[Selected proteins as biomarkers of kidney injury used in the nephrological diagnosis]. / Wybrane bialka jako biomarkery uszkodzenia nerek wykorzystywane w diagnostyce nefrologicznej.

Acute kidney injury (AKI) is an important clinical entity, developing in hospitalized patients due to rapid deterioration of the kidney function, while chronic, progressive glomerulopathies, tubulointerstitial damage, recurrent pyelonephritis, long-lasting nephrolithiasis or systemic diseases affecting kidneys (hypertension, diabetes), result in chronic kidney disease (CKD) development. Early AKI detection enables the implementation of appropriate therapy, which in some cases prevents the irreversible complications, leading to patient's death. Similarly, the correct biochemical assessment allows for monitoring CKD course, which reduces the risk of chronic complications and the development of symptomatic, chronic kidney failure. Therefore, novel laboratory parameters are still sought, endowed with the high sensitivity and specificity, which allow for the reliable AKI diagnosis or estimation of the CKD advancement. The paper focuses on discussing the role of the four proteins: cystatin C, neutrophil gelatinase-associated lipocalin-1 (NGAL), kidney injury molecule-1 (KIM-1) and αKlotho as novel biomarkers in AKI/CKD diagnosis.

Experimental gender related obesity effect of diet.

INTRODUCTION: High-calorie diet is responsible for excessive weight gain. Obesity has recently become world epidemics, affecting not only adults but also children, which makes it the biggest health problem in the world. Yet the underlying mechanism remains a matter of debate. OBJECTIVES: The aim of this study is to clarify the role of gender in high fat diet induced obesity in pups and adult animals. MATERIALS AND METHODS: Female rats were fed low/ high fat diet during mating, pregnancy and lactation. The offspring and adult rats fed different diet had their body weight and temperature measurements taken twice a week. On the 21st day of the experiment the animals underwent anesthesia in order to have their blood samples collected for lipid profile. RESULTS: After 3 weeks on HF diet female pups body weight was higher than in control group (p 〈0.05). Contrary to the female pups, the increase in body weight was higher (p 〈0.05) in male pups and occurred after 2 and 3 weeks. In adult female rats body weight increased after 2 weeks on HF, while in adult male group such weight gain was observed no sooner than after 3 weeks. A er three weeks of the experiment body weight was correlated positively (r = 0.941) with lipid profile of adult both gender groups on HF diet. CONCLUSIONS: In male pups group body weight increased faster and achieved higher values then in female pups. On the contrary, in adult group of females body weight increased faster than in male rats and achieved similar values.

Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field.

Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers. The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis. The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation. A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL. The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs.

The role of prostanoids in the urinary bladder function and a potential use of prostanoid-targeting pharmacological agents in bladder overactivity treatment.

Overactive bladder (OAB) is a syndrome involving urinary urgency with accompanying increased daytime urinary frequency and nocturia, with or without urgency urinary incontinence, in the absence of an urinary tract infection or other obvious pathology. The detailed OAB pathophysiology remains unclear. There is evidence that OAB pathogenesis also includes abnormal bladder paracrine activity, associated with release of local prostanoids. Those agents contribute to disturbances of peripheral neuronal bladder control resulting in detrusor instability. Thus, pharmacological agents abolishing prostanoid-induced bladder overactivity seem to be a potential, future OAB therapeutical option. This paper shortly describes the rationale for nonsteroidal antiinflammatory drugs (NSAIDs) and EP-1 receptor antagonists administration in future OAB pharmacotherapy.

Spectral heart rate variability in rats with cyclophosphamide-induced hemorrhagic cystitis treated with cyclooxygenase inhibitors.

