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Introduction Nowadays, laboratory evaluation of renal damage is based on conventional poorly-sensitive and poorly-specific markers, such as serum creatinine, urea and electrolyte levels. This stimulated continuous research on novel biochemical markers suitable for diagnosis and monitoring of acute kidney injury (AKI) and chronic kidney disease (CKD). Aim The aim of this paper was to review available evidence regarding novel biomarkers of kidney damage. Material and methods The review of available literature was conducted, using search terms ‘kidney damage biomarker’ and ‘kidney injury biomarker.’ Results and discussion Cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, liver-type fatty acid binding protein, selected urinary enzymes (e.g. N-acetyl-β-glucosidase) and low-molecular-weight proteins (e.g. β-2 microglobulin) seem to be the most promising biomarkers of both AKI and CKD. In turn, asymmetric dimethylarginine, inflammatory/fibrosis parameters (e.g. monocyte chemoattractant protein, transforming growth factor-β1) and Klotho-FGF23 axis raise most interest as the most selective markers of CKD. Conclusions Owing continuing progress in nephrology laboratory diagnostics, novel biomarkers of kidney damage are likely to be introduced in routine clinical practice.

Introduction : Pain hypersensitivity, abnormal motility and autonomic dysfunction contribute to functional symptoms of inflammatory bowel disease (IBD). Material and methods : The aim of this study was to assess: nociceptive thresholds for mechanical allodynia (MA) and thermal hyperalgesia (TH), intestinal motility (distal colonic transit and emptying), and cardiac autonomic neuropathy (indices of heart rate variability – HRV) in male Wistar rats with experimental trinitrobenzene sulfonic acid (TNBS) induced colitis. To identify a potential vagal contribution the bilateral subdiaphragmatic vagotomy (SDV) was performed. Results: Experimental colitis resulted in a significant decrease in pain threshold (MA 23.60 ±2.12, p < 0.001, TH 8.51 ±1.49, p < 0.001), reduced expulsion time (6.2 ±3.5, p < 0,01) and increase in the sympathetic autonomic activity (LFnu 32.54 ±21.16, p < 0.03). The animals with diminished vagal integrity presented with reduced gastrointestinal motility (39.8 ±25.1, p < 0.01) and a decrease in the parasympathetic high-frequency domain of HRV (HFnu 55.37 ±22.80, p < 0.002). The vagotomized rats with colitis showed the strongest nociceptive response (MA 22.46 ±3.02, p < 0.004; TH 7.99 ±1.12, p < 0.003) as well as significant changes in sympatho-vagal balance on HRV testing (LFnu 28.25 ±14.66, p < 0.04; HFnu 71.34 ±14.55, p < 0.04). Conclusions : The relationship between the cardiovascular and gastrointestinal system is modulated by neural, hormonal and inflammatory factors. This leads to dysregulation of the brain-gut interactions in the course of IBD. Sensitization and visceral-somatic convergence trigger pain hypersensitivity and autonomic sympathovagal imbalance. While integral vagal innervation impacts analgesic mechanisms via modulation of the immune response, SDV raises sympathetic activity and induces excessive hyperalgesia.

