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1.
Sci Rep ; 12(1): 18751, 2022 Nov 05.
Article in English | MEDLINE | ID: mdl-36335151

ABSTRACT

Potassium hexavanadate (K2V6O16·nH2O) nanobelts have been synthesized by the LPE-IonEx method, which is dedicated to synthesis of transition metal oxide bronzes with controlled morphology and structure. The electrochemical performance of K2V6O16·nH2O as a cathode material for lithium-ion batteries has been evaluated. The KVO nanobelts demonstrated a high discharge capacity of 260 mAh g-1, and long-term cyclic stability up to 100 cycles at 1 A g-1. The effect of the vanadium valence state and unusual construction of the nanobelts, composed of crystalline and amorphous domains arranged alternately were also discussed in this work. The ex-situ measurements of discharged electrode materials by XRD, MP-AES, XAS and XPS show that during the subsequent charge/discharge cycle the potassium in the K2V6O16·nH2O structure are replacing by lithium. The structural stability of the potassium hexavandate during cycling depends on the initial vanadium valence state on the sample surface and the presence of the "fringe free" domains in the K2V6O16·nH2O nanobelts.

2.
J Environ Manage ; 262: 110314, 2020 May 15.
Article in English | MEDLINE | ID: mdl-32250797

ABSTRACT

This article considers intertwined issues relating to the green economy, protected areas, green jobs, and the Environmental Goods and Services Sector (EGSS). The article discusses the most common approaches towards greening economies, all these being based on the concept of sustainable development, and presents an analysis of how green jobs can be used to address the issue of unemployment among young people in Poland, the Czech Republic and Belgium. Data were compared for selected groups in the European Classification of Economic Activities (NACE). It is observed that in both Poland and Belgium around 15% of young people find their first employment in the green jobs sector, but in the Czech Republic, the proportion is far lower (1.83%). It is concluded that an increasing emphasis on building the green economy provides excellent employment opportunities for young people seeking their first job.


Subject(s)
Employment , Belgium , Czech Republic , European Union , Poland
3.
Pharmazie ; 71(11): 655-659, 2016 11 02.
Article in English | MEDLINE | ID: mdl-29441971

ABSTRACT

Phospholipids play an important role in the biochemical and physiological processes of cells. An association between disturbed phospholipids metabolism in neuronal tissue and anxiety it was shown. The aim of this study was to examine the anxiolytic properties of phospholipids obtained from a new generation of eggs enriched in n-3 PUFA and its effect on locomotor activity in rat behavioral studies N-3 PUFA-enriched egg yolk phospholipids ("super lecithin") were added to the standard feed. Rats were fed by chow without (control group) or with (experimental group) addition of phospholipids. After six weeks of supplementation, the effect of phospholipids on locomotor activity in the open field test and anxiolytic properties in elevated plus maze and Vogel conflict test were examined. In the open field test the total distance traveled in the experimental group was similar to the control group. In the elevated plus maze test a six weeks phospholipids' administration significantly prolonged the time spent on the open arms by rats from experimental group compared to control group. The number of entries into the open arms was also increased but the difference was not statistically significant. The number of punished drinking water in the Vogel conflict test increased significantly in experimental versus control group. The obtained results suggest that the phospholipids isolated from n-3 PUFA enriched egg yolk have a specific anxiolytic effect, without general sedative influence.


Subject(s)
Anti-Anxiety Agents/pharmacology , Behavior, Animal/drug effects , Egg Yolk/chemistry , Fatty Acids, Omega-3/pharmacology , Phospholipids/pharmacology , Animals , Conflict, Psychological , Exploratory Behavior/drug effects , Male , Motor Activity/drug effects , Rats , Rats, Wistar
4.
J Physiol Pharmacol ; 66(2): 233-47, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25903954

