Wyniki wyszukiwania - Biblioteka Nauki

1

Metabotropic glutamate receptors as targets for psychotropic drugs

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Slawinska A. , Wieronska J. M. , Stachowicz K. , Lason M. , Gruca P. , Papp M. , Kusek M. , Tokarski K. , Doller D. , Pilc A.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

EN

Several studies have suggested that modulation of the glutamatergic system via metabotropic glutamate receptors (mGlu) could be a new, efficient way to achieve antipsychotic-like effects. Such an activity was shown for mGlu2/3 and mGlu5 receptor agonists/positive modulators, as well as for ACPT-I or LSP1-2111, a non-selective mGlu group III receptors orthosteric agonists. Herein, we report the pharmacological actions of Lu AF21934 and Lu AF32615, a novel, selective and brain-penetrant positive allosteric modulators (PAMs) of the mGlu4receptor with proven anxiolytic, but not antidepressant-like activity, in several tests reflecting positive, negative and cognitive symptoms of schizophrenia in rodents. MK-801- and amphetamine-induced hyperactivities, as well as DOI-induced head twitches in mice were used as models for positive symptoms. Furthermore, the effect of Lu AF21934 on DOI-induced frequency of spontaneous excitatory postsynaptic currents (EPSCs) in slices from mouse brain frontal cortices was investigated. The MK-801 induced disruption of social interaction and of spatial delayed alternation in rats were used as models for negative and cognitive symptoms, respectively. Lu AF21934 (0.1, 0.5, 2 and 5 mg/kg) and Lu AF32615 (2, 5 and 10 mg/kg) dose-dependently inhibited both MK-801 and amphetamine-induced hyperactivities. Concomitantly, Lu AF 21935, an inactive enantiomer of Lu AF21934, was not effective. Moreover, the drugs antagonized DOI-induced head twitches in mice. DOI-induced increased frequency of spontaneous EPSCs was also decreased by Lu AF21395 and Lu AF32615. The MK-801-induced disruption in the social interaction test, measured as number of episodes and total time of episodes between two rats, was abolished by Lu AF21394 at a dose of 0.5 mg/kg and Lu AF32615 at a dose of 10 mg/kg. In the delayed spatial alternation test, the effective doses of Lu AF21934 were 1 and 2 mg/kg, and the AF32615 was active at a dose of 10 mg/kg. Altogether, we propose that mGlu4 receptor can be consider as promising target for the development of novel antipsychotic drugs, acting as a positive allosteric modulators of the receptor.

2

Photochemically-induced vascular damage in brain cortex. Transmission and scanning electron microscopy study

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Gajkowska B. , Frontczak-Baniewicz M. , Gadamski R. , Barskov I.

Acta Neurobiologiae Experimentalis

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1997

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tom 57

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nr 3

3

Denervation of arterial muscle rings in the limbs of the experimental animals

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Wegrzyn M. , Tokarska E. , Huk-Wieliczuk E.

Bulletin of the Polish Academy of Sciences. Biological Sciences

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1999

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tom 47

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nr 1

4

Ultrastructural evaluation of pancreatic parenchyma in the course of intoxication with ethanol

100%

Kot K. , Boratynski Z. , Pedrycz A. , Mendocha J. , Rubaj J. , Cichacz B. , Plaskota W.

Bulletin of the Veterinary Institute in Puławy

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2008

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tom 52

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nr 3

EN

The experiment was performed on rats that were given ethanol ad libitum for 4 weeks. After decapitation of the animals, pancreatic sections were prepared for an electron microscopy. A significant broadening of the rough endoplasmic reticulum cisterns in the vesicular cells was observed as well as the presence of nuclei with irregular outlines resulted from placation of the nuclear membrane, which is worth of attention. Such a picture suggests that the examined cells had a lowered metabolic ability.

5

Central beta-adrenergic receptors are involved in the mechanism of porphyrin-induced convulsive effect in mice

84%

Maksym B. , Habdas J. , Plech A.

Pestycydy

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2005

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nr 4

55-63

6

mGluR5 NAMs as a potential treatments for L-DOPA-induced dyskinesia, Fragile X and gastroesophageal reflux

84%

Danysz W. , Dekundy A. , Gravius A. , Hechenberger M. , Klein K. U. , Parson C. G.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