The pathogenesis of cyclophosphamide-induced hemorrhagic cystitis (CP-HC) is complex, involving the im- pact of many systemically and locally released agents on autonomic nervous system (ANS) activity, that affects bladder functioning. The purpose of our study was to provide an indirect evaluation of ANS functional status in experimental CP-HC model, involving prostaglandin synthesis block resulting from administration of cyclooxygenase inhibitors. The ANS activity was estimated through the spectral analysis of heart rate variability (HRV) in CP-HC rats divided into three study groups: 1-control, 2-treated with meloxicam (MLX) that preferentially blocks COX-2, and 3-treated with piroxicam (PRX) that inhibits COX1 and 2 activity. In animals treated either with MLX or PRX, the percent distribution of the spectrum in relation to components of very low (VLF) and low (LF) frequency was not different from the control group. PRX-treated group displayed nearly two times lower percent share of the high frequency (HF) component compared to the control. Moreover, an increase of the normalized LF (nLF) value with simultaneous reduction of the normalized HF (nHF) value were noted in PRX-treated rat with no change of these parameters for MLX-treated rats. The HRV analysis in CP-HC rats receiving PRX, indicated a functional reorganization manifested by reduced parasym- pathetic activity and increased sympathetic tonus. A partial prostaglandin synthesis block caused by COX-2 inhibitor (meloxicam) caused no significant changes of evaluated HRV parameters compared to the control. Assessing functional changes of the ANS caused by prostaglandin synthesis block it should be stated that prostaglandins synthesized by the constitutive COX-1 isoform seem to maintain the parasympathetic activity, which may be associated with the cholinergic anti-inflammatory pathway and resolution of inflammation in course of cyclophosphamide-induced cystitis.

Electromagnetic field induced biological effects in humans.

Exposure to artificial radio frequency electromagnetic fields (EMFs) has increased significantly in recent decades. Therefore, there is a growing scientific and social interest in its influence on health, even upon exposure significantly below the applicable standards. The intensity of electromagnetic radiation in human environment is increasing and currently reaches astronomical levels that had never before experienced on our planet. The most influential process of EMF impact on living organisms, is its direct tissue penetration. The current established standards of exposure to EMFs in Poland and in the rest of the world are based on the thermal effect. It is well known that weak EMF could cause all sorts of dramatic non-thermal effects in body cells, tissues and organs. The observed symptoms are hardly to assign to other environmental factors occurring simultaneously in the human environment. Although, there are still ongoing discussions on non-thermal effects of EMF influence, on May 31, 2011--International Agency for Research on Cancer (IARC)--Agenda of World Health Organization (WHO) has classified radio electromagnetic fields, to a category 2B as potentially carcinogenic. Electromagnetic fields can be dangerous not only because of the risk of cancer, but also other health problems, including electromagnetic hypersensitivity (EHS). Electromagnetic hypersensitivity (EHS) is a phenomenon characterized by the appearance of symptoms after exposure of people to electromagnetic fields, generated by EHS is characterized as a syndrome with a broad spectrum of non-specific multiple organ symptoms including both acute and chronic inflammatory processes located mainly in the skin and nervous systems, as well as in respiratory, cardiovascular systems, and musculoskeletal system. WHO does not consider the EHS as a disease-- defined on the basis of medical diagnosis and symptoms associated with any known syndrome. The symptoms may be associated with a single source of EMF or be derived from a combination of many sources. Reported symptoms associated with electromagnetic fields are characterized by the overlapping effect with other individuals with these symptoms exhibited a broad spectrum of clinical manifestations, related to exposure to a single or multiple sources of EMF. The phenomenon of electromagnetic hypersensitivity in the form of dermatological disease is associated with mastocytosis. The biopsies taken from skin lesions of patients with EHS indicated on infiltration of the skin layers of the epidermis with mastocytes and their degranulation, as well as on release anaphylactic reaction mediators such as histamine, chymase and tryptase. The number of people suffering from EHS in the world is growing describing themselves as severely dysfunctional, showing multi organ non-specific symptoms upon exposure to low doses of electromagnetic radiation, often associated with hypersensitivity to many chemical agents (Multiple Chemical Sensitivity-MCS) and/or other environmental intolerances (Sensitivity Related Illness-SRI).

Indirect autonomic nervous system activity assessment with heart rate variability in rats with cyclophosphamide-induced hemorrhagic cystitis treated with melatonin or agomelatine.

