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Anna Tomusiak-Plebanek,1 Piotr Heczko,1 Beata Skowron,2 Agnieszka Baranowska,2 Krzysztof Okoń,3 Piotr J Thor,2 Magdalena Strus1 1Department of Microbiology, Jagiellonian University Medical College, Poland; 2Department of Pathophysiology, Jagiellonian University Medical College, Poland; 3Department of Pathomorphology, Jagiellonian University Medical College, Poland Purpose: Some lactobacilli, which possess superoxide dismutase-like activity and catalase activity naturally, have strong antioxidative properties. The aim of this study was to identify such strains and check which of them play a crucial role in alleviating intestinal inflammation. Methods: We selected two Lactobacillus strains for use in animal studies: L. plantarum 30B (which has the highest catalase activity) and L. acidophilus 900 (which has the highest dismutase-like activity). Forty mice (C57B1/6J) were divided into four experimental groups with ten mice in each group. Group I (control group) was not supplemented with Lactobacillus, group II (catalase group) was orally supplemented with L. plantarum 30B, group III (dismutase-like group) was supplemented with L. acidophilus 900, and group IV (mixed group) was supplemented with both Lactobacillus strains. For 23 days, the temperature and body mass of each mouse were recorded and fecal samples for microbiological examination were collected. On day 23, the animals were sacrificed, and their intestines were removed for microbiological and histopathological studies. Results: Compared to the control group, the highest drop in the body temperature was observed in groups II (P

The administration of cyclophosphamide (CP) is associated with the risk of developing cystitis as well as kidney injury. The aim of the study was to verify the uroprotective effect of N-acetylcysteine (NAC), as well as the evaluation of renal function in the experimental model of acute CP-induced cystitis. Rats from group 1 received intraperitoneally only a single dose of 200 mg/kg b.w. of CP. Individuals from groups 2 and 3 additionally received a single dose of 200 mg/kg b.w. of NAC, respectively, orally (p.o.) and intraperitoneally (i.p.). After the administration of the drugs, animals were subject to individual monitoring in metabolic cages to assess 24-hour diuresis and basic vital signs, and then finally sacrificed for the purpose of collecting blood and organs for histopathological analysis. Classic renal parameters (creatinine, urea, uric acid, electrolytes) as well as new markers reflecting renal function, within the filtration-resorption range - cystatin C (CysC), renal tubular integrity - kidney injury molecule-1 (KIM-1) and the condition of the glomerular filtration barrier (nephrin) were determined in the obtained serum and urine samples. In group 1 histopathological development of cystitis was confirmed with the absence of significant pathomorphological disorders of the kidneys, and the initial results of the parameters determined were obtained. In both groups 2 and 3, a decrease of inflammatory changes in urinary bladder was observed, while there were still no morphological disturbances in kidneys. The administration of NAC in both groups 2 and 3 also resulted in a decrease of concentrations in urine and a reduction in 24-hour excretion with urine of all assessed proteins (CysC, KIM-1 and nephrin). NAC, thus exhibited a uroprotective effect, which was accompanied by a functional nephroprotective effect (more accentuated during intraperitoneal administration of this compound), manifested by the reduction of urinary excretion of proteins indicative of developing renal dysfunction.

