Biomedical subjects

D Jezova

Publications and source records attributed to D Jezova.

At least 19 recordsLinked to original sources

PubMed2006

Oxytocin levels in the posterior pituitary and in the heart are modified by voluntary wheel running.

We hypothesized that voluntary wheel running results in increased secretion of oxytocin, a peptide involved in the stress response. An additional hypothesis was that prolonged exercise affects oxytocin levels in the heart, which is in line with the potential role of oxytocin in cardiovascular functions. Voluntary wheel running lasted 3 weeks and daily running distances increased progressively reaching maximum levels about 8 km (Sprague-Dawley rats) and 4 km (Lewis strain). The exercise resulted in significant reduction of epididymal fat, slight increase in glucose transporter GLUT4 mRNA levels and significant enhancement of plasma density. Voluntary exercise failed to influence plasma oxytocin levels either in Lewis or Sprague-Dawley rats, but it resulted in a significant decrease of oxytocin concentrations in the posterior pituitary. Plasma oxytocin concentrations were not modified even if the measurements were made in the dark phase of the day. In voluntary wheel running Sprague-Dawley rats, the content of oxytocin in the right heart atrium was lower than in controls. Thus, the present findings demonstrate that prolonged voluntary wheel running results in a decrease in pituitary oxytocin content without evident changes in hormone concentrations in peripheral blood. However, prolonged exercise used has a significant impact on oxytocin levels in the heart.

Animals↗

PubMed2006

Perception of potentially inappropriate medication in elderly patients by Slovak physicians.

PURPOSE: The aim of the present study was to determine the risk perception of potentially inappropriate drug treatment of elderly patients by Slovak physicians. In Slovakia, a list of such drugs is not available. METHODS: The study sample consisted of 600 patients aged > or =65 years hospitalized at the Department of Internal Medicine in a Slovak general hospital between 1 December 2003 and 31 March 2005. The use of potentially inappropriate drugs at the time of hospital admission and discharge was compared. Potentially inappropriate drug use was defined by Beers 2003 criteria. In addition, 206 physicians were asked to mark the drugs that they considered potentially inappropriate for elderly patients out of a list provided in a questionnaire analysis. RESULTS: Out of 600 patients 20.2% and 20% were treated with at least one potentially inappropriate drug at the time of hospital admission and discharge, respectively. Hospitalization had no significant influence on the number of potentially inappropriate medicines used. The most frequently prescribed potentially inappropriate drugs were digoxin >0.125 mg/day and ticlopidine. Out of 206 responding physicians only 4.9% considered ticlopidine as potentially inappropriate for elderly patient. On the other hand, more than 20% of respondents were aware of the potential inappropriateness of amitriptyline, diazepam and chlordiazepoxide. Mentioned drugs were observed in less than 2% of study population (n = 600). CONCLUSIONS: The results of the questionnaire analysis in physicians as well as the prevalence of potentially inappropriate medication demonstrate that Slovak clinicians are aware of the risk of certain treatments in elderly patients.

Aged↗

PubMed2006

Effect of pentoxifylline on endothelaemia and hypothalamic-pituitary-adrenocortical axis activation in female rats under stress exposure.

Endothelial dysfunction may belong to negative consequences of stress exposure accompanied by activation of several stress systems including the hypothalamic-pituitary-adrenocortical (HPA) axis. The present experiments were aimed at testing the hypotheses that i) immobilization (IMO) stress results in sustained increase in endothelaemia for 24 h and that ii) pentoxifylline, a drug with endothelium protective properties, attenuates the rise in endothelaemia and HPA axis activation in female rats as shown previously in males. Circulating endothelial cells increased immediately after the IMO for 2 h, returned back to control levels at 12 h and increased again at 24 h. Stress-induced rise in adrenocorticotropic hormone (ACTH) and corticosterone levels was particularly high immediately after the IMO. Pretreatment with pentoxifylline (20 mg/kg subcutaneously for 7 days) attenuated the rise in endothelaemia and adrenal corticosterone measured at 24 h following IMO. Plasma levels of ACTH and proopiomelanocortin gene expression in the anterior pituitary were not affected by pentoxifylline treatment. The present results indicate that IMO stress in female rats induces a biphasic rise in endothelaemia early at the time of stress exposure and than 24 h thereafter. Based on these data and our previous study we can conclude that intensive stress has a negative influence on endothelial cells in both sexes and no gender differences seem to be present in the protective action of pentoxifylline.