ABSTRACT

Fenofibrate, a well-known normolipidemic drug, has been shown to exert strong anticancer effects against tumors of neuroectodermal origin including glioblastoma. Although some pharmacokinetic studies were performed in the past, data are still needed about the detailed subcellular and tissue distribution of fenofibrate (FF) and its active metabolite, fenofibric acid (FA), especially in respect to the treatment of intracranial tumors. We used high performance liquid chromatography (HPLC) to elucidate the intracellular, tissue and body fluid distribution of FF and FA after oral administration of the drug to mice bearing intracranial glioblastoma. Following the treatment, FF was quickly cleaved to FA by blood esterases and FA was detected in the blood, urine, liver, kidney, spleen and lungs. We have also detected small amounts of FA in the brains of two out of six mice, but not in the brain tumor tissue. The lack of FF and FA in the intracranial tumors prompted us to develop a new method for intracranial delivery of FF. We have prepared and tested in vitro biodegradable poly-lactic-co-glycolic acid (PLGA) polymer wafers containing FF, which could ultimately be inserted into the brain cavity following resection of the brain tumor. HPLC-based analysis demonstrated a slow and constant diffusion of FF from the wafer, and the released FF abolished clonogenic growth of glioblastoma cells. On the intracellular level, FF and FA were both present in the cytosolic fraction. Surprisingly, we also detected FF, but not FA in the cell membrane fraction. Electron paramagnetic resonance spectroscopy applied to spin-labeled phospholipid model-membranes revealed broadening of lipid phase transitions and decrease of membrane polarity induced by fenofibrate. Our results indicate that the membrane-bound FF could contribute to its exceptional anticancer potential in comparison to other lipid-lowering drugs, and advocate for intracranial delivery of FF in the combined pharmacotherapy against glioblastoma.


Subject(s)
Biodegradable Plastics/pharmacokinetics , Brain Neoplasms/drug therapy , Brain/metabolism , Drug Carriers/pharmacokinetics , Fenofibrate/analogs & derivatives , Glioblastoma/drug therapy , Animals , Brain/drug effects , Cell Line, Tumor , Female , Fenofibrate/pharmacokinetics , Fenofibrate/pharmacology , Humans , Lactic Acid/pharmacokinetics , Mice , Mice, Nude , Polyglycolic Acid/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers/pharmacokinetics , Tissue Distribution
5.
Biomed Mater Eng ; 25(2): 117-25, 2015.
Article in English | MEDLINE | ID: mdl-25813950

ABSTRACT

The aim of the present study was to determine the degradability of aliphatic polyurethanes, based on a different amount of synthetic, atactic poly[(R,S)-3-hydroxybutyrate] (a-PHB), in hydrolytic (phosphate buffer) and oxidative (H2O2/CoCl2) solutions. The soft segments were built with atactic poly[(R,S)-3-hydroxybutyrate] and polycaprolactone or polyoxytetramethylenediols, whereas hard segments were the reaction product of 4,4'-methylenedicyclohexyl diisocyanate and 1,4-butanediol.The selected properties - density and morphology of polymer surfaces - which could influence the sensitivity of polymers to degradation processes - were analyzed.The analysis of molecular mass (GPC), thermal properties (DSC) and the sample weight changes were undertaken to estimate the degree of degradability of polymer samples after incubation in environments studied.Investigated polyurethanes were amorphous with the very low amount of crystalline phases of hard segments.The polyurethane synthesized with a poly[(R,S)-3-hydroxybutyrate] and polyoxytetramethylenediol at a molar ratio of NCO:OH=3.7:1 (prepolymer step) appeared as the most sensitive for both degradative solutions. Its weight and molecular mass losses were the highest in comparison to other investigated polyurethanes.It could be expected that playing with the amount of poly[(R,S)-3-hydroxybutyrate] in polyurethane synthesis the rate of polyurethane degradation after immersion in living body would be modeled.


Subject(s)
3-Hydroxybutyric Acid/chemistry , Biocompatible Materials/chemistry , Polyurethanes/chemistry , Butylene Glycols/chemistry , Calorimetry, Differential Scanning , Cobalt/chemistry , Hydrogen Peroxide/chemistry , Hydrolysis , Isocyanates/chemistry , Microscopy , Molecular Weight , Polyesters/chemistry
6.
Pharmazie ; 68(8): 685-8, 2013 Aug.
Article in English | MEDLINE | ID: mdl-24020125

ABSTRACT

Polyunsaturated fatty acids play an important role in the human organism. They guarantee a normal function of nervous cells, influence neurotransmission, and build some elements of cellular membranes. Several reports indicate an association between a deficiency of polyunsaturated fatty acids and depression. The aim of this study was to examine the effects of diet supplemented with fish oil, which is rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) and n-3 PUFAs enriched phospholipids ("super lecithin") obtained from designed eggs on anhedonic-like response and body weight in the rat chronic mild stress (CMS) model of depression. The results showed that neither fish oil nor n-3 PUFAs enriched egg yolk phospholipids supplementation reversed disturbances caused by CMS, such as anhedonic-like state or reduction of body weight gain.