AIM OF THE STUDY: Melatonin (MLT) is reported to exert uroprotective effect due to its antioxidant/anti-inflammatory properties. It is unknown whether that effect also results from melatonin receptor activation, or it is attributed to the modulation of the autonomic nervous system (ANS) activity. Our purpose was to evaluate the effect of MLT and agomelatine (AMT) - melatonin receptor agonist on ANS activity, indirectly assessed by heart rate variability (HRV), in rats with cyclophosphamide-induced hemorrhagic cystitis (CP-HC). MATERIAL AND METHODS: CP-HC was induced in all rats by four doses of cyclophosphamide given intraperitoneally (i.p.) at the dose of 75 mg/kg/dose. Rats were divided on three experimental groups and during induction of cystitis were treated i.p. with: (1) saline (control group); (2A/2B) MTL given at the dose of 40 or 100 mg/kg/dose; (3A/3B) AMT given at the dose of 40 or 100 mg/kg/dose. HRV recordings were performed in anesthetized rats at the eight day of the study. RESULTS: Both 2A and 2B animals were characterized by an increase in all non-normalized components in HRV spectrum. Furthermore, normalized LF (nLF) increase along with normalized HF (nHF) decrease were demonstrated in 2B rats. AMT treatment resulted only in an increase in total power (TP) and very low frequency (VLF) in 3A animals. CONCLUSIONS: CP-HC rats treated with MLT were characterized by global ANS activity elevation, with a marked sympathetic tone predominance in subgroup 2B. Since the AMT treatment had no effect on autonomic function, it seems that melatonin modulates autonomic activity via non-receptor mechanisms.

Urine uromodulin estimation in partial bladder outlet obstruction and cyclophosphamide-induced haemorrhagic cystitis models in rats.

INTRODUCTION: Uromodulin (UMOD) is a glycoprotein excreted by the thick ascending limb of the Henle's loop and distal convoluted tubule cells, playing various, yet still unclear roles. An abnormal urinary UMOD excretion is observed in many pathophysiological conditions. The aim of our study was to assess urine UMOD excretion in experimental partial bladder outlet obstruction (PBOO), reflecting BPH in humans, and in cyclophosphamide-induced haemorrhagic cystitis (CP-HC). MATERIALS AND METHODS: PBOO and CP-HC rats and two appropriate control groups were studied. The PBOO model was surgically induced by partial proximal urethral obstruction and CP-HC by four i.p. cyclophosphamide administrations (every two days). 24-hour urine collections were performed in both PBOO (on 3rd, 7th, 12th and 15th day after surgery) and CP-HC rats (on 1st, 3rd, 5th and 7th day). UMOD was determined with the ELISA method. Both 24-hour urinary UMOD excretion and urinary UMOD concentrations were determined. RESULTS: In the overall assessment, PBOO rats were characterized by decreased mean urinary UMOD concentration. However, as the urine volume, except for transient drop on 3rd day following PBOO operation, was steadily increasing, the daily urinary uromodulin excretion did not differ from the control one. Contrary to PBOO, CP-HC rats demonstrated mean urinary concentration similar to that of the control rats, while their 24hr UMOD excretion in urine was almost doubled due to urine volume increase (from 1.6 up to almost 3 fold). The highest UMOD urinary output was observed after the 3rd and 4th doses of cyclophosphamide. DISCUSSION: A reduced urinary UMOD excretion in early PBOO phase may be considered as a marker of distal tubular cells damage due to incomplete bladder emptying and increased pressure retrograding to distal tubules. This effect disappears with structural, adaptive histological changes of the bladder wall leading to an improved voiding. In CP-HC animals, the elevated urinary UMOD level may be associated with complex inflammatory response due to the cytotoxic CP action. UMOD assessment in this model may reflect renal and urological toxicity as UMOD excretion rises with the cumulative cyclophosphamide dose.

The influence of piroxicam, a non-selective cyclooxygenase inhibitor, on autonomic nervous system activity in experimental cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction in rats.

