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Eduard Ujházy, Mojmír Mach, Jana Navarová, Ingrid Brucknerová and Michal Dubovický

Safety assessment of the pyridoindole derivative SMe1EC2: developmental neurotoxicity study in rats

The present study deals with effect of prenatal and neonatal administration of the synthetic pyridoindole derivative SMe1EC2 (2-ethoxycarbonyl-8-methoxy-2,3,4,4a, 5,9b-hexahydro-1H-pyrido-[4,3b] indolinium chloride) on postnatal and neurobehavioral development of the rat offspring. The substance tested was administered to pregnant rats orally in the doses 5, 50 and 250 mg/kg from day 15 of gestation to day 10 post partum (PP). From the day 4 PP, the postnatal development and neurobehavioral characteritics of offspring were evaluated. The following variables were observed: body weight, pinna detachment, incisor eruption, ear opening, eye opening, testes descent and vaginal opening, righting reflex, negative geotaxia, startle reflex, dynamic air righting and exploratory behavior in a new environment. No maternal death, abortion or dead fetuses occurred either in the control or SMe1EC2 groups. Dynamic righting reflex was delayed one day in the groups of animals treated via their mothers with 5 and 50 mg/kg SMe1EC2. The delay in the development of this reflex was only transient. On day 20 PP, all pups tested had a positive score of the reflex. Administration of SMe1EC2 did not reveal any significant changes in other variables of somatic growth and maturation, reflex and neuromotor development and exploratory behavior, either of young or adult animals of both genders, assessed by analysis of variance.

Open access

Ruzena Sotnikova, Viera Nosalova and Jana Navarova

Abstract

Reactive oxygen species has been implicated to contribute significantly to tissue injury associated with ulcerative colitis. Thus compounds with antioxidant properties could be potential therapeutic agents in this disease. Flavonoid compounds are known to possess antioxidative and antiinflammatory properties. Two derivatives of the flavonoid quercetin (Q), chloronaphthoquinone quercetin (CNC) and monochloropivaloyl quercetin (MCP), showed improved antioxidant properties and moreover, they efficiently inhibited aldose reductase activity in vitro. The aim of the work was to test the potential efficacy of quercetin and these synthetic derivatives in vivo in prevention of intestinal inflammation during ulcerative colitis in rats. Colitis was induced by intracolonic administration of acetic acid (4% solution). The control group received the same volume of saline. The vehicle dimethyl sulfoxide (DMSO) and the drugs Q, CNC or MCP were administered orally two hours and then one hour before the acetic acid or saline instillation. After 48 hours, the animals were sacrificed and the colon was weighed, measured and scored for visible damage. Acetic acid triggered an intense inflammatory response of the colon, characterised by haemorrhage, ulceration and bowel wall thickening. From the drugs tested, only CNC (2 × 50 mg/kg) effectively depressed inflammatory damage of the colon. The mechanism of this beneficial effect remains to be elucidated.

Open access

Rumyana Simeonova and Nikolai Danchev

Abstract

The aim of the present study was to evaluate local irritant effects to rabbit skin following a single application of test samples of non-sterile polyamide non-absorbable surgical sutures POLYMED ®. The polar and nonpolar extracts were prepared by using saline solution and olive oil, respectively, after sinking the materials tested (2.0 g) in 10 ml of the corresponding liquid. Incubation was carried out at the temperature of 37°C for 72 h. The saline solution and pure olive oil, which had no contact with the materials tested, were used as negative control samples and were incubated under the same conditions as above. Assessments of the extracts from each material were conducted on 2 albino rabbits of the New Zealand breed. On the back of each animal, 5 intracutaneous injections of the extract tested and 5 injections of the control solution, each of 0.2 ml, were carried out. The degree of irritation was scored at 4, 24, 48, 72 hours after injection and no skin changes were found. The intracutaneous irritation index (III) was calculated and yielded 0.0. Hence it was concluded that under the experimental conditions the extracts of the material tested, i.e. non-sterile polyamide non-absorbable surgical sutures POLYMED ®, were ‘non-irritant’ to the skin of rabbits when compared with the respective control groups. The experimental procedure was conducted according to ISO10993-10.