Subject(s)
Anhedonia , Body Weight/drug effects , Depression/pathology , Depression/psychology , Egg Yolk/chemistry , Fatty Acids, Omega-3/pharmacology , Fish Oils/pharmacology , Phospholipids/chemistry , Stress, Psychological/drug therapy , Stress, Psychological/psychology , Analysis of Variance , Animals , Diet , Dietary Supplements , Lecithins/pharmacology , Male , Rats , Rats, Wistar
7.
Toxicology ; 280(1-2): 24-32, 2011 Feb 04.
Article in English | MEDLINE | ID: mdl-21108985

ABSTRACT

This paper examines the effect of pre- and neonatal exposure of rats to lead (0.1% lead acetate in drinking water, resulting in rat offspring whole blood lead concentration (Pb-B) 4µg/dL) on the energy status of neuronal mitochondria by measuring changes in ATP, ADP, AMP, adenosine, TAN concentration, adenylate energy charge value (AEC) and mitochondrial membrane potential in primary cerebellar granule neurons (CGC) in dissociated cultures. Fluorescence studies were performed to imaging and evaluate mitochondria mass, mitochondrial membrane potential, intracellular and mitochondrial reactive oxygen species (ROS) production. The Na(+)/K(+) ATPase activity in intact CGC was measured spectrophotometrically. Our data shows that pre- and neonatal exposure of rats to Pb, even below the threshold of whole blood Pb value considered safe for people, affects the energy status of cultured primary cerebellar granule neurons through a decrease in ATP and TAN concentrations and AEC value, inhibition of Na(+)/K(+) ATPase, and increase in intracellular and mitochondrial ROS concentration. These observations suggest that even these low levels of Pb are likely to induce important alterations in neuronal function that could play a role in neurodegeneration.


Subject(s)
Cerebellum/drug effects , Energy Metabolism/drug effects , Fetus/drug effects , Lead/toxicity , Adenosine Triphosphate/biosynthesis , Animals , Animals, Newborn , Cells, Cultured , Cerebellum/cytology , Cerebellum/metabolism , Female , Lead/metabolism , Membrane Potential, Mitochondrial/drug effects , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors
8.
Pharmazie ; 64(9): 595-7, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19827302

ABSTRACT

The involvement of nitric oxide in the gastroprotective effect of ACEA (arachidonyl-2-chloroethylamide), a selective cannabinoid CB1 receptor agonist, on aspirin-induced gastric ulceration was studied in rats. ACEA (3 mg/kg i.p.) significantly reduced gastric ulcer formation. The gastroprotection of ACEA was attenuated by pretreatment with L-NAME (25 and 50 mg/kg i.p.), a nitric oxide synthase inhibitor. The combination of L-arginine (300 mg/kg i.v.), a precursor of nitric oxide with L-NAME (50 mg/kg i.p.) reversed the protective activity of ACEA (3 mg/kg i.p.). These results suggest that endogenous nitric oxide may be involved in the protective effect of ACEA.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Anti-Ulcer Agents , Arachidonic Acids/pharmacology , Aspirin , Nitric Oxide/physiology , Receptor, Cannabinoid, CB1/agonists , Stomach Ulcer/prevention & control , Animals , Arginine/pharmacology , Enzyme Inhibitors/therapeutic use , Female , Male , NG-Nitroarginine Methyl Ester/therapeutic use , Nitric Oxide Synthase/antagonists & inhibitors , Rats , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/physiopathology
9.
Pharmazie ; 64(9): 598-601, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19827303

