Publications by authors named "Kukorelli T"

Mycotoxin fumonisin B1 (FB1) a natural inhibitor of ceramide synthase contaminating mainly the corn-based food and feed may cause dysfunctions in the nervous system. In the present study peripheral neural dysfunctions were biomonitored after dietary FB1 exposure in rats. Daily oral doses of 6.

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Investigation of new neuromuscular blocking agents was started 30 years ago in Richter Ltd. This paper presents the results obtained by Richter's scientists. 2 compounds out of 100 bisquaternary ammonio steroid having androstane skeleton were selected for further pharmacological study.

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Investigation of agents with indol skeleton was started in Richter Ltd. 50 years ago. This paper presents the results obtained by Richter's scientists.

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Article Synopsis
  • Bimoclomol (BML) is a drug developed to manage symptoms of diabetic neuropathy and retinopathy, while BRX-220 is a new compound targeting diabetic complications and insulin resistance.
  • In a study on rats with induced type 1 diabetes, BRX-220 significantly improved nerve function, with motor and sensory nerve conduction velocities increasing by up to 91.3% and 93.2% respectively after a month of treatment.
  • Additionally, BRX-220 effectively reduced severe insulin resistance in both the STZ-induced diabetic rats and Zucker diabetic fatty rats, indicating its potential benefits for managing diabetes-related issues.
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Corn pellets, containing 30 mg/kg bw/day fumonisin B1 (FB1) or containing no FB1 were fed in two series of experiments to rats. Spontaneous and evoked potentials were measured in the neocortex both in vivo and in vitro in "corn fed control" rats and in rats after a five day dietary exposure to FB1. The FB1 content of corn was quantitated by HPLC.

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The influence of serotonergic and benzodiazepine type anxiolytic drugs on the cortical activation and sleep-wakefulness cycle were compared by evaluating the effects of ritanserin and deramciclane (EGIS-3886), two 5-HT2 receptor antagonists, and chlordiazepoxide on the electroencephalogram (EEG) in freely moving rats. Following drug administration (1, 3, and 10 mg/kg, PO for all drugs), EEG was continuously sampled for 6 h and power spectra were calculated for every 5 s to assess changes in slow wave activity and sleep phases. In a separate test, anticonvulsant effects of the drugs were examined in mice.

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A silent process involving both neural and vascular structures in diabetic retina persists for several years before clinically detectable retinopathy. Recordings of the electroretinogram (ERG) and visual evoked potential (VEP) provide early warning of abnormalities in the visual pathway of diabetic patients and animal models. Treatment of streptozotocin-diabetic rats for 1 or 2 months with the heat-shock protein coinducer bimoclomol, a drug ameliorating experimental neuropathy, prevented and corrected the abnormal increase in latency and reduction of amplitude of ERG and VEP waves both in acute and chronic experiments.

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A reduction in nerve conduction velocity and an increase in resistance to ischemic conduction failure are early signs of neural dysfunction in both diabetic patients and animal models of diabetes. The effect of Bimoclomol (BRLP-42), a drug under clinical development for the treatment of diabetic complications, on experimental peripheral neuropathy was examined in rats made diabetic by injection of streptozotocin. Daily oral doses of Bimoclomol (10 or 20 mg/kg) or control dose of gamma-linolenic acid (260 mg/kg), an agent with known neuropathy-improving effects, were administered for 3 months.

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Hypnogenic (HS) or arousing (AS) stimulations of the small intestine (INT), splanchnic (SPL), and vagal (VAG) nerves were used to modify the predatory behavior (PB) elicited by stimulating the lateral hypothalamus (LHS). HS induced EEG synchronization and sleep. AS aroused the cat from slow-wave sleep.

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Several techniques were developed to prevent sleep in animals in order to examine the biological role fulfilled by sleep; however, most were either stressful or difficult to accomplish routinely, especially in such a large animal as the cat. Electrical stimulation of activating structures in the brain presents a very attractive alternative to peripheral stimulation used by the usual sleep deprivation methods although it has been rarely tried. The paper describes a microcomputer-based system used to achieve sleep deprivation in cats by stimulating the hypothalamic predatory area with short trains.

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Neuronal activity was investigated by extracellular microelectrodes in the pallidal region of freely moving cats during wakefulness (W), slow-wave sleep (SWS) and paradoxical sleep (PS). The firing of 150 units from 35 points was examined. On the basis of the modifications of firing rates and patterns during the sleep-wakefulness cycle, 5 groups of neurons were distinguished.

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The effects of glutaurine (gamma-L-glutamyl taurine, Litoralon, Chinoin, Budapest) on the aggressive behaviour and sleep-wakefulness cycle were studied in freely moving cats. Glutaurine, even in doses as low as 0.1 microgram/kg, was found significantly to shorten the latency of the rat-killing reaction elicited by hypothalamic stimulation.

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Neuronal responses from the ventro-postero-medial (VPM) and reticular (NR) nuclei of cat thalamus to vagal stimulation was recorded during wakefulness (W), slow-wave-sleep (SWS), and paradoxical sleep (PS) using chronically implanted microelectrodes. Cellular firing was facilitated in NR and depressed in VPM when weak, hyponogenic stimuli were delivered to the vagal nerve during W and SWS. Higher intensity vagal stimulation increased firing frequency and duration of discharge in both nuclei.

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Neuronal activity was studied in the basal forebrain area (BFA) of freely moving cats during wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS). Two classically synchronizing and hypnogenic regions, the preoptic area (POA) and the olfactory tubercle (OT) were explored by microelectrodes. Compared to W, the discharge rate in most of the POA cells was not modified or was slightly reduced by SWS, but it was increased by PS.

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The effects of classic conditioning on the viscerosensory evoked potentials (EPs) were studied in twenty cats during wakefulness (W), slow-wave-sleep (SWS) and paradoxical sleep (PS). Four types of the experiment were performed on four groups of animals. Weak, non-painful stimulation of the small intestine or of the left splanchnic nerve was used as conditional stimulus (CS) in all experiments.

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Modification of the viscerosensory evoked potentials (EPs) were studied during the sleep-wakefulness cycle of the rat. Electrical stimuli of various intensity were delivered either to the mucosal surface of a fistula of the small intestine or to the left splanchnic nerve during wakefulness (W), drowsiness (D), slow-wave-sleep (SWS), and paradoxical sleep (PS). The average EPs were recorded from the somatosensory (SI and SII) and associative (AS) areas of the cortex, the ventrobasal complex of the thalamus (VPL), the posterior hypothalamus (HPT) and the dorsal hippocampus (HPC).

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The effects of vagal and radial stimulation on neuronal activity in the basal forebrain area (BFA) of chloralose-anaesthetized cats were studied. Sixty-five neurones were examined from 29 points of BFA. The observed neurones were divided into four groups according to spike amplitudes and spontaneous firing rates.

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The influence of afferent impulses of intestinal origin on the sleep stages was studied in fed and starved cats. Low-frequency electrical stimulation of the mucosal surface in a small intestinal fistula reduced the latency of sleep onset. The number of slow wave sleep episodes decreased, but their mean duration increased during stimulation.

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1. In freely moving cats, the cortical desynchronization elicited by painless rhythmic distension, or by low voltage electric stimulation, of the small intestine in drowsiness and slow wave sleep is extinguished following a few repetitions. After extinction of the arousal reaction, similar intestinal stimulation was systematically followed by the appearance of synchronized activity, or an increase of spontaneous synchronization, in the explored cortical areas (parieto-occipital).

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