153 results on '"SIEKLUCKA‐DZIUBA, M."'
Search Results
52. ChemInform Abstract: Synthesis and Pharmacological Evaluation of N-Aryl(pyrimidinyl) piperazinylalkyl(hydroxyalkyl) Derivatives of 1,2,3,4-Tetra- and 1,2,3, 4,5,6-Hexahydropyrido(3,4-d)pyridazines.
- Author
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SLADOWSKA, H., POTOCZEK, J., RAJTAR, G., SIEKLUCKA-DZIUBA, M., MLYNARCZYK, M., and KLEINROK, Z.
- Published
- 1996
- Full Text
- View/download PDF
53. ChemInform Abstract: Synthesis, Chemical and Pharmacological Properties of Some N- Aminoalkyl Derivatives of 3,4-Pyridinedicarboximides.
- Author
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SLADOWSKA, H., POTOCZEK, J., SIEKLUCKA-DZIUBA, M., SEMCZUK, A., and KLEINROK, Z.
- Published
- 1996
- Full Text
- View/download PDF
54. ChemInform Abstract: Synthesis and Biological Evaluation of 7-Azaanalogues of Ipsapirone.
- Author
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MALINKA, W., SIEKLUCKA-DZIUBA, M., RAJTAR, G., MAROWSKA, D., and KLEINROK, Z.
- Published
- 1996
- Full Text
- View/download PDF
55. ChemInform Abstract: Investigations on the Synthesis and Properties of Some N- Arylpiperazinylalkyl Derivatives of 1,4-Dioxo(1,4,5-trioxo)-1,2,3,4- tetra (and 1,2,3,4,5,6-Hexa)hydropyrido(3,4-d)pyridazines.
- Author
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SLADOWSKA, H., POTOCZEK, J., SIEKLUCKA-DZIUBA, M., RAJTAR, G., MLYNARCZYK, M., and KLEINROK, Z.
- Published
- 1995
- Full Text
- View/download PDF
56. ChemInform Abstract: Synthesis and Properties of 1-Aryl(pyrimidinyl)piperazinylalkyl Derivatives of Ethyl 3-Phenyl-7-methyl-2,4-dioxo-1,2,3,4- tetrahydropyrido(2,3-d)pyrimidine-5-carboxylate.
- Author
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SLADOWSKA, H., SIEKLUCKA-DZIUBA, M., STANIAK, L., and KLEINROK, Z.
- Published
- 1995
- Full Text
- View/download PDF
57. Effect of lead exposure on memory processes in mice after cerebral oligemia.
- Author
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Lukawski K and Sieklucka-Dziuba M
- Subjects
- Animals, Avoidance Learning drug effects, Carotid Stenosis complications, Dose-Response Relationship, Drug, Exploratory Behavior drug effects, Female, Hypoxia, Brain etiology, Injections, Intraperitoneal, Maze Learning drug effects, Mice, Motor Activity drug effects, Behavior, Animal drug effects, Environmental Pollutants toxicity, Hypoxia, Brain physiopathology, Memory drug effects, Organometallic Compounds toxicity
- Abstract
The purpose of this study was to find out whether the effect of acute exposure to lead on memory processes in mice could be exacerbated by cerebral oligemia. Adult mice were subjected to 30 min of bilateral clamping of carotid arteries (BCCA) and then treated intraperitoneally with lead acetate at a single dose of: 29.3 mg/kg, 58.6 mg/kg or 87.9 mg/kg. Long-term memory was assessed in the passive avoidance task while spontaneous alternation was evaluated using the Y-maze task. Performance of the tasks was tested on the 2nd, 7th and 14th post-surgical day. On the 14th post-surgical day, significant retention deficits in passive avoidance performance were only observed in BCCA mice injected with the 87.9 mg/kg lead. Co-exposure to cerebral oligemia and lead did not change spontaneous alternation in the Y-maze task. These results show that cerebral oligemic hypoxia combined with acute lead exposure may cause selective and long-lasting impairment in memory function.
- Published
- 2007
58. Cerebral oligemic hypoxia and MK-801 treatment: effect on alternation behavior in mice.
- Author
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Józwiak L, Lukawski K, and Sieklucka-Dziuba M
- Subjects
- Animals, Behavior, Animal drug effects, Behavior, Animal physiology, Constriction, Hypoxia, Brain physiopathology, Male, Mice, Motor Activity physiology, Dizocilpine Maleate pharmacology, Hypoxia, Brain complications, Maze Learning drug effects, Motor Activity drug effects
- Abstract
It is known that glutamatergic system is one of neurotransmitter systems affected by a transiently reduced oxygen supply. The aim of the present study was to examine the effects of MK-801, a noncompetitive NMDA receptor antagonist, on spontaneous alternation in mice exposed to cerebral oligemic hypoxia. Spontaneous alternation behavior and locomotor activity were evaluated using the Y-maze task. Transient cerebral oligemia was induced by bilateral clamping of carotid arteries (BCCA) for 30 min under pentobarbital anesthesia. MK-801 was injected 48 h after BCCA or sham surgery, 30 min before the test session. Treatment with MK-801 (0.1 mg/kg ip) impaired spontaneous alternation both in sham-operated and BCCA mice. MK-801 (0.1 mg/kg ip) significantly enhanced the locomotion of mice. The effects of MK-801 were not exacerbated by BCCA. These results show that cerebral oligemic hypoxia induced by BCCA does not change alternation behavior of mice treated with MK-801.
- Published
- 2006
59. Competitive NMDA receptor antagonists and agonists: effects on spontaneous alternation in mice exposed to cerebral oligemia.
- Author
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Jóźwiak L, Łukawski K, Czuczwar SJ, and Sieklucka-Dziuba M
- Subjects
- 2-Amino-5-phosphonovalerate administration & dosage, 2-Amino-5-phosphonovalerate pharmacology, Animals, Behavior, Animal drug effects, Carotid Artery Injuries drug therapy, Carotid Artery Injuries physiopathology, Cerebrovascular Circulation drug effects, Cerebrovascular Circulation physiology, Drug Administration Schedule, Drug Evaluation, Preclinical methods, Hypovolemia, Male, Maze Learning drug effects, Mice, Motor Activity drug effects, N-Methylaspartate pharmacology, Orientation drug effects, Placebos, Poland, Receptors, N-Methyl-D-Aspartate therapeutic use, Time Factors, 2-Amino-5-phosphonovalerate analogs & derivatives, Hypoxia, Brain drug therapy, Hypoxia, Brain physiopathology, Receptors, N-Methyl-D-Aspartate agonists, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
- Abstract
The purpose of the present study was to investigate the effects of competitive NMDA receptor antagonists,D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) and its ethyl ester (CGP 39551), or agonist, N-methyl-D-aspartate (NMDA) on spontaneous alternation in mice exposed to cerebral oligemia. Alternation behavior was evaluated in an Y-maze. Transient cerebral oligemic hypoxia was induced by bilateral clamping of carotid arteries (BCCA) for 30 min under pentobarbital anesthesia. In BCCA mice, CGP 37849 (5 mg/kg, ip) impaired spontaneous alternation when given 48 h or 7 days after surgery. CGP 39551 (5 mg/kg, ip) had no effect.NMDA (50 mg/kg, sc) improved performance of the task in BCCA mice when tested 48 h after surgery. These results suggest that cerebral oligemic hypoxia induced by BCCA leads to functional disturbances in the central nervous system, such as spontaneous alternation impairment and increased susceptibility to NMDA receptor-related drugs. Adverse potential of cerebral oligemia may limit a therapeutic use of NMDA receptor antagonists.
