Development of dual V1a/V2 antagonists containing triazolobenzazepine scaffold.

The development of a dual V1a/V2 antagonist compound is a complex and challenging task. Conivaptan is up to now the only known V1a/V2 antagonist which was approved for the treatment of euvolemic hyponatremia. Previously, we reported RGH-122, a novel selective V1a antagonist compound.

First Experimental Application of DNA-Layered Salmonid Alphavirus-Based Replicon Vaccine in Non-Salmonid Fish: Induced Early Semi-Specific Protection against Spring Viraemia of Carp Virus (SVCV) in Common Carp ().

Our study demonstrates the first application of the salmonid alphavirus-based replicon vector system (pSAV) as a DNA vaccine in a non-salmonid fish species, in common carp () against spring viraemia of carp virus (SVCV). SAV replicon encoding the glycoprotein of the SVCV was used as a DNA-layered plasmid, and its efficacy was compared with a previously described conventional DNA vaccine construct (pcDNA3.1 based vector) and with a control group (pcDNA3.

Discovery and Characterization of RGH-122, a Potent, Selective, and Orally Bioavailable V1a Receptor Antagonist.

The V1a receptor is a major contributor in mediating the social and emotional effects of arginine-vasopressin (AVP); therefore it represents a promising target in the treatment of several neuropsychiatric conditions. The aim of this research was to design and synthesize novel and selective V1a antagonists with improved and profiles. Through optimization and detailed SAR studies, we developed low nanomolar antagonists, and further characterizations led to the discovery of the clinical candidate compound (RGH-122).

New Insights into the Morphological Diversity of (Oomycota) Strains under In Vitro Culture Conditions.

Coker, 1923 is a primary fish pathogen and one of the most common water molds in freshwater ecosystems. In our study, nineteen strains of were isolated, identified, and characterized using morphological and genetic markers. On the basis of the abundance of zoosporangia, gemmae, the formation of gemma chains, and the induction of zoospore release, three morphotypes were differentiated.

Vasopressin receptor antagonists: a patent summary (2018-2022).

Introduction: Arginine-vasopressin hormone (AVP) is a key regulator in many essential physiological processes. The effect of AVP is mediated through three receptors within the body, these are the G protein-coupled vasopressin receptors, namely V1a, V1b (also called V3), and V2. Numerous studies investigated the role of these receptors in certain pathological conditions; therefore, stimulation or inhibition of these receptors may be a treatment option in these diseases.

Herbivorous Juvenile Grass Carp () Fed with Genetically Modified MON 810 and DAS-59122 Maize Varieties Containing Cry Toxins: Intestinal Histological, Developmental, and Immunological Investigations.

Feeding experiments with juvenile grass carp () fed with genetically modified maize MON 810 or DAS-59122 dried leaf biomass were carried out with 1-, 3- and 6-month exposures. Dosages of 3-7 μg/fish/day Cry1Ab or 18-55 μg/fish/day Cry34Ab1 toxin did not cause mortality. No difference occurred in body or abdominal sac weights.

Synthesis and Characterization of New V Antagonist Compounds: The Separation of Four Atropisomeric Stereoisomers.

A new class of selective vasopressin receptor 1A (V) antagonists was identified, where "methyl-scan" was performed around the benzene ring of the 5-hydroxy-triazolobenzazepine core. This led to the synthesis of two 10-methyl derivatives, each possessing a chiral axis and a stereogenic center. The four atropisomeric stereoisomers (involving two enantiomer pairs and atropisomeric diastereomers) could be successfully isolated and spectroscopically characterized.

Intussusception caused by intestinal neoplasia in mature rainbow trout (Oncorhynchus mykiss, Walbaum 1792).

The aquaculture industry is growing and includes the farming and breeding of more than 580 aquatic species worldwide. The rainbow trout (Oncorhynchus mykiss, Walbaum 1792) is the most commonly bred trout species in Hungary. As broodfish form the basis of most fish farms, investigation into tumours occurring in trout, although under-researched, has proven to be a valuable and necessary field of study.