Adrenocorticotropic Hormone↗

PubMed2005

Neuroendocrine changes in adult female rats prenatally exposed to phenytoin.

Neuroendocrine changes in fetal hydantoin syndrome have not been described yet. This study was aimed to verify the hypothesis that prenatal exposure to phenytoin influences the stress response of adult female offspring in an animal model. To study possible development of depression like state, hedonic behavior and long-term changes in neuropeptide gene expression in the hypothalamus were investigated. Treatment consisted of per os administration of 150 mg/kg of phenytoin or water daily, from day 7-18 of gestation. Adult female offspring (6 animals per group) were acutely stressed by 1 min handling. Blood was collected in conscious rats via tail artery cannulas before, 1, 15 and 30 min after the handling. Exposure to phenytoin in uterus resulted in increased catecholamine and corticosterone concentrations in response to a mild stressor of 1 min handling in adult offspring. The gestational treatment used in this study did not induce a depression like state nor long-term changes in neuropeptide gene expression in the adult offspring. In conclusion, prenatal exposure to phenytoin treatment enhanced the stress response of adult female offspring. Possible new component of fetal hydantoin syndrome is the increase in catecholamine release in response to a mild stressor in adulthood.

Adrenocorticotropic Hormone↗

PubMed2005

Felbamate reduces hormone release and locomotor hypoactivity induced by repeated stress of social defeat in mice.

Glutamatergic neurotransmission plays a role in stress hormone release and the development of mood diseases. The aim of these studies was to verify the hypothesis that repeated treatment with felbamate, an antiepileptic drug modulating glutamatergic neurotransmission, affects hormone release in response to chronic stress. A mouse model of repeated social defeat (nonaggressive male mouse repeatedly defeated by aggressive counterparts) was used. The results showed that acute treatment with felbamate reduced hypolocomotion in an open field induced by repeated social conflict. The same stress procedure resulted in increased release of corticosterone and dopamine. Felbamate decreased noradrenaline concentrations and inhibited stress-induced rise in corticosterone and dopamine. It is suggested that modulation of stress hormone release may be induced by the action of felbamate on glutamate neurotransmission, and neuroendocrine changes could contribute to behavioural effects of the drug. Antidepressant action of this mood-stabilizing drug suggested by clinicians needs further verification.

Animals↗

PubMed2005

Xylazine activates oxytocinergic but not vasopressinergic hypothalamic neurons under normal and hyperosmotic conditions in rats.

Role of central alpha2-adrenoceptors in the regulation of hypothalamic magnocellular cells was studied under hyperosmotic challenge elicited by hypertonic saline (HS). Rats pretreated with receptor agonist, xylazine (XYL), were injected intraperitoneally with different (low: 0.375, moderate: 0.75, high: 1.5 M) HS 30 min later. The activity of the paraventricular (PVN) and supraoptic (SON) vasopressin and oxytocin perikarya was established by Fos-dual-immunohistochemistry 60 min after HS administration. Results showed that 1/XYL is a potent stimulus for oxytocin but not vasopressin magnocellular cells under basal and weak hyperosmotic conditions 2/highHS completely overlaps the effect of XYL. In addition, XYL partially suppressed Fos expression in the parvocellular PVN cells activated by highHS. The data suggest that alpha2-adrenoceptors may play an important role in the regulation of oxytocinergic PVN and SON neurons under basal and weak hyperosmotic conditions and that alpha2-adrenoceptors may also participate in the control of PVN parvocellular cells under intense osmotic challenge.

Adrenergic alpha-Agonists↗

PubMed2005

Experience with problem oriented teaching in pharmacology.