Purpose Dyspeptic symptoms present a severe problem in gastrointestinal (GI) cancer patients. The aim of the study was to analyze an association between gastric myoelectric activity changes and dyspeptic symptoms in gastrointestinal cancer patients. Material and Methods The study included 80 patients (37 men and 43 women, mean age 61.2 ± 7.8 years) diagnosed with GI tract malignancies: colon (group A), rectal (group B) and gastric cancers (group C). Gastric myoelectric activity in a preprandial and postprandial state was determined by means of a 4-channel electrogastrography. Autonomic nervous system was studied based on heart rate variability analysis. The results were compared with the data from healthy asymptomatic controls. Results In a fasted state, GI cancer patients presented with lesser percentages of normogastria time (A:44.23 vs. B:46.5 vs. C:47.10 vs. Control:78.2%) and average percentage slow wave coupling (ACSWC) (A:47.1 vs. B:50.8 vs. C:47.2 vs. Control:74.9%), and with higher values of dominant power (A:12.8 vs. B:11.7 vs. C:12.3 vs. Control:10.9) than the controls. Patients did not show an improvement in the percentage of normogastria time, dominant power, dominant frequency and ACSWC in response to food. The severity of dyspeptic symptoms correlated with the values of electrogastrography parameters. Patients showed lower values of heart rate variability parameters than the healthy controls, that indicate abnormal autonomic nervous system activity. Conclusion GI cancers affect the gastric myoelectric activity, decreasing normogastria and slow wave coupling. These patients do not show adequate gastric motility response to food. Impaired gastric electric motility may result from cancer-induced autonomic disturbances.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is well established for treating the motor symptoms for advanced Parkinson's disease (PD) but its effects on gastric myoelectrical activity and gastrointestinal symptoms have not been well studied. The aim of this study was to evaluate the effect of STN-DBS on gastric motility using electrogastrography (EGG).Twenty patients with PD (5 females, 15 males; mean aged 58.0 ± 9.0 years) who underwent STN-DBS were studied. EGG was performed in fasting and postprandial conditions before STN-DBS and 3 months after the surgery. We also evaluated the frequency and severity of gastrointestinal symptoms based on a structured gastrointestinal dysfunction questionnaire.After STN-DBS the percentage of normogastria (47.8 ± 20.7 vs 51.3 ± 15.1) and period dominant power (PDP) (11.8 ± 1.2 vs 12.3 ± 0.9) significantly increased, the percentage of arrhythmia decreased compared to the baseline during fasting and postprandial state. Abnormal response to a meal (power ratio of PDP1 after meal) decreased from 70% to 55% after 3 months follow-up. The abnormal EGG (the percentage of normogastria70%) decreased in both fasting (from 80% to 65% patients) and postprandial state (from 80% to 60% patients), respectively after the surgery. The most common GI symptoms reported prior to the surgery were constipation 95%, difficulty with defecation 85% and dysphagia 50%. After STN-DBS all gastrointestinal symptoms improved, the greatest improvement was observed in difficulty with defecation.Our results suggest that STN-DBS improves gastric motility as well as gastrointestinal symptoms in PD. Further studies of gastrointestinal motility in PD are warranted.

The purpose of this study was to determine the activity of the autonomic nervous system (ANS), using spectral analysis of the heart rate variability (HRV) in the model of partial bladder outlet obstruction (PBOO) in rats treated with selected non-steroidal anti-inflammatory drugs (NSAID): piroxicam (PRX) or meloxicam (MLX), and following administration of PGF2a prostaglandin analogue (Enzaprost F5). Neither the use of PGF2a analogue nor of MLX, caused significant changes in the HRV spectrum (except for HRV spectrum total power reduction with MLX). The use of PRX caused reduction of the total power and powers of all components of the HRV spectrum (except for VLF). Moreover, increased nLF and reduced nHF were observed. The obtained results suggest that the total prostaglandin synthesis block with a non-selective cyclooxygenase inhibitor (PRX) results in reduced ANS total activity, with decreased parasympathetic activity and a relative sympathetic predominance. The preferential cyclooxygenase-2 block (MLX) caused reduction of the total ANS activity as well, however with no clear disproportion of any part of the ANS. Therefore, prostaglandin synthesis inhibition and associated decrease of parasympathetic activity may constitute an additional and favourable feature of NSAID pharmacodynamics in the treatment of BPH.

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 complex pathogenesis of cyclophosphamide-induced hemorrhagic cystitis involves arachidonic acid-derived inflammatory mediators, among them leukotrienes. Montelukast, a leukotriene receptor antagonist, is reported to exert an alleviatory effect in the course of cystitis associated with overactive bladder symptoms. The aim of this study was to verify whether the effect of montelukast is also associated with its influence on autonomic activity. The experiment included 20 rats with cyclophosphamide-induced hemorrhagic cystitis (75 mg/kg, four doses every second day), among them, 10 treated with oral montelukast (10 mg/kg for 8 days) and 10 controls. Time and frequency domain analyses of heart rate variability (HRV) were conducted in all the rats as an indirect measure of their autonomic activity. The montelukast-treated animals showed an increase in root mean square of successive differences (rMSSD), as well as an increase in HRV spectrum total power (TP) and power of very low (VLF) spectral component. This suggests that due to its anti-inflammatory and its anti-leukotriene effect, montelukast improves overall autonomic activity, with no preferential influence on either the sympathetic or parasympathetic part. Furthermore, the increase in VLF corresponds to attenuation of inflammatory response. In conclusion, this study showed that aside from its antagonistic effect on leukotriene receptors, montelukast can also modulate autonomic activity.