- Published
- 2004
60. Synthesis and properties of tetra(hexa)hydropyrazolo [1,2-a]pyrido[3,4-d]pyridazine derivatives.
- Author
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Sladowska H, Filipek B, Sapa J, Sieklucka-Dziuba M, Szymańska M, Kleinrok Z, and Sokołowska M
- Subjects
- Analgesics, Non-Narcotic pharmacology, Analgesics, Non-Narcotic toxicity, Animals, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology, Blood Pressure drug effects, Lethal Dose 50, Mice, Microbial Sensitivity Tests, Motor Activity drug effects, Mycobacterium drug effects, Pain Measurement drug effects, Pyrazoles pharmacology, Pyrazoles toxicity, Pyridazines pharmacology, Pyridazines toxicity, Rats, Rats, Wistar, Analgesics, Non-Narcotic chemical synthesis, Pyrazoles chemical synthesis, Pyridazines chemical synthesis
- Abstract
The synthesis of tetra(hexa)hydropyrazolo[1,2-a]pyrido[3,4-d]pyridazine derivatives (14-21) and the results of pharmacological screening are described in this paper. All compounds tested were non-toxic and showed a significant analgesic action. The analgesic effects were associated with the suppression of the spontaneous locomotor activity. Furthermore most of the synthesized compounds displayed a weak antimycobacterial action in the preliminary screening.
- Published
- 2003
61. Urine iodine excretion in schoolchildren living in urban area.
- Author
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Borzecki A, Sałaga-Pylak M, Nieradko B, Przybyła I, and Sieklucka-Dziuba M
- Subjects
- Child, Female, Humans, Male, Poland, Thyroid Diseases urine, Iodine urine, Urban Population
- Abstract
Iodine is a microelement necessary for thyroid gland hormones production. It is essential for the growth and development of human body. The aim of the study was to determine urine iodine excretion in schoolchildren living in urban area. We found out that approximately 42% of the examined children excreted small amounts of iodine with urine, which proves low dietary intake of the element. Therefore, it is necessary to promote the right dietary patterns and iodine supplementation in developing children.
- Published
- 2003
62. Nociceptin, OP4 receptor ligand in different models of experimental epilepsy.
- Author
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Rubaj A, Zgodzinski W, Gustaw K, and Sieklucka-Dziuba M
- Subjects
- Animals, Bicuculline, Disease Models, Animal, Electric Stimulation, Epilepsy chemically induced, Female, Mice, N-Methylaspartate, Opioid Peptides pharmacology, Pentylenetetrazole, Receptors, Opioid drug effects, Nociceptin Receptor, Nociceptin, Epilepsy drug therapy, Opioid Peptides therapeutic use, Receptors, Opioid metabolism
- Abstract
The anticonvulsive activity of nociceptin, endogenous OP4 receptors agonist was investigated in pentylenetetrazole (PTZ), N-methyl D-aspartic acid (NMDA), bicucculine (BCC) and electrically evoked seizure models of experimental epilepsy. Nociceptin, at the dose of 10 nmol, suppressed the clonic seizures induced by PTZ, NMDA and BCC. [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 which has been proposed to be selective antagonist OP4 receptors, did not prevent the action of nociceptin. The effect of [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 on seizures induced by PTZ, NMDA and BCC was very similar to that of nociceptin. These data support the hypothesis that it possesses agonistic properties. Naloxone did not reverse the anticonvulsive action of nociceptin as well as [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 which excludes the participation of opioid receptor in this action. On the other hand in the electroconvulsive model of generalized seizures, nociceptin as well as [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 influenced neither the electroconvulsive threshold nor the maximal electroshock test. The data suggest that nociceptin and [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 can exert anticonvulsive action. These properties depend on OP4 but not opioid receptors activation.
- Published
- 2002
- Full Text
- View/download PDF
63. [Study of hygienic habits of children and youth in the commune of Horyniec].
- Author
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Nieradko B, Swies Z, Mazurkiewicz M, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Child, Cross-Sectional Studies, Exercise, Feeding Behavior, Female, Habits, Humans, Hygiene, Male, Poland, Surveys and Questionnaires, Hand Disinfection, Health Behavior, Oral Hygiene statistics & numerical data, Rural Health
- Abstract
Health behaviour of children and youth is being taught from the earliest years of their lives. Hygiene, dental care, hygiene of work and rest as well as proper nutritional habits determinate health condition of a child and, later on, of an adult. The aim of this work was to evaluate the hygienic habits of children and youth in the commune of Horyniec. An especially designed questionnaire was used as an examination tool. It consisted of 27 questions. 151 students of primary and grammar school were examined. The highest percentage of the interviewed students (37.1%) washed their hands 4-5 times a day. After using WC 78.1% of them washed hands, whereas the rest of them neglected that routine. Only 21.2% of the examined children brushed their teeth after every meal. An average student of the primary or grammar school spent daily 7 hours at school. They did homework or studied themselves usually 2 hours a day. Vast majority of them slept 8-9 hours every night. The most numerous group of the examined children watched TV about 2 hours a day. 57% of the students did physical activities more of ten than twice a week, 29.1% once a week and 13.3% less frequently. 85% of the kids regularly had three meals a day. The study of hygienic habits of children and youth in the commune of Horyniec shows that most of them have proper nutritional habits. Unfortunately, majority of them neglect brushing teeth after every meal and washing hands. Too many children don't do sports intensively enough.
- Published
- 2002
64. Psycho-social problems of HIV carriers.
- Author
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Borzecki A, Sałaga-Pylak M, Swies Z, Jaskułowska L, and Sieklucka-Dziuba M
- Subjects
- Adaptation, Psychological, Adult, Attitude to Death, Caregivers psychology, Female, Humans, Male, Middle Aged, Poland, Rejection, Psychology, Suicide, Attempted psychology, Carrier State psychology, HIV Seropositivity psychology, Sick Role, Social Adjustment
- Abstract
HIV carrier state and AIDS generate multiple medical, psychological, social and legal problems. The aim of the work was to evaluate selected psycho-social problems among HIV carriers. The examination method was a questionnaire. We interviewed 60 HIV carriers. The results obtained confirmed the existence of the problems affecting the carriers and their families. It creates need for social education in this field.
- Published
- 2002
65. Urinary iodine excretion in inhabitants of rural region living in the Lublin Province.
- Author
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Borzecki A, Borzecka H, Zajaczkowska M, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Adult, Age Factors, Aged, Agriculture, Child, Female, Humans, Male, Middle Aged, Poland, Predictive Value of Tests, Reference Values, Sex Factors, Iodine deficiency, Iodine urine, Mass Screening, Rural Population
- Abstract
Iodine is the element necessary for the human organism to function properly. Iodine is essential especially for the synthesis of thyroid hormones that regulate the cellular metabolism of the whole organism. The purpose of the work was to estimate the concentration of iodine in urine among the inhabitants of a typical agricultural region as a simple method of detecting deficiency of iodine in the human organism. The biggest iodine excretion was observed in a group above 40 years of age. The amount of the excretion of iodine together with urine was similar among men and women up to 40 years old. Monitoring of iodine concentration in urine is a sensitive marker of iodine deficiency in the human organism.
- Published
- 2002
66. [Frequency analysis of the use of addictive substances by adolescents attending secondary schools in Sanok].
