. Respective mean values at 9, 16 and 24 months of age were 250.0, 413.9 and 603.7 kg; 116.0, 128.5 and 139.7 cm; and 2.2, 3.2 and 4.3. The heifers with the ideal or lower ones at 3, 9 and 16 month of age produced higher milk yields in the first lactation milk yield by 200-500 kg as compared with the highest index category. Higher index values at 6 months of age resulted in increase of milk yields in the first the lactation. At 24 months of age first lactation milk yields were similar in all indexcategories (8647.2, 8703.5 and 8717.5 kg, respectively). No variations neither in butterfat (3.6%) nor milk protein (3.1%) content were present within the index categories at any ages. In conclusion, findings reveal that the withers height index seems to be an appropriate tool in monitoring of growth and development of replacement heifers for taking corrective actions in feeding and breeding practice.

The impact of two years (2002 and 2003) with different summer temperature extremes on variation in metabolic profile was analyzed in blood and urine samples taken from healthy, primiparous (n = 371) and multiparous (n = 795) high yielding Holstein-Friesian dairy cows. In this study main focus was lead on three most critical physiological phases, thus cows were assigned into three groups as follows: (1) dry cows for 10 days prior to calving; (2) cows 1-30 days after delivery, and (3) cows with more than 31 days post partum. Findings reveal clear response of the cows to heat in selected blood (hemoglobin, plasma aceto-acetic-acid, FFA, AST, glucose, urea) and urine (pH, NABE and urea) parameters. In the majority of cows, glucose and hemoglobin level, one of the most significant blood parameters, indicated symptoms of insufficient energy supply. Further metabolic indicators differed more or less from reference values depending on actual condition. Due to heat load dry matter intake has been decreased even by 10-15 per cent in primiparous cows. They were expected to increase body weight and size and simultaneously produce attain at large milk yields. In doing so that cows would have require large amount of nutrients. Out of parameters such as hemoglobin, glucose, FFA, AST and blood-urea differed from the reference values in most cases; however, this phenomenon seemed to be present in almost every case for hemoglobin and glucose. The lack of energy caused by heat stress can be contributed to the decrease of dry matter intake which has been indicated by the urea levels and pH both in blood and urine prevailing unfavorable and insufficient feeding practice. The results reconfirm the need to reconsider both the actual feeding practice (e.g. to increase of nutrient content in rations, reduce the intake of soluble proteins in rumen, pay attention of crude fiber in Total Mixed Rations (TMR), NDF and ADF, avoid overfeeding of inorganic buffers, to control moisture content in TMR, increase of Na and K intake), and construction of cowsheds with ample airspace, good ventilation and cooling system by remodeling of existing dairy operations.

There is a growing concern of consumers that the meat producing animals are bred, reared, handled and slaughtered in ways that are sympathetic to their welfare status. Good animal welfare is generally considered as a primary requirement and EU and national legislation is in force throughout the total production chain and everyday practice is above the minimum threshold level required. The relative importance of stress during animal production and in the immediate pre-slaughter period as a major determinant of ultimate meat quality has long been recognized. Good welfare may result in better product quality is a powerful additional commercial incentive to improve the way we rear, handle and slaughter animals. In the ante mortem period, good welfare usually results from careful handling of animals that reduces stress and trauma. In contrast, poor ante mortem handling leads to stress and results in poorer meat quality. Critical points within the pre-slaughter period are (a) loading, (b) transport, (c) lairage, (d) stunning.

This paper reviews the welfare assessment with reference to calves. Assessment methods were divided into individual level and farm (system) level. At the farm level the ANI 35L is discussed and the ANSVSA, Romanian evaluation from is presented. Also, the EFSA opinion on poor welfare in intensive calf farming systems is presented.