Open access

Frantisek Drafi, Katarina Bauerova, Viera Kuncirova, Silvester Ponist, Danica Mihalova, Tatiana Fedorova, Juraj Harmatha and Radomir Nosal

Abstract

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. Patients with rheumatoid arthritis have an altered antioxidant defense capacity barrier. In the present study the effect of substances with antioxidative properties, i.e. pinosylvin and carnosine, was determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover carnosine was evaluated in combination therapy with methotrexate. Rats with AA were administered first pinosylvin (30 mg/kg body mass daily per os), second carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28 days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2-times weekly per os), and a combination of methotrexate+carnosine, with the carnosine dose being the same as in the previous experiment. Parameters, i.e. changes in hind paw volume and arthritic score were determined in rats as indicators of destructive arthritis-associated clinical changes. Plasmatic levels of TBARS and lag time of Fe2+- induced lipid peroxidation (tau-FeLP) in plasma and brain were specified as markers of oxidation. Plasmatic level of CRP and activity of γ-glutamyltransferase (GGT) in spleen and joint were used as inflammation markers. In comparison to pinosylvin, administration of carnosine monotherapy led to a significant decrease in the majority of the parameters studied. In the combination treatment with methotrexate+carnosine most parameters monitored were improved more remarkably than by methotrexate alone. Carnosine can increase the disease-modifying effect of methotrexate treatment in rat AA.

Open access

Islam M. Sadiqul, Saimon Mohiful Kabir, Zannatul Ferdous, Khan Mst. Mansura and Rahman Md. Khalilur

. Ecotoxicology 16 : 385–391. Fenech M, Chang WP, Kirsch-Volders HMN, Bonassi S, Zeiger E. (2003). HUMAN project: detailed description of the scoring criteria for the cytokinesis block micronucleus assay using isolated human lymphocyte cultures. Mut Res 534 : 65–75. Finney DJ. (1971). Probit analysis, Cambridge University, Press, London, UK (3 rd Edn.). Folch J, Lees M, Sloane Stanley GH. (1957). A simple method for the isolation and purification of total lipides from animal tissues. J Biochem Chem 226 (1): 497–509. Gerhardt P, Murray RGE, Wood

Open access

Soumalya Mukherjee, Mitali Ray and Sajal Ray

). Environ Sci Pollut Res 20 : 621–629. Duckworth AR, Pomponi SA. (2005). Relative importance of bacteria, micro-algae and yeast for growth of the sponge Halichondria melanadocia (De Laubenfels, 1936): a laboratory study. J Exp Mar Biol Ecol 323 : 151–159. Fenech M, Chang W, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E. (2003). HUMN project: detailed description of the scoring criteria for the cytokinesis block micronucleus assay using isolated human lymphocyte cultures. Mutat Res 534 (1–2): 65–75. Fernàndez-Busquets X, Burger MM. (1999

Open access

Claudia-Mariana Handra, Eugenia Naghi and Marina Ruxandra Oțelea

Abstract

Context. Stress is a complex psychosocial phenomenon that significantly influences health. The individual differences in stress response depend on sensitivity to stressors, named “stress vulnerability”.

Objectives. The aims of the study were to determine the level of perceived vulnerability to stress and compare stress vulnerability among students from 2 universities in Bucharest: University of Medicine “Carol Davila” and National University of Political Studies and Public Administration.

Methods. An approximately equal number of students from the two selected universities completed the Romanian version of the Miller-Smith stress vulnerability questionnaire.

Results. A number of 86 (60 women and 26 men) students agreed to participate. Average age was 23.56 years with a standard deviation of 4.86 years. The high vulnerability group included 18 (38%) medical students and 27 (60%) political science and public administration students. The difference was statistically significant (chi2 test, p=0.02) between the two groups. The average health score for medical students (MS) was 15.97, with a median of 15, while for the political science and administration students (PSPAS) the average health score was 24.91, with a median of 26. The average psychosocial score for MS group was 20.41 and the median was 20. In the PSAPS group, the psychosocial score was 26.14 and the median 24. The difference was statistically significant for both health score (p<0.00001) and psychosocial score (p=0.0006).

Conclusions: Stress is a common problem among undergraduated students. In this study the vulnerability to stress was higher for students PSAPS group compared to the students from MS group.

Open access

Dorota Talarska, Michał Michalak and Patrycja Talarska

Summary

Background. Every chronic illness, including epilepsy, has a negative effect on both the quality of life of the sufferer as well as on their relationship with their surroundings.

Aims. To investigate the quality of life of children suffering from epilepsy and analyse how they assessed and scored their experiences compared to their parents.

Materials and methods. The study included 209 children with epilepsy and their parents. The research tool was a questionnaire for gathering demographic and clinical data as well as the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) questionnaire in two versions, one for 8–12 year olds and one for 13–18 year olds and their parents.