Signs and symptoms of secondary overactive bladder (OAB) are observed both in course of infravesical obstruction of urine outflow in patients with benign prostatic hyperplasia, and as a result of development of hemorrhagic cystitis (HC) following administration of cyclophosphamide (CP). Non-steroidal antiinflammatory drugs (NSAIDs) alleviate symptoms of bladder overactivity reducing local synthesis of prostaglandins (PGs), but precise effects of those agents on functions of the autonomic nervous system (ANS) in course of OAB remain unknown. The purpose of this study was to evaluate the effect of piroxicam-induced prostaglandins (PGs) synthesis block on activity of the ANS in two experimental models of secondary OAB: bladder outlet obstruction (BOO) and cyclophosphamide-induced HC (CP-HC), by heart rate variability analysis (HRV). The experiment was performed on a group of rats with surgically induced 2-week BOO, and on a group of rats that were administered CP five times, with corresponding control groups. Study animals were given piroxicam (PRX) i.p. in two doses: 2 and 10 mg/kg b.w. In the BOO model, PRX in both doses revealed a trend for reduction of value of all non-normalized components of HRV. The lower PRX dose caused an increased nHF value, and PRX administered in the dose of 10 mg/kg b.w. caused an increase of the nLF value. In the CP-HC model, the lower PRX dose caused a trend for an increase of values of all non-normalized components, and the higher dose--for their decrease. Both doses of PRX in that model caused increase of the nLF value. Inhibition of PGs synthesis caused changes of ANS function in both models of OAB. Both in BOO and in CP-HC, PGs seem to be ANS-activating factors, responsible for maintenance of a high parasympathetic activity. In both models, inhibition of PGs synthesis with PRX administered at the dose of 10 mg/kg b.w. lead to functional reconstruction of ANS, with marked sympathetic predominance. That may contribute to reduction of the bladder contractile action and improvement of its compliance in the filling period, which was demonstrated by other authors in urodynamic tests for NSAIDs.

The influence of prostaglandin PGE1 and PGF2alpha analogues on autonomic nervous system activity, estimated with heart rate variability, in cyclophosphamide-induced hemorrhagic cystitis in rats.

UNLABELLED: The cyclophosphamide-induced hemorrhagic cystitis (CP-HC) is a common consequence of cyclophosphamide treatment with complex pathophysiology involving several inflammatory mechanisms and autonomic nervous system dysregulation. THE AIM OF THIS STUDY: To determine effects of prostaglandin PGE1 and PGF2alpha analogues on the activity of the autonomic nervous system (ANS), estimatedindirectly on the basis of heart rate variability (HRV), in an experimental model of cyclophosphamide-induced hemorrhagic cystitis (CP-HC). Moreover we verified if potential changes in autonomic regulation can contribute to uroprotective role of prostaglandins. MATERIAL AND METHODS: The study included three groups of rats with experimentally induced CP-HC. The animals from group 2 and 3 were administered PGE1 and PGF2a analogues, respectively, and the rats from group 1 (controls) did not receive any treatment. The HRV of animals from all the groups was analyzed after seven days of the experiment. RESULTS: Administration of both PGF2alpha and PGE1 was associated with an increase in the power of VLF component and total power on frequency-domain analysis. Moreover, a significant increase in the power of non-normalized components, LH and HF, and two parameters of time-domain analysis, SDN-N and rMSSD, was documented in PGF2alpha-administered animals. Both prostaglandin-treated groups did not differ significantly from the controls in terms of the values of normalized parameters, nLF and nHF. CONCLUSIONS: The analyzed prostaglandin analogues increased total autonomic activity but did not induced preferential changes in sympathetic or parasympathetic activity. Nevertheless, the VLF changes documented on HRV analysis may reflect a decrease in the level of certain pro-inflammatory mediators, thus pointing to, previously postulated in literature, potential beneficial uroprotective effect of prostaglandins in CP-HC.

[Neural control disturbances of the gastrointestinal tract and visceral pain in inflammatory bowel diseases]. / Zaburzenia kontroli nerwowej przewodu pokarmowego i ból trzewny w nieswoistych chorobach zapalnych jelits.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition, the etiology of which is composed of factors such as the environment, genetic predisposition, gut dysbiosis and inadequate immune response. The pathologic findings in Crohn's disease and ulcerative colitis are related to dysfunction of gastrointestinal secretion and motility and also disturbed visceral sensory function, with accompanying intestinal and parenteral complications. The systemic inflammatory response affects neurological control via the gut-brain axis, which modulates the cooperation of the autonomic nervous system (ANS), enteric nervous system (ENS) and gut-associated lymphoid tissue (GALT). In chronic inflammation the intestinal neuropathy disrupts peristalsis and intestinal secretion as well as causing unpleasant symptoms of the patients. Pain receptors are stimulated by inflammatory mediators, and due to the intensified activation of the nociceptive system visceral hypersensitivity through central and peripheral sensitization is generated. Chronic visceral pain negatively influences the course of disease and the quality of the patient's life. The growing knowledge about the neurological control dysfunction of the intestine and immune system dysregulation could provide proper directives for treatment of inflammatory bowel diseases.