ABSTRACT

Through the CB1 receptor cannabinoids modulate serotonin (5-hydroxytryptamine, 5-HT) release in the central nervous system which is connected with some of their pharmacological effects, especially antidepressant activity. 5-HT has many important physiological functions also in the periphery, particularly in the circulatory system and digestive tract. 5-HT dysfunction may be involved in some diseases pathogenesis including hypertension, migraine, cardiac disorders, cerebral ischemia or peripheral vascular diseases. Cannabinoids possible influence on 5-HT release in peripheral tissues may be clinically significant. The aim of the present study was to investigate the influence of ACEA (arachidonyl-2-chloroethylamide), a selective cannabinoid CB1 receptor agonist on whole blood (WB) and platelet-poor plasma (PPP) 5-HT levels. The experiments were carried out on male and female Wistar rats. ACEA (3 mg/kg i.p.) was given alone and in combination with a selective CB1 receptor antagonist AM 251 (3 mg/kg i.p.). Concentrations of 5-HT in WB and PPP were determined by enzyme-linked immunosorbent assay (Serotonin ELISA). ACEA significantly decreased concentration of 5-HT in WB (to 61%, p < 0.02) and its effect was blocked by AM 251. ACEA also reduced of 5-HT in PPP (to 62%) however, the difference was statistically insignificant. Research results reveal that due to CB1 receptor stimulation, ACEA reduces 5-HT contents in bloodstream. This effect is probably the result of inhibition of 5-HT release from gastrointestinal tract.


Subject(s)
Arachidonic Acids/pharmacology , Blood Platelets/physiology , Plasma/chemistry , Receptor, Cannabinoid, CB1/agonists , Serotonin/blood , Animals , Enzyme-Linked Immunosorbent Assay , Female , Male , Piperidines/pharmacology , Pyrazoles/pharmacology , Rats , Rats, Wistar , Receptor, Cannabinoid, CB1/antagonists & inhibitors
10.
Pharmazie ; 61(6): 517-21, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16826970

ABSTRACT

A two-step, general synthesis of 1-phenyl-2-(4-aryl-1,3,4,5-tetrahydropyrido[2,3-b][1,4]diazepin-2-ylidene)-ethanones 3-9 is presented. This synthesis employs a condensation of 2,3-diaminopyridine with benzoylacetone followed by a basic-activated cyclization reaction with substituted benzaldehydes for final closure of the seven-membered ring. Molecular diversity is fixed by appropriate aldehydes: 2-chloro-, 4-chloro-, 2-bromo-, 4-bromo-, 4-fluoro-, 4-trifluoro- and 3-bromo-4,5-dimethoxybenzaldehyde. Compounds 4, 6, 8, 9 and 10 were examined for their anxiolytic activity. The most active was the compound with the chlorophenyl substituent i.e. 1-phenyl-2-{4-(4-chlorophenyl)-1,3,4,5-tetrahydropyrido[2,3-b][1,4]diazepin-2-ylidene}-ethanone (4).


Subject(s)
Anti-Anxiety Agents/chemical synthesis , Anti-Anxiety Agents/pharmacology , Azepines/chemical synthesis , Azepines/pharmacology , Animals , Anti-Anxiety Agents/toxicity , Anxiety/psychology , Azepines/toxicity , Behavior, Animal/drug effects , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred BALB C
11.
Pharmazie ; 61(4): 341-2, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16649551

ABSTRACT

The effect of a selective cannabinoid CB1 receptor agonist, ACEA (arachidonyl-2-chloroethylamide) in an aspirin-induced ulcer model was studied in rats. ACEA (1.25-5 mg/kg i.p.) significantly reduced gastric ulcer formation to 24, 21 and 0.6% respectively. These results confirm the cytoprotective effect of CB1 receptor agonists and suggest that the endocannabinoid system might be the target for a novel class of anti-ulcer drugs.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/antagonists & inhibitors , Anti-Ulcer Agents , Arachidonic Acids/pharmacology , Aspirin/antagonists & inhibitors , Receptor, Cannabinoid, CB1/agonists , Stomach Ulcer/chemically induced , Stomach Ulcer/prevention & control , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Aspirin/toxicity , Dose-Response Relationship, Drug , Gastric Mucosa/pathology , Ranitidine/therapeutic use , Rats , Stomach Ulcer/pathology
12.
Article in English | MEDLINE | ID: mdl-14535055

