Entropy in scalp EEG can be used as a preimplantation marker for VNS efficacy.

Vagus nerve stimulation (VNS) is a therapeutic option in drug-resistant epilepsy. VNS leads to ≥ 50% seizure reduction in 50 to 60% of patients, termed "responders". The remaining 40 to 50% of patients, "non-responders", exhibit seizure reduction < 50%. Our work aims to differentiate between these two patient groups in preimplantation EEG analysis by employing several Entropy methods. We identified 59 drug-resistant epilepsy patients treated with VNS. We established their response to VNS in terms of responders and non-responders. A preimplantation EEG with eyes open/closed, photic stimulation, and hyperventilation was found for each patient. The EEG was segmented into eight time intervals within four standard frequency bands. In all, 32 EEG segments were obtained. Seven Entropy methods were calculated for all segments. Subsequently, VNS responders and non-responders were compared using individual Entropy methods. VNS responders and non-responders differed significantly in all Entropy methods except Approximate Entropy. Spectral Entropy revealed the highest number of EEG segments differentiating between responders and non-responders. The most useful frequency band distinguishing responders and non-responders was the alpha frequency, and the most helpful time interval was hyperventilation and rest 4 (the end of EEG recording).

Pre-implant Heart Activity Differs in Responders and Non-responders to Vagal Nerve Stimulation Therapy in Epileptic Patients.

Vagal Nerve Stimulation (VNS) is used to treat patients with pharmacoresistant epilepsy. However, generally accepted tools to predict VNS response do not exist. Here we examined two heart activity measures - mean RR and pNN50 and their complex behavior during activation in pre-implant measurements. The ECG recordings of 73 patients (38 responders, 36 non-responders) were examined in a 30-sec floating window before (120 sec), during (2x120 sec), and after (120 sec) the hyperventilation by nose and mouth. The VNS response differentiation by pNN50 was significant (min p=0.01) in the hyperventilation by a nose with a noticeable descendant trend in nominal values. The mean RR was significant (p=0.01) in the rest after the hyperventilation by mouth but after an approximately 40-sec delay.Clinical Relevance- Our study shows that pNN50 and mean RR can be used to distinguish between VNS responders and non-responders. However, details of dynamic behavior showed how this ability varies in tested measurement segments.

Response to Vagal Stimulation by Heart-rate Features in Drug-resistant Epileptic Patients.

Vagal Nerve Stimulation (VNS) is an option in the treatment of drug-resistant epilepsy. However, approximately a quarter of VNS subjects does not respond to the therapy. In this retrospective study, we introduce heart-rate features to distinguish VNS responders and non-responders. Standard pre-implantation measurements of 66 patients were segmented in relation to specific stimuli (open/close eyes, photic stimulation, hyperventilation, and rests between). Median interbeat intervals were found for each segment and normalized (NMRR). Five NMRRs were significant; the strongest feature achieved significance with p=0.013 and AUC=0.66. Low mutual correlation and independence on EEG signals mean that presented features could be considered as an addition for models predicting VNS response using EEG.

Pharmacokinetics of boldine in control and Mrp2-deficient rats.

The aim of the present study was to describe the currently poorly understood pharmacokinetics (PK) of boldine in control rats (LW, Lewis rats), and Mrp2 transporter-deficient rats (TR(-)). Animals from the LW and TR(-) groups underwent a bolus dose study with 10 mg/kg of boldine applied either orally or intravenously in order to evaluate the major PK parameters. The TR(-) rats demonstrated significantly reduced total clearance with prolonged biological half-life (LW 12+/-4.6 versus TR(-) 20+/-4.4 min), decreased volume of distribution (LW 3.2+/-0.4 l/kg versus TR(-) 2.4+/-0.4 l/kg) and reduced bioavailability (LW 7 % versus TR(-) 4.5 %). Another set of LW and TR(-) rats were used for a clearance study with continuous intravenous administration of boldine. The LW rats showed that biliary and renal clearance formed less than 2 % of the total clearance of boldine. The treatment of samples with beta-glucuronidase showed at least a 38 % contribution of conjugation reactions to the overall clearance of boldine. The TR(-) rats demonstrated reduced biliary clearance of boldine and its conjugates, which was partly compensated by their increased renal clearance. In conclusion, this study presents the PK parameters of boldine and shows the importance of the Mrp2 transporter and conjugation reactions in the elimination of the compound.

Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description.

Statistical significance of task related deep brain EEG dynamic changes in the time-frequency domain.

We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas.

Nitrites and nitrates in exhaled breath condensate in cystic fibrosis: relation to clinical parameters.

OBJECTIVES: To evaluate correlation of exhaled breath condensate (EBC) nitrite and nitrate concentrations with disease severity in cystic fibrosis (CF) patients. BACKGROUND: Nitrites and nitrates are products of oxidative metabolism of nitric oxide. Impaired metabolism of nitric oxide plays a role in pathogenesis of CF. METHODS: EBC was collected from 46 stable CF patients and from 21 healthy controls. EBC concentrations of nitrites and nitrates were correlated with parameters of lung disease and nutritional status and with systemic inflammatory markers. RESULTS: EBC nitrates concentrations in CF patients were lower than in healthy subjects (5.8 vs 14.3 µmol/l, p<0.001). They correlated positively with FEV1 (p=0.025) and serum albumin values (p=0.016) and negatively with chest radiograph Northern score (p=0.015) and serum C-reactive protein values (p=0.005). EBC nitrites concentrations in CF patients did not differ from those in healthy subjects and were not correlated to any studied parameter. CONCLUSIONS: EBC nitrates concentrations correlate with disease severity in CF patients and are lower than in healthy subjects (Tab. 4, Fig. 1, Ref. 48).

In vivo study of radioprotective effect of NO-synthase inhibitors and acetyl-L-carnitine.

This study investigated the protective effect of two nitric oxide synthase inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.p.) and aminoguanidine (AG, 400 mg/kg i.p.), and an antioxidant acetyl-L-carnitine (ALC, 250 mg/kg i.p., once daily for five days) against radiation-induced damage in Wistar rats. Blood samples were collected 6 h after whole-body irradiation with 8 Gy. Plasma concentrations of nitrite+nitrate (NO(x)) and malondialdehyde (MDA) were measured by high-performance liquid chromatography. A single injection of L-NAME one hour before exposure effectively prevented the radiation-induced elevation of plasma NO(x) and it reduced 2.6-fold the risk for death during the subsequent 30-day period. Pretreatment with ALC prevented the radiation-induced increase in plasma MDA and it had similar effect on mortality as L-NAME did. Presumably due to its short half-life, the partially iNOS-selective inhibitor and antioxidant AG given in a single dose before exposure did not attenuate MDA and NO(x) and it failed to significantly improve the 30-day survival. In conclusion, pretreatment with both the nonspecific NOS inhibitor L-NAME and the antioxidant ALC markedly reduce mortality to radiation sickness in rats. The radioprotective effect may be directly related to effective attenuation of the radiation-induced elevation of NO production by L-NAME and of oxidative stress by ALC.

The posterior medial cortex is involved in visual but not in verbal memory encoding processing: an intracerebral recording study.

The objective is to study the involvement of the posterior medial cortex (PMC) in encoding and retrieval by visual and auditory memory processing. Intracerebral recordings were studied in two epilepsy-surgery candidates with depth electrodes implanted in the retrosplenial cingulate, precuneus, cuneus, lingual gyrus and hippocampus. We recorded the event-related potentials (ERP) evoked by visual and auditory memory encoding-retrieval tasks. In the hippocampus, ERP were elicited in the encoding and retrieval phases in the two modalities. In the PMC, ERP were recorded in both the encoding and the retrieval visual tasks; in the auditory modality, they were recorded in the retrieval task, but not in the encoding task. In conclusion, the PMC is modality dependent in memory processing. ERP is elicited by memory retrieval, but it is not elicited by auditory encoding memory processing in the PMC. The PMC appears to be involved not only in higher-order top-down cognitive activities but also in more basic, rather than bottom-up activities.

Oscillatory changes in cognitive networks activated during a three-stimulus visual paradigm: an intracerebral study.