Autonomic nervous system activity assessment by heart rate variability in experimental bladder outlet obstruction.

A syndrome with urgency, with or without associated urine incontinence and usually accompanied by higher urinary frequency and nocturia has been named "overactive bladder; OAB". OAB is an entity with complex pathophysiology, involving both myogenic and neurogenic (afferent / efferent bladder innervation) disturbances. OAB symptoms accompany benign prostatic hypertrophy--BPH ("obstructive OAB"). The aim of the study was to estimate the autonomic nervous system activity (ANS) in the experimental bladder outlet obstruction (BOO) which was an animal model of the human BPH. The study was conducted using 30 female rats, divided into two groups: BOO animals (n=15), with surgically induced BOO (by partial ligation of the proximal urethra) and control ones (n=15), which underwent sham procedure (without urethral ligation). Two weeks after the surgery, in both groups, ANS activity was estimated using time- and spectral analysis of the heart rate variability recordings. The bladder overactivity in BOO animals was confirmed using urodynamic recordings and bladder histological assessment, juxtaposed against the results of the control group. The key finding of our study was the development of autonomic disturbances in bladder outlet obstruction (BOO) rats. Our study revealed that BOO animals were characterised by diminished rMSSD and spectral HRV parameters: TP, LF and HF, in comparison with the control group. The normalised nLF and nHF parameters did not differ significantly in both groups, although slight changes in the nLF (increased) and nHF (decreased) were noted in BOO group. The absolute VLF value was almost the same in both studied populations, however, the percentage part of this component in the appropriate HRV spectrum differed considerably in both studied groups. In BOO animals, VLF percentage amounted to about 90%, whereas in control animals this parameter reached only about 53% of the total power spectrum. Thus, to sum up, our findings suggest autonomic imbalance with decreased global autonomic tension and diminished parasympathetic activity with relatively sympathetic overactivity.

Heart rate variability after BRL37344, a beta-3 agonist, in experimental bladder outlet obstruction.

INTRODUCTION: Bladder overactivity symptoms accompany benign prostatic hyperplasia (BPH) syndrome. The autonomic nervous system (ANS) disturbances may be involved in bladder dysfunction. An ameliorating effect on bladder overactivity is being assigned to the currently investigated ß-3 adrenoreceptor agonists. However, little is known about the influence of ß-3 agonists on ANS activity. The aim of our study was to estimate ANS activity using heart rate variability (HRV) in experimental model of bladder outlet obstruction (BOO), reflecting human BPH. MATERIAL/METHODS: 30 female rats, divided into control, non-treated BOO (LLBOO), and ß-3 agonist (BRL37344) BOO treated (LLBOO+ß3 agonist) were studied. BOO was evoked by 5-week long partial proximal urethra ligation. Next, 20-minute resting HRV recordings were performed in each of the studied groups following i.p. administration of the vehicle (LLBOO) or BRL37344 (LLBOO+ß3 agonist). RESULTS: LLBOO rats were characterized by diminished NN range, SDNN, and rMSSD in time-domain analysis. Similarly, TP and non-normalized spectral HRV parameters were also decreased. Contrary to these findings, normalized spectral parameters were lower (nLF) and higher (nHF). The animals treated with BRL37344 demonstrated no significant differences in time--domain HRV parameters. In spectral analysis, a decrease in LF and HF, together with a fall in TP, was found. Moreover, both nLF and nHF reached almost the same values in control and ß-3 agonist treated rats. DISSCUSSION: Our data indicates that BRL37344 is an agent abolishing the autonomic imbalance in experimental BOO, which may contribute to relieving the symptoms of bladder overactivity in ß-3 agonists treated participants.

The influence of oxazaphosphorines alkylating agents on autonomic nervous system activity in rat experimental cystitis model.