Gastrointestinal (GI) hormonal peptides play a role in the development of gastrointestinal malignancies, and their abnormal levels may contribute to dysmotility. The aim of this study was to analyze plasma concentrations of enterohormones (motilin, ghrelin, gastrin and pancreatic polypeptide) and to verify if their abnormal levels may contribute to the severity of dyspeptic symptoms in colorectal cancer patients. The study included 60 patients with colorectal malignancies (22 men and 38 women), among them 30 individuals with colon cancers (group A) and 30 subjects with rectal tumors (group B). Fasting plasma levels of pancreatic polypeptide (PP), motilin, gastrin and ghrelin were determined by means of ELISA. The results were compared with the respective parameters of healthy volunteers. Colon cancer patients presented with significantly lower concentrations of ghrelin than the subjects with rectal tumors and healthy controls (156.8±86.7 vs. 260.2±87.6 vs. 258.4±94.2 pg/ml, p=0.02), as well as with significantly higher levels of PP (265.5±66.3 vs. 154.1±54.6 vs. 148.3±64.3 pg/ml, p=0.005). Also the levels of motilin turned out to be lower in colon cancer patients than in the subjects with rectal malignancies and healthy controls. No statistically significant intergroups differences were found in plasma levels of gastrin (388.2±98.6 vs. 475.6±88.7 vs. 428.2±91.2 pg/ml, p>0.05). Epigastric bloating was the most frequent dyspeptic symptom, reported by 63.3% and 40% of patients with colon and rectal tumors, respectively. Our findings imply that colon cancer patients may present with abnormal plasma levels of enterohormones significantly more often than individuals with rectal malignancies. Dysmotility observed in colon cancer patients may result not only from anticancer surgery, but also from abnormal release of enterohormones, induced either by neoplastic process or by changes within the autonomic nervous system.

Background and objective: The application of cytostatic oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide (IF) is associated with the risk of kidney damage that, depending on the type of drug, dose and route of administration, adopts a different clinical entity and severity. The aim of our study was to assess the influence of CP and IF on the kidney histology and function in rats intraperitoneally treated with four doses of either CP or IF. Materials and methods: A total of 30 rats were divided into three groups (10 in each group): group 1 (control), sham treated with saline solution, group 2 (treated with 75 mg/kg b.w. of CP), and group 3 (treated with 60 mg/kg b.w. of IF). After the treatment rats were sacrificed, blood was collected and nephrectomy and cystectomy were performed. Qualitative and quantitative parameters (including neutrophil gelatinase-associated lipocalin-1, NGAL-1) of kidney function were assayed in urine and plasma. Results: CP-treated rats were characterized by a significant polyuria, decreased urine pH and by decreased daily urinary excretion of sodium, potassium, urea and uric acid accompanied by increased NGAL-1 excretion. A significant decrease of the plasma uric acid concentration was also observed. IF-treated animals were also characterized by decreased urine pH but with normal daily urinary excretion of assessed substances (except for reduced uric acid excretion). Both CP and IF treated rats did not show any histopathological abnormalities in their kidneys. Conclusions: CP caused more advanced kidney dysfunction and some indices suggested the development of prerenal acute kidney injury. In the CP-treated group some particularly marked urinary and plasma uric acid disturbances suggested compensation of increased oxidative stress as uric acid is considered to exert also antioxidant properties.

Introduction Autonomic nervous system (ANS) function can be evaluated by analysis of heart rate variability (HRV) and plasma concentration of noradrenaline (NA). Recent studies identified potential, biochemical markers of the ANS activity, including selected co-transmitters, released from either sympathetic (e.g. neuropeptide Y – NPY) or parasympathetic (e.g. vasoactive intestinal peptide – VIP) fibers. Aim The aim of the study was to analyze HRV recordings and to determine plasma level of NA, NPY and VIP in 3–12 months males and females rats under pentobarbital anesthesia. Moreover, our goal was to determine overall and gender-dependent correlation between the HRV indices and abovementioned compounds. Material and methods The experiment included 36 rats with different autonomic tone related to age and gender. Spectral HRV analysis was applied and NA, NPY and VIP were measured by ELISA. Results and discussion Male rats were characterized by significantly higher values of selected HRV indices: total power (TP), very low frequency (VLF) and high frequency (HF) and plasma concentrations of both analyzed neuropeptides comparing to female ones. Similar to the overall assessment, both males and females showed significant correlations between NA and TP, VLF and LF. Moreover, male rats (but not female ones) presented with significant moderate correlations between NPY and LF, VIP and TP, HF and normalized HF (nHF). Conclusions Our preliminary findings imply that NA correlates with global autonomic activity (TP) and with the values of sympathetically-driven components (VLF and LF). Furthermore, VIP seems to correlate with specific measures of parasympathetic drive (HF and nHF), but only in male 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.