Due to their paracrine action, leukotrienes released from the urothelium are involved in control of the bladder function. Anti-leukotriene agents appear to exert an ameliorating effect in bladder overactivity. It is unknown, whether their possible, modulatory impact on the autonomic nervous system (ANS) activity may also contribute to the potentially beneficial effect of those compounds. Therefore, our aim was to indirectly estimate the ANS function using the heart rate variability (HRV) study in rats with experimental partial bladder outlet obstruction (PBOO), reflecting human benign prostatic hyperplasia (BPH), treated with leukotriene receptor antagonist - montelukast (MLKT). Twenty rats with surgically induced PBOO lasting for 14 days, divided into two groups: group 1 (10 control subjects) and group 2 (10 MLKT-treated rats; 2 mg/rat/day) were subjected to HRV recordings, preceded by daily urine collection and a subsequent cystectomy with histopathological evaluation of collected bladders. Standard HRV time and spectral parameters were calculated. MLKT-treated animals demonstrated an increase in power of non-normalized LF (low frequency) and HF (high frequency) components with no change of the total HRV power. Moreover, an increase and decrease in normalized nLF and nHF, respectively, were assessed in those animals compared to the control. Additionally, a decrease in daily diuresis measurement was demonstrated in MLKT-treated animals. Montelukast treatment resulted in the functional ANS status re-arrangement, with sympathetic overdrive and parasympathetic withdrawal. Those changes may contribute to alleviation of bladder overactivity symptoms, independently on leukotriene receptors blockade.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Introduction: The Cajal-like intestitial cells (ICCs) act as a pacemaker and are responsible for generating smooth muscle activity in the gastrointestinal tract (GI). Interstitial cells that resemble ICCs in the GI have been identified in the urinary bladder., Materials and Methods: This review is based on a systemic literature research. The medline/pubmed, scopus, embase, and Web of Science databases were browsed in order to identify original and review articles, as well as editorials relating to cajal-like cells, urinary bladder, detrusor overactivity, overactive bladder, glivec, etc. The controlled vocabulary of the Medical Subject Headings (MeSH) database was used to ensure the sensitivity of the searches. 40 papers met the criteria and were used for this review., Results: Cajal cells lie in close proximity to the muscle cells, autonomic nerve endings, and urothelial cells. There is increasing evidence that ICCs play role in urinary tract dysfunction development (e.g. detrusor overactivity, primary obstructive megaureter, congenital ureteropelvic junction obstruction, etc.). ICCs may be responsible for generating electrical potentials and induction of detrusor muscle contractions. Novel pathomechanisms of detrusor overactivity development have been postulated, as follows: 1) the disturbance of spontaneous contractility caused by altered signal transduction of ICCs between nerves and detrusor muscle cells, and 2). the alteration in signal transduction between urothelium and afferent nerve endings via suburothelial ICCs. The c-kit receptor is not only a detection marker of these cells, but may also play a crucial role in the control of bladder function., Conclusions: Cajal cells in urinary bladder suggest that the c-kit receptor may provide a novel target for treating detrusor overactivity. The review presents the current knowledge of ICCs, its role in urinary bladder function, and potential novel therapeutic strategy.

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.

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 β-3 adrenoreceptor agonists. However, little is known about the influence of β-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 β-3 agonist (BRL37344) BOO treated (LLBOO+β3 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+β3 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 β-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 β-3 agonists treated participants.

Background: Overactive bladder (OAB) is a clinical entity with complex, still incompletely understood pathophysiology, involving central and peripheral autonomic nervous system (ANS) disturbances., Objectives: The aim of the study was to estimate ANS activity using spectral analysis of heart rate variability (HRV) in two experimental overactive bladder models: chemical, evoked by cyclophosphamide treatment (COAB), and obstructive, produced by proximal partial bladder outlet obstruction (OOAB)., Material and Methods: 10 COAB rats and 10 OOAB rats with appropriate control groups were studied (40 animals total were enrolled in the study). In all groups studied, resting HRV recordings were performed. Standard spectral HRV parameters were analysed. The bladder overactivity was confirmed by urodynamic recordings and histological assessment., Results: In COAB, all non-normalized spectral HRV parameters were diminished, while OOAB rats were mostly characterized by pronounced LF (Low Frequency) and HF (High Frequency) decrease. Normalized (nLF and nHF) parameters achieved similar values in both COAB and OOAB. In the analysis of percentages of the individual components in the total HRV power, the OOAB group showed almost double VLF (Very Low Frequency) percentage as compared to the control. OOAB rats also displayed the highest disproportion between VLF and both HF and LF percentages. Contrary to the OOAB, there were small differences in the percentage participation of the separate HRV components in COAB., Conclusions: For both COAB and OOAB models, the authors demonstrated a decrease in the values of spectral HRV parameters, which may reflect ANS disturbances. Moreover, in OOAB animals, apart from total HRV power reduction, exaggerated differences between VLF percentage and the remaining components were revealed. In authors' opinion, their findings concerning VLF differences may reflect increased autonomic disturbances in the OOAB model.

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.

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.

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.