Pharmacology is one of the core subjects for further graduation in both preclinical and clinical area. Medical education is being performed either in the "classical" way (lecture based learning--LBL) or in a more advanced form, such as problem based learning (PBL). According to the Medline database, the interest in PBL is still increasing. At our department, the PBL has been introduced using the knowledge obtained at the the Mac Master University and University of Groningen. PBL in pharmacology requires well-qualified staff with clinical experience. A common character of PBL is the use of selected clinical cases as models and starting points to study certain topics with a student centred approach. In an interview we made on a sample of 88 students of our medical faculty in the last study year, 65.5% of them found the amount of information concerning pharmacotherapy not sufficient for their future clinical practice and 83.3% did not feel able to use the knowledge obtained. More than 90% of students did not see enough opportunities for pharmacotherapy training during clinical subject courses. These results are in support of our orientation of teaching towards the PBL. This type of teaching forces students to be active, trains their skills in communication and selection of knowledge, which is believed to enhance the long-term knowledge retention. By using the hybrid PBL-LBL model at our department we respect the principal proposal of medical education and attempt to improve skills in decision making in training of future medical doctors. (Tab. 3, Fig. 2, Ref. 13.)

Education, Medical↗

PubMed2005

Assessing skills in pharmacology in medical students.

The results of this pilot survey have shown the importance of evaluation of medical student knowledge in pharmacology using three independent parts of the examination. The final mark includes the results of a written test, oral examination and evaluation of seminar essay. We evaluated students with final grade A (n=76) and F (n=61) in relation to the results of tests and seminar essays. Most of the students with grade A (88.2 %) wrote the test in the upper range (90-99 %) and their seminar essay evaluations were grade A in 82.9 %. A significant correlation between the results in the test and the mark obtained in the seminar essay was found (r=0.22, p<0.05). Another group of students with grade F obtained low scores in the test (57.4 %), and a relatively large part of students got satisfactory results in test (42.6 %). In this group the quality of seminar essays was variable ranged from A to E. The evaluation showed that in students with final grade A were all three independent part of exam in agreement with final classification. The differences occurred in group of unsuccessful students who performed much better in written part than in the oral examination. The experience with the final assessment of medical student knowledge in pharmacology showed that the most important essay evaluation seems to be the oral form of exam. The results of seminar evaluations correspond satisfactory with the performance of students during the final exam and their effort may continue in diploma work, which is mandatory for all medical students (Tab. 2, Fig. 1, Ref. 2).

Curriculum↗

PubMed2004

Effect of environmental enrichment on stress related systems in rats.

The aim of this study was to test whether environmental enrichment alters the status and responsiveness of pituitary-adrenocortical and sympathetic-adrenomedullary hormones in rats. Previous studies have shown that rats kept in an enriched environment differ from those kept in standard cages in dendritic branching, synaptogenesis, memory function, emotionality and behaviour. In male Wistar rats kept in an enriched environment for 40 days, we studied basal concentrations of hormones, endocrine responses to 5-HT(1A) challenge and responsiveness and adaptation to repeated handling. Environmental enrichment consisted of large plexiglass cages with 10 rats per cage, which contained variety of objects exchanged three times a week. Rats kept in this enriched environment had higher resting plasma concentrations of corticosterone, larger adrenals and increased corticosterone release to buspirone challenge compared to controls. Lower adrenocorticotropic hormone, corticosterone and adrenaline responses to handling were noticed in rats kept in an enriched environment. Exposure to repeated handling led to a more rapid extinction of corticosterone responses in rats kept in an enriched environment. Thus, environmental enrichment leads to pronounced changes in neuroendocrine regulation, including larger adrenals and increased adrenocortical function, which are so far considered to be indication of chronic stress.

Adaptation, Physiological↗

PubMed2004

Behavioral and neuroendocrine changes during mental stress and repeated treatment with antidepressants in healthy men.

