APS12-2, a non-competitive acetylcholinesterase inhibitor, is one of the synthetic analogues of polymeric alkylpyridinium salts (poly-APS) isolated from the marine sponge Reniera sarai. It is a non-competitive acetylcholinesterase inhibitor. In the present work the effects of APS12-2 were studied on isolated mouse phrenic nerve-hemidiaphragm muscle preparations, using twitch tension measurements and electrophysiological recordings. APS12-2 in a concentration-dependent manner blocked nerve-evoked isometric muscle contraction (IC50 = 0.74 µM), without affecting directly-elicited twitch tension up to 2.72 µM. We studied the influence of APS12-2 on endplate potentials in mouse diaphragm muscle fibers using intracellular microelectrode technique. The compound (0.007–3.40 µM) decreased the amplitude of miniature endplate potentials until a complete block by concentrations higher than 0.68 µM, without affecting their frequency. Full size endplate potentials, recorded after blocking voltage-gated muscle sodium channels, were inhibited by APS12-2 in a concentration-dependent manner (IC50 = 0.36 µM) without significant change in the resting membrane potential of the muscle fibers up to 3.40 µM. The compound also blocked acetylcholine-evoked inward currents in Xenopus oocytes in which Torpedo (α12β1γδ) muscle-type nicotinic acetylcholine receptors (nAChRs) have been incorporated (IC50 = 0.0005 µM) indicating a higher affinity of the compound for Torpedo (α12β1γδ) than for the mouse (α12β1γε) nAChR. Our data show for the first time that APS12-2 blocks neuromuscular transmission by a non-depolarizing mechanism through an action on postsynaptic nAChRs of the skeletal neuromuscular junction.
COBISS.SI-ID: 3587706
Original scientific article describes results about female sex behavior and hypothalamic expression of progesterone receptor in SF-1 knockout mice. It was established that sex differences in both, expression of female sex behavior and immunoexpression of progesterone receptor in the hypothalamus must be partially dependent on genes from sex chromosomes as sex specific differences were found also between male and female SF-1 KO mice that are never exposed to sex steroid hormones.
COBISS.SI-ID: 3520890
The use of large animals as an experimental model for novel treatment techniques has many advantages over the use of laboratory animals, so veterinary medicine is becoming an increasingly important translational bridge between preclinical studies and human medicine. The results of preclinical studies show that gene therapy with therapeutic gene encoding interleukin-12 displays pronounced antitumor effects in various tumor models. A number of different studies employing this therapeutic plasmid, delivered by either viral or non-viral methods, have also been undertaken in veterinary oncology. In cats, adenoviral delivery into soft tissue sarcomas has been employed. In horses, naked plasmid DNA has been delivered by direct intratumoral injection into nodules of metastatic melanoma. In dogs, various types of tumors have been treated with either local or systemic IL-12 electrogene therapy. The results of these studies show that IL-12 based gene therapy elicits a good antitumor effect on spontaneously occurring tumors in large animals, while being safe and well tolerated by the animals. Hopefully, such results will lead to further investigation of this therapy in veterinary medicine and successful translation into human clinical trials.
COBISS.SI-ID: 1383803
The aim of the study was to determine changes of serum cortisol and biochemical, haematological and antioxidant enzyme variables in the blood of horses during pre-slaughter period (in the lairage, 60 minutes before stunning, and in the stunning box) and during exsanguination in order to find out whether the horses will show physiological stress responses to stressors present in the slaughterhouse. A total of 24 Slovenian warm-blooded horses were included in the study. In horses, lactate, glucose and potassium concentrations, the activities of the serum muscle enzymes aspartate aminotransferase and creatine kinase, and values of most of the other biochemical and hematological variables were significantly higher at exsanguination, than in blood sampled while they were in the lairage and in the stunning box, which might partially be attributed to stimulation of the sympathetic nervous system, caused by stunning and bleeding. The values of cortisol, chloride, alanine aminotransferase and antioxidant enzymes, glutathione peroxidase and superoxide dismutase, were not significantly different between the pre-slaughter period and exsanguination. All selected blood variables were not significantly different between the lairage and stunning box sampling time, indicating no physiological stress responses of the investigated horses to stressors, such as novelty of the pre-slaughter environment and handling, present in the slaughterhouse between the lairage and the stunning box.
COBISS.SI-ID: 3495034
There is increasing evidence of an association between periodontal disease, systemic inflammation and systemic oxidative stress in the human and (less) in the veterinary literature. The systemic inflammatory response can also be evaluated by measuring nitric oxide (NO) and nitrites and nitrates (NOx) in biological fluids. Although NO has several important physiologic roles, excessive NO production can lead to nitroxidative tissue damage, which can be estimated by determining the amount of nitrotyrosine (NT) formation in proteins. The aim of this prospective clinical intervention study therefore was to evaluate systemic NO formation and nitroxidative stress in dogs (n = 32) with different stages of periodontal disease and the effect of comprehensive periodontal therapy. There was no significant difference in the NOx plasma levels within each group or across the groups before and after the treatment, but a noticeable increase in NOx plasma levels was observed in most severely affected animals after the treatment. Plasma NT was detected in only one third of the animals. NO levels varied greatly across individual dogs. This study therefore found no correlation between the severity of the periodontal disease and systemic NO status, but possible differences in NO formation/metabolism between the groups should be investigated further. Moreover, the data are suggestive of an overall increase in systemic NO response 2 weeks after periodontal treatment in dogs with advanced periodontal disease, but the response is greatly individually-dependent.
COBISS.SI-ID: 3600506