The oxazaphosphorines alkylating agents (cyclophosphamide; CP and ifosfamide; IF) are often used in common clinical practice. However, treatment with CP/IF is burdened with the risk of many adverse drug reactions, especially including hemorrhagic cystitis (HC) that is associated with bladder overactivity symptoms (OAB). The HC pathophysiology is still not fully displayed; it seems that autonomic nervous system (ANS) functional abnormalities play important role in this disturbance. The aim of our study was to reveal the potential ANS differences in rat experimental HC model, evoked by CP and IF by an indirect ANS assessment--heart rate variability (HRV) study. We carried out our experimental research in three essential groups: control group (group 1), cyclophosphamide-induced HC (CP-HC; group 2) one and ifosfamide-induced HC (IF-HC; group 3) one. CP was i.p. administrated four times in dose of 75 mg/kg body weight while IF-treated rats received i.p. five drug doses; 50 mg/kg body weight. Control rats were administrated i.p. vehicle in appropriate volumes as CP/IF treated animals. HRV studies were performed the next day after the last oxazaphosphorines dose. Standard time- and spectral (frequency) domain parameters were estimated. We confirmed the HC development after both CP/IF in macroscopic assessment and bladder wet weight measurement; however, it was more aggravated in CP-HC group. Moreover, we demonstrated HRV disturbances, suggesting ANS impairment after both studied oxazaphosphorines, however, consistent with the findings mentioned above, the autonomic dysfunction was more emphasized after CP. CP treatment was also associated with changes of non-normalized HRV spectral components percentage distribution--a marked very low frequency--VLF [%] increase together with low frequency--LF [%] and high frequency--HF [%] decrease were observed. Taking into consideration the next findings, demonstrating the lack of both normalized power spectral components (nLF and nHF) values, the VLF percentage change seems to be of special meaning. IF produced smaller autonomic disturbances, and gentler bladders histological abnormalities comparing to CP. However, similar to CP, VLF [%] relative augmentation together with LF [%] and HF [%] drop accompanied the global ANS activity decrease. Additionally, in the case of IF treatment, a slight trend of nLF increase with nHF decrease was noted, suggesting the possible functional rearrangement between sympathetic (nLF) and parasympathetic (nHF) tension. It seems possible that the vagal withdrawal and--as a consequence--sympathetic overactivity, reflected by VLF [%] enlargement and HF and LF [%] diminishing (as well as LF and HF values decrease), may be an evidence of impaired anti-inflammatory cholinergic pathway, aggravating bladder inflammatory lesions. To sum up, our study showed ANS impairment in both CP- and IF-evoked experimental HC that was reflected in HRV recordings. HRV study, thus, may be considered to be a diagnostic tool for CP/IF treated patients, estimating autonomic abnormalities, associated with the HC development risk and its clinical course.

The changes of heart rate variability in response to deep breathing in professional swimmers.

INTRODUCTION: The analysis of heart rate variability (HRV) is a useful tool for the evaluation of adaptation processes of autonomic nervous system (ANS) to physical exercise. The deep breathing test (DB) induces the increased activity of the parasympathetic component of ANS. The aim of the study was to evaluate the influence of DB on ANS activity in professional swimmers and non-trained persons. METHODS: The study included 10 healthy swimmers (5 women and 5 men, mean age 21 ± 2 yrs) in the transitory phase of their training cycle, and a control group comprising 31 healthy volunteers. The evaluation of ANS activity was based on the time and frequency domain indices of HRV determined at rest and during DB. RESULTS: Compared to the controls, swimmers were characterized by significantly higher values of the following HRV indices determined at rest: mRR (902.9 ± 102.5 ms vs. 744 ± 67.5 ms, p <0.05), rMSSD (71.4 ± 46.9 ms vs. 41.3 ± 20.7 ms, p <0.05), pNN50 (28.3 ± 17.4% vs.14 ± 10.7%, p <0.05), LF (603.5 ± 208.2 ms2 vs. 445.2 ± 137 ms2, p <0.03). Also during DB test, the values of the following HRV indices of the swimmers were significantly higher than in the controls: mRR (899.2 ± 69.2 ms vs. 766.4 ± 63.6 ms, p <0.05), SDNN (114.1 ± 45.1 ms vs. 79 ± 27.7 ms, p <0.05), rMSDD (81.9 ± 38.2 ms vs. 50.7 ± 27 ms, p <0.05), pNN50 (32.9 ± 14.3 % vs. 20.6 ± 14.6%, p <0.05), TP (1972.7 ± 809.5 ms2 vs. 1329.7 ± 532 ms2, p <0.05), HF (657.1 ± 330.9 ms2 vs. 405.7 ± 217 ms2, p <0.05), LF (753.3 ± 294 ms2 vs. 533 ± 213.4 ms2, p <0.05). The analysis of value relative DB-induced changes in time and frequency domain HRV indices revealed significant intergroup differences in reaction to parasympathetic stimulation. CONCLUSIONS: Based on the results presented in this study, the swimmers' response to deep breathing seems stronger than in persons without professional training. The deep breathing test may be a useful tool to evaluate the dynamic changes in the parasympathetic activity of ANS of sportspersons.