Kisspeptin Neurons in the Infundibular Nucleus of Ovariectomized Cats and Dogs Exhibit Unique Anatomical and Neurochemical Characteristics.

Neurons co-synthesizing kisspeptin (KP), neurokinin B (NKB), and dynorphin ("KNDy neurons") in the hypothalamic arcuate/infundibular nucleus (INF) form a crucial component of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) "pulse generator." The goal of our study was to characterize KP neuron distribution, neuropeptide phenotype and connectivity to GnRH cells in ovariectomized (OVX) dogs and cats with immunohistochemistry on formalin-fixed hypothalamic tissue sections. In both species, KP and NKB neurons occurred in the INF and the two cell populations overlapped substantially.

Family aggregation analysis shows a possible heritable background of equine grass sickness (dysautonomia) in a Hungarian stud population.

Equine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since its first description over a century ago, several factors, such as the phenotype, intestinal microbiome, environment, management and climate, have been supposed to be associated with the increased risk of dysautonomia.

Discovery of New Heterocyclic Ring Systems as Novel and Potent V Receptor Antagonists.

Autism spectrum disorder is a neurodevelopmental disease with increasing occurrence. Recent studies focus on the development of novel V receptor antagonists which can influence the core symptoms of autism through the AVP pathway. In this study, we describe the synthesis of new heterocyclic ring systems.

New V1a receptor antagonist. Part 1. Synthesis and SAR development of urea derivatives.

Solid preclinical evidence links vasopressin to social behavior in animals, so, extensive work has been initiated to find new vasopressin V1a receptor antagonists which can improve deteriorated social behavior in humans and can treat the core symptoms of autistic behavior, as well. Our aim was to identify new chemical entities with antagonizing effects on vasopressin V1a receptors. Starting from a moderately potent HTS hit (7), we identified a molecule (49) having nanomolar binding strength and functional activity, which is in the same range as the potency of clinically tested V1a antagonists.

New V1a receptor antagonist. Part 2. Identification and optimization of triazolobenzazepines.

Solid preclinical evidence links vasopressin to social behavior in animals, so, extensive work has been initiated to find new vasopressin V1a receptor antagonists which can improve deteriorated social behavior in humans and can treat the core symptoms of autistic behavior, as well. Our aim was to identify new chemical entities with antagonizing effects on vasopressin V1a receptors. Continuing our previous work, we found an in vitro and in vivo orally active V1a selective antagonist molecule (40) among [1,2,4]triazolo[4,3-a][1]benzazepines.

Detection of cyprinid herpesvirus 1 (CyHV-1) in barbel (Barbus barbus): First molecular evidence for the presence of CyHV-1 in fish other than carp (Cyprinus carpio).

Two adult barbels (Barbus barbus) with visible skin tumours were subjected to histopathological and molecular examinations. The fish were caught in the River Danube near Budapest. Papillomas were found around their oral cavity, at the operculum and at the pectoral fins, while epidermal hyperplasias were seen on the body surface.

Molecular detection of a novel cyprinid herpesvirus in roach (Rutilus rutilus) and asp (Leuciscus aspius) showing typical signs of carp pox disease.

In the early spring of 2018, in Lake Balaton (Hungary), a roach (Rutilus rutilus) and an asp (Leuciscus aspius) were found in an fish trap at the outlet of the river Sió showing typical signs of the so-called carp pox disease, such as foci of epidermal hyperplasia on the head and the whole body surface, including the fins. Molecular tests revealed the presence of the DNA of an unknown fish herpesvirus. Three genes encoding the DNA-dependent DNA polymerase, major capsid protein and ATPase subunit of terminase were amplified and sequenced from the alloherpesviral genome.

Discovery and development of extreme selective inhibitors of the ITD and D835Y mutant FLT3 kinases.

Aberrant activation of FMS-like tyrosine receptor kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML) in 20-30% of patients. In this study we identified a highly selective (phenylethenyl)quinazoline compound family as novel potent inhibitors of the FLT3-ITD and FLT3-D835Y kinases. Their prominent effects were confirmed by biochemical and cellular proliferation assays followed by mice xenograft studies.