- Author
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Nieradko B, Swies Z, Milczanowska K, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Alcohol Drinking epidemiology, Cross-Sectional Studies, Female, Health Knowledge, Attitudes, Practice, Humans, Male, Peer Group, Poland epidemiology, Risk-Taking, Social Alienation psychology, Students statistics & numerical data, Surveys and Questionnaires, Adolescent Behavior, Schools statistics & numerical data, Smoking epidemiology, Substance-Related Disorders epidemiology
- Abstract
In recent years more and more adolescents use addictive and psychoactive substances. Lack of love and safety feeling in their families, being in conflict with peer group and the need for acting opposite to social rules are amongst the most pertinent reasons of the matter in hand. The aim of this paper is to find out how may teenagers use and fall in dependence on alcohol, tobacco and drugs. We interviewed 140 pupils aged 17-18 years attending secondary schools in Sanok. 91.4% of the interviewed students said that they had been informed at school about health hazards resulting from drinking alcohol, smoking tobacco and use of drugs. In spite of that all of them said that they did use alcohol. 46.4% of them confirmed that they overused it. 35.7% of the examined students smoked cigarettes. 25.7% of the respondents used drugs at least once in their lives. 62.5% of them used marihuana, 25% hashish, 5.7% hallucinogenic mushrooms, 3.6% LSD, 1.8% amphetamine and 1.8% ecstasy. When asked to evaluate how difficult for them the access to drugs was 27.9% of pupils said that it was easy, 6.45--diffucult, 65.7% didn't know. The results obtained in our study show that adolescents use addictive substances in spite of having knowledge about their hazardous influence on their health.
- Published
- 2002
67. Causes and circumstances of injuries in children.
- Author
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Borzecki A, Łukawski K, Robak L, Borzecka H, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Causality, Child, Cross-Sectional Studies, Female, Humans, Incidence, Male, Poland, Retrospective Studies, Risk Factors, Wounds and Injuries etiology, Accidents statistics & numerical data, Rural Population statistics & numerical data, Urban Population statistics & numerical data, Wounds and Injuries epidemiology
- Abstract
The problem of the incidence of traumas among children is still topical and statistical data confirm an increasing tendency in the last decades. The purpose of the work was to estimate the causes and circumstances of injuries in children at the age of 7 to 15, who were admitted to Surgical Ward of Specialist Paediatric Hospital in Kielce between 30th June 1997 and 30th June 1998. A retrospective analysis of medical documentation concerned 768 patients. Our studies showed that the biggest number of injuries was related to children 10-12 years old (46%). The majority of patients were boys. Most injuries occurred in summer (33%). In the studied population dominant were accidents at home (56%) and then road accidents (18%), injuries at school (13%) and on farms (7%). Accidents and injuries occurred more often in children from the rural areas (53%).
- Published
- 2002
68. [Assessment of health state in the selected population of rural environment in the aspect of environmental exposure to lead].
- Author
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Wójcik A, Wezgraj W, Niedzielski A, Lupa K, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases epidemiology, Causality, Child, Comorbidity, Cross-Sectional Studies, Epidemiological Monitoring, Female, Humans, Incidence, Lead Poisoning epidemiology, Male, Middle Aged, Poland epidemiology, Respiratory Tract Diseases epidemiology, Sex Distribution, Skin Diseases epidemiology, Environmental Exposure analysis, Environmental Monitoring statistics & numerical data, Health Status, Lead, Rural Health statistics & numerical data, Rural Population statistics & numerical data
- Abstract
The research was conducted in the selected population of rural environment. Health state was assessed in the aspect of environmental exposure to lead. While analyzing obtained research results, the higher incidence of the disease was revealed among female population in comparison with male population and it was the highest in the age group above 60 years of age. The predominating group was the diseases of the circulatory system including chronic hypertensive disease and coronary heart disease, then dermatoses and the diseases of the osteo-articular system. The values of delta-amino-laevulinic acid were within the range of valid standards and no toxic risk of the investigated population was revealed.
- Published
- 2002
69. Interaction between local anesthetics and centrally acting antihypertensive drugs.
- Author
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Zółkowska D, Pikuła A, Borzecki A, and Sieklucka-Dziuba M
- Subjects
- Animals, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Drug Interactions, Mathematical Computing, Mice, Pentylenetetrazole, Probability, Anesthetics, Local toxicity, Antihypertensive Agents toxicity, Seizures chemically induced
- Abstract
Unlabelled: Local anesthetics are widely used in alleviating pain concomitant with small surgery procedures and in dentistry. Especially medication in ductal anesthesia after penetrating into systemic circulation can have significant influence on the central nervous system and stimulus conduction in the heart. Clonidine and reserpine are centrally acting antihypertensive drugs. The aim of this study was to examine an interaction of lidocaine, articaine and mepivacaine with some antihypertensive drugs clonidine and reserpine on the pentylenetetrazole induced seizures., In Conclusion: articaine is the most safe local anesthetic and can be used in epileptic patients Co-administration of local anesthetics with centrally acting antihypertensive drugs did not influence seizures activity in mice.
- Published
- 2002
70. Leisure time activities in teenagers in urban and rural areas.
- Author
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Borzecki A, Nieradko B, Gnasś B, and Sieklucka-Dziuba M
- Subjects
- Child, Female, Humans, Male, Poland, Adolescent, Leisure Activities, Rural Population statistics & numerical data, Urban Population statistics & numerical data
- Abstract
The work aimed to determine the leisure time activities in teenagers on weekdays, weekends, during winter and summer holidays. Vast majority of teenagers spend their leisure time resting in a passive way, i.e. watching TV or playing computer games irrespectively of the season. As a result of this, the number of kids with posture defects increase. On weekdays the country teenagers spend much more time doing outdoor sports and games than town children. They also more often help their parents and less frequently travel away from their homes than children living in towns.
- Published
- 2002
71. Life style and the risk of development of circulatory system diseases.
- Author
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Borzecki A, Zółkowska D, and Sieklucka-Dziuba M
- Subjects
- Adult, Aged, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Cross-Sectional Studies, Female, Health Behavior, Health Education, Health Knowledge, Attitudes, Practice, Humans, Male, Middle Aged, Poland epidemiology, Cardiovascular Diseases etiology, Life Style
- Abstract
Circulatory system diseases (c.s.d.) belong to the group of civilization diseases. The risk factors of circulatory system diseases are: stress, overuse of alcohol, smoking cigarettes, bad eating habits, sitting life style. Calorie overconsumption, animal fat rich diet, sitting life style result in the development of android obesity, hypercholesterolemia, that enhance atheromatosis. The most dangerous consequences of atheromatosis are: angina pectoris, hypertension, myocardial infarction, brain insult, type II diabetes. The aim of the work was to evaluate life style and its correlation with development of circulatory system diseases. The results obtained significantly indicate how important is health education about the danger of widely understood unhealthy life style. Propagation of staying healthy model with emphasizing real profit resulting from leading healthy life style is the only righteous way to improve it.
- Published
- 2002
72. Burdensome factors occurring at school according to students.
- Author
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Pikuła A, Swies Z, Borzecki A, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Child, Female, Humans, Male, Poland, Risk Factors, Environment, School Health Services, Social Environment, Stress, Psychological psychology, Students psychology
- Abstract
The aim of the work was to find out about school environment and burdensome factors that occur at school according to students. The research was conducted at Primary School no. 23 in Tarnów. 244 students were examined, including 135 students of 8th form and 109 students of 4th form. Troublesome factors, which students are exposed to, may be divided into two groups. The first group is related to physiochemical environment, the second group are the factors which result from a child's way of living and working in the school environment. On the basis of the analysis of the results, the necessity of restriction of both physical and psychosocial burden of students is emphasised. What seems to be especially crucial is ergonomic school furniture, diminishing of noise, improvement of hygienic condition of toilets, rational school timetable, and elimination of dangers resulting from other students' behaviour.
