PubMed Health⌕ Search

Biomedical subjects

V Kristova

Publications and source records attributed to V Kristova.

9 recordsLinked to original sources

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↗

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↗

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↗

The effect of meloxicam and deendothelisation on vascular responses in the rabbit renal and ear arteries.

BACKGROUND: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is frequently limited by adverse effects resulting from the disruption of homeostatic functions of prostaglandins. OBJECTIVES: This study was aimed at the evaluation of the effect of selective COX-2 inhibitor meloxicam on vasoconstrictor responses to noradrenaline (NA) in rabbit renal artery chosen as a model vessel and in rabbit ear artery as a peripheral artery under in vitro conditions. METHODS: Rabbit renal and ear arteries were perfused at constant flow. Vascular responses to NA before and after meloxicam administration and after deendothelisation by air bubbles were measured and registered as changes in perfusion pressure. RESULTS: It was found out that vasoconstrictor responses to noradrenaline when exposed to meloxicam were not enhanced significantly in both arterial preparations. Deendothelisation itself did not increase responses affected by meloxicam in the renal and ear arteries but in comparison with control groups the responses were significantly augmented, especially in the ear artery. CONCLUSIONS: The results obtained in this study demonstrate that meloxicam had not affected adversely the vasoconstrictor activity in different types of vessels without selectivity on vascular beds. Endothelial removal potentiated vasoconstrictor responses in arteries pre-treated by meloxicam when compared with intact vessels. (Tab. 2, Fig. 4, Ref. 19.)

Animals↗

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↗

Comparison of vasoconstrictor responses to selected NSAIDs in rabbit renal and femoral arteries.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to induce adverse renal effects, which are closely related to physiological inhibition of renal prostaglandin synthesis. AIM: This study was aimed to evaluate the effect of drugs inhibiting both cyclooxygenase (COX) isoforms COX-1 and COX-2 on vasoconstrictor responses to noradrenaline in the rabbit renal artery and to compare these responses with femoral artery as a systemic vessel. METHODS: Rabbit femoral and renal arteries were perfused with a constant flow. Vascular responses to drugs were measured and registered as changes in perfusion pressure. RESULTS: It was found that the vasoconstrictor responses to noradrenaline were significantly enhanced after administration of all NSAIDs in both the renal and femoral arteries. The effect of indomethacin on renal vasoconstrictor responses was more pronounced compared to ibuprofen or phenacetin. Comparison of NSAIDs effects on renal and femoral arteries did not show significant differences. CONCLUSIONS: These results demonstrate an increase of vasoconstrictor activity after NSAIDs administration without significant differences between the renal and femoral arteries. The strongest potentiation of the vasoconstrictor responses in the renal artery was found with indomethacin. (Tab. 1, Fig. 4, Ref. 20.)

Animals↗

Renal damage induced by the treatment with non-opioid analgesics--theoretical assumption or clinical significance.

Non-opioid analgesics are some of the most widely used therapeutic agents in clinical practice today. The number of patients at risk for adverse events related to the use of these agents is rapidly expanding. While the gastrointestinal toxicity of these medications is well known, it has become increasingly apparent that the kidney is also an important target for untoward clinical events. Evidence of the nephrotoxicity of analgesic preparations is not sufficiently completed and available in our region. Analgesic-related renal injury has been classified based on mechanism of action into "classic" analgesic nephropathy and NSAID-related renal toxicity. From clinical point of view the renal side effects induced by analgesics can be classified into hemodynamic (functional) side effects and idiosyncratic side effects. The common link in both types of side effects seems to be renal ischemia related to prostaglandin synthesis inhibition. Key enzyme in this process is cyclooxygenase occurring in two isoforms: COX-1 and COX-2. Antiinflammatory effect of NSAIDs is mediated by COX-2 inhibition, while the side effects (gastrotoxicity, nephrotoxicity) by inhibition of COX-1. COX-1 was more inhibited by indomethacin and piroxicam and COX-2 by 6-MNA (active metabolite of nabumetone), diclofenac and ibuprofen. Nimesulide and meloxicam selectively block COX-2 and are recommended to patients at risk or treated with diuretics. (Tab. 2, Fig. 2, Ref. 38.)

Analgesics, Non-Narcotic↗

Early Postnatal Glutamate Treatment Results in Altered Vascular Responsiveness to Serotonin and Noradrenaline in Adult Rats.

OBJECTIVES: To evaluate possible alterations of vascular responsiveness to vasoactive hormones in the vessel preparations from adult rats treated neonatally with high doses of glutamate. METHODS: The responses to noradrenaline and serotonin in perfused hindlimb vascular bed and isolated renal artery were measured in MSG-treated (2 and 4 mg/g BW) and control groups of adult rats at the age of 10 weeks. Acetylcholine test was used to assess the endothelium-dependent relaxation of the hindlimb vascular preparation. The vessel specimens from this vascular bed were evaluated histologically. RESULTS: Vasoconstrictory responses to noradrenaline and serotonin were significantly reduced in the hindlimb vascular bed in MSG-treated rats. In the renal artery, a significant decrease of the responses to noradrenaline was found without significant changes in the responses to serotonin. The observed changes were more pronounced in groups treated with a high dose of MSG. Comparison of relaxing responses to acetylcholine in the hindlimb preparation did not show any statistically significant differences in control and MSG treated groups. Histological evaluation of this preparations did not reveal any endothelial damage or morphological changes of vessel wall. CONCLUSIONS: The obtained results showed reduced vascular responsiveness to vasoconstrictory agents in adult rats neonatally treated with MSG suggesting that early postnatal administration of glutamate may result in irreversible changes in cardiovascular function.

Journal Article↗

Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ.

Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.

Animals↗