The integrative function of vagal nerves in urinary bladder activity in rats with and without intravesical noxious stimulation.

INTRODUCTION & OBJECTIVES: There is no evidence that vagal nerve innervate the urinary bladder. The aim of the study was to evaluate the effect of left vagal nerve dissection (LVND) on urinary bladder activity in normal rats and after intravesical noxious stimulation (INS). MATERIAL & METHODS: Experiment was performed on 30 rats. All animals were divided into 4 groups--I: control rats (n = 12), II: rats after LVND without (INS) (n = 6), III: rats after INS without LVND (n = 6), IV: rats after LVND with INS (n = 6). Cystometry was performed under urethane anaesthesia. The INS was induced by continuously infusion of hypertonic saline (2080 mOsm/l) at a rate of 0.046 ml/min. RESULTS: LVND induced an increase of basal-BP (+92%), threshold-TP (+21%), and maximal voiding pressure-MVP (+28%), as well as intercontraction intervals-ICI (+84%), functional bladder capacity-fBC (+87%), and compliance (+81%). INS induced detrusor overactivity (DO) characterised by a decrease of ICI (-51%) and fBC (-50%), and also an increase of BP (+118%), detrusor overactivity index-DOI (+413%) and motility index-MI (+33%). LVND diminished the severity of DO characterised by an increase of ICI (+86%), fBC (+84%), compliance (+62%), as well as a decrease of DOI (-50%) and MI (-18%). CONCLUSIONS: The modulation of vagal nerve activity affect the urinary bladder function in naive conditions, as well as in case of INS (hyperosmolar). These data implies the integrative action of visceral vagal nerve innervation in urinary bladder function. However, further evaluations are strongly required in order to understand this action in various conditions.

Effects of vagus nerve stimulation in visceral pain model.

Visceral pain is an important therapeutic problem. A number of studies have established that abdominal vagal afferents modulate somatic pain behavior. Although it is not clear if vagal afferents transmit nociceptive information, a change in their activity can increase or decrease nociceptive transmission in visceral pain. Aims of the present study were to determine whether the subdiaphragmatic vagus nerves play a role in the endogenous pain inhibitory mechanisms in visceral pain model and whether it involves opioidergic pathways. Data obtained in our studies show that vagus nerve plays the direct role in conveying the nociceptive information in the peritonitis model of visceral pain. We have shown, that vagal afferents exhibit an increase in excitability and subdiaphragmatic vagotomy decrease nociceptive behavior in visceral pain in rats. We have also tested two different stimulation parameters of chronic subdiaphragmatic vagal nerve stimulation: VNS1 (high-intensity) and VNS2 (low-intensity) in visceral pain model in rats. Both stimulation parameters increased pain threshold but VNS1 was more effective than VNS2. Naloxone inhibited the antinociceptive effects of VNS, reversing partially increase in the pain threshold in rats and increases number of writhes in visceral pain model. Therefore, our data indicate that this analgesic effect of the VNS is mediated, at least in part, by descending opioidergic pathways. The present study has confirmed the importance of vagal afferents for nociception in general and proven that this role is not limited to somatic pain but also extends to visceral pain.

Pentoxifylline modifies central and peripheral vagal mechanism in acute and chronic pain models.

The inflammatory process gives the way to hyperalgesia that is documented by the animal experimental studies. Pentoxifylline (PTX) has strong antyinflamatory effects, decreases TNF-alpha and other proinflammatory cytokines production. Therefore, the aim of present investigation was to evaluate the effectiveness of PTX in nociception processes, especially in aspects of vagal activity, in experimental pain models: visceral pain (VP), neuropathy (CCI) and neurogenic inflammation (NI). In VP and CCI models we observed significant increase in the pain threshold after blocking proinflammatory cytokines whereas in NI there was no such effect. In our studies we also observed the increase of vagal afferents activity in VP and CCI, on the contrary to NI model. In summary, our study demonstrates that preemptive inhibition of proinflammatory cytokine synthesis by treatment with PTX is useful in antagonizing hyperalgesia in inflammatory pain. Pentoxifylline reduces central and peripheral sensitization processes depend on the vagal component in both acute and chronic pain models but in a different manner and mechanisms. Our results establish the participation of inflammatory and vagal component in nociception. The modulation of the vagal system offers the new possibilities of the pain treatment in patients resistant to the classical analgesic therapy.

