Association between gastric myoelectric activity disturbances and dyspeptic symptoms in gastrointestinal cancer patients.

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.

Lactobacilli with superoxide dismutase-like or catalase activity are more effective in alleviating inflammation in an inflammatory bowel disease mouse model.

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<0.05) and IV (P<0.05). Similarly, groups II (P<0.05) and IV (P<0.05) had the highest drop in body mass. Moreover, histopathological evaluation of colon fragments showed intracryptic abscesses in these groups. Group III mice showed most limited degree of inflammation. CONCLUSION: Lactobacillus strains with dismutase-like activity are more effective in alleviating intestinal inflammation than strains producing catalase, suggesting that superoxide anion radical decomposition is crucial in this process.

Autonomic dysregulation in colon cancer patients.

To the best of our knowledge, only two studies analyzed the relationship between HRV and carcinoembryonic antigen (CEA) in colon cancer patients. The aim of this study was to analyze changes in the autonomic activity of colon cancer patients using heart rate variability (HRV) and blood pressure variability (BPV) measures, and to verify if HRV and BPV parameters correlate with hemodynamic indices in this group and the plasma levels of CEA. Presence of colon cancer is associated with changes in autonomic activity, namely parasympathetic-sympathetic imbalance in form of sympathetic overdrive. Cancer-related autonomic dysfunction may contribute to impairment of gastrointestinal motility.

The influence of oxazaphosphorine agents on kidney function in rats.

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 75mg/kg b.w. of CP), and group 3 (treated with 60mg/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.

Altered sympathovagal balance and pain hypersensitivity in TNBS-induced colitis.

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.

Ghrelin, pancreatic polypeptide plasma concentrations and gastric myoelectric activity in celiac disease.

BACKGROUND/AIMS: The aim of the study was to analyze the effect of celiac disease(CED) on the upper-gut motility and release of enteral hormones (ghrelin and pancreatic peptide (PP)). MATERIALS AND METHODS: the study included 25 patients diagnosed with CED and 30 healthy controls. Gastric myoelectric activities (EGG) in a fasted and fed state were recorded. The plasma concentrations of ghrelin and PP were determined. R e s u l t s: CED patients presented in a fasted state a decreased percentage of normogastria 54.8 ± 24.5 vs. 86 ± 12.3%, p = 0.02 and slow wave coupling (SWC) 52.7 ± 13.4 vs. 77.4 ± 11.9%; p = 0.00001 with increased dominant power (DP) 11.6 ± 1.5 vs. 11.1 ± 1.1. Contrary to the controls, they did not show an improvement in the percentage of normogastria, DP and SWC when examined in a fed state (p 〈0.05). Furthermore, CED patients presented with significantly lower fasting plasma concentrations of ghrelin 156.8 ± 86.7 vs. 260.2 ± 87.6 pg/ml, p = 0.0002 and significantly higher fasting PP levels than did the controls 265.2 ± 306.3 vs. 54.1 ± 54.6 pg/ml, p = 0.0005. C o n c l u s i o n: CED affects gastric myoelectric activity (decreasing normogastria and coupling) and causes changes in fasting concentrations of enteral hormones (decrease in ghrelin and an increase in PP). Gastric myoelectric response to food is abolished in CED patients, probably due to the neurohormonal changes induced by primary inflammation associated with this disease.

THE INFLUENCE OF MONTELUKAST ON THE ACTIVITY OF THE AUTONOMIC NERVOUS SYSTEM ESTIMATED BY HEART RATE VARIABILITY IN EXPERIMENTAL PARTIAL BLADDER OUTLET OBSTRUCTION IN RATS.

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.

Experimental gender related obesity effect of diet.

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

The effect of peripheral chronic salsolinol administration on fat pad adipocytes morphological parameters.

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is thought to regulate dopaminergic neurons and to act as a mediator in the neuroendocrine system. We have previously reported that exogenous salsolinol evokes enteric neuronal cell death, leading to the impairment of myenteric neurons density and abnormal intestinal transit in rats. We also observed significant reduction of body weight, related to the disrupted gastrointestinal homeostasis. e aim of current study was to evaluate the influence of prolonged salsolinol administration body weight, food intake, adipose tissue accumulation and fad pad adipocyte morphological parameters assessed by image analysis. Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol - 200 mg/kg in total with ALZET osmotic mini-pumps (Durtec, USA) for 2 or 4 weeks with either normal or high-fat diet. Appropriate groups served as the controls. Food intake, body weight were measured each morning. Both epididymal fat pads were dissected, weighted and processed for routine hematoxylin and eosin staining. e following parameters: cell area, perimeter, long and short axis, aspect ratio and circularity factor were assessed in stained specimens with the image analysis system (Multiscan, Poland). Salsolinol administration significantly reduced total body mass with no differences in total food intake between the groups. The epididymal fat pad weight over final body mass ratio was lower in salsolinol treated rats on high fat diet in comparison with the control groups. e area, perimeter, short and long axis of the fad pad adipocytes were significantly decreased in salsolinol treated animals in comparison with relevant controls. Salsolinol targets some regulatory mechanisms concerned with the basic rat metabolism. Prolonged peripheral salsolinol administration in rats significantly decreases the adipocyte size, and such effect is related to the weight loss and reduced adipose tissue accumulation.