OBJECTIVE: The aim of this work was to study the oscillatory changes during target and distractor stimuli processing. We focused mainly on responses after distractor stimuli in the prefrontal cortex and their possible relation to our previous results from the basal ganglia. METHODS: Five epilepsy surgery candidates with implanted depth electrodes performed a three-stimulus paradigm. The frequent stimulus (70%; without required response) was a small blue circle, the target stimulus (15%; with motor response) was a larger blue circle, and the distractor stimulus (15%; without required response) was a checkerboard. The SEEG signals from 404 electrode contacts were analysed using event-related de/synchronization (ERD/S) methodology. RESULTS: The main response to the target stimuli was ERD in the alpha and low beta bands, predominantly in the motor control areas, parietal cortex and hippocampus. The distractor stimuli were generally accompanied by an early theta frequency band power increase most markedly in the prefrontal cortex. CONCLUSIONS: Different ERD/S patterns underline attentional shifting to rare target ("go") and distractor ("no-go") stimuli. SIGNIFICANCE: As an increase in lower frequency band power is considered to be a correlate of active inhibition, the prefrontal structures seem to be essential for inhibition of non-required movements.

Assessment of methotrexate hepatotoxicity in psoriasis patients: a prospective evaluation of four serum fibrosis markers.

BACKGROUND: Low-dose oral methotrexate (MTX) is an effective immunosuppressive therapy for chronic plaque psoriasis. However, its use is hampered by the risk of liver fibrosis. AIM: To compare the results of serial measurements of serum fibrosis markers during the remission-induction phase of treatment with MTX to those of patients on biological therapy and long-term MTX therapy (>2 years). SUBJECTS AND METHODS: Serum concentrations of hyaluronic acid, N-terminal propeptide of collagen type III (PIIINP) and the results of two multi-test algorithms Fibrotest and Hepascore were evaluated in patients with chronic plaque psoriasis (N = 24, age: 28-79 years, baseline Psoriasis Area Severity Index PASI 13.5, range 2.2-33) at baseline and weeks 16 and 26 after the start of pharmacokinetically guided therapy with MTX (Group A). Patients on established therapy with biologics (N = 15, Group B) and long-term MTX users (N = 10, Group C) with the mean baseline PASI scores of 0.9 and 1.2 were studied in parallel cohorts. RESULTS: At baseline, HA, Hepascore and PIIINP were correlated with PASI of Group A patients. At weeks 16 and 26, HA decreased by 48% and 40% (P < 0.001) and Hepascore by 31 (P < 0.01) and 20% (P < 0.05) respectively. PASI75 (≥ 75% improvement from baseline PASI) was observed in 76% of Group A patients by week 26 and the absolute decreases in PASI and both fibrosis markers were correlated (HA: r = 0.49, P = 0.018, Hepascore: r = 0.47, P = 0.022). In contrast, no significant within-group differences were found in HA and Hepascore results of patients in the groups B and C. PIIINP and Fibrotest were stable in all groups. CONCLUSION: The fibrosis markers hyaluronic acid and Hepascore (the multiple test algorithm which includes hyaluronic acid) are less liver specific and more prone to reflect psoriasis activity than PIIINP and Fibrotest.

Late divergence of target and nontarget ERPs in a visual oddball task.

Different mental operations were expected in the late phase of intracerebral ERPs obtained in the visual oddball task with mental counting. Therefore we searched for late divergences of target and nontarget ERPs followed by components exceeding the temporal window of the P300 wave. Electrical activity from 152 brain regions of 14 epileptic patients was recorded by means of depth electrodes. Average target and nontarget records from 1800 ms long EEG periods free of epileptic activity were compared. Late divergence preceded by almost identical course of the target and nontarget ERPs was found in 16 brain regions of 6 patients. The mean latency of the divergence point was 570+/-93 ms after the stimulus onset. The target post-divergence section of the ERP differed from the nontarget one by opposite polarity, different latency of the components, or even different number of the components. Generators of post-divergence ERP components were found in the parahippocampal gyrus, superior, middle and inferior temporal gyri, amygdala, and fronto-orbital cortex. Finding of late divergence indicates that functional differences exist even not sooner than during the final phase of the task.

