Risk perception of NSAIDs in South Dakota in comparison with Slovakia and Greece.

AIM: Adverse effects (ADRs) of non-steroidal anti-inflammatory drugs (NSAIDs) represent a public health problem. To decrease the negative effect on the population, an improvement of risk awareness is crucial. We aimed to evaluate the risk perception and the use of NSAIDs in South Dakota in comparison with Slovakia and Greece. METHOD: A structured questionnaire evaluating NSAID use in 185 patients in a hospital in South Dakota. RESULTS: 95.7 % of respondents reported the use of analgesics. On 1-10 visual analogue scale, perceived risk of NSAIDs was 4.27±2.46, similar to Greece (4.36±2.41, p=0.360), but significantly higher than in Slovakia (3.8±1.9, p=0.038). Only 12.4 % were familiar with gastrointestinal ADRs and only 1.1 % were aware of cardiovascular risk. Although 57.8 % were informed about ADRs by their doctor or pharmacist, only 33.0 % were informed spontaneously, without actively asking. Providers in South Dakota were informing patients spontaneously more often than in Slovakia (15.9 %, p≤0.001) and on par with Greece (36.3 %, p=0.631). CONCLUSIONS: Public awareness about NSAID risk is dangerously low. Only a third of providers are informing patients about possible risks spontaneously (Tab. 6, Ref. 15) Keywords: non-steroidal anti-inflammatory drugs, risk perception, adverse effects, cardiovascular risk, gastrointestinal risk.

Drug usage analysis in pregnant women.

BACKGROUND: Drug usage in pregnant women is associated with a problem of possible negative influence on prenatal development. It is always necessary to judge the need for drug administration during pregnancy. OBJECTIVE: The aim of presented study was to analyse data about pregnant women hospitalized in the postpartum period. METHODS: The study was designed as a retrospective observational study including 300 women hospitalized at the 2nd Department of Gynaecology and Obstetrics, University Hospital, Bratislava. Data were obtained through questionnaires in form of an interview. RESULTS: The average age of women was 30.79 ± 4.40 years. Risk pregnancy occured in 20.59 % of women. Chronic disorders before pregnancy required regular pharmacotherapy in 29.24 %. Drug usage analysis: I. trimester, 31 % used at least one drug, 52 % nutritional supplements, 63.3 % drug and/or nutritional supplement; II. trimester, 23 % used at least one drug, 45 % nutritional supplements, 58.3 % drug and/or nutritional supplement; III. trimester, 32 % used at least one drug, 67 % nutritional supplements, 75.3 % drug and/or nutritional supplement. CONCLUSION: Drug usage during pregnancy requires great precaution at choosing pharmacotherapy. The benefit of pharmacotherapy should always outweight the potential risk of administered drug (Tab. 3, Fig. 3, Ref. 37).

Risk perception of NSAIDs in hospitalized patients in Greece.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics worldwide in different syndromes. There is a relevant evidence about NSAIDs various adverse effects (AEs) on gastrointestinal, cardiovascular, renal, pulmonary, nervous systems. Many of these problems are preventable with respects to appropriate patient´s risk perception. OBJECTIVES: The main goal of our study was to examine drug risk perception with relation to participation factors as comorbidities in patients. METHODS: A structured questionnaire was delivered to 124 patients hospitalized at Department of Internal Medicine in a selected General Hospital in Greece. Data were evaluated using a descriptive statistics. RESULTS: Low awareness of NSAID risk was recorded, with 45.16 % of respondents unaware of any particular AEs. Lack of this knowledge appears to be attributed to low communication of physicians and pharmacists with patients about possible risk from comorbidity, over half of respondents (55.8 %) had history of hypertension, and 25.9 % were diabetics, which would increase the risk of NSAID therapy. CONCLUSION: Our study revealed a restricted knowledge about risk of NSAIDs in the studied population and showed some important data related to the presence of comorbidity in patients, which could potentiate the risk of cardiovascular AEs (Fig. 5, Ref. 22).

Effect of sulodexide on vascular responses and liver mitochondrial function in diabetic rats.