- Published
- 2002
73. Influence of iodine ions in drinking water on their excretion with urine.
- Author
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Borzecki A, Borzecka H, Zajaczkowska M, Smarkala B, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Male, Middle Aged, Poland, Reference Values, Iodine supply & distribution, Iodine urine, Water Supply analysis
- Abstract
The purpose of the work was to appraise the correlation between magnitude of iodine excretion with urine and concentration of iodine ions in drinking water in the population living in the Lublin province. The tests were also performed among the citizens of the Zamość voivodship. Mean concentration of iodine in urine of the tested citizens was 132.0 micrograms/g creatinine. Mean value of I ions in drinking water was 27.5 micrograms/l. The obtained results of concentration of iodine both in urine and drinking water did not differ as shown in references. Statistically significant correlation between the measure of I excretion in urine and I ions concentration in drinking water was confirmed. There is no ascertained deficiency of iodine in Zamość region inhabitants. The concentration of iodine in drinking water from adjacent wells was fluctuating in wide limits, but did not differ from recommended norms. There is a positive correlation between concentration of iodine in drinking water and its level in excreted urine.
- Published
- 2002
74. Synthesis and in vivo pharmacology of new derivatives of isothiazolo[5,4-b]pyridine of Mannich base type.
- Author
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Malinka W, Karczmarzyk Z, Sieklucka-Dziuba M, Sadowski M, and Kleinrok Z
- Subjects
- Analgesics, Non-Narcotic chemistry, Analgesics, Non-Narcotic pharmacology, Animals, Crystallography, X-Ray, Drug Evaluation, Preclinical, Injections, Intraperitoneal, Mice, Molecular Structure, Motor Activity drug effects, Pain drug therapy, Pyridines chemical synthesis, Pyridines chemistry, Rats, Serotonin Agents chemistry, Structure-Activity Relationship, Thiazoles chemical synthesis, Thiazoles chemistry, Analgesics, Non-Narcotic chemical synthesis, Pyridines pharmacology, Thiazoles pharmacology
- Abstract
Recently we reported on 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridine (V), which exhibited high anorectic action in animal models as a result of stimulation of serotoninergic system. This paper describes the synthesis of the series 3-5 of analogues of V prepared from 2-hydroxymethyl-4,6-dimethylisothiazolopyridine (2) and corresponding 4-substituted-piperazines(piperidines) or tetrahydroisoquinoline. The 12 compounds obtained were screened in standard CNS tests in in vivo (mice and rats). In contrast to V, none of its analogues showed serotoninergic activity, whereas several of these compounds were found to be active as weak to moderate analgesic agents. According to X-ray and molecular modeling studies the different pharmacological profile of V and its o-OCH3 analog 3a, taken as an example, should be referred back to the conformational restriction incorporated by the o-substitution rather than effects of different lipophlicity or basicity of these compounds.
- Published
- 2001
- Full Text
- View/download PDF
75. The evaluation of noise level in different points of urban area.
- Author
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Wójcik A, Czarnopyś M, and Sieklucka-Dziuba M
- Subjects
- Environmental Monitoring statistics & numerical data, Poland, Urbanization, Vibration, Environmental Exposure analysis, Noise, Transportation statistics & numerical data
- Abstract
The aim of the study was measuring noise intensity in the selected points of traffic routes in the city of Lublin. Investigations were carried out at 11 points located in the centre of the city and at escape roads. Noise value levels showed variable intensity, the highest being observed in the morning and afternoon hours. The highest mean level of noise intensity was recorded at the crossing of Solidarności Avenue and Sikorskiego Street, and the lowest in Narutowicza Street.
- Published
- 2001
76. Effect of adenosine A1 and A2 receptor stimulation on hypoxia-induced convulsions in adult mice.
- Author
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Zgodziński W, Rubaj A, Kleinrok Z, and Sieklucka-Dziuba M
- Subjects
- Adenosine pharmacology, Animals, Anticonvulsants therapeutic use, Bicuculline pharmacology, Brain drug effects, Brain physiopathology, Convulsants pharmacology, Disease Models, Animal, Electroshock, Female, Hypoxia drug therapy, Mice, N-Methylaspartate adverse effects, N-Methylaspartate pharmacology, Neuroprotective Agents therapeutic use, Pentylenetetrazole pharmacology, Purinergic P1 Receptor Antagonists, Seizures chemically induced, Seizures drug therapy, Theobromine pharmacology, Time Factors, Adenosine analogs & derivatives, Aging physiology, Anticonvulsants pharmacology, Hypoxia physiopathology, Neuroprotective Agents pharmacology, Purinergic P1 Receptor Agonists, Seizures physiopathology, Theobromine analogs & derivatives
- Abstract
Clinical observations indicate that seizures induced by hypoxia are common kind of convulsive activity in both infants and elderly patients. The occurrence of seizure episode during hypoxia is important risk factor of epilepsy development in the future. Experimental hypoxia was obtained by exposure of adult (20-23 g) Albino Swiss mice to spontaneous breathing in gas mixture composed of 5% oxygen and 95% nitrogen. The latency time to convulsive activity was determined. Single sublethal episode of seizures induced by hypoxia (HS) resulted in higher susceptibility to pentetrazol (PTZ), bicuculline (BCC), N-methyl-D-aspartic acid (NMDA) but not in electrically induced convulsions. Adenosine A1 receptor agonist, R(-)N6-(2-phenyl-isopropyl)adenosine (R-PIA) (0.01; 0.05; 0.1 mg/kg, i.p.) prolonged the latency to HS-induced convulsions. A1 receptor antagonist, 8-cyclopentyltheophylline (CPT), reversed the protective action of R-PIA. A2 receptor agonist, N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]ethyladenosine (DPMA), only at the highest dose (5 mg/kg i.p.) prolonged the latency time to convulsive activity. This effect was only partially reversed by A2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). Administered immediately after episode of HS R-PIA diminished the higher susceptibility to PTZ, BCC, NMDA at 3rd day after HS, while DPMA appeared to be ineffective. These results confirm the important role of adenosine A1 receptor agonist in protection against acute and chronic epileptogenic effect of hypoxia. The role of adenosine A2 receptors seems to be of minor importance.
- Published
- 2001
77. Delta aminolevulinic acid urinary excretion in rural region inhabitants.
- Author
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Borzecki A, Borzecka H, Nieradko B, and Sieklucka-Dziuba M
- Subjects
- Adolescent, Adult, Aged, Air Pollutants analysis, Child, Environmental Exposure analysis, Epidemiological Monitoring, Female, Humans, Lead Poisoning epidemiology, Lead Poisoning urine, Male, Middle Aged, Poland epidemiology, Sex Factors, Aminolevulinic Acid urine, Environmental Monitoring statistics & numerical data, Rural Health
- Abstract
The purpose of the work was to estimate to what extent the inhabitants of a typical agricultural region are exposed to the influence of lead compounds. 132 people at the age of 9 to 74 were included in the research. Urinary delta aminolevulinic acid (ALA) excretion was determined. The highest excretion of ALA was observed among the examined who were up to 18 years old, while the lowest was among those who were above 60 years old. These differences, however, were not statistically significant.
- Published
- 2001
78. Vitamin E influence on selected parameters in rats after ochratoxin A intoxication.
- Author
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Borzecki A, Borzecka H, Sobieszek-Dziuba U, Wilgat E, and Sieklucka-Dziuba M
- Subjects
- Animals, Ergotism drug therapy, Erythrocyte Count, Female, Leukocyte Count, Rats, Rats, Wistar, Vitamin E pharmacology, Mycotoxins toxicity, Ochratoxins toxicity, Vitamin E therapeutic use
- Abstract
The aim of the research was to evaluate vitamin E influence on ochratoxin A (OTA) toxicity based on analysis of selected parameters of white and red cell system in rats. The animals were divided into groups: I--control, II--treated with OTA, III--treated with OTA and vitamin E. In group II a significant decrease in the values of hematocrit, hemoglobin level, red and white cell counts was observed. In group III an average hematocrit, hemoglobin level were significantly lower than in control group, nevertheless they were higher than in group II.