Cyclophosphamide (CP) treatment is associated with the risk of haemorrhagic cystitis (HC). Moreover, CP-induced HC is complicated by autonomic nervous system (ANS) dysfunction. Pemirolast is thought to be a mast cell stabiliser that inhibits the release of many inflammatory mediators and sensory neuropeptides, and thus, it may be considered a potential chemoprotective HC agent. The aim of the study was to indirectly estimate the effect of pemirolast in experimental HC by measuring ANS activity with the heart rate variability (HRV) method. In CP-treated rats, we found a decreasing trend of overall autonomic activity, together with an imbalance between the main components, and a dominant very low frequency (VLF) power component. Pemirolast treatment did not improve the total HRV power value or the main non-normalized HRV components. Moreover, CP-HC animals treated with pemirolast displayed a different disproportion of normalized spectral components as compared to both control and CP-HC animals without pemirolast treatment, with the balance between normalized low frequency (nLF) and normalized high frequency (nHF) shifted towards nLF. This finding, together with a relatively high VLF tension, indicates that the pemirolast treatment resulted in high sympathetic activity that may contribute to HC exacerbation; thus, this agent seems to be ineffective in CP-induced HC.

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.

Introduction Two main pathophysiological concepts of overactive bladder (OAB) are postulated: the neurogenic and myogenic theories. Autonomic nervous system (ANS) dysfunction is also involved in OAB pathophysiology. The purpose of our study was to estimate ANS activity by heart rate variability (HRV) assessment in two OAB experimental models evoked by cyclophosphamide administration: acute (AOAB) and chronic (COAB) overactive ones.

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.The aim of this study is to clarify the role of gender in high fat diet induced obesity in pups and adult animals.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.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.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.

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.Ostre uszkodzenie nerek (AKI) jest istotnym problemem klinicznym, rozwijającym się u hospitalizowanych pacjentów w wyniku nagłego pogorszenia funkcji nerek. Natomiast w następstwie przewlekłych glomerulopatii, cewkowo-śródmiąższowych chorób nerek, nawracających odmiedniczkowych zapaleń nerek, kamicy lub chorób systemowych uszkadzających nerki (nadciśnienie tętnicze, cukrzyca) rozwija się przewlekła choroba nerek (CKD). Wczesne rozpoznanie AKI pozwala na wdrożenie odpowiedniej terapii, co w części przypadków zabezpiecza przed nieodwracalnymi powikłaniami prowadzącymi do zgonu chorego. Analogicznie, właściwa ocena biochemiczna pozwala na monitorowanie przebiegu CKD, co zmniejsza ryzyko powstania przewlekłych powikłań i rozwoju pełnoobjawowej, przewlekłej niewydolności nerek. Stąd, wciąż są poszukiwane nowe parametry laboratoryjne, obdarzone wysoką czułością i specyficznością, umożliwiające wiarygodne rozpoznanie AKI lub zaawansowanie CKD. Niniejsza praca koncentruje się na omówieniu roli czterech białek: cystatyny C, lipokaliny 1 związanej z żelatynazą neutrofili (NGAL-1), cząsteczki uszkodzenia nerek (KIM-1) oraz białka αKlotho jako nowych biomarkerów w diagnostyce AKI/CKD.

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).

The aim of the study was to determine the correlations between intracellular calcium ion level and a cell's ability to survive. The intracellular concentration of Ca(2+) ions, maintained through different mechanisms, plays an important role in signalling in cells. The deregulation of these mechanisms by various cell stressors (e.g. cytotoxic agents) can disturb Ca(2+) homeostasis and influence Ca(2+)-dependent signalling pathways in the cell. Perturbations of intracellular electrochemical equilibrium may lead to changes in cell function or even to cell death. According to some experimental results, one of the cell stressors may be exposure to magnetic fields (MF). Because of the wide distribution of MF sources in our environment, magnetic fields have recently been intensively examined in relation to the occurrence of cancer. Nevertheless, two questions still remain unanswered: Is the influence of MF on cells positive or negative, and what mechanism(s) underlie the effects of MF action on cells? Most studies focus on the influence of MF on Ca(2+) ion fluxes as calcium ions play the role of intracellular second messengers, triggering many signalling cascades. Physical models assuming the mechanisms generating the disturbance of ionic transport and/or the dysfunction of ion-protein complexes in cells due to MF action have been widely discussed in the literature, but a detailed explanation of experimental results is still awaited. The dynamics of the concentration of intracellular calcium ions can be detected by various methods, including optical and non-optical techniques. This review combines an insight into basic intracellular Ca(2+) regulative mechanisms and common techniques used to detect changes in Ca(2+) concentration inside the cell. The emphasis here is on the determination of Ca(2+) regulative mechanisms developed in non-excitable cells (e.g. U937 cells, HeLa, etc.), which are probably mainly involved in cell responses to external stress (e.g. MF stimuli).