Excessive stress loadings in daily life are believed to play a role in the development of affective disorders. Our recent finding of enhanced neuroendocrine activation during stress of hypoglycemia after repeated antidepressant treatment in healthy men supports the hypothesis that the clinical effects of antidepressant treatment may be partly due to the adjustment of the stress response, which was reported to be blunted in depressive patients. The present double-blind placebo-controlled study investigated the effects of 6 days of treatment with the antidepressants citalopram or tianeptine on neuroendocrine activation during mental stress. Blood pressure, heart rate, and salivary cortisol values were measured. The stress procedure, lasting 17 min, consisted of a short intelligence test followed by the Stroop word-color interference test. Citalopram treatment was associated with a significant enhancement of stress-related increase in systolic and diastolic blood pressure. No differences were observed in the heart rates and salivary cortisol. Comparisons based on cluster analysis revealed that subjects with poor performance in the Stroop test displayed a significantly lower rise of systolic and diastolic blood pressure values after the stress procedure and lower prestress cortisol levels in saliva when compared to the good performing subjects. Our findings show that antidepressant treatment can enhance the neuroendocrine response also during mental stress, and suggest that mental performance during stress is related to the pattern of cardiovascular and adrenocortical activation.

Adult↗

PubMed2004

Does orthostatic stress influence the neuroendocrine response to subsequent hypoglycemia in humans?

Neuroendocrine response to stress stimuli is influenced by previous stimuli of different nature. The aim of the study was to test whether antecedent orthostatic stress may affect the neuroendocrine response to subsequent hypoglycemia. A group of 12 (6 men, 6 women) nonobese, healthy volunteers aged 19 to 27 y (mean 24 +/- 0.8) participated in the study in two sessions: controlled insulin-induced hypoglycemia to 2.7 mmol/L for 15 min either with or without antecedent orthostatic stress (30 min of 60 degrees head-up tilt before insulin administration). Orthostatic stress caused a significant decrease in plasma volume (-9.6%; P < 0.001) and a significant increase in plasma renin activity, aldosterone, norepinephrine (P < 0.01), and adrenocorticotropic hormone (ACTH) concentrations (P < 0.05) in all subjects. Growth hormone response to hypoglycemia was diminished in women (P < 0.01). The epinephrine response to hypoglycemia was diminished in women in comparison to men (P < 0.001), but was unaffected by antecedent orthostatic stress. Hypoglycemia failed to induce the ACTH release after its elevation during orthostatic stress. ACTH response to moderate hypoglycemia without previous orthostatic stress was evident only in men in comparison to women (P < 0.05). We conclude that the epinephrine, growth hormone, and ACTH responses to hypoglycemia were diminished in women. Except ACTH, the neuroendocrine response to mild hypoglycemia was not affected by previous orthostatic stress in healthy subjects. In the case of ACTH, the first stress stimulus is consequential for the subsequent response of this hormone, probably due to short-loop negative feedback effects.

Adult↗

PubMed2003

Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome.

AIMS/HYPOTHESIS: Hypertriglyceridaemia is an important risk factor for coronary heart disease, especially in the context of the insulin resistance syndrome where it often occurs with hypertension. The two phenotypes are also associated in the hereditary hypertriglyceridaemic (hHTg) rat. The aim of this study was to map quantitative trait loci that affect plasma triglyceride concentration in the hHTg rat and determine whether they co-localize with loci for blood pressure. METHODS: Second filial generation progeny (n=189) from a cross of the hHTg rat with the Brown Norway rat were phenotyped for fasting plasma triglyceride, glucose and insulin concentrations, and direct unrestrained resting blood pressure. A partial genome-scan was conducted using 153 microsatellite markers that were polymorphic between the two strains. RESULTS: A major locus (lod score 6.5) influencing plasma triglyceride concentration in a co-dominant fashion was mapped to chromosome 4 between D1Mit 5 and D1Mit17. Chromosome 8 contained multiple peaks with a lod score greater than 4.0 influencing triglyceride concentration. Importantly, none of the triglyceride loci had an effect on blood pressure. The triglyceride locus on chromosome 4 co-localized with a locus for fasting plasma insulin (lod score 4.1), although the effect on insulin concentration was in the opposite direction to that on triglyceride. CONCLUSION/INTERPRETATION: We have mapped the major loci that affect plasma triglyceride concentration in the hHTg rat. These loci do not influence blood pressure suggesting that these commonly associated phenotypes of the insulin resistance syndrome are not be due to pleiotropic effects of the same gene(s).

