Search results for "Azine"
showing 10 items of 1589 documents
Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats
2019
Abstract Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE). Here, we performed video-EEG recording in behaving rats treated with the pro-convulsant age…
Mitochondrial Fatty Acid β-Oxidation Inhibition Promotes Glucose Utilization and Protein Deposition through Energy Homeostasis Remodeling in Fish.
2020
BACKGROUND: Fish cannot use carbohydrate efficiently and instead utilize protein for energy supply, thus limiting dietary protein storage. Protein deposition is dependent on protein turnover balance, which correlates tightly with cellular energy homeostasis. Mitochondrial fatty acid β-oxidation (FAO) plays a crucial role in energy metabolism. However, the effect of remodeled energy homeostasis caused by inhibited mitochondrial FAO on protein deposition in fish has not been intensively studied. OBJECTIVES: This study aimed to identify the regulatory role of mitochondrial FAO in energy homeostasis maintenance and protein deposition by studying lipid, glucose, and protein metabolism in fish. M…
Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent.
2018
Abstract Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in the response towards cholestatic hepatotoxins after short-term (48–72 hours) and long-term repeated exposures (14 days). The cholestatic liabilities of drugs were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid mixture. In 2D-sw culture, cyclosporine A and amiodarone presented cl…
Behavioral and Cortical Correlates of Self-Suppression, Anticipation, and Ambivalence in Rat Tickling.
2019
The relationship between tickling, sensation, and laughter is complex. Tickling or its mere anticipation makes us laugh, but not when we self-tickle. We previously showed rat somatosensory cortex drives tickling-evoked vocalizations and now investigated self-tickle suppression and tickle anticipation. We recorded somatosensory cortex activity while tickling and touching rats and while rats touched themselves. Allo-touch and tickling evoked somatotopic cortical excitation and vocalizations. Self-touch induced wide-ranging inhibition and vocalization suppression. Self-touch also suppressed vocalizations and cortical responses evoked by allo-touch or cortical microstimulation. We suggest a glo…
Ranolazine-Mediated Attenuation of Mechanoelectric Feedback in Atrial Myocyte Monolayers.
2020
[EN] Background Mechanical stretch increases Na(+)inflow into myocytes, related to mechanisms including stretch-activated channels or Na+/H(+)exchanger activation, involving Ca(2+)increase that leads to changes in electrophysiological properties favoring arrhythmia induction. Ranolazine is an antianginal drug with confirmed beneficial effects against cardiac arrhythmias associated with the augmentation ofI(NaL)current and Ca(2+)overload. Objective This study investigates the effects of mechanical stretch on activation patterns in atrial cell monolayers and its pharmacological response to ranolazine. Methods Confluent HL-1 cells were cultured in silicone membrane plates and were stretched to…
1,3,5-Triazines: A promising scaffold for anticancer drugs development
2017
This review covering literature reports from the beginning of this century to 2016 describes the synthetic pathways, the antitumor activity, the structure-activity relationship and, whenever reported, the possible mechanism of action of 1,3,5-triazine derivatives as well as of their hetero-fused compounds. Many 1,3,5-triazine derivatives, both uncondensed and hetero-fused, have shown remarkable antitumor activities and some of them reached clinical development.
Discovery and characterization of two novel CB1 receptor splice variants with modified N-termini in mouse
2017
Numerous studies have been carried out in the mouse model, investigating the role of the CB1 cannabinoid receptor. However, mouse CB1 (mCB1) receptor differs from human CB1 (hCB1) receptor in 13 amino acid residues. Two splice variants, hCB1a and hCB1b, diverging in their amino-termini, have been reported to be unique for hCB1 and, via different signaling properties, contribute to CB1 receptor physiology and pathophysiology. We hypothesized that splice variants also exist for the mCB1 receptor and have different signaling properties. On murine hippocampal cDNA, we identified two novel mCB1 receptor splice variants generated by splicing of introns with 117 bp and 186 bp in the N-terminal dom…
Levosimendan protects human hepatocytes from ischemia-reperfusion injury.
2017
Background Ischemia-reperfusion injury (IRI) is a major challenge in liver transplantation. The mitochondrial pathway plays a pivotal role in hepatic IRI. Levosimendan, a calcium channel sensitizer, was shown to attenuate apoptosis after IRI in animal livers. The aim of this study was to investigate the effect of levosimendan on apoptosis in human hepatocytes. Methods Primary human hepatocytes were either exposed to hypoxia or cultured under normoxic conditions. After the hypoxic phase, reoxygenation was implemented and cells were treated with different concentrations of levosimendan (10ng/ml, 100ng/ml, 1000ng/ml). The overall metabolic activity of the cells was measured using 3-(4,5-dimeth…
Inhibited fatty acid β-oxidation impairs stress resistance ability in Nile tilapia (Oreochromis niloticus)
2017
Energy metabolism plays important roles in stress resistance and immunity in mammals, however, such functions have not been established in fish. In the present study, Nile tilapia (Oreochromis niloticus) was fed with mildronate, an inhibitor of mitochondrial fatty acid (FA) β-oxidation, for six weeks subsequently challenged with Aeromonas hydrophila and ammonia nitrogen exposure. Mildronate treatment reduced significantly l-carnitine concentration and mitochondrial FA β-oxidation efficiency, while it increased lipid accumulation in liver. The fish with inhibited hepatic FA catabolism had lower survival rate when exposed to Aeromonas hydrophila and ammonia nitrogen. Moreover, fish fed mildro…
Patient-derived solitary fibrous tumour xenografts predict high sensitivity to doxorubicin/dacarbazine combination confirmed in the clinic and highli…
2017
Abstract Background Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. Material and methods Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were tr…