Background Interstitial cells of Cajal (ICCs) play an important role in the regulation of gut motility. There is growing evidence that interstitial Cajal-like cells (ICLCs) are present in the gallbladder wall. We hypothesize that changes in the density of ICLCs in the gallbladder wall may lead to the development of cholelithiasis due to the impairment of the gallbladder motility. The purpose of this study was to identify ICLCs in the gallbladders of patients with gallstones and to assess their densities. Methods Data from 30 patients with gallstones and 25 individuals without gallstones were compared. Tissue samples were obtained during surgery, embedded in paraffin, and cut into sections. Following staining for CD117 and mast cell tryptase, the number of ICLCs and mast cells was determined using image analysis. Key Results Cells positive for the c-Kit receptor (CD117) were detected in the gallbladder wall in all cases examined. Interstitial Cajal-like cells were most frequently observed in the muscularis propria. The density of ICLCs in the muscularis propria was significantly lower in the patients with gallstones than the density observed in the controls (26.24 ± 10.89 vs 56.29 ± 13.35 cells/mm2). In contrast, the number of mast cells in the gallbladder was increased in the patients with gallstones when compared with the controls (143 ± 24 vs 112 ± 19 cells/mm2). Conclusions & Inferences The histopathological differences observed in this study may help elucidate the pathophysiology of gallstones. Gallbladder motility may be affected by the decreased number of ICLCs in patients with cholelithiasis.

Summary Background The main mechanism underlying irritable bowel syndrome is currently believed to be a dysfunction of the brain-gut axis. Autonomic nervous system dysfunction can contribute to development of irritable bowel syndrome symptoms by disturbing visceral sensations. Material/Methods Thirty patients with a diagnosis of constipation-predominant irritable bowel syndrome and 30 healthy volunteers were included in the study. Resting and functional autonomic nervous system tests and percutaneous electrogastrography were performed. Plasma adrenalin, noradrenalin, insulin, ghrelin and cholecystokinin activity was analyzed. Results Increased sympathetic activation with disturbed parasympathetic function was demonstrated. Patients had substantially higher plasma catecholamine concentration, which confirms sympathetic overbalance. Hyperinsulinemia may explain sympathetic predominance followed by gastric and intestinal motility deceleration. Abnormal, reduced ghrelin and cholecystokinin titre may disturb brain-gut axis functioning and may be responsible for gastric motility deceleration. In electrogastrography, distinctly lower values of fasting normogastria percentage and dominant power were observed. Patients had substantially lower slow wave coupling percentage both in fasting and postprandial periods, which negatively correlated with plasma catecholamines level. Gastric myoelectrical activity disturbances may result from lack of sympatho-parasympathetic equilibrium. Conclusions Central sympathetic influence within the brain-gut axis is most probably responsible for myoelectrical activity disturbances in irritable bowel syndrome patients.

Recent studies of Parkinson's disease indicate that dorsal motor nucleus of nerve vagus is one of the earliest brain areas affected by alpha-synuclein and Lewy bodies pathology. The influence of electrical stimulation of vagus nerve on elemental composition of dopamine related brain structures in rats is investigated. Synchrotron radiation based X-ray fluorescence was applied to the elemental micro-imaging and quantification in thin tissue sections. It was found that elements such as P, S, Cl, K, Ca, Fe, Cu, Zn, Se, Br and Rb are present in motor cortex, corpus striatum, nucleus accumbens, substantia nigra, ventral tectal area, and dorsal motor nucleus of vagus. The topographic analysis shows that macro-elements like P, S, Cl and K are highly concentrated within the fiber bundles of corpus striatum. In contrast the levels of trace elements like Fe and Zn are the lowest in these structures. It was found that statistically significant differences between the animals with electrical stimulation of vagus nerve and the control are observed in the left side of corpus striatum for P (p = 0.04), S (p = 0.02), Cl (p = 0.05), K (p = 0.02), Fe (p = 0.04) and Zn (p = 0.02). The mass fractions of these elements are increased in the group for which the electrical stimulation of vagus nerve was performed. Moreover, the contents of Ca (p = 0.02), Zn (p = 0.07) and Rb (p = 0.04) in substantia nigra of right hemisphere are found to be significantly lower in the group with stimulation of vagus nerve than in the control rats.

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.

