Pre-exercise cryotherapy reduces myoglobin and creatine kinase levels after eccentric muscle stress in young women.

Introduction: The aim of this study was to investigate the effect of pre-exercise whole-body cryotherapy (WBC) on muscle damage indicators following eccentric treadmill exercise in young women. Methods: Twenty-seven participants underwent two 1-h downhill treadmill runs, replicating 60% of their maximal oxygen uptake, with a 4-week intermission for recovery and treatment application. In this intermission, one group underwent 20 sessions of WBC, delivered five times a week at -120°C for 3 min each, while the comparison group received no such treatment. Markers of muscle injury-serum myoglobin concentration, creatine kinase and lactate dehydrogenase activity and also uric acid, and cell-free DNA concentration-were measured before and after downhill runs. Results: The study observed a notable reduction in post-exercise myoglobin and CK levels in the WBC group after the second running session. Discussion: The results suggest that WBC can have a protective effects against muscle damage resulting from eccentric exercise.

Effect of regular winter swimming on blood morphological, rheological, and biochemical indicators and activity of antioxidant enzymes in males.

BACKGROUND: Exposure of the human body to cold water triggers numerous beneficial physiological changes. The study aimed to assess the impact of regular winter swimming on blood morphological, rheological, and biochemical indicators and activity of antioxidant enzymes in males. METHODS: The study involved 10 male winter swimmers (the same participants examined before the season and after the season) and 13 males (not winter swimming, leading a sedentary lifestyle) in the control group. Fasting blood was collected twice: in November and in March of the following year. Basic blood morphological indicators, red cell elongation index (EI) and aggregation index (AI), concentrations of testosterone, cortisol, urea, and creatinine, as well as plasma activity of antioxidant enzymes of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were determined. RESULTS: The data were collected from the same winter swimmers at the beginning and end of the season. Winter swimming resulted in a significant increase of EI values at a shear stress of 0.30 (p = 0.40), 0.58 (p < 0.001), 4.24 (p = 0.021), 8.23 (p = 0.001), 15.59 (p = 0.001), 30.94 (p = 0.004), and 60.00 Pa (p = 0.043); haemoglobin was lower than before the season (p < 0.027). No significant changes were observed in AI, AMP, T1/2, the levels of urea, creatinine, eGFR, testosterone, cortisol, or the activity of CAT or SOD. There was a statistically significant increase in GPx activity (p = 0.014) and increase in testosterone concentration (p = 0.035) in the group of winter swimmers examined before the season as compared with the control group. No statistically significant differences were found for the mean values of blood morphological indicators and other parameters. CONCLUSIONS: Winter swimming can prove to be a health-promoting factor in males, as indicated by a rise in the deformability of red blood cells in the blood vessel system after a full season of winter swimming, leading to better body oxygenation, and improves the antioxidant defence and testosterone concentration (within standard limits) in the group of winter swimmers examined before the season as compared with the control group. Winter swimming helps maintain appropriate levels of blood rheological indicators, urea, creatinine, eGFR, cortisol, testosterone, and activity of antioxidant enzymes. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06223087, 15.01.2024.

The Effect of Physical Activity and Repeated Whole-Body Cryotherapy on the Expression of Modulators of the Inflammatory Response in Mononuclear Blood Cells among Young Men.

Background: Series of whole-body cryotherapy (WBC) among healthy and physically active individuals can potentially reduce inflammatory response, although exact mechanisms remain unclear. Methods: The impact of whole-body cryotherapy on inflammation modulators among 28 young males, categorized as non-training (NTR, N = 10), non-training with WBC (NTR-WBC, N = 10), and training with WBC (TR-WBC, N = 8), is investigated in this study. Over a period of eight weeks, NTR-WBC and TR-WBC subjects underwent 24 WBC treatments (-130 °C for 3 min, three times a week), examining changes in mRNA expressions of IL-1A, IL-6, IL-10, IFN-G, SIRT1, SIRT3, SOD2, GSS, and ICAM-1. Results: The received data indicate an acute inflammatory response to initial WBC (increased IL-1A, IL-6, and SIRT), with a greater effect in NTR-WBC. Subsequent sessions showed enhanced expressions of antioxidative genes in both WBC groups, particularly non-trained, suggesting improved oxidative stress adaptation. A notable decrease in ICAM-1 mRNA post-24 WBC treatments in NTR-WBC signifies a potential systemic anti-inflammatory effect. Conclusions: The findings of the study suggest that the combination of regular physical activity with WBC administered three times per week can potentially modulate inflammatory and antioxidant responses. This modulation is evidenced by changes in the expression of genes related to these processes.