ABSTRACT

Prematurity is of one of the main causes of neonatal morbidity and mortality. Clinical observations show, that periodontitis in pregnant women can be a direct risk factor for preterm labor, with a greater influence rate compared to other risk factors. The aim of the study was to asses the relationship between periodontal diseases and PLBW in the population of women from the Lower Silesian Region (Poland), and the evaluation of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) levels in gingival cervicular (GCF) and blood serum in women with PLBW and women giving birth on time as well as secretion of these proinflammatory mediators in whole blood after bacterial lipopolysaccharide stimulation. The study group consisted of 84 women with PLBW (39.2% primiparous), aged 17-41 (mean 27.57). The controls were 44 women (47.7% primiparous) aged 16-38 (mean 26.36) who gave birth on time to a normal birthweight baby. PGE2 and IL-1 beta concentrations in serum and GCF were determined by means of immunoenzymatic method (EIA). In the studied population women over 28 years and exposed to medical risk factors had more frequent PLBW occurrence probability. In primiparous over 28 there is 4 times greater probability of preterm labor, and in case of the severe and generalized periodontitis presence there is 3.9 times higher possibility of PLBW compared to women with healthy periodontium. In all women with PLBW there is a significantly higher PGE2 and IL-1 beta concentration in GCF, and in primiparous also PGE2 level in blood serum, compared to controls.


Subject(s)
Dinoprostone/metabolism , Infant, Low Birth Weight , Infant, Premature , Interleukin-1/metabolism , Periodontal Diseases/physiopathology , Adolescent , Adult , Case-Control Studies , Chronic Disease , Dinoprostone/blood , Female , Gingival Crevicular Fluid/metabolism , Humans , Infant, Newborn , Inflammation Mediators/blood , Inflammation Mediators/physiology , Interleukin-1/blood , Lipopolysaccharides/pharmacology , Periodontal Diseases/classification , Periodontal Index , Pregnancy , Risk Factors , Statistics, Nonparametric
13.
J Pept Res ; 62(3): 125-33, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12895274

ABSTRACT

A correlation between KI (equilibrium dissociation constants) and IC50 (concentration at 50% inhibition) inhibitors for the family of blockers of the small conductance potassium ion channels and their intrinsic characteristics like molecular mass and volume have been investigated. Most of the blockers in the family are not selective, in contrast to apamin - an 18 amino acid bee venom toxin - that is known to be a highly potent and selective blocker of these channels. Differences and similarities between the blockers have been analyzed, pointing toward the origin of their selectivity and relative potency. In conclusion, an ion channel blocking is a process controlled mainly by diffusion, in accordance with previous experimental results.


Subject(s)
Apamin/chemistry , Apamin/pharmacology , Models, Molecular , Potassium Channel Blockers/pharmacology , Potassium Channels/drug effects , Calcium/metabolism , Molecular Conformation , Potassium Channel Blockers/chemistry , Statistics as Topic
14.
Arch Pharm (Weinheim) ; 333(11): 357-64, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11129977

ABSTRACT

The pharmacological activity of nine anti-arrhythmic phenytoin derivatives was assessed in preventing chloroform-induced arrhythmia. The compounds were tested in vitro on isolated heart of the rat. Four compounds were chosen as representative of the spatial characteristics of the studied group, and X-ray structure analyses were carried out on them. Because the protonated form is present in physiological milieu, conformational analysis was performed on the protonated form of the four representatives and in addition on the compound showing the highest anti-arrhythmic activity. It was found that substitution of the imidazolidinone ring of phenytoin at position 3 by a chain containing a tertiary amine nitrogen atom changes the affinity profile from inactivated (phenytoin-like) to activated (quinidine-like) cardiac sodium channels. The activity of the studied compounds relies on the presence of protonated tertiary nitrogen atom, at least one phenyl ring, and flexibility of the molecule, which enables the spacer to assume a desired length.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Heart Rate/drug effects , Heart/physiology , Phenytoin/analogs & derivatives , Phenytoin/pharmacology , Animals , Anti-Arrhythmia Agents/chemistry , Coronary Circulation/drug effects , Heart/drug effects , In Vitro Techniques , Models, Molecular , Molecular Conformation , Phenytoin/chemistry , Rats , Structure-Activity Relationship
15.
Med Wieku Rozwoj ; 4(2 Suppl 3): 29-42, 2000.
Article in Polish | MEDLINE | ID: mdl-11328968