Findings of research and experiences gained in commercial practice reveal needs for efforts in order to reinforce further development in the subject matter of calving difficulty and stillbirth in dairy cattle with special emphasis on causes and effects. Direct costs such as loss of calf, death of dam, labour, veterinary assistance and other ones influencing economics in longer term e.g. higher culling rate, reduced milk yield and fertility have to be evaluated and interpreted. The effects of non-genetic factors, parity, sex of calf, age at first calving, season, level of nutrition during gestation and their supposed modes of action has to be considered. In the genetic model for calving traits estimates the following components has to be included such as direct, maternal, and direct-maternal interaction. Thus, accurate and complete reporting of calving ease and stillbirth data is critical for several reasons: increase the accuracy of sire calving ease and daughter calving ease evaluations; allow the development of national stillbirth evaluations; the farmer can enhance future sire selection opportunities for the herd. The aim is to reduce economic losses, improve welfare status of animals, meeting increased concern of consumer acceptance of milk and dairy products.

The aim of the study was to analyse the relationship between the body condition and the results of metabolic profile tests done in the milk (DIM) of dairy cows in different days. Moreover, critical points in the early pre- and postpartum period were also analysed. In the experiment, blood and urine samples were taken from 1984 clinically healthy cows (from 49 large scale dairy farms in Hungary), selected randomly from various groups of cows with different physiological stage of lactation and gestation, 3-5 hours after the morning feeding. During the experiment body condition scoring (BCS) was measured on 1-5 scale, as well. It was concluded, that the BCS (body condition score) decreased from the 1st day of lactation (3.48) onwards till the 44th day (2.65) and slightly increased till the day 218 (2.89). The haemoglobin value and the glucose concentration in blood samples were ranging within the physiological range and followed the tendency of BCS and the relationship between them and DIM was (P

According to the Amsterdam Treaty, animals are sentient creatures and animal welfare requirements should be precisely met while preparing and implementing the Commission laws. Accomplishing this, cultural, religious and regional characteristics should be considered. However, more and more regulations and laws are continuously introduced in Europe and worldwide. Ongoing WELANIMAL Project was financed by EU Commission adapting of vocational training products and results of training tools of WELFOOD related to the animal welfareenvironment-food quality interactions is being enriched with consideration of cultural, socio-economic and religious approaches in order to determine a common work definition for all sectorial workers having different moral and social values on the subject of animal welfare and food safety Central and South-eastern Europe region. Although there is slight differences, national legislation in partner countries of EU in Project were harmonious with legal framework in EU regarding for all farm species. It is expected that three draft regulations in compliance with legal requirements animal protection in farms and during transportation and slaughtering and killing in Turkey, as a candidate country to membership into EU, in 2009. Also, due to in participating countries to the Project have ethnicity, history, tradition and religious structure show a great diversity it has been guessed that welfare concept which is a moral issue can be effected by people’s cultural, religious and social composition. In the WELANIMAL Project, the effects of socio-cultural, religious and regional historical differences of workers and consumers within animal production chain on understanding of animal welfare concepts are being analysed. Furthermore in the light of obtained data a common vocational animal welfare definition and animal welfare, food quality and environment interaction will be evaluated. Through the Project web page (www.welanimal.aku.edu.tr) interactive training and certification will be accomplished. This paper intents to provide an overview of legal framework including Council Directives and National legislation laying down minimum welfare standards and traditional practices in Central and Sought eastern Europe in which WELANIMAL Project is ongoing.

For early-stage non-small cell lung cancer, surgical resection remains the best treatment option. Currently, sublobar resection, including segmentectomy, is recommended in these cases, as it provides a better quality of life with the same oncological outcomes; however, is requires adequate resection margins. Accurate preoperative planning and proper identification of the intersegmental planes during thoracic surgery are crucial for ensuring precise surgical management and adequate resection margins. Three dimensional computed tomography reconstruction and near-infrared-guided intersegmental plane identification can greatly facilitate the surgical procedures. Three-dimensional computed tomography reconstruction can simulate both the resection and resection margins. Indocyanine green is one of the most frequently used and affordable fluorophores. There are two ways to identify the intersegmental planes using indocyanine green: intravenous and transbronchial administration. Intravenous application is simple; however, its effectiveness may be affected by underlying lung disease, and it requires the isolation of segmental structures before administration. Transbronchial use requires appropriate bronchoscopic skills and preoperative planning; however, it also allows for delineation deep in the parenchyma and can be used for complex segmentectomies. Both methods can be used to ensure adequate resection margins and, therefore, achieve the correct oncological radicality of the surgical procedure. Here, we summarise these applications and provide an overview of their different possibilities., 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., (© 2024 Libor, Pécsy, Szűcs, Lantos, Bakos, Lázár and Furak.)