Changes in the concentration of bone turnover markers in men after maximum intensity exercise.

Background: Physical activity is an important factor in modelling the remodelling and metabolism of bone tissue. The aim of the study was to evaluate the changes in indices demonstrating bone turnover in men under the influence of maximum-intensity exercise. Methods: The study involved 33 men aged 20-25, divided into two groups: experimental (n = 15) and control (n = 18). People training medium- and long-distance running were assigned to the experimental group, and non-training individuals to the control. Selected somatic, physiological and biochemical indices were measured. The level of aerobic fitness was determined using a progressively increasing graded test (treadmill test for subjective fatigue). Blood samples for determinations were taken before the test and 60 minutes after its completion. The concentration of selected bone turnover markers was assessed: bone fraction of alkaline phosphatase (b-ALP), osteoclacin (OC), N-terminal cross-linked telopeptide of the alpha chain of type I collagen (NTx1), N-terminal propeptide of type I progolagen (PINP), osteoprotegerin (OPG). In addition, the concentration of 25(OH)D3 prior to the stress test was determined. Additionally, pre and post exercise, the concentration of lactates in the capillary blood was determined. Results: When comparing the two groups, significant statistical differences were found for the mean level of: 25(OH)D3 (p = 0.025), b-ALP (p < 0.001), OC (p = 0.004) and PINP (p = 0.029) prior to the test. On the other hand, within individual groups, between the values pre and post the stress test, there were statistically significant differences for the average level of: b-ALP (p < 0.001), NTx1 (p < 0.001), OPG (p = 0.001) and PINP (p = 0.002). Conclusion: A single-session maximum physical effort can become an effective tool to initiate positive changes in bone turnover markers.

Whole-Body Cryotherapy Improves Asprosin Secretion and Insulin Sensitivity in Postmenopausal Women-Perspectives in the Management of Type 2 Diabetes.

Type 2 diabetes (T2DM) is a global problem. The effect of whole-body cryotherapy (WBC) on metabolism in humans is postulated. The aim of this study was to determine the effect of WBC on asprosin concentrations, glucose homeostasis and insulin resistance in postmenopausal women with T2DM. Changes in fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, asprosin, insulin-resistance indices (HOMA-IR, Quicki), the triglyceride-glucose index (TyG) and C-reactive protein (CRP) were determined. Determination was carried out after 30 WBCs (3 min, -120 °C), applied in six series of five treatments, with 2-day breaks in postmenopausal women with T2DM and the results were compared to changes in postmenopausal women without T2DM (CON). Blood was collected before 1 WBC (T0), after 30 WBCs (T1) and 2 weeks after their completion (T2). In the T2DM group, there was a significant decrease in FBG and HbA1c in T1 and T2, as well as a significant decrease in insulin, HOMA-IR and CRP, and an increase in the Quicki index in T2. In the CON group, the concentration of asprosin at T2 was significantly lower than at T0. There was a significantly positive correlation between asprosin and FBG and HOMA-IR, and a trend towards a decrease of asprosin concentration in T2 in postmenopausal women with T2DM.

Whole-Body Cryotherapy Alters Circulating MicroRNA Profile in Postmenopausal Women.