EN

Subtype 5 metabotropic glutamate receptors (mGluR5) have been implicated in the control of movement, mood, cognition, and nociception. Correspondingly, different mGluR5 antagonists have been shown to alleviate L-DOPA-induced dyskinesia (LID), anxiety, and pain in experimental animals. A novel proprietary mGluR5 antagonist 6,6-dimethyl-2-phenylethynyl-7,8-dihydro-6H-quinolin-5-one (MRZ-8676) having ~20 nM affinity to mGluR5, was tested in the rat models of LID, persistent pain, and anxiety. Effects of MRZ-8676 on motor performance and on learning were investigated. Presence of MRZ-8676 at target receptor in the brain was ascertained by measuring its extracellular concentrations and mGluR5 occupancy in vivo. MRZ-8676 had 20–25% bioavailability after oral treatment reaching Tmax at 2.9 h while T1/2 was 11.2 h. At 25 mg/kg p.o. Cmax was 348 ng/ml and AUC 2045 ng*h/ ml). In in vivo microdialysis experiments, pharmacologically effective p.o. doses of MRZ-8676 were found to achieve free brain concentrations sufficient to completely block mGluR5, i.e. above 100 nM. This finding was further confirmed by the results of the in vivo mGluR5 receptor occupancy study showing ED50 of ca. 5 mg/kg after i.p. administration. MRZ-8676 strongly and dose-dependently reduced abnormal involuntary movements in the 6-hydroxydopamine (6-OHDA) rat model of LID starting at 25 mg/kg. No tolerance of the antidyskinetic effects was observed upon subchronic (6-day) treatment with 75 mg/kg p.o. MRZ-8676 produced moderate anxiolytic effect in two rodent anxiety models, the contextual fear conditioning (at 25 mg/kg) and the elevated plus maze (25 mg/kg). At the same dose, MRZ-8676 also attenuated reaction to pain in the first phase of formalin test, the rat model of persistent pain induction. MRZ-8676 did not produce any detrimental effects on motor performance of rats as investigated rotarod test up to 150 mg/kg p.o. In the open field short lasting increase in locomotor activity was observed (25–150 mg/kg). However, MRZ-8676 dose dependently impaired learning in aversive learning paradigm of the contextual fear conditioning test reaching significance at 75 mg/kg which is above minima effective dose in tests for dyskinesia, pain or anxiety. Summing up, MRZ-8676 has clear-cut antidyskinetic properties with a sufficient therapeutic window. Moreover, it has anxiolytic and analgesic properties. Receptor occupancy and microdialysis studies indicate that the behavioural effects of MRZ-8676 are associated with blockade of mGluR5 in the brain. Moreover, preclinical rational and status of clinical trials with mGluR5 NAMs in Parkinson´s disease, Fragile X and gastroesophageal reflux will be presented.

7

Zastosowanie próby na traszkach (Triturus cristatus) w celu szybkiego rozpoznawania własciwosci rakotwórczych barwników. Część II

84%

Krauze S. , Stec E. , Mlodecki H.

Roczniki Państwowego Zakładu Higieny

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1963

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tom 14

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nr 2

8

Effect of lead and quercetin administration on magnesium exchange in tissues of experimental rats

84%

Andrusishina I. , Stezhka V. , Lampeka E. , Holub I.

Journal of Elementology

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2004

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tom 09

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nr 4

543-549

9

Visual discrimination learning in spontaneously hypertensive [SHR] and Wistar normontensive rats: computerized analysis of choice strategies

84%

Niewiadomska G. , Niewiadomski W.

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nr 2

10

Dual response of cerebrocortical blood flow and arterial blood pressure to transient CO2 stimulus after inhibition of nitric oxide synthesis in rats

84%

Wolk R. , Sieminska J. , Trzebski A.

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nr 2

11

Free-radical method for L-ascorbic acid determination in tissues of experimental animals

84%

Gonet B.

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tom 18

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nr 2

12

Potato genetically modified by 14-3-3 protein repression in growing rat diets. Part II: Health status of experimental animals

84%

Kosieradzka I. , Sawosz E. , Szopa J. , Bielecki W.

Polish Journal of Food and Nutrition Sciences

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2008

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tom 58

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nr 3

EN

For 4 weeks, male outbred IF2Jaz rats, divided into 4 groups (n=10), were administered ad libitum diets with 30% addition of dried tubers of transgenic potatoes with repression of isoform a, c as well as a and c of 14-3-3 protein (experimental groups) or with the addition of non-transgenic potatoes of Desiree cultivar (control group). The administration of transgenic potatoes did not affect the growth rate of model animals nor most of the analysed parameters of their health status. Neither anti-nutritional, nor immunostimulatory or toxic effects of the experimental diets were demonstrated. Yet, in liver tissue of rats fed a diet with transgenic potatoes J4 and G1 the concentration of 8-oxo-2’deoxyguanosine – a biomarker of oxidative damage to DNA – was higher than in animals administered a diet with non-transgenic potatoes. Results obtained in the study indicate a threat to the health status of animals fed diets with a high content of genetically-modified potatoes with repression of 14-3-3 protein.

13

Regulation of feeding behaviour, with special reference to histamine

84%

Tuomisto L.

Journal of Physiology and Pharmacology

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1994

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tom 45

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nr 4

14

Healthly properties of Jerusalem artichoke flour [Helianthus tuberosus L.]

84%

Cieslik E. , Kopec A. , Praznik W.