Results. Cronbach’s alpha coefficient for the entire PedsQL 4.0 questionnaire was 0.91 and 0.93 for children with epilepsy and their parents respectively. Children rated their Total Scale Score higher (67.5 points) than their parents (62.5 points). Whilst analyzing children’s functioning in different areas it was observed that girls’ assessments were higher than boys’, except for Emotional Functioning. Both parents and children scored School Functioning the lowest. The greatest agreement of responses was observed in the domain of Physical Functioning, the smallest in the domain of Emotional Functioning.

Conclusions. Quality of life was rated higher by both age groups of children suffering from epilepsy than by their parents. A statistically significant difference was found when comparing the assessment scores of children and parents in light of the following variables; child age, gender, illness duration, seizure frequency and treatment effectiveness.

Open access

Iulia-Rahela Marcu, Ion Toma and Adrian Costin Bighea

Abstract

Quality of life studies in patients with knee osteoarthritis (OA) attest to the significant impact of the disease on day-to-day activities and social interactions. The aim of this study was to assess the efficacy of a physical exercise program on functional status and quality of life in patients with work-related knee osteoarthritis. The present study included 144 participants with knee osteoarthritis, 72% women, mean age (SD) 47.2 (11.1) years. The patients were randomly assigned in two lots based on the type of kinetic treatment: lot A-with knee OA and medication (72 patients) and lot B- with knee OA, medication and exercise program (72 patients). They followed for 12 days ambulatory exercise programs based on increasing knee flexion, muscular strength and endurance, improving balance, coordination, and respiratory exercises. The patients in the control group continued their daily living activities. The evaluation was made at the beginning of the study (T0), after 2 weeks (T1) and 8 weeks after the 12 days of exercise program (T2) and was based on the following parameters: knee mobility (knee flexion), muscular strength, pain assessment on a Visual Analogue Scale (VAS), functional status (Western Ontario &McMaster Universities Osteoarthritis Index - WOMAC) and quality of life evaluation using SF-36 Questionnaire (36-Item Short Form Survey). Out of 144 participants who completed the initial evaluation, 138 also completed the 2 weeks and the 8 weeks follow-up assessments: 70 patients from the control lot and 68 patients from the exercise lot. The benefits of the kinetic programs were shown by a significant improvement in knee mobility and muscular strength for knee extensors (quadriceps muscle) and knee flexor muscles. Testing the linear correlations between the SF-36 score and the VAS (r=0.71, p<0.05) and WOMAC (r=0.83, p<0.05) indicators demonstrates a highly positive relationship between the quality of life expression, the pain assessment score and the functional status score in patients with knee OA. The physical exercise program improves both functional status and quality of life in patients with work-related knee osteoarthritis by increasing the range of motion and muscular strength and by reducing pain.

Open access

Vladimir V. Kalinin, Daniya M. Nazmetdinova and Alexander V. Basamygin

Summary

Introduction. The current knowledge of significance of some neurobiological and clinical variables for the development of cognitive deterioration in patients with epilepsy remains sparse and controversial.

Aim. The current study has been carried out in order to elucidate the role of handedness in terms of influence on cognitive processing and intelligence in patients with epilepsy.

Material and methods. One hundred and thirty two patients (62 males, 70 females, aged 27.8 ± 8.9 years) with epilepsy participated in the study. Patients were divided into two groups. The first group included 112 patients that were characterized by intelligence and cognitive impairment while the second group (20 patients) had no mental deterioration and was regarded as controls. The two diagnostic categories accorded with ICD-10 criteria. The diagnosis of Dementia (F-02.8) was confirmed in 54 patients, while the diagnosis of Mild Cognitive Impairment (F-06.7) was confirmed in 58 patients.

Results. Our results show that the level of left-handers among patients with cognitive Impairment achieved 14.2%, whilst in the group without cognitive deterioration there were no left-handers, and this difference was statistically significant (p = 0.051). An analysis of possible influence of motor lateralization on degree of cognitive deterioration, revealed that left-handedness determines the higher degrees of intelligence deterioration compared with right-handedness (χ2 = 6.64; p < 0,05). These data were confirmed by use of Wechsler Adult Intelligence Scale (WAIS) and the Mini Mental State Examination (MMSE) tests, and all left-handed epilepsy patients achieved lower scores on MMSE, total WAIS, as well as verbal and nonverbal WAIS scores.

Conclusion. Our data confirm a role of some neurobiological variables, with emphasis on cerebral motor lateralization, in their influence upon intelligence level and cognitive deterioration in epilepsy. These data may be used for predictive purposes of intelligence assessment in patients with epilepsy.