This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg(-1). SLX was administered i.p., at dose 100 IU.kg(-1) daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO(2)(S(3))], [QO(2)(S(4))] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function.

Vascular reactivity of arteria femoralis in adult and aged spontaneously hypertensive and Wistar-Kyoto rats.

AIM: The relationship of age and hypertension on endothelial dysfunction and increased responses to vasoconstrictor stimuli. BACKGROUND: Hypertension is a disease accompanied by endothelial dysfunction and is characterized by an impaired vascular reactivity and enhanced activity of sympathetic nervous system. MATERIALS AND METHODS: In our experiment, we used spontaneously hypertensive rats representing model of essential hypertension and the Wistar-Kyoto rats as normotensive strain. Femoral arteries of adult and aged rats were put into the chamber of Mulvany-Halpern isometric myograph. As the nutrient solution, the modified Krebs-Henseleit solution having temperature 37 °C and bubbled with O2 was used. After 30 minutes stabilization of blood vessels, a dose-dependent curve of norepinephrine response was recorded (concentrations 3x10-8 M, 10-7 M, 3x10-7 M, 10-6 M, 3x10-6 M, 10-5 M, 3x10-5 M, 10-4 M), followed by a dose-dependent curve of acetylcholine response (concentrations 3x10-8 M, 10-7 M, 3x10-7 M, 10-6 M, 3x10-6 M). RESULTS: Our experiments recorded an increased reactivity to contraction stimuli in spontaneously hypertensive animals. Vascular reactivity to norepinephrine at 5 month and 12 month old rats from the same group was not significantly affected. Our experiments on the other hand, did not record a reduced endothelium-dependent relaxation in hypertensive compared to normotensive animals, neither in different age groups. CONCLUSIONS: Increased norepinephrine-induced contraction occurs even before development of reduced acetylcholine-induced relaxation in SHR rats. We predict that in our experiment hypertension plays a bigger role in the development of endothelial dysfunction than aging (Fig. 2, Ref. 22).

Consumption of three strong opioids (morphine, oxycodone and fentanyl) in seven European countries during seven years (2003-2009).

PURPOSE: The aim was to analyse the consumption of selected strong opioid analgesics during a seven-year period of 2003-2009 in order to compare Slovak consumption with that in six other European countries and to determine our position. METHODS: Drug consumption data from the State Institute for Drug Control in Slovak Republic were used. As to the data from other countries, annual health statistics published on websites were used in comparison. RESULTS: Obviously the consumption of one of studied opioid drugs with transdermal aplication route, particularly fentanyl, tended to increase in all countries during the observed period. Oxycodone tends to yield a rapid increase in consumption as well. As opposed to the latter drugs, the consumption of morphine was decreasing throughout the observed period. The consumption of these drugs in Slovakia remains low (except for that of fentanyl). CONCLUSION: Our analysis confirmed a clear shift from oral to transdermal therapy as well as usage of newer drugs. Drug consumption data are a relatively new source of information for health research. Our analysis showed increasing trends in fentanyl (patch opioid) consumption in all compared countries as well as an increasing consumption of oxycodone and decreasing consumption of morphine (Fig. 3, Ref. 17).

Modified problem-based learning in pharmacology.

OBJECTIVE: The aim of this study was to determine differences between PBL as compared to modified PBL with special focus on acquiring EBM principles. METHODS: Two groups consisted of total 152 students (139 respectively). The use of EBM principles means integrating individual expertise with the best available external clinical evidence by using available data sources and national guidelines. CONCLUSION: Our findings suggest that modified PBL with extended EBM approach could be superior to "classical" PBL (Fig. 3, Ref. 29). Full Text (Free, PDF) www.bmj.sk.

Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats.

Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10-week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes.

Mathematical model indicates nonlinearity of noradrenaline effect on rat renal artery.