- Published
- 2001
79. Brain tolerance and preconditioning.
- Author
-
Rejdak R, Rejdak K, Sieklucka-Dziuba M, Stelmasiak Z, and Grieb P
- Subjects
- Brain metabolism, Brain Chemistry, Brain Injuries physiopathology, Brain Injuries prevention & control, Cerebral Infarction physiopathology, Convulsants pharmacology, Disease Models, Animal, Excitatory Amino Acid Antagonists pharmacology, Heat-Shock Proteins metabolism, Heat-Shock Proteins pharmacology, Humans, Hypoxia, Brain physiopathology, Ischemic Attack, Transient physiopathology, Brain blood supply, Brain physiology, Ischemic Preconditioning
- Abstract
In this review article the authors describe a phenomenon of "brain tolerance" which represents transient resistance of brain tissue to a lethal insult established by preconditioning with a mild insult of short duration. Tolerance evoked by brief ischemia resembles transient ischemic attack(s) (TIA) often preceding full-blown ischemic stroke in a clinical setting. A series of recent studies have described another relevant phenomenon termed "chemical preconditioning". Several substances interfering with cellular energy metabolism applied in subtoxic doses may provide protection against lethal insults of a different type. For example, 3-nitropropionic acid (3-NP), antibiotics erythromycin and kanamycin, acetylsalicylic acid, and 2-deoxyglucose have been shown to evoke tolerance. Recently, we have reported that NMDA receptor antagonists and 2-deoxyglucose used at relatively low doses were potent agents to potentiate the protective anticonvulsant effect induced by transient brain mild ischemia. Further studies are expected to prove similar action of these drugs in other experimental models. Based on the accumulated experimental and clinical data the brain tolerance subsequently reinforced by pharmacological intervention might become a successful prophylactic strategy against serious brain insults in patients.
- Published
- 2001
80. Lead levels in body fluids of workers of an automobile factory with clinically diagnosed arterial hypertension.
- Author
-
Wójcik A, Brzeski Z, and Sieklucka-Dziuba M
- Subjects
- Air Pollution, Indoor analysis, Automobiles, Humans, Hypertension etiology, Lead blood, Lead urine, Occupational Exposure standards, Occupations, Hypertension epidemiology, Lead analysis
- Abstract
The aim of the study is the evaluation of lead levels in body fluids in a chosen study group with diagnosed arterial hypertension employed in a car factory. The study was carried out on workers diagnosed with various stages of arterial hypertension who had been subjected to long-term lead exposure at different workplaces. The examination of the patients included medical history, physical examination and biochemical tests of blood and urine, following routine in the laboratory diagnosis in order to assess medical condition in terms of subclinical symptoms of lead exposure. Mean values of the lead level in blood and urine of studied population are insignificantly higher than in the control group. The obtained results seem insufficient to confirm the effect of occupational exposure to lead in subthreshold doses on the development of arterial hypertension, and are within the recommended hygienic standards.
- Published
- 2001
81. The evaluation of intensity of traffic noise in different points of town routes.
- Author
-
Wójcik A, Sudół R, and Sieklucka-Dziuba M
- Subjects
- Environmental Monitoring methods, Poland, Time Factors, Urbanization trends, Environmental Exposure analysis, Noise, Transportation statistics & numerical data
- Abstract
The aim of the study was measuring noise intensity in the selected points of traffic routes in the town of Lublin. Investigations were carried out at 11 points located in the centre of the town and at escape roads. Noise value levels showed variable intensity, the highest being observed in the morning and afternoon hours. The highest mean level of noise intensity was recorded at the crossing of Solidarności Avenue and Sikorskiego Street, and the lowest in Narutowicza Street.
- Published
- 2001
82. Effect of MK-801 on pilocarpine-evoked seizures in mice exposed to transient incomplete brain ischemia.
- Author
-
Rejdak R, Rejdak K, and Sieklucka-Dziuba M
- Subjects
- Animals, Behavior, Animal drug effects, Ischemic Attack, Transient complications, Male, Mice, Motor Activity drug effects, Pilocarpine pharmacology, Seizures chemically induced, Seizures physiopathology, Dizocilpine Maleate pharmacology, Excitatory Amino Acid Antagonists pharmacology, Ischemic Attack, Transient physiopathology, Muscarinic Agonists pharmacology, Pilocarpine antagonists & inhibitors, Seizures prevention & control
- Abstract
The aim of the study was to examine the role of NMDA receptors in the modulation of brain tolerance after transient cerebral ischemia. Adult mice were exposed for 30 min to bilateral clamping of common carotid arteries (BCCA) under anaesthesia. The non-competitive NMDA antagonist, MK-801 was administered intraperitoneally (ip) in two experimental paradigms: a) acute: twice at 1.0 mg/kg; 1 h before the clamping of the vessels and 6 h after re-circulation; b) chronic at a dose of 0.1 mg/kg, started 24 h after recirculation and continued once daily for 13 days with the last injection 24 h before the induction of convulsions. Seizures were evoked with pilocarpine (400 mg/kg, ip) 14 days after BCCA. It was found that transient incomplete brain ischemia induced protection against pilocarpine toxicity. The acute treatment with MK-801 did not diminish the anticonvulsant action of the procedure. In contrast, the chronic treatment with the drug led to a marked potentiation of the effect. In conclusion, it can be suggested that studied NMDA receptor antagonist used at relatively low dose may enhance the brain tolerance activated after a transient ischemic episode.
- Published
- 2000
83. Synthesis and preliminary screening of derivatives of 2-(4-arylpiperazin-1-ylalkyl)-3-oxoisothiazolo[5,4-b] pyridines as CNS and antimycobacterial agents.
- Author
-
Malinka W, Sieklucka-Dziuba M, Rajtar G, Zgodziński W, and Kleinrok Z
- Subjects
- Analgesics pharmacology, Animals, Anti-Anxiety Agents chemical synthesis, Anti-Anxiety Agents pharmacology, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents toxicity, Anticonvulsants chemical synthesis, Anticonvulsants pharmacology, Behavior, Animal drug effects, Blood Pressure drug effects, Central Nervous System Agents pharmacology, Central Nervous System Agents toxicity, Lethal Dose 50, Magnetic Resonance Spectroscopy, Mice, Microbial Sensitivity Tests, Motor Activity drug effects, Psychomotor Performance drug effects, Pyridines pharmacology, Pyridines toxicity, Rats, Spectrophotometry, Infrared, Thiazoles pharmacology, Thiazoles toxicity, Anti-Bacterial Agents chemical synthesis, Central Nervous System Agents chemical synthesis, Mycobacterium drug effects, Pyridines chemical synthesis, Thiazoles chemical synthesis
- Abstract
We have synthesized several new isothiazolopyridines possessing a side chain at the isothiazole ring typical, among others, for trazodone or NAN-195. Representatives of the novel isothiazolopyridines were examined for acute toxicity and in several commonly used CNS tests in mice and for arterial blood pressure in rats. Three of the five compounds tested showed significant analgesic activity. The most active compound (3b) exhibited analgesic action in the "writhing" test in a dose 1/1280 of LD50 (LD50 = 1135.5 mg/kg) after administration i.p. to mice. Additionally, the compounds described here and related isothiazolopyridines obtained previously were evaluated against Mycobacterium tuberculosis H37Rv at 12.5 micrograms/ml in in vitro assays. Seven of the nineteen compounds tested showed 100% inhibition of that mycobacterium.