The incidence of metabolic syndrome (MetS) increases with age, especially in women. The role of microRNAs (miRs) in the regulation of metabolism is postulated. The aim of the study is to identify miRs that may be markers of MetS and to assess changes in miRs expression as a result of 10 and 20 whole-body cryotherapy treatments (WBC; 3 min, -120 °C) in postmenopausal women with MetS (M-60, BMI 30.56 ± 5.38 kg/m2), compared to healthy postmenopausal (H-60, BMI 25.57 ± 2.46 kg/m2) and healthy young women (H-20, BMI 22.90 ± 3.19 kg/m2). In a fasting state, before 1 WBC and after 10 WBCs, as well as 20 WBCs, the expression of miR-15a-5p, miR-21-5p, miR-23a-3p, miR-146a-5p, miR-197-3p, miR-223-3p, fasting blood glucose (FBG) and blood lipid profile were determined. miR-15a-5p and miR-21-5p were down-regulated in M-60, while miR-23a-3p and miR-197-3p were up-regulated, and miR-223-3p down-regulated in M-60 and H-60, compared to H-20. Significant positive correlations between up-regulated (mostly for miR-23-3p and miR-197-3p) and significant negative correlations between down-regulated (mostly for miR-15a-5p) miRs and markers of body composition as well as metabolic disorders were observed. After 20 WBCs, miR-15a-5p expression was up-regulated in all groups. In H-60, down-regulation of miR-197-3p expression occurred after 10 WBCs and 20 WBCs. Following 10 WBCs, FBG decreased in all groups, which intensified in M-60 post-20 WBCs. In our research, it has been shown that miR-23a-3p and miR-197-3p are accurate markers of MetS and MetS risk factors, while miR-15a-5p and miR-23a-3p are precise markers of body composition disorders. WBC is an effective treatment for up-regulating miR-15a-5p and lowering glucose levels in young and postmenopausal women and down-regulating miR-197-3p expression in postmenopausal women. It may be an adjunctive effective treatment method in MetS and hyperglycemia.

Nordic Walking at Maximal Fat Oxidation Intensity Decreases Circulating Asprosin and Visceral Obesity in Women With Metabolic Disorders.

OBJECTIVE: Excess visceral adipose tissue is associated with insulin resistance and other metabolic disorders, including deregulation of adipokine secretion, which may be corrected by aerobic exercise training. Asprosin is a novel adipokine responsible for the regulation of appetite and the release of glucose from the liver, and its levels are pathologically elevated in obesity. The aim of the study was to evaluate the effects of 8-week Nordic walking (NW) training at maximal fat oxidation intensity (FAT max ) on changes in body mass, as well as those in insulin resistance and asprosin levels among young women with visceral obesity and metabolic disorders. MATERIALS AND METHODS: The study was completed by 14 women (30.14 ± 3.63 years) representing low levels of physical activity, visceral obesity (waist circumference 105.50 ± 14.87 cm, BMI 33.85 ± 5.48 kg/m2) and with metabolic disorders, who for 8 weeks (three times a week, 60 min), participated in NW training at the FAT max intensity (61.92 ± 6.71% HR max , 42.33 ± 8.69% VO2max) controlled on the basis of heart rate (114.21 ± 14.10 bpm). RESULTS: After 4 and 8 weeks of NW training, a significant decrease in the concentration of asprosin, waist and hip circumference (HC), waist-to-height ratio and body adiposity index (BAI) (p < 0.05, large effect size) were found. CONCLUSION: The 8-week NW training at an FAT max intensity decreases the concentration of asprosin in the blood as well as visceral obesity in young women with metabolic disorders.

Whole-Body Cryotherapy Increases the Activity of Nitric Oxide Synthase in Older Men.