The aim of this work is to present the efficacy of a previously introduced computational procedure, developed for evaluation of vascular responsiveness. On this reason, as an example a common study of noradrenaline (NA) effect on a rat renal artery under in vitro conditions was arbitrarily selected. The response of the arterial segment to NA doses (0.1-10 microg) was digitally recorded on a PC and employed to develop mathematical model of NA effect. Using the model, the following NA effect variables were determined: the vessel sensitivity parameter, mean effect time and rate constant, respectively, characterizing the effect intensity, duration, and regression and also classic response variables: the maximal effect and time of the maximal effect. The two-way analysis of variance followed by Bonferroni's test revealed a significant influence of the increasing NA dose on the vessel sensitivity parameter and mean effect time. These findings indicated nonlinearity of processes underlying NA effect on the rat renal artery over the given range of NA doses. The procedure exemplified has the potential for use as an effective adjunct to routine studies of vascular responsiveness as it enables the extraction of meaningful information which cannot by obtained by common manual evaluation procedures.

Current opinions on the role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the main cases of mortality and morbidity of population worlwide. In spite of enormous efforts there are not pharmacological agents evidently influencing natural course of disease available. Besides looking for new drugs influencing the long term outcome of patients with COPD, there is also running the process of reevaluation of the role of several already established drug groups. METHODS: Through the use of recent knowledge and results from large-scale clinical studies as well as metaanalyses we give a view on action of inhaled corticosteroids in the pathophysiological mechanisms of COPD and complex summary of their role in the therapeutic management of the disease. CONCLUSION: Contrary to systemic corticosteroids, agreement regarding usage of inhaled corticosteroids necessary by acute exacerbations of disease has not been reached yet. Recent meta-analyses of the long-term clinical studies have clearly demonstrated that inhaled corticosteroids could pose with ability of slowing down the progressive deterioration of lung functions and lead to the prolongation of life in broad population of patients with COPD. Benefit of treatment insists in decrease of frequency and severity of exacerbations, mildering symptoms, improving overall health state as well as exercise tolerance in patients with COPD. Clinical relevant is also reduction of the number of hospitalizations and mortality related to progression of COPD (Tab. 2, Ref 45) Full Text (Free, PDF) www.bmj.sk.

Trastuzumab in the adjuvant treatment of breast cancer.

Four large randomized trials to assess efficacy and toxicity of trastuzumab in adjuvant systemic therapy of breast cancer have been initiated. Results clearly demonstrate, that adjuvant treatment of trastuzumab significantly improves outcomes for women with HER2 positive breast cancer. The clinically most significant adverse events of trastuzumab are serious-infusion related reactions and cardiotoxicity. Benefit for patient should be considered according to advantage versus risk (Tab. 1, Fig. 2, Ref. 17) Full Text (Free, PDF) www.bmj.sk.

Genetic tests for predicting the toxicity and efficacy of anticancer chemotherapy.

The standard anticancer therapy based "on one size fits all" modality has been determined to be ineffective or to be the cause of adverse drug reactions in many oncologic patients. Most pharmacogenetic and pharmacogenomic studies so far have been focused on toxicity of anticancer drugs such as 6-mercaptopurine, thioguanine, irinotecan, methotrexate, 5-fluorouracil (5-FU). Variation in genes are known to influence not only toxicity, but also efficacy of chemotherapeutics such as platinum analogues, 5-FU and irinotecan. The majority of current pharmacogenetic studies focus on single enzyme deficiencies as predictors of drug effects; however effects of most anticancer drugs are determined by the interplay of several gene products. These effects are polygenic in nature. This review briefly describes genetic variations that may impact efficacy and toxicity of drugs used in cancer chemotherapy.

Perception of drug risk in the database of Drug Information Centre in Bratislava.