- Published
- 2000
84. Synthesis of some N-substituted 3,4-pyrroledicarboximides as potential CNS depressive agents.
- Author
-
Malinka W, Sieklucka-Dziuba M, Rajtar G, Rejdak R, Rejdak K, and Kleinrok Z
- Subjects
- Amphetamine antagonists & inhibitors, Amphetamine pharmacology, Analgesics, Non-Narcotic chemical synthesis, Analgesics, Non-Narcotic pharmacology, Animals, Anticonvulsants chemical synthesis, Anticonvulsants pharmacology, Behavior, Animal drug effects, Blood Pressure drug effects, Central Nervous System Depressants pharmacology, Central Nervous System Depressants toxicity, Central Nervous System Stimulants antagonists & inhibitors, Central Nervous System Stimulants pharmacology, Female, Lethal Dose 50, Magnetic Resonance Spectroscopy, Male, Mice, Motor Activity drug effects, Pain drug therapy, Pain psychology, Psychomotor Performance drug effects, Pyrroles pharmacology, Pyrroles toxicity, Rats, Rats, Wistar, Spectrophotometry, Infrared, Central Nervous System Depressants chemical synthesis, Pyrroles chemical synthesis
- Abstract
As a continuation of our work on N-[4-aryl(heteroaryl)piperazin-1-ylalkyl]-3,4-pyrro ledicarboximides, which were characterized by strong analgesic activity and CNS depressive action, several novel N-substituted 3,4-pyrroledicarboximides were prepared and eleven representatives were examined in a series of in vivo CNS tests. A few of these compounds displayed a similar profile of biological selectivity to that of 3,4-pyrroledicarboximides described previously; their structure-activity relationships are discussed.
- Published
- 2000
85. Synthesis and pharmacological properties of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimi dine-5 -carboxylic acid.
- Author
-
Sladowska H, Sieklucka-Dziuba M, Rejdak R, and Kleinrok Z
- Subjects
- Analgesics, Non-Narcotic chemical synthesis, Animals, Behavior, Animal drug effects, Mice, Pyridines chemical synthesis, Pyrimidinones chemical synthesis, Analgesics, Non-Narcotic chemistry, Analgesics, Non-Narcotic pharmacology, Motor Activity drug effects, Pyridines chemistry, Pyridines pharmacology, Pyrimidinones chemistry, Pyrimidinones pharmacology
- Abstract
The synthesis of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimid ine-5- carboxylic acid and the results of the preliminary pharmacological screening are described in this paper. Some of them showed a weak analgesic action and caused suppression of the spontaneous locomotor activity of mice.
- Published
- 2000
- Full Text
- View/download PDF
86. Investigations on the synthesis and pharmacological properties of amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4- dioxo-1,2,3,4-tetrahydropyrido[2,3-d]-pyrimidine-5-carboxylic acid.
- Author
-
Sladowska H, Sieklucka-Dziuba M, Rajtar G, Sadowski M, and Kleinrok Z
- Subjects
- Amides chemistry, Analgesics, Non-Narcotic chemistry, Animals, Dose-Response Relationship, Drug, Female, Lethal Dose 50, Magnetic Resonance Spectroscopy, Male, Mice, Molecular Structure, Pyridines chemical synthesis, Pyridines chemistry, Pyridines pharmacology, Pyrimidinones chemistry, Rats, Rats, Wistar, Amides chemical synthesis, Amides pharmacology, Analgesics, Non-Narcotic chemical synthesis, Analgesics, Non-Narcotic pharmacology, Pyrimidinones chemical synthesis, Pyrimidinones pharmacology
- Abstract
Synthesis of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (6-10) and their 1-[2-hydroxy-3(4-phenyl-1-piperazinyl)propyl] derivatives (11-15) are described. Some of them displayed strong analgesic activity.
- Published
- 1999
- Full Text
- View/download PDF
87. Synthesis and pharmacological screening of some N-(4-substituted-piperazin-1-ylalkyl)-3,4-pyrroledicarboximides.
- Author
-
Malinka W, Sieklucka-Dziuba M, Rajtar G, Rubaj A, and Kleinrok Z
- Subjects
- Analgesics, Non-Narcotic pharmacology, Analgesics, Non-Narcotic toxicity, Animals, Anti-Anxiety Agents pharmacology, Anticonvulsants chemical synthesis, Anticonvulsants pharmacology, Behavior, Animal drug effects, Blood Pressure drug effects, Chemical Phenomena, Chemistry, Physical, Electroshock, Female, Lethal Dose 50, Magnetic Resonance Spectroscopy, Male, Mice, Motor Activity drug effects, Pain Measurement drug effects, Piperazines pharmacology, Piperazines toxicity, Postural Balance drug effects, Rats, Rats, Wistar, Analgesics, Non-Narcotic chemical synthesis, Piperazines chemical synthesis
- Abstract
As an extension of our previous work we describe the synthesis and pharmacological investigation of a new series of derivatives of pyrrole-3,4-dicarboximide possessing the 4-substituted-piperazin-1-ylalkyl group linked to the imide nitrogen. The products were evaluated for acute toxicity, and effectiveness in a series of CNS and arterial blood pressure tests. The preliminary pharmacological screening was determined in animal models. Several compounds demonstrated moderate to high analgesic activity in the 'writhing syndrome' test (5f-1/640 LD50). Some of the structure-activity relationships are also discussed.
- Published
- 1999
- Full Text
- View/download PDF
88. Influence of hypoxia-induced convulsions on morphological structure of hippocampal cells.
- Author
-
Sieklucka-Dziuba M, Rubaj A, Sekita-Krzak J, Zgodziński W, Czerny K, and Kleinrok Z
- Subjects
- Animals, Ischemic Attack, Transient chemically induced, Mice, Nitrogen, Pyramidal Cells pathology, Brain Diseases etiology, Brain Diseases pathology, Hippocampus pathology, Ischemic Attack, Transient complications, Seizures complications
- Published
- 1999
89. Investigations on the synthesis and properties of N-phenyl derivatives of 1,4-dioxo(1,4,5-trioxo)-1,2,3,4-tetra(1,2,3,4,5,6-hexa) hydropyrido-[3,4-d]pyridazines and allied compounds.
- Author
-
Sladowska H, Potoczek J, Sokołowska M, Rajtar G, Sieklucka-Dziuba M, Kocki T, and Kleinrok Z
- Subjects
- Animals, Anti-Infective Agents chemical synthesis, Anti-Infective Agents chemistry, Female, Injections, Intraperitoneal, Lethal Dose 50, Male, Mice, Molecular Structure, Motor Activity drug effects, Pyridazines pharmacology, Pyridazines toxicity, Rats, Rats, Wistar, Structure-Activity Relationship, Pyridazines chemical synthesis, Pyridazines chemistry
- Abstract
2-(1-Piperidino)- and 2-(4-methyl-1-piperazinyl)-6-methyl-3,4-pyridinedicarboximides (1, 2) react with N-phenylhydrazine yielding N-phenylamino-3,4-pyridinedicarboximides (7, 8). The same reaction with 1,6-dimethyl-2-oxo-1,2-dihydro- and 2-chloro-6-methyl-3,4-pyridinedicarboximides (3, 17) gives the salts of the corresponding N-phenylpyridopyridazines with phenylhydrazine (13, 18), which transform into N-phenylaminoimides (14, 19) during boiling in 80% acetic acid. Compounds 7, 8 and 14 isomerize to the corresponding 2-phenyl-1,4-dioxo(1,4,5-trioxo)-1,2,3,4-tetra(1,2,3,4,5,6-hexa) hydropyrido[3,4-d]pyridazines (9, 10, 15) under the influence of heating in alcoholic solution of C2H5ONa or CH3ONa. Only in the case of imide 19 are 2- and 3-phenyl isomers (20 and 21) formed under these conditions. Some of the obtained compounds were pharmacologically active.
- Published
- 1998
- Full Text
- View/download PDF
90. Investigations on the synthesis and properties of 4-aminosubstituted 2,6,7-trimethyl-1,5-dioxo-1,2,5,6-tetrahydropyrido[3,4-d]pyridazines.