Glutamate is the basic excitatory neurotransmitter acting via N-methyl-D-aspartate receptors (NMDARs). It co-regulates many important physiological functions, including learning, memory, and behaviour. An excess of glutamate, as well as NMDAR over-activity, produce pathological effects. Glutamate-related neurotoxicity is involved in the pathogenesis of many neurological conditions. This article briefly describes the role of the glutamate system in the pathophysiology of brain ischemia, selected neurodegenerative disorders, and schizophrenia. It also reviews the current and potential future status of agents targeting NMDARs in neuropsychopharmacology.

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.

The purpose of this study was to characterize the action of exogenous PYY, an ileocolonic peptide released by fatty meal, and that released by Heal perfusion with oleate on intestinal and gallbladder motility patterns and the posssible role of the adrenergic pathway in this action. Dogs were equipped with chronic duodenal electrodes for recording myoelectric activity and with a cannula in the gallbladder fundus for measuring the gallbladders intraluminal pressure and volume and calculating its motility index (MI) and emptying rate. After intravenous infusion of PYY, there was a dose-dependent prolongation of the migrating motor complex (MMC) interval and almost complete abolition of the contractions and emptying of gallbladder during the duodenal activity front. After meat feeding or during intravenous infusion of cerulein, 50 pmol/(kg · h), the MMC was interrupted and replaced by irregular spike activity, accompanied by a marked increase in the gallbladder MI and about 80% to 90% reduction of its volume. PYY, 200 pmol/(kg · h), reduced significantly the meal- or cerulein-induced duodenal spike activity but failed to affect the MI and volume of the gallbladder. Similar changes in fasted and fed patterns of motility were observed after Heal oleate (16 mM/h), producing plasma PYY levels in a range similar to that observed after infusion of exogenous PYY. The inhibitory effects of PYY or Heal fat on intestinal myoelectric activity were reversed in part by α-adrenergic blockade (phentolamine). We conclude that exogenous PYY or endogenous hormone released by Heal oleate inhibits the interdigestive and postprandial motility pattern of the small bowel but does not affect gallbladder motility, and that the inhibition of intestinal motility involves, at least in part, the adrenergic pathway.

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.

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.

Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral electrical vagus nerve stimulation on changes in lipid composition and in protein secondary structure within dopamine-related brain structures in rats. It was found that the chronic vagal nerve stimulation strongly affects the chain length of fatty acids within the ventral tegmental area, nucleus accumbens, substantia nigra, striatum, dorsal motor nucleus of vagus and the motor cortex. In particular, the level of lipid unsaturation was found significantly increasing in the ventral tegmental area, substantia nigra and motor cortex as a result of vagal nerve stimulation. When it comes to changes in protein secondary structure, we could see that the mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by vagus nerve stimulation. This is due to the co-occurrence of statistically significant changes in the content of non-ordered structure components, alpha helices, beta sheets, and the total area of Amide I. Macromolecular changes caused by peripheral vagus nerve stimulation may highlight a potential connection between the gastrointestinal system and the central nervous system in rat during the development of neurodegenerative disorders.

Introduction. Impairment of the enteric nervous system has been suggested to occur within the pathogenesis of neurodegenerative diseases. Thus, in the current study, we consider salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL) as a substance that can potentially induce myenteric neurodegen­eration. Material and methods. Male Wistar rats were subjected to continuous intraperitoneal dosing of salsolinol (200 mg/kg in total) with osmotic mini-pumps for either two or four weeks. An equivalent group of rats served as the control. Jejunal myenteric neurons were subjected to immunofluorescence staining to detect neuron specific protein — protein gene product (pan-neuronal marker, PGP 9.5), nitric oxide synthase (NOS), choline acetyltransferase (ChAT), Bax-protein and alpha-synuclein. In search of any functional impairment within the gastrointestinal tract, gut motility was assessed by determining the residual solid food contents in the stomach and the small and large intestine transit. Results. The myenteric neuron count, the mean size of the neuron body, the area of ganglia and the diameter of nerve strands were decreased in both of the salsolinol-treated groups compared with the controls. The number of NOS-positive cells was lower in the salsolinol-treated groups, while the number of ChAT-positive cells remained unchanged in comparison with the controls. Neurons expressing the pro-apoptotic Bax protein and alpha-synuclein deposits were observed among the myenteric neurons of the salsolinol-treated rats. Conclusions. Salsolinol evokes enteric neuronal cell death via initiation of apoptosis and leads to the formation of pathological aggregates of alpha-synuclein. Impairment of myenteric neurons, mainly the inhibitory motor neurons, might be responsible for the abnormal intestinal transit. Thus, salsolinol might be regarded as a suitable compound for inducing experimental enteric neurodegeneration in rats.