Animals↗

PubMed2003

Voluntary wheel running modulates glutamate receptor subunit gene expression and stress hormone release in Lewis rats.

Lewis rats that are known to be addiction-prone, develop compulsive running if they have access to running wheels. The present experiments were aimed 1) to evaluate the activation of stress systems following chronic and acute voluntary wheel running in Lewis rats by measurement of hormone release and gene expression of neuropeptides related to hypothalamic-pituitary-adrenocortical (HPA) axis activity and 2) to test the hypothesis that wheel running as a combined model of addictive behavior and stress exposure is associated with modulation of ionotropic glutamate receptor subunits in the ventral tegmental area. Voluntary running for three weeks but not for one night resulted in a rise in plasma corticosterone and adrenocorticotropic hormone (ACTH) levels (p<0.05) compared to those in control rats. Principal component analysis revealed the relation between POMC gene expression in the intermediate pituitary and running rate. Acute exposure of animals to voluntary wheel running induced a significant decrease in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 subunit mRNA levels (p<0.01), while repeated voluntary physical activity increased levels of GluR1 mRNA in the ventral tegmentum (p<0.05). Neither acute nor chronic wheel running influenced N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA levels in the ventral tegmental area. Thus, the present study revealed changes in AMPA receptor subunit gene expression in a reward-related brain structure as well as an activation of HPA axis in response to compulsive wheel running in Lewis rats. It may be suggested that hormones of HPA axis and glutamate receptors belong to the factors that substantiate higher vulnerability to addictive behavior.

Adrenocorticotropic Hormone↗

PubMed2003

Involvement of glutamate neurotransmission in the development of excessive wheel running in Lewis rats.

Physical activities such as long-distance running can form a habit and might be related to drug-induced addictive behaviors. We investigated possible modulations of N-methyl-D-aspartate (NMDA) receptor subunits during voluntary wheel running in brain regions implicated in reward and addiction. It was observed that Lewis rats progressively increased their amount of daily running, reaching maximum levels of 4-6 km/day. After 3 weeks of running, mRNA levels coding for NR2A and NR2B subunits were increased in the ventral tegmental area, while only NR2A mRNA levels were found to be elevated in the frontal cortex. Long-term wheel running was also associated with increased binding of specific NMDA receptor antagonist [3H]CGP39653 in the frontal cortex. Moreover, pharmacological inhibition of glutamate release by repeated administration of phenytoin (20 mg/kg IP for 21 days) significantly suppressed daily running. These results suggest that glutamatergic neurotransmission might be related to neurobiological mechanisms underlying the compulsive character of voluntary wheel running.

Animals↗

PubMed2003

Cortisol elimination from plasma in premenopausal women with rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that cortisol elimination from plasma can contribute to relatively low cortisol in premenopausal women with rheumatoid arthritis (RA). METHODS: Twelve premenopausal female patients with RA (39.8 (1.8) years) and nine healthy control women matched for age and body mass index (42 (3.3) years) were enrolled in the study. None of the patients had previously been receiving treatment with glucocorticoids. After dexamethasone suppression (2 mg by mouth) the evening before the study, 20 mg of hydrocortisone was given. Blood and saliva samples were drawn six hours after injection of hydrocortisone. Plasma and salivary cortisol were measured. RESULTS: Dexamethasone administration suppressed plasma cortisol concentrations to an almost undetectable level in all subjects, except one with RA. In this subject, a raised concentration of plasma cortisol was verified by repeated analysis despite the fact that cortisol concentration in the saliva sample measured simultaneously was not raised. No significant difference in the disappearance curve of cortisol in plasma or in salivary cortisol levels was found between the patients with RA and the healthy controls. CONCLUSIONS: The profile of disappearance of total cortisol from plasma, and salivary cortisol levels during the elimination phase after its intravenous administration, are unchanged in premenopausal women with RA. Alterations in cortisol clearance are not likely to have a role in cortisol availability in patients with RA.