- Author
-
Sladowska H, Stanasiuk J, Sieklucka-Dziuba M, Saran T, and Kleinrok Z
- Subjects
- Analgesics chemistry, Animals, Antineoplastic Agents chemistry, Female, Injections, Intraperitoneal, Lethal Dose 50, Male, Mice, Molecular Structure, Motor Activity drug effects, Pyridazines chemistry, Rats, Rats, Wistar, Structure-Activity Relationship, Analgesics chemical synthesis, Analgesics toxicity, Antineoplastic Agents chemical synthesis, Antineoplastic Agents toxicity, Pyridazines chemical synthesis, Pyridazines toxicity
- Abstract
Synthesis of 4-aminosubstituted 2,6,7-trimethyl-1,5-dioxo-1,2,5,6-tetrahydropyrido[3,4-d]pyridazin es 2-11 and the results of the preliminary pharmacological screening of the selected compounds 2, 4, 5, 10, 11 are described in this paper.
- Published
- 1998
- Full Text
- View/download PDF
91. 2-Substituted-3-oxoisothiazolo[5,4-b]pyridines as potential central nervous system and antimycobacterial agents.
- Author
-
Malinka W, Ryng S, Sieklucka-Dziuba M, Rajtar G, Głowniak A, and Kleinrok Z
- Subjects
- Analgesics chemical synthesis, Analgesics chemistry, Analgesics toxicity, Animals, Anti-Anxiety Agents toxicity, Antitubercular Agents toxicity, Female, Lethal Dose 50, Male, Mice, Microbial Sensitivity Tests, Molecular Structure, Motor Activity drug effects, Pyridines toxicity, Rats, Rats, Wistar, Structure-Activity Relationship, Anti-Anxiety Agents chemical synthesis, Anti-Anxiety Agents chemistry, Antitubercular Agents chemical synthesis, Antitubercular Agents chemistry, Pyridines chemical synthesis, Pyridines chemistry
- Abstract
The 2-[3-(substituted-amino)-2-hydroxypropyl]-4,6-dimethyl-3-oxo-2,3- dihydroisothiazolo[5,4-b]pyridines 3 were synthesized and pharmacologically evaluated in animal models. The preliminary pharmacological screening study showed that the investigated compounds were toxic and had no significant activity in central nervous system (CNS) tests. Additionally, compounds 3, and several other 2-substituted-4,6- dimethyl-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridines described here (2), together with those (4) reported in a previous paper, were evaluated in vitro against Mycobacterium tuberculosis H37Rv. For comparison, products of the rearrangement of some isothiazolopyridine 1,1-dioxides (4a,b) with the corresponding pyrido[3,2-e]-1,2-thiazines (5a,b) and different N2-substituted derivatives of the latter (5c-i) were also prepared and investigated in antimycobacterial tests. The most potent antituberculars of the 23 compounds assayed are 2-[3-(4-benzylpiperidin-1-yl)-2-hydroxypropyl]-4,6-dimethyl-3-oxo- 2,3- dihydroisothiazolo[5,4-b]pyridine 3d and ethyl (4,6-dimethyl-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridin-2-yl)acet ate 4c (MIC < 12.5 micrograms/ml, 100 and 98% inhibition, respectively).
- Published
- 1998
- Full Text
- View/download PDF
92. Synthesis and pharmacological screening of pyrazolo[3,4-c]pyridazine derivatives.
- Author
-
Zabska R, Kołodziejczyk A, Sieklucka-Dziuba M, Morawska D, and Kleinrok Z
- Subjects
- Amphetamine antagonists & inhibitors, Animals, Anticonvulsants chemical synthesis, Anticonvulsants pharmacology, Body Temperature drug effects, Central Nervous System Agents pharmacology, Central Nervous System Agents toxicity, Central Nervous System Stimulants antagonists & inhibitors, Female, Lethal Dose 50, Male, Mice, Motor Activity drug effects, Pyridazines pharmacology, Rats, Rats, Wistar, Central Nervous System Agents chemical synthesis, Pyridazines chemical synthesis
- Abstract
Ethyl 3-chloro-6-(4-chlorophenyl)-pyridazine-4-carboxylate [VII] was cyclized with some nucleophilic reagents (hydrazine hydrate or N-monosubstituted hydrazines) to the new derivatives of pyrazolo[3,4-c]pyridazine [IXa-d]. The structures of the novel compounds were confirmed by elemental and spectral analyses. The effect of several synthesized derivatives on the central nervous system was studied.
- Published
- 1998
93. Behavioral studies of the effects of moderate oligemic hypoxia caused by bilateral clamping of carotid arteries in mice. Impairment of spatial working memory.
- Author
-
Jóźwiak L, Sieklucka-Dziuba M, and Kleinrok Z
- Subjects
- Anesthesia, Animals, Carotid Arteries surgery, Catalepsy chemically induced, Catalepsy prevention & control, Constriction, Frontal Lobe blood supply, Frontal Lobe chemistry, Hippocampus blood supply, Hippocampus chemistry, Male, Maze Learning physiology, Mice, Motor Activity physiology, Motor Skills physiology, Nafronyl pharmacology, Pain Measurement, Scopolamine pharmacology, Time Factors, Visual Cortex blood supply, Visual Cortex chemistry, Behavior, Animal physiology, Brain blood supply, Brain Chemistry, Hypoxia complications, Memory physiology, gamma-Aminobutyric Acid analysis
- Abstract
The experiments carried out on Albino Swiss mice indicated that bilateral clamping of carotid arteries (BCCA) for 30 min caused no neuronal damage but produced an increase in GABA content in the hippocampus, striatum and frontal cortex. The behavioral studies have shown that BCCA did not influence the motor coordination, the spontaneous locomotor activity, the reactivity to pain and the cataleptic response to haloperidol of the mice. However, a significant increase in amphetamine-induced hyperactivity was observed after BCCA. In mice, BCCA did not impair long-term memory and spatial working memory, reflected by alternation behavior in the Y-maze. The same dose of scopolamine impaired the working memory in mice which underwent BCCA much more than sham-operated controls. Naftidrofuryl improved the working memory in mice subjected to BCCA as measured 48 h after the surgery. Pretreatment with naftidrofuryl protected the animals against the impairment of alternation behavior caused by scopolamine administration.
- Published
- 1998
94. Central action of glucagon.
- Author
-
Morawska D, Sieklucka-Dziuba M, and Kleinrok Z
- Subjects
- Analgesics pharmacology, Animals, Anti-Anxiety Agents pharmacology, Anticonvulsants pharmacology, Blood Glucose metabolism, Brain Chemistry drug effects, Catalepsy chemically induced, Catalepsy psychology, Exploratory Behavior drug effects, Female, Glucagon administration & dosage, Injections, Intraventricular, Male, Mice, Motor Activity drug effects, Psychomotor Performance drug effects, Rats, Rats, Wistar, Reaction Time drug effects, Sleep drug effects, Behavior, Animal drug effects, Central Nervous System drug effects, Glucagon pharmacology
- Abstract
The central action of the peptide of intestinal tract, glucagon, was studied in Albino Swiss mice (20-25 g) and Wistar rats (200-220 g). Glucagon was injected intracerebroventricularly (icv) at the dose of 0.25, 0.5 and 1 microgram in 1 microliter of distilled water per mouse or 5 micrograms in 5 microliters per rat. It was found that glucagon administered icv increased glucose content in the peripheral blood serum. Behavioral studies have shown that glucagon diminished spontaneous locomotor activity in rats and mice, impaired exploratory activity and reduced amphetamine-induced hyperactivity. The results were not dependent on hyperglycaemia because the administration of 20% glucose solution po did not cause above effects. In addition, glucagon potentiated cataleptogenic effects of haloperidol. Icv injection of glucagon did not change the pain sensitivity or seizure susceptibility. The substance did not show the anxiolytic properties and did not affect the duration of hexobarbital-induced sleep. In biochemical studies it was found that glucagon injected icv induced the decrease in GABA content while the DA content was increased. The utilization of DA was not changed. The obtained results indicated, that glucagon injected icv exerted the central action, which was manifested by the central regulation of glucose level in the periphery. Moreover, glucagon inhibited the locomotor and exploratory activity as well as the amphetamine-induced hyperactivity and enhanced haloperidol-induced catalepsy. These effect could be connected with the inhibition of the central dopaminergic structures by glucagon.