The dynamics of autonomic nervous system activity and hemodynamic changes in pregnant women.

OBJECTIVE: The purpose of this research was to assess the dynamics of autonomic nervous system(ANS) and hemodynamic activity changes during uncomplicated pregnancy. METHODS: We enrolled 36 pregnant women (mean age 29 ± 4.8 years) and a control group of 10 non-pregnant women (mean age 25.9 ± 0.88 years). The examination was performed in the 1st, 2nd, and 3rd trimester. Continuous registration of BP, ECG, and cardioimpedance was performed with Task Force Monitor 3040i. ANS activity was measured using the following parameters: HRV, BPV, BRS at rest, and in response to autonomic tests. RESULTS: Compared to the 1st trimester, an increase in HR (73 vs. 92 bpm; p < 0.001) and mean BP (80 vs. 85 mmHg, p < 0.01) was observed in the 3rd trimester. In the 1st trimester, the BRS of pregnant women was insignificantly higher than in the controls (24.8 vs. 22.3 ms/mmHg); subsequently, it decreased significantly, to 13.4 ms/mmHg in the 3rd trimester (p = 0.0004). An increase in nLF (39.57 ± 13.75 vs. 58.73 ± 15.55; p = 0.001) and LF/HF ratio (1.03 ± 0.76 vs. 1.85 ± 0.8; p < 0.00002) was revealed in HRV analysis conducted in the 3rd trimester, as compared to the 1st tri- mester, along with a decrease in nHF (60.43 ± 13.71 vs. 41.26 ± 15.55; p < 0.001). An increase in LF/HF-sBPV (1.05 ± 0.48 vs. 1.58 ± 0.44; p = 0.01) was recorded in BPV analysis at rest in the 3rd trimester as compared to the respective 1st trimester value. CONCLUSION: Our findings suggest that pregnancy is associated with dynamic changes in autonomic balance, namely doubled dominance of the sympathetic component. Hypervolemia seems the major factor responsible for autonomic and hemodynamic changes observed during pregnancy, as it causes an increase in BP and simultaneous decrease in BRS.

The effect of subthalamic deep brain stimulation on gastric motility in Parkinson's disease.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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 PDP <1 after meal) decreased from 70% to 55% after 3 months follow-up. The abnormal EGG (the percentage of normogastria <70%) 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. CONCLUSION: 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.

Cell viability modulation through changes of Ca(2+)-dependent signalling pathways.

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).

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

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

Nutritional parameters and carbohydrate and fat metabolism after prolonged salsolinol administration in rats fed normal or high-fat diets.

OBJECTIVES: Previous studies have reported that exogenous salsolinol might contribute to myenteric cell death and altered gastrointestinal motility. Because the entire gut mucosal, entero-endocrine and motor functions are integrated by the enteric nervous system, the aim of the present study was to investigate if prolonged intraperitoneal salsolinol administration alters basic metabolism and nutritional parameters in adult Wistar rats fed normal or high-fat diets. METHODS: Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol with ALZET osmotic mini-pumps for 2 or 4 weeks and fed either a normal or high-fat diet. Appropriate groups served as the controls. Nutritional status (food intake, body weight, and epididymal fat pads weight), residual solid food in the stomach and biochemical parameters (GIP, GLP-1, CRF, glucose, TG, LDL, HDL) were assessed. RESULTS: Prolonged salsolinol treatment significantly reduced total body mass and adipose tissue accumulation. The effects were more pronounced in the salsolinol-treated rats fed a high-fat diet. In salsolinol-treated rats, serum postprandial GIP levels were elevated, and serum postprandial GLP-1 levels were lower compared with the appropriate controls. CONCLUSIONS: Salsolinol might influence the regulatory mechanisms of body weight and epididymal fat pad accumulation through neurohormonal pathways.

Urinary kidney injury molecule-1 (KIM-1) excretion in rats with experimental cystitis induced by oxazaphosphorines.