Melatonin (MT) is a neurohormone synthesized and secreted by the pineal gland. MT plays an important role in the regulation of physiological and neuroendocrine functions. The purpose of this study was to assess the overall effect of melatonin on neuropathic pain, the type of melatonin receptor involved, and potential role of the opioid system and GABA(A) receptors. The experiments were conducted by using the animal neuropathic pain model (CCI). The rats with CCI showed the characteristic for the mechanical allodynia and thermal hyperalgesia signs that were calculated by using the von Frey's and Hargreaves' tests. The conducted studies measured the effects of intraperitoneal administration of naloxone (opioid antagonist), prazosin (MT3 antagonist), luzindole (MT1/MT2 receptor antagonist), picrotoxin (GABA(A) antagonist) and flumazenil (benzodiazepine antagonist) on the antinociceptive effects caused by melatonin. Melatonin caused the increase in the pain threshold of the mechanical allodynia and the slight increase in the threshold of the thermal hyperalgesia. The pre-treatment with naloxone completely abolished the antinociceptive effects of melatonin in von Frey's test, but not thermal sensation in the Hargreaves's test. Prazosin did not have any effects, while administration of luzindole significantly suppressed the antinociceptive effect of melatonin. The antiallodynic effect of MT was also abolished by flumazenil and picrotoxin. Melatonin influences the mechanical allodynia but not thermal hyperalgesia via activation of opioid system and benzodiazepine-GABAergic pathway. Antinociceptive effects of melatonin are mostly related to the MT1/MT2 receptors interaction.

Current studies were aimed to elucidate influence of pulsed electromagnetic field stimulation on cell viability and apoptosis induction pathways. For the experimental model we have chosen monocytic cell line MonoMac6 and several apoptosis inducers with different mechanism of death induction like puromycin, colchicine, cyclophosphamide, minocycline and hydrogen peroxide. MonoMac6 cell line was grown at density 1x10(5) cells/well in 96-well culture plates. To induce cell death cell cultures were treated with different apoptosis inducers like puromycin, colchicine, cyclophosphamide, minocycline, hydrogen peroxide and at the same time with pulsed electromagnetic field 50 Hz, 45±5 mT (PEMF) for 4 hour per each stimulation, three times, in 24 hours intervals. Afterwards, cells were harvested for flow cytometry analysis of cell viability measured by annexin V-APC labeled and propidium iodide staining. Expression of apoptosis related genes was evaluated by semi quantitative reverse transcription (RT)-PCR assay. NuPAGE Novex Western blot analysis was carried out for apoptosis inducing factor (AIF) abundance in cytosolic and nuclear extracts of MonoMac6 cells. Puromycin, colchicine and minocycline activated cells and simultaneously treated with PEMF have shown out diminished percentage of annexinV positive (AnV+) cells comparing to controls without PEMF stimulation. MonaMac6 cells puromycin/colchicyne and PEMF treated were to a higher extent double stained (AnV+,PI+), which means increased late apoptotic as well as necrotic (PI+) cells, than non-stimulated controls. On the other hand, minocycline activated cells prior to PEMF treatment showed diminished amount of apoptotic and necrotic (annexin V, annexin V and propidium iodide, propidium iodide positive staining) cells. The opposite effect of PEMF on the percentage of annexin V positively stained cells has been achieved after treatment of MonoMac6 culture with cyclophoshamide and hydrogen peroxide. PEMF enhanced early phase of apoptosis induced by both apoptosis inducing agents. The analysis of expression of the apoptosis related genes in MonoMac6 cultures treated with puromycin and exposed to PEMF performed in reverse transcription of polymerase chain reaction (PCR) assay has shown changes in mRNA of genes engaged in intrinsic apoptotic pathway and pathway with AIF abundance. The most influenced was expression of gene belonging to pro-apoptotic family of Bcl-2 and AIF agent. Examination of immunoblots developed with anti-AIF antibody showed that cytosol content of AIF protein was diminished after puromycin and PEMF treatment of MonoMac6 cells. The obtained results indicate that PEMF affects induction of apoptosis in MonoMac6 cells stimulated to death with inducing agents to a different extent. Main finding of the current results is that, PEMF stimulation of MonoMac6 cells simultaneously treated with puromycin caused changes in the Bcl-family genes expression as well as in caspase independent pathway of apoptosis inducing factor (AIF).