Aging causes oxidative stress, endothelial dysfunction and a reduction in the bioavailability of nitric oxide. The study aim was to determine whether, as a result of repeated whole-body exposure to cryogenic temperature (3 min -130 °C), there is an increase of inducible nitric oxide synthase (iNOS) concentration in senior subjects (59 ± 6 years), and if this effect is stronger in athletes. In 10 long-distance runners (RUN) and 10 untraining (UTR) men, 24 whole-body cryotherapy (WBC) procedures were performed. Prior to WBC, after 12th and 24th treatments and 7 days later, the concentration of iNOS, asymmetric dimethylarginine (ADMA), 3-nitrotyrosine (3-NTR), homocysteine (HCY), C-reactive protein (CRP) and interleukins such as: IL-6, IL-1ß, IL-10 were measured. In the RUN and UTR groups, after 24 WBC, iNOS concentration was found to be comparable and significantly higher (F = 5.95, p < 0.01) (large clinical effect size) compared to before 1st WBC and after 12th WBC sessions. There were no changes in the concentration of the remaining markers as a result of WBC (p > 0.05). As a result of applying 24 WBC treatments, using the every-other-day model, iNOS concentration increased in the group of older men, regardless of their physical activity level. Along with this increase, there were no changes in nitro-oxidative stress or inflammation marker levels.

Antidepressants Differentially Regulate Intracellular Signaling from α1-Adrenergic Receptor Subtypes In Vitro.

Currently utilized antidepressants have limited effectiveness and frequently incur undesired effects. Most antidepressants are thought to act via the inhibition of monoamine reuptake; however, direct binding to monoaminergic receptors has been proposed to contribute to both their clinical effectiveness and their side effects, or lack thereof. Among the target receptors of antidepressants, α1­adrenergic receptors (ARs) have been implicated in depression etiology, antidepressant action, and side effects. However, differences in the direct effects of antidepressants on signaling from the three subtypes of α1-ARs, namely, α1A-, α1B- and α1D­ARs, have been little explored. We utilized cell lines overexpressing α1A-, α1B- or α1D-ARs to investigate the effects of the antidepressants imipramine (IMI), desipramine (DMI), mianserin (MIA), reboxetine (REB), citalopram (CIT) and fluoxetine (FLU) on noradrenaline-induced second messenger generation by those receptors. We found similar orders of inhibition at α1A-AR (IMI < DMI < CIT < MIA < REB) and α1D­AR (IMI = DMI < CIT < MIA), while the α1B-AR subtype was the least engaged subtype and was inhibited with low potency by three drugs (MIA < IMI = DMI). In contrast to their direct antagonistic effects, prolonged incubation with IMI and DMI increased the maximal response of the α1B-AR subtype, and the CIT of both the α1A- and the α1B-ARs. Our data demonstrate a complex, subtype-specific modulation of α1-ARs by antidepressants of different groups.

Psychosocial Crowding Stress-Induced Changes in Synaptic Transmission and Glutamate Receptor Expression in the Rat Frontal Cortex.

This study demonstrates how exposure to psychosocial crowding stress (CS) for 3, 7, and 14 days affects glutamate synapse functioning and signal transduction in the frontal cortex (FC) of rats. CS effects on synaptic activity were evaluated in FC slices of the primary motor cortex (M1) by measuring field potential (FP) amplitude, paired-pulse ratio (PPR), and long-term potentiation (LTP). Protein expression of GluA1, GluN2B mGluR1a/5, VGLUT1, and VGLUT2 was assessed in FC by western blot. The body's response to CS was evaluated by measuring body weight and the plasma level of plasma corticosterone (CORT), adrenocorticotropic hormone (ACTH), and interleukin 1 beta (IL1B). CS 3 14d increased FP and attenuated LTP in M1, while PPR was augmented in CS 14d. The expression of GluA1, GluN2B, and mGluR1a/5 was up-regulated in CS 3d and downregulated in CS 14d. VGLUTs expression tended to increase in CS 7d. The failure to blunt the effects of chronic CS on FP and LTP in M1 suggests the impairment of habituation mechanisms by psychosocial stressors. PPR augmented by chronic CS with increased VGLUTs level in the CS 7d indicates that prolonged CS exposure changed presynaptic signaling within the FC. The CS bidirectional profile of changes in glutamate receptors' expression seems to be a common mechanism evoked by stress in the FC.

Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D2 receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62). The polypharmacology profile of 62, characterized by partial 5-HT1AR agonism, 5-HT2A/5-HT7/D2/D3R antagonism, and blockade of SERT, reduced the "positive"-like, and "negative"-like symptoms of psychoses. Compound 62 produced no catalepsy, demonstrated a low hyperprolactinemia liability and displayed pro-cognitive effects in the novel object recognition task and attentional set-shifting test. While association of in vitro features with the promising in vivo profile of 62 is still not fully established, its clinical efficacy should be verified in further stages of development.

Assessment of leukocyte activity in mice devoid of the glucocorticoid receptor in the noradrenergic system (GRDBHCre).

Disturbances in brain monoamines, overactivity of the hypothalamo-pituitary adrenal (HPA) axis and pro-inflammatory tendency in the immune system are the key features of depressive disorders. Recently, several murine lines with mutations in glucocorticoid receptors (GRs) have been generated and these animals may be utilized for study depressive-like disorders. In the present study, we have investigated whether selective ablation of GRs in noradrenergic neurons affects functional properties of leukocytes and redirects them towards pro-inflammatory activity. Transgenic mice selectively devoid of GRs on noradrenergic cells were constructed using the Cre/loxP approach. Peritoneal leukocytes were collected from mutant and wild type (WT) animals of both sexes and were cultured in vitro for 24h both in basal conditions and after application of selected pro- or anti-inflammatory stimuli. Metabolic activity and adherence were measured in basal conditions. Nitric oxide (NO) synthesis and arginase (ARG) activity were assessed as the markers of functional status of the cells. Because adult mutant mice lack adrenal medulla and thereby peripheral adrenaline, we modulated pro- and anti-inflammatory culture conditions by addition of noradrenaline (10-6M). Finally, effects of in vivo pro-inflammatory challenge (with intraperitoneal administration of lipopolysaccharide) on properties of leukocytes were assessed 24h (in both sexes) and 48h later (in males only). The experiments indicated that selective ablation of GR in noradrenergic neurons did not affect fundamental properties of peritoneal leukocytes and exerted effects only under conditions of selected pro- or anti-inflammatory stimuli in vitro. Stronger response to pro-inflammatory stimulation in terms of NO synthesis and ARG activity may suggest pro-inflammatory tendency in mutant mice. In vivo inflammatory challenge failed to show any effect of GR ablation on selected parameters of leukocyte activity. Both in vitro studies and in vivo challenge revealed mainly sex-related differences in leukocyte activity.

Transgenic mice lacking CREB and CREM in noradrenergic and serotonergic neurons respond differently to common antidepressants on tail suspension test.

Evidence exists that chronic antidepressant therapy enhances CREB levels and activity. Nevertheless, the data are not conclusive, as previous analysis of transgenic mouse models has suggested that CREB inactivation in fact contributes to antidepressant-like behavior. The aim of this study was to evaluate the role of CREB in this context by exploiting novel transgenic mouse models, characterized by selective ablation of CREB restricted to noradrenergic (Creb1DBHCre/Crem-/-) or serotonergic (Creb1TPH2CreERT2/Crem-/-) neurons in a CREM-deficient background to avoid possible compensatory effects of CREM. Selective and functional ablation of CREB affected antidepressant-like behavior in a tail suspension test (TST) after antidepressant treatment. Contrary to single Creb1DBHCre mutants, Creb1DBHCre/Crem-/- mice did not respond to acute desipramine administration (20 mg/kg) on the TST. On the other hand, single Creb1TPH2CreERT2 mutants displayed reduced responses to fluoxetine (10 mg/kg) on the TST, while the effects in Creb1TPH2CreERT2/Crem-/- mice differed by gender. Our results provide further evidence for the important role of CREM as a compensatory factor. Additionally, the results indicate that new models based on the functional ablation of CREB in select neuronal populations may represent a valuable tool for investigating the role of CREB in the mechanism of antidepressant therapy.