Introduction: Oxazaphosphorine agents (cyclophosphamide - CP, ifosfamide - IF) are causative factors of cystitis and also exert a characteristic nephrotoxic effect, clinically manifested by a broad spectrum of disturbances. The aim of the study was to estimate the toxic effect of the abovementioned oxazaphosphorines on the renal tubules by assessment of diuresis and urinary concentration and daily urinary excretion of the kidney injury molecule-1 (KIM-1) in rats with induced and histologically confirmed cystitis. Material and Methods: The study involved 60 rats (equal amounts of ♀ and ♂), including animals treated with CP, administrated four times at the dose 75 mg/kg (group 1; n=10) and treated with IF, administrated four times at the dose 50 mg/kg IF (group 2; n=10) with the suitable control group A (group 3; n = 10), as well as animals receiving either a single dose 150 mg/kg of CP (group 4) or IF (group 5), with an appropriate control group B (group 6). Results: In both groups 1 and 4, a significant increase in the daily diuresis and decrease of the urinary pH were revealed, compared to the appropriate control group A (group 3) and B (group 6), while IF-treated animals, regardless of the applied doses (groups 2 and 5), were characterized by a urinary pH decrease. KIM-1 urinary concentration in rats from group 1 and 4 was almost three times higher compared to the appropriate control groups A or B, respectively, and the difference was statistically significant. In animals with chronic (group 2) and acute (group 5) ifosfamide- induced cystitis, no statistically significant difference concerning KIM- 1 urinary concentration compared to a control A and B groups was revealed, although a clear tendency of increase of the parameter was observed in the IF-treaded animals. Analysis of daily KIM-1 urinary excretion showed a statistically significant, almost six-fold increase in group 1 and almost two-fold increase in group 2. In the groups with acute model of cystitis, the highest, nearly eight-fold, daily KIM-1 urinary excretion, was revealed in animals treated with single CP dose, compared to the respective control B group, while rats treated with a single IF dose were characterized by a daily urinary KIM -1 excretion, comparable to animals with IF-induced chronic cystitis. The histopathological analysis confirmed cystitis in all animals treated with either CP or IF (groups 1,2,4,5), while no altered kidney microscopic morphology, compared to respective control groups A and B, was observed in those rats. Conclusions: The study confirmed the proximal tubular dysfunction in rats with both cyclophosphamide- and ifosfamide-induced cystitis, which was reflected by an increased urinary KIM-1 excretion. The disturbance was more emphasized in CP-treated animals, especially in those ones treated with the single, high CP dose. The functional tubulopathy was not accompanied by a structural kidney damage in rats treated with either CP or IF.

Benign prostatic hyperplasia - progress in pathophysiology and management.

Benign prostatic hyperplasia (BPH) is a common disease of the aging male population, in affected individuals often accompanied by metabolic syndrome. BPH is manifested by a complex range of symptoms originating from the lower urinary tract (LUTS - lower urinary tract symptoms), including disturbances resulting from impaired bladder compliance and bladder overactivity (e.g. frequency, nocturia, urinary incontinence, dysuria) and symptoms associated with the bladder outlet obstruction (e.g. the difficulty in voiding initiating, intermittency, involuntary interruption of voiding, weak urinary stream, straining to void). Despite numerous studies, the pathogenesis of BPH remains not completely understood, and the condition awaits a comprehensive description. The current pathophysiological view emphasizes the role of hormonal dysregulation, locally released in the prostate growth factors action and a complex inflammatory, BPH-associated process with the release of a number of pro-proliferative mediators. The current BPH pharmacotherapy involves administration of α-1-blockers, 5-α-reductase inhibitors, antimuscarinic drugs (cholinolytics) and phosphodiesterase- 5-inhibitors. Progress in the BPH pathophysiology allows the disclosure of additional, potential targets of pharmacological intervention, such as ß-3 adrenoreceptor or CB1 cannabinoid receptor agonists, P2X1 purinergic or ETA endothelin receptors antagonists, RhoA/Rho kinase system inhibitors, nitric oxide donors, drugs indirectly (luteinizing hormone - releasing hormone antagonists) or directly (antiandrogens) abolishing the effect of testosterone and its derivatives or agents blocking the action of proinflammatory cytokines. The article briefly discusses the pathophysiology of the aforementioned issues and the current BPH management along with the future, potential opportunities for pharmacotherapy of the.

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

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

Peripheral vagus nerve stimulation significantly affects lipid composition and protein secondary structure within dopamine-related brain regions in rats.

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.

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

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

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol.

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 neurodegen-eration. 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.