Introduction of a new fetal examination protocol for on-field and clinical equine practice.

Prepartum fetal surveillance techniques have been widely used in both human and veterinary obstetrics, although these tests differ in their sensitivity for the assessment of fetal well-being. In equine reproduction, the 'gold standard' examination technique is the equine biophysical profile (EBP) described by Virginia Reef in 1995. Although this fetal assessment has many benefits, its accuracy, sensitivity and specificity have not been evaluated so far.

Characterization of new, efficient Mycobacterium tuberculosis topoisomerase-I inhibitors and their interaction with human ABC multidrug transporters.

Drug resistant tuberculosis (TB) is a major worldwide health problem. In addition to the bacterial mechanisms, human drug transporters limiting the cellular accumulation and the pharmacological disposition of drugs also influence the efficacy of treatment. Mycobacterium tuberculosis topoisomerase-I (MtTopo-I) is a promising target for antimicrobial treatment.

Discovery of N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides as Novel AXL Kinase Inhibitors.

The overexpression of AXL kinase has been described in many types of cancer. Due to its role in proliferation, survival, migration, and resistance, AXL represents a promising target in the treatment of the disease. In this study we present a novel compound family that successfully targets the AXL kinase.

Applicability of fetal thoracic aortic diameter measurement in the prediction of birth weight in Holstein-Friesian cows - Short communication.

Transabdominal ultrasonography has been shown to be a useful and reliable method for assessing fetal well-being in horses and cattle. To test the applicability of fetal aortic diameter measurement in cattle, 44 late-term pregnant cows and heifers were examined 21 to 0 days prior to calving. Mean fetal aortic diameter was 2.

l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in Zebrafish Embryo Model.

This work establishes the zebrafish embryo model for ionizing radiation (IR) modifier research and also evaluates the protective effect of l-alpha glycerylphosphorylcholine (GPC). Embryos were exposed to a single-fraction whole-body gamma irradiation (5, 10, 15, and 20 Gy) at different postfertilization time points and were serially assessed for viability and macro- and micromorphologic abnormalities. After toxicity evaluation, 194 μM of GPC was added for certain groups with 3-h incubation before the radiation.

Design and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells.

Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyridine or imidazo[1,2-a]pyrazine scaffold was designed and synthesized to investigate their in vitro efficacy against the A375P human melanoma cell line.

Pregnancy-associated changes of serum biochemical values in Lipizzaner broodmares.

The aims of this study were to detect physiological changes in blood biochemical parameters throughout gestation, to compare the findings in nonpregnant and pregnant Lipizzaner mares in early-mid and late pregnancy, and to provide reference values for clinical chemistry parameters in this horse breed. A total of 136 venous blood samples were collected from 20 pregnant and 10 nonpregnant (control) asymptomatic Lipizzaner broodmares for biochemical analyses. Twelve parameters (albumin, total protein, urea, triglycerides, glucose, creatinine, alkaline phosphatase, aspartate transaminase, glutamate dehydrogenase, gammaglutamyltransferase, creatine kinase and lactate dehydrogenase) were measured.

Equine alpha-fetoprotein levels in Lipizzaner mares with normal pregnancies and with pregnancy loss.

Alpha-fetoprotein has proved to be a good indicator of fetal well-being in human medicine for decades. Although this molecule is present in most of the mammalian species including horses, reference values in healthy and high-risk pregnant mares have not yet been published. The aim of the present study was to determine whether equine alpha-fetoprotein (eqAFP) is a good indicator of complicated pregnancies in Lipizzaner mares.

Vector-borne transmission of Besnoitia besnoiti by blood-sucking and secretophagous flies: epidemiological and clinicopathological implications.

Background: Bovine besnoitiosis has been recently diagnosed in a three-parted herd of 796 Aubrac and Charolais beef cattle in Hungary. A large scale serological, histological and molecular survey was initiated in order to uncover important factors in the local epidemiology of the disease.

Findings: Blood samples were collected (three times from the whole herd, and repeatedly from selected animals) for serological screening by ELISA.