Depressive-like immobility behavior and genotype × stress interactions in male mice of selected strains.

In this study, we investigated whether basal immobility time of C57BL/6J mice, which are commonly used in transgenesis, interferes with detection of depressive-like behavior in the tail suspension test (TST) after chronic restraint stress (CRS). We included in the study mice of the C57BL/6N strain, not previously compared with C57BL/6J for behavior in the TST, and contrasted both strains with NMRI mice which exhibit low basal immobility. NMRI, C57BL/6J, and C57BL/6N male mice (n = 20 per strain) were tested under basal conditions and after CRS (2 h daily for 14 d). NMRI and C57BL/6J mice were differentiated in the TST by low and high basal immobility times, respectively, while the C57BL/6N and NMRI mice showed similar levels of basal immobility. CRS extended the immobility time of NMRI mice in the TST, whereas both C57BL/6J and C57BL/6N mice were unaffected regardless of their initial phenotype. We explored whether detailed analysis of activity microstructure revealed effects of CRS in the TST, which are not apparent in the overall comparison of total immobility time. Interestingly, unlike C57BL/6J and/6N strains which showed no sensitivity to CRS, stressed NRMI mice displayed distinct activity microstructure. In contrast to behavioral differences, all stressed mice showed significant retardation in body weight gain, decreased thymus weight and increased adrenal cortex size. However, after CRS, enlargement of the adrenal medulla was observed in both C57BL/6J and C57BL/6N mice, suggesting similar sympatho-medullary activation and stress coping mechanism in these substrains.

Inactivation of glucocorticoid receptor in noradrenergic system influences anxiety- and depressive-like behavior in mice.

The aim of this study was to investigate whether conditional inactivation of the glucocorticoid receptors (GRs) in noradrenergic neurons affects animal behavior in mice. Selective ablation of GRs in the noradrenergic system was achieved using the Cre/loxP approach. We crossed transgenic mice expressing the Cre recombinase under the dopamine beta-hydroxylase (DBH) promoter with animals harboring the floxed GR gene. The resulting GR(DBHCre) mutant mice exhibited no alterations in terms of normal cage behavior, weight gain, spatial memory or spontaneous locomotor activity, regardless of gender. To assess depressive- and anxiety-like behaviors we performed the Tail Suspension Test and the Light-Dark Box Test. While male mutant animals did not show any alternations in both tests, female GR(DBHCre) mutants displayed depressive- and anxiety-like behavior. Additionally, male GR(DBHCre) mice were exposed to chronic restraint stress but still exhibited immobility times and anxiety statuses similar to those of non-stressed animals while stressed control mice clearly revealed depressive- and anxiety-like phenotype. Thus, in males the effects of the mutation were precipitated only after chronic restraint stress procedure. Our data reveal a possible gender-dependent role of GRs in the noradrenergic system in anxiety- and depressive-like behavior in mice.

Gender-dependent activity of CYP3A is indirectly modified by GR in the noradrenergic system.

BACKGROUND: The noradrenergic system is involved in the regulation of cytochrome P450 activity in the liver. We investigated the effect of selective ablation of the glucocorticoid receptor in the noradrenergic systemon the activity of the CYP3A isoform in mouse liver. METHODS: The activity of CYP3A was studied by measuring the rate of testosterone 6ß-hydroxylation in liver microsomes. RESULTS: In mutant mice, the activity of CYP3A was reduced to 68% of the control in females, but remained unchanged in males. Chronic restraint stress increased CYP3A activity in mutant mice only. CONCLUSIONS: The total basal activity of mouse CYP3A may be indirectly modulated by the glucocorticoid receptor in the noradrenergic system during a pubertal period.

Effects of co-administration of fluoxetine and risperidone on properties of peritoneal and pleural macrophages in rats subjected to the forced swimming test.