In many therapeutic processes the future medicine will go away from the traditional pharmacological methods and will apply active stimulation of organs with implanted neurostimulators. The classical examples are nowadays the pacemakers. From the inspiration of Pathophysiology Department in Collegium Medicum of Jagiellonian University the Institute of Electron Technology undertook the research work in the field of implanted neurostimulators. The authors presented in the paper the hitherto achieved results of research works, including the analysis of electrical signals course in excited and non-excited vagus nerve and impedance measurement of nerve fibre, necessary for determining the parameters of neurostimulator such as the amplitude, duration and the repetition rate of stimulator pulses. From the point of view of circuit theory neurostimulator is a kind of self-excited or microprocessor controlled pulse generator. In the paper the structure of neurostimulator is presented and the choice of electrodes material and encapsulation resin is explained, taking into account the problem of biocompatibility. Some experimental results of laboratory tests on experimental animals with implanted neurostimulators are shown.

Melatonin, considered as a main pineal product, may be also synthetized in the gastrointestinal tract from L-tryptophan. Melatonin has been recently shown to affect insulin release and its receptors have been characterized in the pancreas however, the effects of melatonin on the pancreatic enzyme secretion have not been examined. The aim of this study was to investigate the effects of melatonin or L-tryptophan on amylase secretion in vivo in anaesthetized rats with pancreato-biliary fistulas, and in vitro using isolated pancreatic acini. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) given to the rats as a intraperitoneal (i.p.) bolus injection produced significant and dose-dependent increases in pancreatic amylase secretion under basal conditions or following stimulation of enzyme secretion by diversion of bile-pancreatic juice. This was accompanied by a dose-dependent rise in melatonin plasma level. Stimulation of pancreatic enzyme secretion caused by melatonin or L-tryptophan was completely abolished by vagotomy, deactivation of sensory nerves with capsaicin or pretreatment with CCK 1 receptor antagonists (tarazepide or L-364,718). Pretreatment with luzindole, an antagonist of melatonin MT 2 receptor failed to affect melatonin- or L-tryptophan-induced amylase secretion. Administration of melatonin (1, 5 or 25 mg/kg i.p.) or L-tryptophan (10, 50 or 250 mg/kg i.p.) to the rats resulted in the dose-dependent increase of cholecystokinin (CCK) plasma immunoreactivity. Enzyme secretion from isolated pancreatic acini was not significantly affected by melatonin or L-tryptophan used at doses of 10 -8 -10 -5 M. We conclude that exogenous melatonin, as well as that produced endogenously from L-tryptophan, stimulates pancreatic enzyme secretion in vivo while increasing CCK release. Stimulatory effect of melatonin or L-tryptophan on the exocrine pancreas involves vagal sensory nerves and the CCK release by these substances.

The paper describes an original method of endoluminal electrical stimulation of the stomach developed by authors. The aim of the study was to compare two types of electrical stimulation: low frequency (LF) and high frequency (HF) in human patients. Twenty-three patients with postoperative gastroparesis (after abdominal surgery) were involved in the study and randomized into two groups. Group A consisted of 13 subjects treated by LF stimulation (mean age 52 ± 11; five males, eight females) and group B of 10 patients scheduled for HF stimulation (mean age 61 ± 8; six males, four females). A computer preprogrammable stimulator was used and the following parameters were evaluated: gastric retention every 12 h and symptoms score on the days 0, 1, 3, and 5. Gastric retention decreased in group A on consecutive days of pacing from 1,593 to 623, 407, 315, 246, to 192 ml, and in group B from 1,980 to 570, 218, 80, 15, to 0 ml (p