The design and development of hybrid compounds as a new class of drug candidates remains an excellent opportunity to improve the pharmacological properties of drugs (including enzymatic stability, efficacy and pharmacokinetic and pharmacodynamic profiles). In addition, considering various complex diseases and/or disorders, the conjugate chemistry approach is highly acceptable and justified. Opioids have long been recognized as the most potent analgesics and serve as the basic pharmacophore for potent hybrid compounds that may be useful in pain management. However, a risk of tolerance and physical dependence exists. Since dopamine receptors have been implicated in the aforementioned adverse effects of opioids, the construction of a hybrid with dual action at opioid and dopamine receptors is of interest. Herein, we present nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulation results for LENART01, an opioid-ranatensin hybrid peptide. Apart from molecular docking, protein-ligand interactions were also assessed in vitro using a receptor binding assay, which proved LENART01 to be bound to mu-opioid and dopamine receptors, respectively.

Opiate alkaloids and their synthetic derivatives are still widely used in pain management, drug addiction, and abuse. To avoid serious side effects, compounds with properly designed pharmacological profiles at the opioid receptor subtypes are long needed. Here a series of 17-N-substituted derivatives of normorphine and noroxymorphone analogues with five- and six-membered ring substituents have been synthesized for structure-activity study. Some compounds showed nanomolar affinity to MOR, DOR and KOR in in vitro competition binding experiments with selective agonists [ 3 H]DAMGO, [ 3 H]Ile 5,6 -deltorphin II and [ 3 H]HS665, respectively. Pharmacological characterization of the compounds in G-protein signaling was determined by [ 35 S]GTPγS binding assays. The normorphine analogues showed higher affinity to KOR compared to MOR and DOR, while most of the noroxymorphone derivatives did not bind to KOR. The presence of 14-OH substituent resulted in a shift in the pharmacological profiles in the agonist > partial agonist > antagonist direction compared to the parent compounds. A molecular docking-based in silico method was also applied to estimate the pharmacological profile of the compounds. Docking energies and the patterns of the interacting receptor atoms, obtained with experimentally determined active and inactive states of MOR, were used to explain the observed pharmacological features of the compounds., (© 2023. The Author(s).)

Despite the large arsenal of analgesic medications, neuropathic pain (NP) management is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers telmisartan and losartan, and particularly their combination with morphine on rat mononeuropathic pain following acute or chronic oral administration. The impact of telmisartan on morphine analgesic tolerance was also assessed using the rat tail-flick assay. Morphine potency and efficacy in spinal cord samples of treated neuropathic animals were assessed by [ 35 S]GTPγS-binding assay. Finally, the glutamate content of the cerebrospinal fluid (CSF) was measured by capillary electrophoresis. Oral telmisartan or losartan in higher doses showed an acute antiallodynic effect. In the chronic treatment study, the combination of subanalgesic doses of telmisartan and morphine ameliorated allodynia and resulted in a leftward shift in the dose-response curve of morphine in the [ 35 S]GTPγS binding assay and increased CSF glutamate content. Telmisartan delayed morphine analgesic-tolerance development. Our study has identified a promising combination therapy composed of telmisartan and morphine for NP and opioid tolerance. Since telmisartan is an inhibitor of AT1 and activator of PPAR-γ, future studies are needed to analyze the effect of each component.

Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn in a carrageenan-evoked inflammation model. Both naturally occurring CART(55-102) and CART(62-102) peptides are present in the spinal cord. CART(55-102) is not involved in acute nociception but regulates spinal pain transmission during peripheral inflammation. While the full-length peptide with a globular motif contributes to hyperalgesia, its N-terminal inhibits this process. Although the anti-hyperalgesic effects of CART(55-102), CART(55-76), and CART(62-76) are blocked by opioid receptor antagonists in our inflammatory models, but not in neuropathic Seltzer model, none of them bind to any opioid or G-protein coupled receptors. DPP4 interacts with Toll-like receptor 4 (TLR4) signalling in spinal astrocytes and enhances the TLR4-induced expression of interleukin-6 and tumour necrosis factor alpha contributing to inflammatory pain. Depending on the state of inflammation, CART(55-102) is processed in the spinal cord, resulting in the generation of biologically active isoleucine-proline-isoleucine (IPI) tripeptide, which inhibits DPP4, leading to significantly decreased glia-derived cytokine production and hyperalgesia.

Aims: We aimed to identify the short-term effects of a glucocorticoid (GC) and a mineralocorticoid (MC) on non-pregnant and late pregnant rat uterine contractions to estimate their tocolytic potential., Methods: The in vitro contractility studies were performed with uterine tissues from non-pregnant and 22-day pregnant SPRD rats. The cumulative dose-response of fludrocortisone (FLU) and dexamethasone (DEX) was measured alone or in the presence of steroid receptor antagonist mifepristone (MIF) or spironolactone (SPR). [ 35 S]GTPγS and cAMP immunoassays were carried out to detect the activated G-proteins and cAMP, respectively. The in vivo uterine action of single doses of FLU and DEX was measured by smooth muscle electromyography. The results were statistically analyzed with an unpaired t-test., Results: FLU and DEX relaxed both pregnant (33 and 34%) and non-pregnant (37 and 34%) uteri in vitro. MIF inhibited the relaxing effect of DEX, especially in the pregnant uterus, but reduced the effect of FLD only in non-pregnant tissues. GTPγS studies showed a MIF-sensitive elevation in activated G-proteins both in pregnant and non-pregnant uteri by DEX, whereas FLU induced activation only in non-pregnant samples. DEX relaxed pregnant and non-pregnant uteri in vivo in a MIF-sensitive way., Significance: DEX can inhibit contractions in the late pregnant uterus in a non-genomic manner, while FLU seems to be ineffective. Its action is mediated by a G-protein-coupled receptor that can be blocked by mifepristone. Further investigations are necessary to determine the required dose and duration of GCs in the therapy of premature birth., (Copyright © 2022. Published by Elsevier B.V.)

Despite the progress in early diagnostic and available treatments, pancreatic cancer remains one of the deadliest cancers. Therefore, there is an urgent need for novel anticancer agents with a good safety profile, particularly in terms of possible side-effects. Recently dopaminergic receptors have been widely studied as they were proven to play an important role in cancer progression. Although various synthetic compounds are known for their interactions with the dopaminergic system, peptides have recently made a great comeback. This is because peptides are relatively safe, easy to correct in terms of the improvement of their physicochemical and biological properties, and easy to predict. This paper aims to evaluate the anticancer activity of a naturally existing peptide-ranatensin, toward three different pancreatic cancer cell lines. Additionally, since there is no sufficient information confirming the exact character of the interaction between ranatensin and dopaminergic receptors, we provide, for the first time, binding properties of the compound to such receptors., Competing Interests: The authors declare no conflicts of interest.