BACKGROUND: Literature data show that administration of atypical antipsychotic drug, risperidone (RIS), enhances antidepressive action of fluoxetine (FLU). As antidepressive treatments also regulate immune functions, we examined whether combined administration of FLU and RIS to rats subsequently subjected to a forced swimming test (FST) modifies parameters of macrophage activity that are directly related to their immunomodulatory functions, i.e., arginase (ARG) activity and nitric oxide (NO) synthesis. METHODS: Antidepressive action of the drugs was assessed with FST. Peritoneal and pleural cells were eluted and selected parameters of immunoreactivity were assessed colorimetrically. RESULTS: We found that the concomitant administration of FLU (10 mg/kg) and RIS (0.1 mg/kg) produced antidepressive-like effects in the FST,whereas the drugs were ineffective if administered separately. Stress related to the FST affected immune cell redistribution and changed some of the metabolic and immunomodulatory properties of macrophages. FLU administered to rats at a suboptimal dose for antidepressive action potently influenced macrophage immunomodulatory properties and redirected their activity toward anti-inflammatory M2 functional phenotype, as manifested by changes in the ARG/NO ratio. These effects resulted from a direct cellular influence of the drug, as well as its action via neuroendocrine pathways, as evidenced in peritoneal and pleural cells. Addition of RIS did not augment immunomodulatory action of FLU, though the combination showed antidepressant-like activity in the FST. CONCLUSIONS: Our results suggest that when the drugs were administered together, FLU was potent enough to redirect macrophages toward M2 activity. It is also postulated that drug-induced changes in the immune system are not so closely related to antidepressant-like effects or might be secondary to those produced in the neuroendocrine system.

[Long-term fever as a first symptom of neoplasmatic process in young patients--case reports]. / Dlugotrwala goraczka, jako pierwszy objaw choroby nowotworowej u osób mlodych--opis przypadków.

UNLABELLED: Fever is a thermoregulation disorder with body temperature increased (above 38 degrees C). The most often accompanies infections, but it may also be a symptom of neoplasmatic disease. CASE REPORTS: In our paper we described 2 patients, who were admitted to the Department of Infectious Diseases and Neuroinfections with fever as a main symptom. Laboratory tests excluded the infection as causative agents of a long term fever. Wide spectrum diagnosis in both cases led to diagnosis of neoplasmatic disease. Presented cases indicate that in patents with long term fever, even in young age, neoplasmatic process should be taken into consideration.

[Statistical analysis of influence of meteorological data on the incidence rate of tick-borne encephalitis in Bialystok]. / Statystyczna analiza wplywu czynników meteorologicznych na zapadalnosc na kleszczowe zapalenie mózgu w Bialymstoku.

The paper describes estimating the tick-born encephalitis incidence rate by meteorological data using linear regression method. The study shows 2 models of TBE incidence. First one describes general dependency between temperatures and TBE incidence (1972-2004). The second one (1994-2004) tries to find out more specific characteristics.

[Serum concentration of selected adhesive molecules in early localised and late disseminated Lyme borreliosis]. / Stezenia rozpuszczalnych form wybranych czasteczek adhezyjnych we wczesnej zlokalizowanej oraz póznej rozsianej boreliozie z Lyme.

Serum concentration of soluble form ICAM-1, PECAM-1, VAP-1, E-selectin, VCAM-1 in 20 patients with Erythema migrans and 20 patients with Lyme arthritis before and after 4-weeks antibiotic treatment were estimated. Comparing group consited 8 healthy volunteers. Concentrations of soluble molecules were performed with ELISA kits(Bender MedSystem, Austria). Results of the study indicate involvment of soluble form ICAM-1, PECAM-1, VAP-1, E-selectin and VCAM-1 in immunopathogenesis of Lyme borreliosis, and different engagement of molecules in depend on stage of disease. In early localized stage of disease, results suggest participation molecules engaged in all stages of "adhesion cascade" whilst in disseminated, late stage of Lyme borreliosis molecules of tight adhesion. The measurement of soluble form od aadhesion molecules can be useful of in differentiation of localized and disseminated late stages of Lyme borreliosis helpful in clinical diagnosis.