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 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.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.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, p0.05), rMSSD (71.4 ± 46.9 ms vs. 41.3 ± 20.7 ms, p0.05), pNN50 (28.3 ± 17.4% vs.14 ± 10.7%, p0.05), LF (603.5 ± 208.2 ms2 vs. 445.2 ± 137 ms2, p0.03). 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, p0.05), SDNN (114.1 ± 45.1 ms vs. 79 ± 27.7 ms, p0.05), rMSDD (81.9 ± 38.2 ms vs. 50.7 ± 27 ms, p0.05), pNN50 (32.9 ± 14.3 % vs. 20.6 ± 14.6%, p0.05), TP (1972.7 ± 809.5 ms2 vs. 1329.7 ± 532 ms2, p0.05), HF (657.1 ± 330.9 ms2 vs. 405.7 ± 217 ms2, p0.05), LF (753.3 ± 294 ms2 vs. 533 ± 213.4 ms2, p0.05). The analysis of value relative DB-induced changes in time and frequency domain HRV indices revealed significant intergroup differences in reaction to parasympathetic stimulation.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 autonomic nervous system (ANS) function in hyperthyroidism has been so far investigated mainly from the cardiovascular point of view. The aim of this study is to show that the ANS dysfunction in hyperthyroidism is also expressed in gastric myoelectrical activity disturbances and gastric emptying disorders and to search for a correlation between the severity of clinical manifestation and free thyroid hormone levels and the degree of the ANS dysfunction. The analyzed group included 50 recently diagnosed patients with hyperthyroidism who were examined twice: before and after 3 months of thyrostatic treatment. Results were compared with those of a sex-, age- and BMI-matched control group of 50 healthy volunteers. The study included: heart rate variability analysis in time and frequency domain, at rest and during a deep-breathing test, surface electrogastrography in preprandial and postprandial periods measured simultaneously with the ultrasound assessment of gastric emptying time by Bolondi method. In patients with hyperthyroidism in comparison with the control group, the following significant differences were observed: a sharp reduction of the high-frequency component and a decrease of heart rate variability, a high incidence of dysrhythmia with dominant bradyarrhythmia, and a delay of gastric emptying. The degree of disorders related to the degree of clinical manifestation of hyperthyroidism's symptoms and free triiodothyronine serum concentration both. All the disorders were functional and disappeared in a stable euthyroidism. To conclude, the ANS dysfunction in hyperthyroidism results not only in withdrawal of vagal inhibitory effect on sinoatrial node, but in impaired mutual neuro-hormonal regulation (decrease of vagal influence) of gastric myoelectrical activity followed by delay of gastric emptying.

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.

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).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.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.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.

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).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.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%).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.

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.

The major mechanisms of gallstone formation include biliary cholesterol hypersecretion, supersaturation and crystallization, mucus hypersecretion, gel formation and bile stasis. Gallbladder hypomotility seems to be a key event that triggers the precipitation of cholesterol microcrystals from supersaturated lithogenic bile. Telocytes, a new type of interstitial cells, have been recently identified in many organs, including gallbladder. Considering telocyte functions, it is presumed that these cells might be involved in the signalling processes. The purpose of this study was to correlate the quantity of telocytes in the gallbladder with the lithogenicity of bile. Gallbladder specimens were collected from 24 patients who underwent elective laparoscopic cholecystectomy for symptomatic gallstone disease. The control group consisted of 25 consecutive patients who received elective treatment for pancreatic head tumours. Telocytes were visualized in paraffin sections of gallbladders with double immunofluorescence using primary antibodies against c‐Kit (anti‐CD117) and anti‐mast cell tryptase. Cholesterol, phospholipid and bile acid levels were measured in gallbladder bile. The number of telocytes in the gallbladder wall was significantly lower in the study group than that in the control group (3.03 ± 1.43 versus 6.34 ± 1.66 cell/field of view in the muscularis propria, P < 0.001) and correlated with a significant increase in the cholesterol saturation index. The glycocholic and taurocholic acid levels were significantly elevated in the control subjects compared with the study group. The results suggest that bile composition may play an important role in the reduction in telocytes density in the gallbladder.

Introduction. The Cajal–like intestitial cells (ICCs) act as a pacemaker and are responsible for generat ing 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 pathophysiology of functional disorders of the urinary bladder is still relatively poorly understood, although the mechanisms controlling the lower urinary tract function have been quite accurately described. The rich innervation of afferent and efferent urinary tract, multi-level neural control of micturition process, the diversity of the autonomic nervous system neurotransmitters, as well as "neuronal activity" of the urotelium determines the correct filling and emptying of the bladder. Functional diseases (OAB - such as overactive bladder) include sensory and/or motor dysfunction of the urinary bladder, leading to sleep disturbances, psychosomatic disorders, lower quality of life, etc. It is known that sensory afferent C fibers and vanilloid TRPV1 receptors are important in the pathogenesis of OAB. Modulation of the activity of these fibers and/or TRPV1 receptors by a number of substances (such as capsaicin, lidocaine, etc.) reduces the symptoms of OAB. Detailed knowledge of the neurophysiology of the lower urinary tract is a prerequisite for proper treatment of functional disorders of the urinary tract. The paper discusses the neurophysiologic basis, the importance of afferent C fibers and vanilloid TRPV1 receptors in lower urinary tract.