ABSTRACT

OBJECTIVES: To compare the early response to natural and synthetic surfactant in premature babies with respiratory distress syndrome (RDS). METHODS: This is a prospective study of 21 newborns with respiratory distress syndrome treated with natural or synthetic surfactant. The response rapidity after administration of natural or synthetic surfactant was compared by parameters of mechanical ventilation (FiO2, Pmax, IO) in the first 6 hours and during the following 7 days of life. The frequency of respiratory complications, presence of patent ductus arteriosus (PDA) and its treatment and causes of death were evaluated. RESULTS: Definitely quicker decrease in ventilation parameters was observed after the administration of natural surfactant as compared to the synthetic one. Statistically significant differences were observed during 72 hours and then they decreased. CONCLUSION: The response after the administration of natural surfactants in premature babies with RDS within the first six hours of treatment was significantly quicker than after synthetic surfactant. This improves the parameters of mechanical ventilation much quicker and prevents complications. Longitudinal studies of the development of children treated with both kinds of surfactant are necessary in order to evaluate the effects of the treatment in the neonatal period.


Subject(s)
Pulmonary Surfactants/administration & dosage , Respiratory Distress Syndrome, Newborn/drug therapy , Female , Humans , Infant, Newborn , Infant, Premature , Male , Prospective Studies , Time Factors , Treatment Outcome
16.
Med Wieku Rozwoj ; 4(2 Suppl 3): 43-57, 2000.
Article in Polish | MEDLINE | ID: mdl-11328969

ABSTRACT

The mortality of very preterm infants has significantly improved after introducing into clinical practice the antenatal use of glucocorticoid steroids prior to premature births and postnatal treatment with pulmonary surfactant which effectively decreases the tendency of the alveoli to collapse. The period of necessary mechanical ventilation was shortened. Reducing the concentration of inspired oxygen and inflation pressures became possible. In spite of this, long-term damage of lung tissue in immature infants is still a major clinical problem. However, its origin seems to be slightly different. A new form of bronchopulmonary dysplasia (BPD) has been recently evaluated. The most important factors in the pathogenesis of the "new" BPD are: lung tissue immaturity, infections initiating a cascade of events caused by formation of free oxygen radicals and cytokines and the presence of persistent patent ductus arteriosus. Primary prevention of BPD is possible by reducing the rates of prematurity and intrauterine infections. Secondary prevention includes antenatal steroids administration and postnatal surfactant treatment according to the accepted known standards. When protracted mechanical ventilation is necessary, low and subsequently reduced doses of i.v. glucocorticoid steroids in the second and third week of life are administrated, together with diuretics, bronchodilators and suitably high calorie feeding.


Subject(s)
Bronchopulmonary Dysplasia/physiopathology , Bronchopulmonary Dysplasia/therapy , Anti-Inflammatory Agents/therapeutic use , Bronchopulmonary Dysplasia/drug therapy , Bronchopulmonary Dysplasia/prevention & control , Glucocorticoids/therapeutic use , Humans , Infant, Newborn , Infant, Premature , Oxygen/therapeutic use , Primary Prevention , Pulmonary Surfactants/therapeutic use , Respiration, Artificial
17.
J Vet Pharmacol Ther ; 22(2): 153-60, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10372600

ABSTRACT

The participation of central cholecystokinin-8 (CCK-8) receptors in the modulatory effect of D-Ala2, N-Me-Phe4, Gly5-ol enkephalin (DAGO), a selective mu-opioid receptor agonist, on the spike burst activity of the gastrointestinal tract (rumen, reticulum, antrum, duodenum, colon and caecum) in sheep was investigated. DAGO was infused intracerebroventricularly (i.c.v.) at doses of 0.1-1 microg/kg body weight (BW). It was shown that DAGO significantly inhibited myoelectrical activity of the wall of the forestomachs, abomasum and colon but stimulated this activity in the duodenum (rate of myoelectrical migrant complex-MMC). The effects of DAGO were prevented by CCK-8 antagonists (L-364.718 and L-365.260) previously infused at doses of 5-20 microg/kg BW. The results of this present study indicate that central receptors of CCK-8 participated in the modulatory action of an opioid on myoelectrical activity of the gastrointestinal tract in sheep. Furthermore, this result suggests that CCK-8 is released in response to mu-receptor stimulation, because CCK-8 antagonists (L-364.718 and L-365.260) prevented the modulatory action of DAGO on the gastrointestinal motility in sheep.