OBJECTIVE: The aim of the presented study was to analyse the types and quantity of inquiries received at Drug Information Centre in Bratislava during the period from May 1997 to May 2006. The study analyses also the profile of the users of the latter centre with focus on the perception of drug risk, adverse drug reactions, and drug interactions. BACKGROUND: The Drug Information Centre (Druginfo) was established in Slovak Republic as part of the Department of Pharmacology in May 1997. In 2002 Druginfo became a member of International Register of Drug Information Services of the Society of Hospital Pharmacists of Australia. Druginfo provides voluntary free of charge drug information for healthcare professionals. METHODS: Statistical processing of all inquiries received at Druginfo during a 10-year period focused on the aspect of drug risk perception. RESULTS: 867 inquiries were received in total. The most frequent inquiries came from hospital teaching clinics in Bratislava. Questions concerning pregnancy/lactation (25 %), adverse drug reactions (16 %), basic information about drugs (14 %) and interactions (13 %) were asked most frequently. CONCLUSION: The types of inquiries and inquirers using the service are generally similar to those recorded at many others Druginfos within Europe and USA. The number of questions is lower than in other centres. Druginfo in Bratislava has a very important role in providing independent drug information (Tab. 1, Fig. 8, Ref. 9). Full Text (Free, PDF) www.bmj.sk.

Endothelaemia--a marker of vascular damage.

OBJECTIVES: The aim of the study was to determine the amount of circulating endothelial cells (CECs) in patients with an advanced cardiovascular (CV) disease, compare the values with a control group and finally to ascertain if there are statistically significant differences within the studied patient groups. BACKGROUND: Endothelaemia has been intensively studied as a marker of vascular injury. Clinical studies have demonstrated an increased endothelaemia in patients at high CV risk but also in certain non-cardiovascular disorders. Its possible usage in the diagnostics of the acute coronary syndrome and for CV risk assessment needs further investigations. METHODS: Thirty six hospitalized patients were studied. Quantitative measurement of endothelaemia was performed by the method developed by J. Hladovec. It is based on ECs counting in Bürker's chamber after their isolation with platelets and the removal of the latter by an addition of adenosine-diphosphate. RESULTS: The mean baseline endothelaemia was significantly higher in patients with increased cardiovascular risk when compared with the control group (1.38 +/- 0.899): ACS (4.9 +/- 1.59, p < 0.05) and PAOD (3.74 +/- 0.61, p < 0.05). When comparing the mean endothelaemia values in patients with PAOD before (2.67 +/- 0.86) and after (3.88 +/- 0.77) surgery, a significant increase of endothelaemia was observed (p < 0.05). CONCLUSION: Our pilot study, though limited by a relatively small number of patients, proved a significant increase of endothelaemia in patients at high CV risk, which is consistent with other available data. The introduction of newer specific methods based on immunomagnetic principles may provide a wider use of endothelaemia measurement in clinical settings (Fig. 3, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

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.

Red wine polyphenols prevent endothelial damage induced by CCl4 administration.

It became evident in the present study that carbon tetrachloride (CCl(4)), in addition to its known liver and renal toxicity, causes serious damage to endothelial cells. The preventive effect of red wine on cardiovascular diseases has been documented in a number of human population studies as well as in animal experimental models. In this study, the endothelium protective effect of polyphenolic compounds isolated from red wine was studied in rats administered 0.5 ml of CC(4)/kg body weight intraperitoneally twice a week for 8 weeks. Endothelemia (endothelial cells/10 microl of plasma) was used as the marker of endothelial cell injury in vivo. Chronic CCl(4) treatment for 8 weeks lead to a 3-fold increase of free endothelial cells circulating in the blood when compared to the baseline values (2.5+/-0.3). Parallel oral administration of polyphenols 40 mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone did not produce significant changes. Three weeks of spontaneous recovery after the 8-week treatment with CCl(4) did not lead to a marked decrease of endothelemia, but the administration of red wine polyphenols during the 3-week period significantly decreased free endothelial cells in the blood. It can be concluded that long-term administration of CCl(4) may serve as a useful experimental model of endothelial damage. The red wine polyphenolic compounds exert a powerful protective effect on endothelial cells from the injury caused by CCl(4). This effect was documented by decreased endothelemia that corresponded to diminished endothelial cell swelling and detachment evaluated by histology of the vascular intima. The endothelium protective effect may be one of the key factors that contribute to the preventive action of red wine on cardiovascular diseases.

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.)

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).

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.)

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.