Összefoglaló. Az urachus tumorai és egyéb betegségei ritkák. A 67 éves férfi anamnézisében ismétlődő húgyúti fertőzés szerepelt ciprofloxacinterápiával. Cisztoszkópia során a húgyhólyag felső részének másodlagos érintettségére utaló bullosus nyálkahártya képe mutatkozott. Az ezt követő CT-felvételek alapján az alsó medián hasfallal, húgyhólyaggal, belekkel összefüggő tumor iránydiagnózisát állították fel. A kivizsgálás során kialakuló ileus miatt Hartmann-műtétet végeztek, a tumoros jellegű elváltozás teljes és az érintett szervek részleges eltávolításával. A kórszövettani vizsgálat daganatos elváltozást nem talált, hasi, vélhetően urachuseredetű actinomycosist igazolt: erre az eredetre a lokalizáció és a tünetek közt szereplő köldökváladékozás alapján lehetett gondolni, annak ellenére, hogy urachusmaradványt szövettanilag nem sikerült igazolni a mikroabszcedáló gyulladás által érintett szövetekben. A betegnél amoxicillinterápia indult. Átmeneti, hólyag melletti vizeletcsorgást követően a beteg tünet- és panaszmentesen távozott a kórházból, de 13 nappal később a hasfali seb sterilnek véleményezett szétválása miatt ismét hospitalizálni kellett. Negatív nyomású sebkezelést követően sikerült a hasat ismét zárni. A beteg ismét tünetmentessé vált, és fenntartott antibiotikumkezelés mellett hagyta el a kórházat. Az urachuskörnyéki tumorszerű elváltozások között az actinomycosis lehetőségét is szem előtt kell tartani a differenciáldiagnosztikában. Orv Hetil. 2022; 163(4): 157-160. Summary. Tumours and other diseases of the urachus are rare. A 67-year-old male presented with a history of recurrent urinary tract infection and ciprofloxacin therapy. Cystoscopy suggested secondary involvement of the bullous upper bladder wall. The subsequent CT-based diagnosis was of a tumour infiltrating the lower median abdominal wall, the urinary bladder and bowels. Bowel obstruction developed and this led to partial resection of the involved organs along with a Hartmann's procedure. Histology revealed no neoplastic conditions, but proved abdominal actinomycosis of probable urachal origin based on the location of the tumour-like lesion and umbilical discharge among the symptoms. Urachal remnants were not identified in the perivesical tissues involved by the microabscess forming inflammation. Amoxicillin therapy was initiated. After a temporary urine leakage from the bladder, the patient became symptomless and was emitted from hospital. After 13 days, he was readmitted because of abdominal wound disruption, which was treated with negative-pressure wound therapy before the abdomen could be closed. At the time of reporting, he is still on amoxicillin, and has become symptomless again. Actinomycosis should be considered in the differential diagnosis of mass lesions of the urachal region. Orv Hetil. 2022; 163(4): 157-160.

Opioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats. Necrotizing AP was induced by the intraperitoneal injection of L-ornithine-HCl or intra-ductal injection of Na-taurocholate, while intraperitoneal caerulein administration caused edematous AP. Disease severity was determined by laboratory and histological measurements. Mu opioid receptor (MOR) expression and function was assessed in control and AP animals. MOR was expressed in both the pancreas and brain. The pancreatic expression and function of MOR were reduced in AP. Fentanyl post-treatment reduced necrotizing AP severity, whereas pre-treatment exacerbated it. Fentanyl did not affect the outcome of edematous AP. Morphine decreased vacuolization in edematous AP, while buprenorphine pre-treatment increased pancreatic edema during AP. The overall effects of morphine on disease severity were negligible. In conclusion, the type, dosing, administration route, and timing of opioid treatment can influence the effects of opioids on AP severity. Fentanyl post-treatment proved to be beneficial in AP. Clinical studies are needed to determine which opioids are best in AP.

The use of α-amino-γ lactam of Freidinger (Agl) may serve as an impressive method to increase the biological stability of peptides and an appropriate tool to elucidate their structure-activity relationships. The endomorphin-2 (EM-2) and [D-Ala 2 , des-Leu 5 ] enkephalin amide (DAPEA) are two linear opioid tetrapeptides agonists of MOR and MOR/DOR respectively. Herein, we investigated the influence of the incorporation of (R/S)-Agl in position 2 and 3 on the biological profile of the aforementioned products in vitro and in vivo. Receptor radiolabeled displacement and functional assays were used to measure in vitro the binding affinity and receptors activation of the novel analogues. The mouse tail flick and formalin tests allowed to observe their antinociceptive effect in vivo. Data revealed that peptide A2D was able to selectively bind and activate MOR with a potent antinociceptive effect after intracerebroventricular (i.c.v.) administration, performing better than the parent compounds EM-2 and DAPEA. Molecular docking calculations helped us to understand the key role exerted by the Freidinger Agl moiety in A2D for the interaction with the MOR binding pocket., (Copyright © 2021 Elsevier Inc. All rights reserved.)