Electronic Journal of Polish Agricultural Universities. Series Food Science and Technology

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2005

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tom 08

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nr 2

EN

The research was undertaken to determine the effect of Jerusalem artichokes tuber flour - Jerusalem artichoke flour on total cholesterol content, concentrations of HDL, LDL+VLDL lipoproteins and triglycerides in blood of experimental rats. The animals were divided into four experimental groups and fed for 24 days with mixtures containing various proportions of Jerusalem artichoke flour. On the last day of the experiment the rodents were anaesthetised and blood was sampled directly from the heart. Total cholesterol, HDL and triglycerides were assayed in blood serum. The content of LDL+ VLDL lipoproteins were calculated from the difference between total cholesterol and HDL lipoproteins. A declining tendency was observed for total cholesterol level and LDL+VLDL lipoproteins when the diet was supplemented with the Jerusalem artichoke flour. On the other hand the amount of triglycerides decreased statistically significantly in blood serum of animals fed diets with 10% and 15% supplement of Jerusalem artichoke flour.

15

The morphological and histochemical neurosecretory magnocellular system in the rat after administration of chlorpromazine

84%

Arciszewska E. , Borowska H. , Sawicki B.

Folia Morphologica

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2004

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tom 63

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nr 1

EN

The effect of chlorpromazine (CPZ) on the neurosecretory action of the hypothalamo-hypophyseal system was investigated in 72 male rats. The experimental animals received CPZ in a dose of 0.4 mg, 4.0 mg and 20.0 mg/kg b.w. for 30 days. The rats were sacrificed by decapitation at 24 h and 7 days after the last dose of the drug. The neurosecretory material was stained with paraldehyde fuchsin in the supraoptic nucleus, paraventricular nucleus, eminentia mediana and neurohypophysis, the tigroid was stained with toluidine blue and the acid phosphatase activity was evaluated histoenzymatically. It was found that CPZ reduced the content of the neurosecretory material after 24 h, while an increase was observed 7 days after the last drug administration.

16

Effect of short time exposure of rats to extreme low temperature on some plasma and liver enzymes

84%

Romuk E. , Birkner E. , Skrzep-Poloczek B. , Jagodzinski L. , Stanek A. , Wisniowska B. , Sieron A.

Bulletin of the Veterinary Institute in Puławy

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2006

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tom 50

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nr 1

17

Sources of the autonomic and afferent fibers in the horns and body of the uterus in dogs

84%

Boratynski Z. , Flieger S. , Strzalka B. , Zacharko A. , Wrona Z.

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tom 44

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nr 1

EN

The study was conducted on sexually mature female dogs. The extirpation of the different parts (both homs and body) of the uterus was performed. After 21 days, the following material for examination was collected: the brain stem, the thoraco-lumbo-sacral part of the spinal cord with its all spinal ganglia, sympathetic chain and also the ganglia and nerve plexuses of the abdominal and pelvic cavities. The experiments produced retrograde changes in nerve cells of the central and peripheral nervous system in the experimental animals. The comparison of the localization of retrograde changes in the neurons of the experimental animals and those of the control animal provided the basis for tracing the localization of the nerve cells which are the source of the nerve fibres supplying the horns and body of the uterus. The observations performed establish that these fibres are of multisource origin.

18

Dzialanie insektycydow N-metylokarbaminianowych na aminy katecholowe nadnerczy szczura

67%

Jablonska J. , Brzezinski J.

Roczniki Państwowego Zakładu Higieny

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1992

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tom 43

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nr 1

75-84

PL

Badano wpływ zatrucia karbarylem i propoksurem na poziom adrenaliny i noradrenaliny w nadnerczach szczura. Stwierdzono zmiany poziomu tych amin katecholowych. Zakres ilościowy i kierunek zmian był współzależny od czasu działania oraz sposobu i wysokości dawkowania insektycydów.

EN

The influence of acute (50% LD50), subacute (10% and 20% LD50) and 12-weeks (5% LD50 intoxication with carbaryl and propoxur on the adrenaline (A) and noradrenaline (NA) level in the rat adrenal glands was investigated. The level of A and NA was decreased to very low values after acute intoxication with carbaryl. Probably this effect reu sit from increase of release of accumulated acetylcholine during poisoning. With lower dosages of carbaryl and propoxur (10% and 20% LD50) different biochemical effect in adrenal glands has been observed. There was a significant decrease in the level of A and simultaneously increase in the NA level. Intoxication with 20% LD50 dose of propoxur has caused smaller alterations than the same dose of carbaryl. Carbaryl when given in a dose of 5% LD50 (12 weeks) produced within first six weeks similar changes to that which can be observed during subacute poisoning. Such character of changes (increase of NA level and decrease of A level) indicate that probably N-methylcarbamate insecticides inhibited the last step of biosynthesis of adrenaline. It can be due to inhibition of N-methyltransferase noradrenaline activity.

19

Dyskusje nad etyka w doswiadczalnictwie i hodowli zwierzat

67%

Barabasz B.

Biuletyn Informacyjny dla Hodowców Szynszyli

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1998

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nr 3

15-16

20

Selenite and selenium enriched yeast in experimental cadmium intoxication in rats

67%

Laszczyca P. , Kawka-Serwecinska E. , Chrascina M. , Migula P.

Acta Biologica Silesiana

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1993

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tom 23

55-65