The use of oxazaphosphorines (cyclophosphamide, ifosfamide) in the treatment of numerous neoplastic disorders is associated with their essential adverse effect in the form of hemorrhagic cystitis, which considerably limits the safety and efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced by toxic oxazaphosphorines metabolite - acrolein with subsequent immunocompetetive cells activation and release of many proinflammatory agents. However, there are some chemoprotectant agents which help reduce the HC exacerbation. The article briefly discuses the mechanism of action of oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development and currently accepted chemopreventive agents, applied to the objective of urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals administration as novel bladder protective compounds accompanying cyclophosphamide or ifosfamide therapy was also mentioned.

The evidence of electromagnetic therapy (EMT) efficacy in stress and/or urge urinary incontinence, as well as in detrusor overactivity is generally lacking in the literature. The potential EMT action of neuromuscular tissue depolarization has been described. Because there is no data on the influence of pulsating electromagnetic fields (PEMF) on the urothelium, we evaluated the effect of PEMF stimulation on rat urothelial cultured cells (RUCC). In our study 15 Wistar rats were used for RUCC preparation. RUCC were exposed to PEMF (50 Hz, 45±5 mT) three times for 4 hours each with 24-hour intervals. The unexposed RUCC was in the same incubator, but in a distance of 35 cm from the PEMF generator. Annexin V-APC (AnV+) labelled was used to determine the percentage of apoptotic cells and propidium iodide (PI+), as standard flow cytometric viability probe to distinguish necrotic cells from viable ones. The results are presented in percentage values. The flow cytometric analysis was carried out on a FACS calibur flow cytometer using Cell-Quest software. In PEMF-unstimulated RUCC, the percentage of AnV+, PI+, and AnV+PI+ positive cells were 1.24±0.34%, 11.03±1.55%, and 12.43±1.96%, respectively. The percentages of AnV+, PI+, and AnV+PI+ positive cells obtained after PEMF stimulation were 1.45±0.16% (p=0.027), 7.03±1.76% (p<0.001), and 9.48±3.40% (p=0.003), respectively. The PEMF stimulation of RUCC induces apoptosis (increase of AnV+ cells) and inhibits necrosis (decrease of PI+ cells) of urothelial cells. This leads us to the conclusion that a low-frequency pulsating electromagnetic field stimulation induces apoptosis and diminishes necrosis of rat urothelial cells in culture.

Background: Numerous studies are ungoing to develop a substitute for the native urinary bladder wall. The principals of tissue engineering approaches to urinary bladder wall augmentation require a favorable environment for smooth muscle regeneration, which is crucial for bladder function. This study was performed to evaluate bone marrow mesenchymal stem cells (BMSC) seeded on to amniotic membranes fixed to Tachosil sponges as grafts for urinary bladder muscle layer augmentation in a syngenic rat model., Materials and Methods: Amniotic membranes seeded with BMSC and covered by Tachosil sponges were implanted as multilayer grafts into nine rats to regenerate the urinary bladder wall. The control group consisted of 12 healthy rats. Urodynamic examinations included contraction, elasticity, compliance, and urinary bladder motor activity. Hematocylin and eosin and Masson's trichrome stains were used to evaluate muscle regeneration; histological data were digitally analyzed with the ImageJ tool., Results: The area of muscle bundles ranged from 5% to 25% or 32% to 41% in control versus reconstructed bladders, respectively. Among nine animals with reconstructed urinary bladders, urodynamic evaluation revealed bladder motor hyperactivity with regular (n = 4) or irregular (n = 1) storage and voiding phases, as well as proper bladder motor activity with a large bladder capacity (n = 1). No bladder contractility was recorded in one case and large stones developed in two animals, which made functional studies impossible., Conclusions: Regenerated smooth muscle cells created an autonomic cell population that was poorly assimilated to the rest of the urinary bladder wall. The histological presence of a regenerated muscle layer did not guarantee proper urinary bladder function., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Highly concentrated urine may induce a harmful effect on the urinary bladder. Therefore, we considered osmolarity of the urine as a basic pathomechanism of mucosal damage. The influence of both cyclophosphamide (CYP) and hyperosmolar stimuli (HS) on the urothelium are not well described. The purpose was to evaluate the effect of CYP and HS on rat urothelial cultured cells (RUCC). 15 Wistar rats were used for RUCC preparation. RUCC were exposed to HS (2080 and 3222 mOsm/l NaCl) for 15 min and CYP (1 mg/ml) for 4 hrs. APC-labelled annexin V was used to quantitatively determine the percentage of apoptotic cells and propidium iodide (PI) as a standard flow cytometric viability probe to distinguish necrotic cells from viable ones. Annexin V-APC (+), annexin V-APC and PI (+), and PI (+) cells were analysed as apoptotic, dead, and necrotic cells, respectively. The results were presented in percentage values. The flow cytometric analysis was done on a FACSCalibur Flow Cytometer using Cell-Quest software. Treatment with 2080 and 3222 mOsm/l HS resulted in 23.7 ± 3.9% and 26.0 ± 1.5% apoptotic cells, respectively, 14.3 ± 1.4% and 19.4 ± 2.7% necrotic cells, respectively and 60.5 ± 1.4% and 48.6 ± 5.3% dead cells, respectively. The effect of CYP on RUCC was similar to the effect of HS. After CYP the apoptotic and necrotic cells were 23.1 ± 0.3% and 17.9 ± 7.4%, respectively. The percentage of dead cells was 57.7 ± 10.8%. CYP and HS induced apoptosis and necrosis in RUCC. 3222 mOsm/l HS had the most harmful effect based on the percentage of necrotic and apoptotic cells.