Gastric dysfunction in dialysed patients with chronic renal failure.

BACKGROUND: Gastric motor functions are disturbed in patients with chronic renal failure (CRF). The aim of this study was to find the relationship between GI symptoms, gastric myoelectrical activity and regulatory peptides (gastrin, motilin, VIP, CCK) in patients with CRF treated with hemodialyses (HD) and peritoneal dialyses (CAPD). METHODS: Gastric myoelectric activity was evaluated with cutaneously recorded electrogastrographs (EGGs) measurement in: group A: 23 pts with CRF treated with CAPD, group B: 21 pts treated with HD and group C: 48 matched healthy controls. GI symptoms severity was quantified with specially designed questionnaire. The laboratory evaluation of plasma parameters, such as: gastrin, motilin, VIP and CCK was performed. RESULTS: The patients with CRF treated with CAPD and HD showed a significantly lower percentage of normal 2-4 cpm wave's rhythm in both fasting (65.3 +/- 29.3% vs 43.5 +/- 35.9% vs 86.4 +/- 10.2%) and fed conditions (72.7 +/- 34.2% vs 69.5 +/- 22.1% vs 89.3 +/- 9.5%) in comparison to controls. In the fasting state, none of the healthy controls had an abnormal EGG, whereas the 27 patients with CRF (61.3%) had an abnormal EGG. In the fed state the 18 patients with CRF (40.9%). No significant increase of the dominant power (PDP) after meal in CRF patients was observed. The plasma concentrations of gastrin, CCK were increased in fasted and fed CRF patients, whereas VIP and motilin only in fed state. CONCLUSIONS: The patients with CRF showed impaired gastric myoelectrical activity in response to food and high levels of GI hormones. Gastric dysmotility and high peptides appears to be partially responsible for GI symptoms.

Laboratory diagnostics of renal function in an experimental model of ascending pyelonephritis with high-virulent Escherichia coli.

INTRODUCTION: Urinary tract infections (UTI) are caused in 95% of cases by bacteria--E. coli. UTIs usually are limited to the lower urinary tract, but it may also evolve into pyelonephritis and acute kidney injury. OBJECTIVES: The aim of this study was the laboratory evaluation of renal function in an experimental model of ascending pyelonephritis caused by intravesical infusion of E. coli. MATERIAL & METHODS: In female Wistar rats UTI was induced by intravesical administration of E. coli suspension in a dose 10(5) c.f.u./ml (Group 1), and 10(7) c.f.u./ml (Group 2). On the 0,7th, 14th and 21st day of the experiment the animals underwent the procedures of collecting blood and urine samples. RESULTS: The results shown that in group 2 on the 7th and 14th day of the study the creatinine clearance decreased by 36%, and on 21th by 34%. The increase in serum uric acid concentration (micromol/l) in group 2 was observed on the 7th (229.75 +/- 79.05) and 21st day (98.5 +/- 11.33) with respect to day 0 (77.12 +/- 11.63). In group 2 on the 7th day of the experiment there was observed the increased levels of potassium (mmol/l) in serum (13.5 +/- 1.48) with respect to day 0 (7.74 +/- 0.88). In group 2 in the 7th (1.06 +/- 0.18) and 14th day (1.32 +/- 0.26) there was noted the decreased excretion of potassium in the urine (mmol/24h) with respect to day 0 (3.75 +/- 1.9). The decrease in serum sodium levels (mmol/l) in group 2 was recorded on 14th day (121.5 +/- 8.7) with respect to day 0 (131.62 +/- 4.07). Increased factional sodium excretion--FENa (%) was observed in group 2 on 14th day (0.25 +/- 0.06) with respect to day 0 (0.12 +/- 0.06). CONCLUSIONS: Our main finding is that--independently of the amount bacteria present in urinary bladder--in this inflammatory model there occurs inevitably acute kidney injury, however higher bacteria amount depicts a very clear profile of laboratory parameters that point at the kidney impaired function.