Subject(s)
Cholecystokinin/physiology , Gastrointestinal Motility/drug effects , Narcotics/pharmacology , Animals , Benzodiazepinones/pharmacology , Devazepide/pharmacology , Electromyography , Enkephalin, Ala(2)-MePhe(4)-Gly(5)- , Enkephalins/administration & dosage , Enkephalins/pharmacology , Female , Injections, Intraventricular , Intestines/drug effects , Phenylurea Compounds/pharmacology , Receptors, Cholecystokinin/drug effects , Receptors, Cholecystokinin/physiology , Receptors, Opioid, mu/agonists , Receptors, Opioid, mu/physiology , Sheep , Stomach/drug effects
18.
Acta Pol Pharm ; 56(1): 91-2, 1999.
Article in English | MEDLINE | ID: mdl-10635354

ABSTRACT

The effect of 2H-4,5-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3- oxo-2,3-dihydroisothiazolo[5,4-b]pyridine on feeding in rats was investigated. The tested compound decreased food intake in food-deprived rats and in rats receiving palatable-diet.


Subject(s)
Appetite Depressants/pharmacology , Eating/drug effects , Pyridines/pharmacology , Animals , Male , Pyridines/chemistry , Rats , Rats, Wistar
19.
Acta Pol Pharm ; 55(5): 397-402, 1998.
Article in English | MEDLINE | ID: mdl-9921118

ABSTRACT

5-Ethoxalyl-4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin -2-one [I] was treated with some selected secondary amines (dimethyl-, diethyl-, dipropyl-, disobutylamine or with morpholine) and methyl-hydrazine. Amides II-IV and hydrazide VII were obtained. Compounds II, IV and VI were tested for their psychotropic activity; they showed a weak toxicity. Compounds II and VI showed an anxiolytic activity. Compounds I, II, IV, VI and VII were screened for their cytotoxic (anti-proliferative) activity in vitro by using different human cancer cell lines. None of them revealed any inhibiting effect against the tumor lines used.


Subject(s)
Antineoplastic Agents/chemical synthesis , Benzodiazepinones/chemical synthesis , Psychotropic Drugs/chemical synthesis , Animals , Anti-Anxiety Agents/chemical synthesis , Anti-Anxiety Agents/pharmacology , Antineoplastic Agents/pharmacology , Benzodiazepinones/pharmacology , Drug Screening Assays, Antitumor , Humans , Male , Mice , Psychotropic Drugs/pharmacology
20.
Arch Pharm (Weinheim) ; 330(4): 91-9, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9230526

ABSTRACT

In a search for new anticonvulsants, two series of compounds, viz. derivatives of N-benzylamides of alpha-(4-phenylpiperazine)-gamma-hydroxybutyric acid (A) and derivatives of N-benzylamides of alpha-(4-benzylpiperazine)-gamma-hydroxybutyric acid (B), were investigated. These amides were obtained by aminolysis of 3-(4-phenyl-, or 4-benzylpiperazine)-tetrahydrofuran-2-one with primary arylalkylamines (i.e. 2-phenylethylamine and 2,3,4-substituted derivatives of benzylamine). Preliminary pharmacological tests, a maximal electroshock (MES) and a subcutaneous metrazole (scMet), and a rotorod toxicity assay were employed. All compounds displayed anticonvulsant activity at range of doses 100-300 mg/kg in the MES screens. In order to point to some structural features correlating with the MES anticonvulsant activity crystal structure analysis followed by conformational analysis was carried out on two representative compounds of series A and B.


Subject(s)
Anticonvulsants/chemistry , Anticonvulsants/pharmacology , Piperazines/chemistry , Piperazines/pharmacology , Animals , Anticonvulsants/chemical synthesis , Convulsants/pharmacology , Crystallography, X-Ray , Drug Evaluation, Preclinical , Electroshock , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred Strains , Molecular Structure , Pentylenetetrazole/pharmacology , Piperazines/chemical synthesis , Rats , Rats, Inbred Strains , Structure-Activity Relationship
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