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.

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.

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.

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.

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.

Introduction: Overactive bladder (OAB) is a common disease entity with complex pathogenesis that involves neurogenic, myogenic and abnormal paracrine urothelial activity mechanisms. Our objective was to estimate bladder functioning in urodynamic studies in experimental, both acute (AOAB) and chronic (COAB) cyclophosphamide (CYP)-evoked OAB model in response to melatonin (MLT; antioxidant and MT receptor agonist) or agomelatine (AMT; MT receptor agonist and 5HT2C receptor antagonist)., Material/methods: Seven groups were studied: 1--control, 2-4--MLT treated AOAB and COAB rats, 5-7--AMT treated AOAB and COAB rats. AOAB model was evoked by single CYP administration (IP 200 mg/kg body weight), while COAB one was induced by a four-time administration of CYP (IP 75 mg/kg body weight). Each group underwent urethane anesthesia to perform urodynamic recordings in resting conditions and after administration 50 (group 2 or 5), 75 (group 3 or 6) or 100 mg/kg (group 4 or 7) of melatonin (groups 2-4) or agomelatine (groups 5-7), followed by classical urodynamic parameters assessment., Results: Neither melatonin nor agomelatine did not affect urodynamic parameters in the AOAB rats. In COAB model, after 75 and 100 mg/kg of MLT we revealed an improvement in urodynamic parameters. AMT (75 and 100 mg/kg) administration caused deterioration of urodynamic findings suggesting bladder overactivity exacerbation. DISSCUSSION: In summary, melatonin ameliorates bladder overactivity in cyclophosphamide-induced COAB. Agomelatine, contrary to melatonin, aggravates bladder dysfunction in this group. These findings suggest that the improvement in urodynamic parameters after melatonin administration may be due to its antioxidative profile and is not related to MT receptors activation. However, agomelatine's unfavorable action on the bladder, resulting in its overactivity in COAB group, may not only be the result of MT receptor activation without the concomitant antioxidative effects but may also occur secondarily to co-existing 5HT2C receptor antagonism.

Background/aims: The aim of this study was to evaluate gastric myoelectric activity and autonomic activity in patients with esophageal varices treated by an analogue of vasopressin., Methodology: Included in this study are 20 patients divided into two groups: Group A: 10 patients treated with terlipressin (the bleeding from oesophageal varices) and Group B: 10 healthy persons matched with age and gender. The studies were performed before and after intravenous administration of vasopressin (VP) analogue. In both groups the fasting plasma levels of vasopressin, adrenaline and noradrenaline were measured by immunochemistry., Results: In group A disturbances of gastric myoelectric activity with high timing of dysrhythmic pattern were observed before VP. VP administration further increased the timing of gastric dysrhythmia from 35 ± 16 to 41 ± 13%, and decreased PDF from 1.4 ± 0.6cpm to 1.19 ± 0.6cpm, PDP from 1891 ± 851μV2 to 718 ± 678μV2. VP induced an increase in SDANN, lnLF, nLF (p<0.05) as well as a decrease in SDNN, pNN50, lnHF (p<0.05). Although there was no retching or vomiting, 80% of patients presented with nausea and exhibited a significant increase in plasma levels of VP, adrenaline and noradrenaline after administration of VP analogue., Conclusions: VPinduced gastroparesis is characterized by suppressed slow wave amplitude and with increase of their frequency. The existing parasympathetic impairment and increased sympathetic drive of the autonomic system is responsible for vasopressin-induced gastric dysrrhythmia and its clinical consequences.