Involvement of the subthalamic nucleus and globus pallidus internus in attention.

We studied the appearance of cognitive event-related potentials (ERPs) and event-related de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and globus pallidus internus (GPi). We particularly focused on the rare non-target (distractor) stimuli processing. ERPs and ERD/S in the alpha and beta frequency range were analyzed in seven Parkinson's disease patients and one primary dystonia patient with implanted deep brain stimulation (DBS) electrodes. A visual three-stimulus protocol was used (frequent stimulus, target stimulus, and distractor). The non-target and distractor-related waveforms manifested similar shapes. A specific positive ERP peak around 200 ms and a low alpha frequency ERS were detected from the STN as a response to the distractor stimuli in six of the patients with Parkinson's disease and also in the primary dystonia patient's GPi. This positivity probably reflects an attentional orienting response to the distractor stimuli. The STN and GPi are probably involved in attentional cerebral networks.

Steady-state of azathioprine during initiation treatment of pediatric inflammatory bowel disease.

BACKGROUND AND AIM: Azathioprine (AZA) has a slow onset of action in treatment of pediatric inflammatory bowel disease (IBD). It is anticipated, that this delay correlates to the kinetics of 6-thioguanine nucleotides (6-TGN) accumulation. The aim of this study was to evaluate the time to steady state of 6-TGN concentration in red blood cells. METHODS: The inclusion criteria were: a) age 0-19 years b) IBD diagnosis c) AZA treatment initiation. High performance liquid chromatography was used for the 6-TGN analysis. Concentrations of metabolites were studied in weeks 0, 1, 2, 5, and 8 after beginning of treatment. RESULTS: The inclusion criteria were matched to 18 patients with IBD. The median time to steady state of 6-TGN was 55.3 days. The mean 6-TGN concentration at the steady state achieved 326 (SD 154) pmol/8.108 erythrocytes. High erythrocyte TPMT activity corresponds to the low steady state 6-TGN concentration and vice versa. This correlation reached statistical significance (p<0.01) for the dose expressed in mg per square meter of body surface area. CONCLUSION: The time to steady state of 6-TGN erythrocyte concentration is significantly shorter than would expected according to clinical observation describe earlier.

Methotrexate bioavailability after oral and subcutaneous dministration in children with juvenile idiopathic arthritis.

OBJECTIVE: To compare the bioavailability of oral and subcutaneous methotrexate (MTX) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventeen JIA patients were administered oral (6.1-22.5 mg/m(2)) or subcutaneous (8.8-28.6 mg/m(2)) MTX. Blood samples were drawn pre-dose, and at 1, 2, and 4 hours after administration. Plasma MTX was determined by high-performance liquid chromatography. Non-compartmental pharmacokinetic analysis included the maximum concentration of plasma MTX (C(max)) and the area under the plasma concentration-time curve in the interval of 0-4h (AUC(0-4h)). RESULTS: The slopes of the regression lines of the dose-corrected parameters Cmax and AUC(0-4h) plotted against the dose were negative for oral administration indicating non-linearity in pharmacokinetics, while they did not differ from zero for subcutaneous MTX. In two groups dosed orally with < or = 10 or >10 mg/m(2) (the average doses: 7.8 vs. 13.8 mg/m(2), p<0.002), the C(max) and AUC(0-4h) were comparable (p > or = 0.32). In four patients switched from oral to subcutaneous administration of the same dose, the bioavailability of oral MTX tended to be 11-15% lower when compared to subcutaneous route. CONCLUSION: The differences in the pharmacokinetic measures of early systemic exposure between oral and subcutaneous routes support the view that lower and saturable intestinal absorption of oral MTX limits its bioavailability and efficacy within the range of standard doses used to treat children with JIA. In light of this evidence it can be recommended to use parenteral route of administration when MTX dose around and above 10-15 mg/m(2) is needed to achieve sufficient response.

Pharmacokinetics of flubendazole and its metabolites in lambs and adult sheep (Ovis aries).