Adult↗

PubMed2003

Body position and the neuroendocrine response to insulin-induced hypoglycemia in healthy subjects.

Changes in body fluid distribution are known to influence neuroendocrine function. The aim of the present study was to test the hypothesis that changes in plasma volume affect the counterregulatory neuroendocrine response to hypoglycemia. The tests were performed in 12 subjects in two situations: 'head-up' (+60 degrees head-up tilt standing for 30 min and hypoglycemia in sitting position afterwards) and 'leg-up' (leg-up position for 30 min and hypoglycemia in leg-up position afterwards) in a random order. Insulin-induced hypoglycemia was adjusted to 2.7 mmol/l for 15 min by glucose infusion. Plasma volume was greater by 2.2% (p < 0.001) in leg-up and lower by 9.6% (p < 0.001) in head-up position compared to the basal value in sitting position. Head-up position was associated with increases in ACTH, aldosterone, norepinephrine levels and plasma renin activity (p < 0.01). Leg-up position resulted in decreases in plasma growth hormone and epinephrine concentrations (p < 0.05). Except epinephrine, the neuroendocrine response to hypoglycemia, if any, was mild. Hypoglycemia failed to activate ACTH release after head-up position. Body fluid redistribution did not modify hormonal changes during insulin hypoglycemia. In conclusion, we suggest that body position and accompanying plasma volume changes do not appear to affect neuroendocrine and counterregulatory responses to moderate, short duration hypoglycemia in healthy subjects.

Adrenocorticotropic Hormone↗

PubMed2003

Stress-induced rise in endothelaemia, von Willebrand factor and hypothalamic-pituitary-adrenocortical axis activation is reduced by pretreatment with pentoxifylline.

Stress is considered to be a risk factor of several diseases. The following hypotheses were tested: (1) single exposure to an intensive stressor is followed by endothelial stimulation and/or damage to endothelial cells, (2) potential stress-induced endothelial cell damage is reduced by repeated pretreatment with pentoxifylline and (3) pentoxifylline treatment modifies neuroendocrine activation during stress reflected by changes in hypothalamic-pituitary-adrenocortical (HPA) axis function. Rats were treated with saline or pentoxifylline (20 mg/kg, s.c.) once daily for 7 days and then exposed to single immobilization stress for 20 or 120 min. In saline pretreated rats, stress exposure was followed by a rise in endothelaemia, von Willebrand factor concentrations, adrenocorticotropic hormone (ACTH) and corticosterone release, as well as by enhanced gene expression of hypothalamic corticotropin releasing factor (CRH). Stress-induced changes were reduced by pretreatment with pentoxifylline. Significant inhibition was observed in endothelaemia, plasma ACTH and corticosterone concentration in the adrenals. Thus, signs of endothelial injury as well as stress-induced hormone levels were reduced by pretreatment with pentoxifylline, although there is no evidence for a causal relationship. This protective action of pentoxifylline might be of benefit in the prevention and therapy of some stress-related disorders.

Adrenal Glands↗

PubMed2003

Low number of insulin receptors but high receptor protein content in adipose tissue of rats with monosodium glutamate-induced obesity.

In order to better understand the mechanisms leading to insulin resistance, the number of fat tissue insulin receptors, their affinity and insulin receptor protein in rats with monosodium glutamate-induced obesity were studied. Obese rats displayed significantly lower number of insulin receptors with high affinity. Surprisingly, the amount of insulin receptor protein was significantly elevated in these animals. The same relations have been already reported for angiotensin II binding and AT1 receptor protein in the same model of obesity. Therefore we suggest an existence of general defect of adipocyte cell membrane in monosodium glutamate-induced obesity characterized by the presence of high quantity of impaired receptor protein.

Adipose Tissue↗