Overactive bladder (OAB) is a condition characterized by urgency with or without urgency incontinence (UI), usually with increased daytime frequency and nocturia, which affects even 8-14% of adult population. The gold standards of OAB treatment are antimuscarinics, although this clinical entity is often poorly controlled with these agents. Thus, a progress in OAB pharmacotherapy is expected and takes place. The purpose of this article is to short review the present management of the overactive bladder with paying special attention on development of new drugs indicated for OAB treatment.

Unlabelled: The study investigated the mechanisms through which the hyperosmolarity might induce detrusor overactivity (DO). We compared the bladder activity in response to partial and complete blockade of TRPV1-6 and TRPA1 receptors. Experiments were performed on 42 rats. DO was induced by using hyperosmolar saline. All animals were randomly divided into six groups. The measurements represent the average of five bladder micturition cycles. Hyperosmolar saline induced DO. The complete blockade of TRPV1-6 and TRPA1 prevented DO. The partial blockade of TRPV1 didn't prevented DO. In the voiding phase periodical bladder contractions complexes occurred leading to slow urine flow due to bladder distension. Ruthenium red and capsaicin resulted in complete disorganisation of detrusor muscle contractility impairing urine voiding and leading to constantly lasting urine retention in healthy rats., Conclusions: hyperosmolar-induced DO is mediated by TRPV and TRPA1 channels; the hyperosmolar stimuli of urinary bladder might be transmitted mostly via ruthenium red sensitivity pathway.

Vagus nerve as a part of brain-gut axis transmits peripheral information to the brain via vagovagal reflexes. Electric properties of the vagus are not exactly known. Analysis of electric changes in vagal nerves evoked by physiologic impulse such as stomach distention by food would facilitate applying better documented and therefore safer vagal neuromodulation. The aim of our study was analysis and interpretation of electric properties of the left vagus in vivo in fasted and satiated Wistar rats. Silver measuring electrodes connected to analog amplifier (A-M Systems 3000) were attached to the nerve in the neck region. The signal was filtered and probing by computer recording system (ADInstruments Power Lab) and additional analyses were performed using GNU Octave programme. Our resuts have shown that the higher amplitude the smaller number of counted impulses in the vagus was detected. This relationship was true only till the maximum level typical for each recording (about 15-20 dB). We note that observed inter spike interval can be approximated with log-normal distribution, and that its mu parameter is enough to characterize a particular recording. Satiated rats were characterized by higher number of spikes per second in the nerve than fasted ones (0.9 vs 0.26) indicating that food intake increased nervous activity 3-4 times comparing to fasted state. The outcomes encourage us to state that good quality characteristic of the left vagus nerve activity provides an effective tool for detection of peripheral signals which are transmitting via vagal afferents to the higher centres. Target vagal neuromodulation to obtain certain terapeutic effects may be possible.

Infertility is defined as the inability to conceive in a given pair, despite regular sexual intercourse for at least 12 months. In 2004, the World Health Organization has recognized infertility as a social disease. Nowadays, the problem of infertility, meets 1 to 6 pairs, which affects approximately 13-15% of couples the world's population. In Poland, this problem affects between 700 thousand to a million pairs. Male infertility may arise from the use of pharmacotherapy and adverse drug reactions. This publication provides an overview of the type of drugs impairing function of male genitalia and to discuss mechanisms for their action on the process of spermatogenesis.