Flubendazole (FLU) is indicated for control of helminthoses in pig and avian species (monogastric animals) and its corresponding pharmacokinetics are well known. The information on FLU's pharmacokinetic behavior in animal species with forestomach (ruminants) has been limited although the use of FLU in these species could be beneficial. The aim of this study was to investigate the pharmacokinetics of FLU and its main metabolites in sheep. The effects of animal age (sexually immature and mature ones) and gender were also studied. FLU was orally administered in a single experimental dose (30 mg/kg of body weight) in the form of oral suspension. Treated immature animals (aged 3 months) and 5 months later the same mature individuals (aged 8 months) were kept under the same conditions (food, water and management) and treated with FLU. Within 72 h after FLU administration, plasmatic samples were collected and FLU and its Phase I metabolites were quantified using high-performance liquid chromatography. FLU was detected in very low concentrations only, reduced FLU (FLU-R) was identified as the main metabolite, and hydrolyzed FLU (FLU-H) as the minor one. Formation of FLU-R was stereospecific with (+)-FLU-R domination. The plasmatic concentrations of (+)-FLU-R reached 10-15 times higher values than those of FLU, (-)-FLU-R and FLU-H. A significant gender effect on pharmacokinetics of FLU or (+)-FLU-R metabolite in the mature animals was found and a wide significant difference between lambs and adult sheep in FLU including both metabolites has been proved.

A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment.

BACKGROUND: Clinical studies of low-dose oral methotrexate (MTX) in the treatment of psoriasis and rheumatoid arthritis document a large interpatient variability in the pharmacokinetics of MTX, including its polyglutamates (MTXPGs) in erythrocytes (RBC). This can be a factor contributing to the variability of therapeutic and toxic effects. AIM: This pilot trial aimed to investigate the MTXPG concentrations in RBC as well as their relation to therapeutic and adverse effects during the initial 4 months of pharmacokinetically guided therapy with a divided-dose schedule (three doses of MTX separated by 12-h intervals once a week). SUBJECTS AND METHODS: Sixteen psoriatic patients (4 men and 12 women; mean age, 53 years; range, 28-69 years) with moderate-to-severe chronic plaque psoriasis [mean Psoriasis Area and Severity Index (PASI) = 24; range, 9-42] were enrolled in the study. Concentrations of plasma MTX and that of MTXPGs in RBC were assayed using liquid chromatography methods. The area under the concentration-time curve of plasma MTX in the interval 0-8 h post-dose (AUC(0-8 h)) was measured after a test bolus dose of 10 mg, and the starting weekly dose was individualized in order to achieve the target AUC(0-8 h) of 1800 nmol.h/L. The PASI, biochemistry, and haematology tests and MTXPGs levels in RBC were evaluated at baseline and at 4-week intervals. RESULTS: The AUC(0-8 h )achieved 1360 +/- 425 nmol.h/L (mean +/- SD: range, 778-2400 nmol.h/L). The mean (range) of individualized doses was 14.5 mg/week (7.5-22.5 mg). The mean (SD) steady-state concentration of total MTXPGs observed between days 85 to 110 reached 113 (34.6) nmol/L (range, 66.1-174 nmol/L). The PASI decreased from 24.0 +/- 8.0 (mean +/- SD) at baseline to 8.0 +/- 6.1 at day 110 (P < 0.001). Thirteen patients (87%) achieved a greater than 50% improvement in baseline PASI, and seven (47%) experienced a greater than 75% improvement. There was no relationship between the percent improvement from baseline PASI and the steady-state concentration of MTXPGs in RBC. All patients tolerated MTX well. Throughout the study period, there was a continuous increasing trend in the geometric mean values of the mean corpuscular volume from 92.6 to 96.4 fL (P < 0.001) and of plasma homocysteine from 9.5 to 12.3 micromol/L (P < 0.005). The geometric mean serum alanine aminotransferase (ALT) activity slightly increased from 0.49 to 0.80 microkat/L (P < 0.05). However, only two patients had the ALT activity transiently elevated above twice the upper limit of normal. CONCLUSION: Results of this pilot trial show that the steady-state levels of MTXPGs in RBC vary less than threefold between patients and did not correlate with the change in PASI observed after 4 months of therapy with an individualised weekly dose of MTX. Whether pharmacokinetically guided dosing can improve the results of psoriasis therapy with MTX should be prospectively tested in large controlled studies.