- Published
- 1998
95. [The effect of lithium chloride on the rat behavior after short-term oligemic hypoxia].
- Author
-
Sieklucka-Dziuba M, Gustaw K, Dziuba J, and Kleinrok Z
- Subjects
- Amphetamine pharmacology, Animals, Brain physiopathology, Catalepsy chemically induced, Catalepsy complications, Catalepsy physiopathology, Drug Synergism, Haloperidol, Ischemic Attack, Transient complications, Ischemic Attack, Transient physiopathology, Male, Rats, Rats, Wistar, Behavior, Animal drug effects, Ischemic Attack, Transient drug therapy, Lithium Chloride pharmacology, Psychomotor Performance drug effects
- Abstract
The experiments were carried out on male Wistar rats. The influence of brain oligemic hypoxia and lithium chloride (LiCl) on some behavioural parameters was investigated. Reduction of brain blood supply was performed by surgical clamping of both carotid arteries for 60 min in general anaesthesia induced by brietal (Methoxitone sodium, 10 mg/kg i.p.). Control animals had their vessels separated, but not clamped (sham operated). 6 days after surgery animals received LiCl (2.5 mEq/kg i.p.). Behavioral experiments were performed 24 h and 7 days after lithium administration. Experimental groups consisted of 12 animals. It was found that oligemic hypoxia reduced inconsiderably spontaneous locomotor and exploratory activity in rats. Similar influence of LiCl was observed. But LiCl administered to animals after oligemic hypoxia prevented them against locomotor and exploratory impairment. In addition, LiCl strongly enhanced amphetamine-induced hyperactivity and diminished haloperidol-induced catalepsy in hypoxic animals. These effects were not observed in sham operated animals. The above results could be connected with antidepressive action of LiCl and the model of moderate oligemic hypoxia used in present work could be a useful model for investigation of new antidepressive compounds.
- Published
- 1998
96. Central action of some cytostatics--methotrexate (MTX) and doxorubicin (DXR). I. Long-term influence on the pain sensitivity and activity of brain dopaminergic system in mice.
- Author
-
Sieklucka-Dziuba M, Dziuba J, Patyra H, and Kleinrok Z
- Subjects
- Animals, Body Weight drug effects, Brain drug effects, Catalepsy chemically induced, Catalepsy prevention & control, Drug Interactions, Female, Haloperidol antagonists & inhibitors, Male, Mice, Norepinephrine metabolism, Pain physiopathology, Analgesics pharmacology, Behavior, Animal drug effects, Brain metabolism, Doxorubicin pharmacology, Exploratory Behavior drug effects, Locomotion drug effects, Methotrexate pharmacology
- Published
- 1998
97. Central action of some cytostatics--methotrexate (MTX) and doxorubicin (DXR). II. The influence on the seizure activity and the learning and memory processes in mice.
- Author
-
Sieklucka-Dziuba M, Saczonek J, Dziuba J, and Kleinrok Z
- Subjects
- Animals, Brain metabolism, Drug Interactions, Female, Hexobarbital pharmacology, Male, Mice, Pentylenetetrazole, Seizures chemically induced, Sleep drug effects, gamma-Aminobutyric Acid metabolism, Brain drug effects, Doxorubicin pharmacology, Learning drug effects, Memory drug effects, Methotrexate pharmacology
- Published
- 1998
98. Transformation of some pyrido[2,3-d]pyrimidine derivatives into other di- and triheterocyclic systems.
- Author
-
Sladowska H, Bodetko M, Sieklucka-Dziuba M, Rajtar G, Zółkowska D, and Kleinrok Z
- Subjects
- Analgesics chemistry, Analgesics pharmacology, Animals, Blood Pressure drug effects, Female, Heart Rate drug effects, Kinetics, Magnetic Resonance Spectroscopy, Male, Mice, Motor Activity drug effects, Pyrimidines pharmacology, Rats, Rats, Wistar, Spectrophotometry, Infrared, Pyrimidines chemistry
- Abstract
It was stated that three analogous ethyl 2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylates (7-9) react with hydrazine hydrate giving derivatives of the new heterocyclic system pyrido[2,3,4-ef]pyridazino[3,4-e]-1,2,4-triazepine (10-12), pyrido[3,4-d]pyridazine (16-18) and pentaazaphenalene (13-15). The latters were formed in low yields. The results of the preliminary pharmacological study of 2 of these compounds are reported.
- Published
- 1997
99. Central action of insect neuropeptide, periplanetin CC-1, in mice.
- Author
-
Sieklucka-Dziuba M, Morawska D, Lombarska-Sliwińska D, Konopińska D, and Kleinrok Z
- Subjects
- Animals, Anticonvulsants pharmacology, Blood Glucose metabolism, Brain Chemistry drug effects, Electroshock, Exploratory Behavior drug effects, Female, Hexobarbital pharmacology, Hypnotics and Sedatives pharmacology, Injections, Intraventricular, Male, Mice, Motor Activity drug effects, Neurotransmitter Agents metabolism, Pain Measurement drug effects, Pentylenetetrazole, Postural Balance drug effects, Sleep drug effects, Behavior, Animal drug effects, Insect Hormones pharmacology, Neuropeptides pharmacology, Oligopeptides pharmacology
- Abstract
The central action of periplanetin CC-1 (Pea-HrTH) (Glp-Val-Asn-Phe-Ser-Pro-Asn-TrpNH2), octapeptide of the insect adipokinetic hormone family (AKH-family), isolated from American cockroach-Periplaneta americana, was studied in Albino Swiss mice (20-25 g). CC-1 was injected intracerebroventricularly (i.c.v.) in the volume of 5 microliters at the dose of 50 ng/mouse. It was found that CC-1 showed strong analgesic activity in "writhing syndrome" test and in "hot plate" test. In addition, periplanetin CC-1 decreased the threshold for tonic seizures and increased mortality in pentetrazole-induced seizures, having no influence on the electric convulsions. CC-1 is known to be a glucagon-like AKH in insects. However, administered i.c.v. to mice, it did not increase the peripheral blood glucose level. The obtained results indicate that periplanetin CC-1 shows a biological action in vertebrates, but its metabolic effects are different than in insects.
- Published
- 1997
100. Investigations on the synthesis and properties of some N-[4-phenyl(2-pyrimidinyl)-1-piperazinyl]alkyl (hydroxyalkyl)-3,4-pyridinedicarboximides.
- Author
-
Sladowska H, Potoczek J, Rajtar G, Sieklucka-Dziuba M, Zółkowska D, and Kleinrok Z
- Subjects
- Animals, Blood Pressure drug effects, Central Nervous System drug effects, Drug Evaluation, Preclinical, Female, Heterocyclic Compounds, 1-Ring pharmacology, Imides pharmacology, Lethal Dose 50, Male, Mice, Motor Activity drug effects, Pyrimidines pharmacology, Rats, Rats, Wistar, Heterocyclic Compounds, 1-Ring chemical synthesis, Imides chemical synthesis, Pyrimidines chemical synthesis
- Abstract
Synthesis of 2-substituted N-(4-phenyl-1 piperazinyl)propyl(butyl)- and N-2-hydroxy-3[4-phenyl(2-pyrimidinyl)-1-piperazinyl]propyl-6-methyl-3,4- pyridinedicarboximides [VI-XIV] is described. Some of them displayed depressive action on the central nervous system.
- Published
- 1996
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