This study was designed to investigate the effects of melatonin on the bladder hyperactivity in hyperosmolar-induced overactive bladder (OAB) rats. Additionally, the influence of melatonin on the autonomic nervous system (ANS) using heart rate variability (HRV) analysis was assessed. 40 rats were divided into four groups: I--control (n = 12), II--rats with hyperosmolar OAB (n = 6), III--rats with melatonin pretreatment and hyperosmolar OAB (n = 6) and IV--control with melatonin pretreatment (n = 6). In group III and IV melatonin in dose of 100 mg/kg was given. HRV measurements in 10 rats, as follow: control (n = 2), control after melatonin treatment (n = 2), rats with hyperosmolar OAB without (n = 3), and after (n = 3) melatonin treatment were conducted. This study demonstrates marked influence of melatonin on urinary bladder activity in hyperosmolar-induced OAB rats. These rats showed significantly reduced the detrusor motor overactivity resulting in the improvement of cystometric parameters after melatonin treatment when compared to the control, as follow: a significant increase of intercontraction interval (70%) and functional bladder capacity (67%), as well as a decrease of the basal pressure, detrusor overactivity index and motility index of 96%, 439% and 40%, respectively. ANS activity analysis revealed sympathetic overactivity in OAB rats, and parasympathetic superiority in melatonin treated OAB rats. Melatonin treatment in rats with hyperosmolar OAB (group III) caused significant increase of nuHF parameter (from 51.00 +/- 25.29 to 76.97 +/- 17.43), as well as a decrease of nuLF parameter (from 49.01 +/- 25.26 to 23.03 +/- 17.43) and LF/HF ratio (from 1.280 +/- 0.980 to 0.350 +/- 0.330). In conclusion, melatonin suppresses hyperosmolar OAB, and modulates ANS activity by inhibition of the sympathetic drive. Therefore, melatonin may become a useful agent for OAB management.

Most of the drugs in the treatment of functional disorders of the urinary bladder has a peripheral effect. Their work consists mainly in reducing detrusor contractility of the bladder, or effects on the afferent innervation. Anticholinergics are the first drugs of choice. An alternative pharmacological treatment is to eliminate the overactivity by acting on the bladder afferent innervation, while not inhibiting its contractility. One option is to modulate the pharmacological activity of sensory mechanisms governing the functioning of the bladder via the vanilloid receptor (TRPV1) and ancyrin (TRPA1). Intravesical treatment with capsaicin or lidocaine only partially reduces bladder sensation. Furthermore, clinical use of lidocaine in the treatment of overactive bladder (OAB) is reduced to intravesical supply before capsaicin instillation to reduce the symptoms associated with initial phase of C-fibres sensitization. This paper presents the current state of knowledge regarding the use of capsaicin and lidocaine in functional disorders of the urinary bladder, as well as discusses the impact of these substances on afferent C-fibres and the activity of the urinary bladder. Based on previous studies intravesical capsaicin and lidocaine therapy is one of the alternative treatment options in selected patients with functional disorders of the urinary bladder (in particular OAB) in addition to standard anticholinergics therapy or the newer generation of therapies using botulinum toxin.

Hyperosmolar factors induce the neurogenic inflammatory response, leading to bladder overactivity (OAB). The aim of the study was to compare the bladder motor activity in a hyperosmolar and acute cyclophosphamide (CYP)-induced model of OAB. Furthermore, we set our sights on defining the most physiological model of OAB in experimental practice. Forty-two female rats were divided randomly into 5 groups. All animals underwent cystometry with the usage of isotonic saline or saline of increasing concentration. Acute chemical cystitis was induced by CYP to elicit OAB. The following cystometric parameters were analyzed: basal pressure, threshold pressure, micturition voiding pressure, intercontraction interval, compliance, functional bladder capacity, motility index, and detrusor overactivity index. CYP and hypertonic saline solutions induced OAB. Having been compared with CYP OAB, none of the rats infused with hypertonic solution exhibited macroscopic signs of bladder inflammation. The comparison of CYP and hyperosmolar models of OAB revealed that the greatest similarity existed between the 2080 mOsm/L OAB model and the acute CYP-induced model. We postulate that the 2080 mOsm/L model of OAB can be established as being a less invasive and more physiological model when compared with the CYP-induced OAB model. Additionally, it may also be a more reliable experimental tool for evaluating novel therapeutics for OAB as compared with CYP-induced models.

Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

Overactive bladder (OAB) is a complex of lower urinary tract symptoms (LUTS) frequently encountered in the clinical practice. In most cases, OAB may be managed quite well by the primary care physician who has an understanding of the pathophysiology of OAB. This article reviews all pathophysiological theories describing the development of OAB. An understanding of the pathophysiology of OAB may facilitate effective treatment of this disorder.