Executive functions processed in the frontal and lateral temporal cortices: intracerebral study.

OBJECTIVE: The study was designed to investigate the neurocognitive network in the frontal and lateral temporal cortices that is activated by the complex cognitive visuomotor tasks of letter writing. METHODS: Eight epilepsy surgery candidates with implanted intracerebral depth electrodes performed two tasks involving the writing of single letters. The first task consisted of copying letters. In the second task, the patients were requested to write any other letter. The cognitive load of the second task was increased mainly by larger involvement of the executive functions. The task-related ERD/ERS of the alpha, beta and gamma rhythms was studied. RESULTS: The alpha and beta ERD as the activational correlate of writing of single letters was found in the sensorimotor cortex, anterior cingulate, premotor, parietal cortices, SMA and the temporal pole. The alpha and beta ERD linked to the increased cognitive load was present moreover in the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex and surprisingly also the temporal neocortex. Gamma ERS was detected mostly in the left motor cortex. CONCLUSIONS: Particularly the temporal neocortex was activated by the increased cognitive load. SIGNIFICANCE: The lateral temporal cortex together with frontal areas forms a cognitive network processing executive functions.

Neural chaos and schizophrenia.

Recent data indicate that random-like processes are related to the defects in the organization of semantic memory in schizophrenia which is more disorganized and less definable than those of controls with more semantic links and more bizarre and atypical associations. These aspects of schizophrenic cognition are similar to characteristics of chaotic nonlinear dynamical systems. In this context, the hypothesis tested in this study is that dynamic changes of electrodermal activity (EDA) as a measure of brain and autonomic activity may serve as a characteristic which can be used as an indicator of possible neural chaotic process in schizophrenia. In the present study, bilateral EDA in rest conditions were measured in 40 schizophrenic patients and 40 healthy subjects. Results of nonlinear and statistical analysis indicate left-side significant differences of positive largest Lyapunov exponents in schizophrenia patients compared to the control group. This might be interpreted that the neural activity during rest in schizophrenic patients is significantly more chaotic than in the control group. The relationship was confirmed by surrogate data testing. These data suggest that increased neural chaos in patients with schizophrenia may influence brain processes that can cause random-like disorganization of mental processes.

Analysis of exhaled leukotrienes in nonasthmatic adult patients with seasonal allergic rhinitis.

BACKGROUND: Leukotrienes (LTs) are increased in exhaled breath condensate (EBC) in patients with asthma. So far no data have been reported about LT levels in nonasthmatic patients with seasonal allergic rhinitis (SAR). The aim of the study was to find out whether the LT levels in EBC were increased in the nonasthmatic adult patients with SAR both during and after the pollen season in comparison with healthy controls and to assess the changes of the LT levels after the pollen season. METHODS: Twenty-nine nonasthmatic adult patients with SAR underwent measurement of exhaled LTs in the EBC during and after the pollen season. Leukotrienes B(4), C(4), D(4) and E(4) were analysed by a specific and sensitive gas chromatography/mass spectrometry (GC/MS) assay and compared with 50 healthy nonsmoking controls. Spirometry, skin prick tests and nonspecific IgE were evaluated. RESULTS: Leukotrienes concentrations (B(4), E(4) but not D(4)) were significantly increased in and after the pollen season in patients with SAR in comparison with healthy controls. In most of the samples, LT C(4) was undetectable. The values of all exhaled LTs were significantly decreased after the pollen season compared with the seasonal baseline: LTB(4) (P = 0.023), LTD(4) (P = 0.020), LTE(4) (P = 0.047). CONCLUSIONS: Levels of exhaled LTB(4) and LTE(4) were higher in SAR patients than in healthy controls and decreased after the pollen season as compared with levels in season. The SAR patients with the highest in season LT levels had also the post-season levels elevated and this may be an early marker of inflammatory process in the lower airways despite the absence of clinical symptoms of asthma.