Previous studies have suggested that, different types of unmyelinated bladder afferent C-fibres, such as capsaicin-sensitive and capsaicin-resistant mediate the voiding reflex in overactive bladder (OAB). Considering its polymodal features, we explored the urodynamic effect of primary afferent neurons modulation on detrusor activity in normal and OAB rats. Experiments were performed on 48 female rats. OAB was induced by intraperitoneal administration of cyclophosphamide. All the surgical procedures and urodynamic studies were performed under urethane anaesthesia. Cystometry was done after a 1 h recovery period from the surgical procedure. All animals were randomly divided into six groups: control, chronic OAB, chronic OAB after capsaicin or lidocaine instillation, control capsaicin or lidocaine instillation. The measurements represent the average of five bladder micturition cycles. We analyzed: basal, threshold, micturition voiding pressure; intercontraction interval; compliance; functional bladder capacity; motility index; detrusor overactivity index. We used chronic cyclophosphamide OAB model for further investigations. In healthy rats, intravesical instillation of capsaicin caused complete inhibition of detrusor contractility preventing from proper voiding function of the bladder. Contrary, lidocaine has no influence on micturition cycles in intact animals. Also, intravesical instillation of capsaicin and lidocaine reduced the severity of detrusor overactivity of OAB rats leading to improvement of cystometric parameters.

Background: The aim was to evaluate the interactions between the effects of vagal stimulation by sham feeding (nonbaroreflex) and deep breathing (baroreflex) on heart rate variability (HRV) and gastric myoelectrical activity (GMA) in pre- and postmenopausal women with essential hypertension., Material/methods: One hundred five post- and premenopausal women with hypertension and 60 premenopausal normotensive women were observed. The study protocol consisted of 5 min of resting HRV followed by 5 min of deep breathing (DB), then 6 min of sham feeding (SF) with 30-min electrogastrography (EGG) before and after SF. The fasting plasma level of noradrenalin was measured., Results: The HRV parameter values at rest in the hypertensive group were half those in the control group (p<0.05). There were notably higher HRV parameter values in the premenopausal women. Plasma noradrenalin level was higher in the postmenopausal women (p=0.0009). The effect of DB was similar before and after menopause; however, HRV parameters in response to DB were lower in the hypertensive women than in the controls (p<0.05). In the controls there was a marked increase in the main HRV parameters in response to DB. In fasting electrogastrography the lowest normogastria percentage was observed in the postmenopausal women. EGG showed that only SF significantly affected the period dominant power (PDP) in all groups and the bradygastria percentage in the postmenopausal women., Conclusions: This study suggests that the interactions that occur between the effects of non-baroreflex and baroreflex vagal stimulation in hypertensive women may contribute to gastric motility disorders and dyspeptic symptoms.

The functional gastrointestinal diseases (FGIDs) are often noticed disturbances. Functional dyspepsia (FD) is the most frequent FGID of the upper part of the gastrointestinal tract while irritable bowel syndrome (IBS) occurs in the lower gastrointestinal part. Both clinical entities are characterized by rich symptomatology and the pattern of the diagnostic guidelines. Recognition and the classification of FGIDs are difficult, consisting in exclusion of all possible organic disorders and subordinating on the predominant symptom basis to most appropriate class, acording to Rome III classification. The present FGIDs pharmacotherapy is limited mostly to the symptomatical treatment and it is based on medicines conventionally used in various gastrointestinal organic illnesses (antisecretory, gastroprotective agents, antidiarrhoeal and laxative drugs). Some of them which seem to diminish visceral hypersensitivity acting via serotonin receptors are also used, including 5-HT4 agonists and 5-HT3 antagonists. Many investigations over the new causal acting medicines last at present, which would be able to abolish the main pathophysiological FD and IBS mechanisms: visceral hypersensitivity and both myoelectrical and dysmotility phenomena. Thus, new pharmacological agents influencing opioid, purinergic, NMDA, CCK-A, or NK receptors are studied. The article is the mini-review, representing classification and the outline of the FGIDs pathogenesis, the present concepts of their pharmacological treatment and the future perspectives of pharmacoherapy with the use of new, interfering into key pathomechanisms drugs.

Many theories describe the lithogenesis within urinary tract. In addition, trace amounts of some heavy metals have been found in urinary calculi. However, their role in lithogenesis is still debated. Trace and heavy metals may be involved in induction of crystallization, depending on the relationships between metals and solutes able to crystallize in urine. Many papers have evaluated the elemental concentration of kidney stones, however there are still less data concerning the elemental composition of kidney and ureteral stones.