Evaluation of selected protein biomarkers of renal function in rats with an experimental model of acute cyclophosphamide-induced cystitis treated with N-acetylcysteine.

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

Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, uromodulin, and cystatin C concentrations in an experimental rat model of ascending acute kidney injury induced by pyelonephritis.

Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C (CysC), uromodulin (UMOD), and some interleukins (IL-6 and IL-18) can be considered as diagnostic markers of acute kidney injury (AKI). The aim of this study was to verify the applicability of four urinary (u) markers, namely uNGAL, uKIM-1, uCysC, and uUMOD, for the diagnosis of ascending AKI induced by bacterial pyelonephritis. The study included 30 female rats that were divided into three groups (n = 10 each) and were inoculated transurethrally with various doses of Escherichia coli to induce isolated pyelonephritis (group 1, 105 CFU/ml), pyelonephritis-induced AKI (group 2, 107 CFU/ml), or AKI and urosepsis (group 3, 109 CFU/ml). The inoculate contained a highly virulent E. coli strain isolated from a patient with pyelonephritis. Urine samples were obtained prior to the inoculation and 7, 14, and 21 days thereafter. The concentrations of all assessed proteins were determined in the urine samples by ELISA. All the study groups showed elevated concentrations of uNGAL and uCysC at all study time points. The concentrations of uKIM-1 in group 1 were the same as that at the baseline, whereas it was elevated in groups 2 and 3 at all study time points. The concentrations of uUMOD in groups 1 and 2 tended to decrease with the time from inoculation, whereas it rapidly increased in group 3 at 21 days postinfection. uKIM-1 seems to be the only marker of ascending AKI associated with urinary tract infection. Elevated concentrations of uNGAL, uCysC, and uUMOD were found in both AKI and isolated pyelonephritis. Thus, it can be concluded that none of these markers can be used as a single diagnostic marker of ascending AKI, as it may produce false-negative results, leading to incorrect diagnosis, lack of adequate treatment, and increased mortality risk.

Effect of the different doses of acrylamide on acetylocholinoesterase activity, thiol groups, malondialdehyde concentrations in hypothalamus and selected muscles of mice.

Acrylamide is a chemical compound that typically forms in starchy food products during high-temperature cooking, including frying, baking and roasting. Acrylamide is a known lethal neurotoxin. Its discovery in some cooked starchy foods in 2002 prompted concerns about the carcinogenicity of those foods. Little is known about acrylamide's influence on the peripheral nerves. In our research we measured acrylamide's influence on the acetylcholinesterase activity in hypothalamus, heart muscle, skeletal muscles of the thigh and smooth muscle of the small intestine (males, Swiss strain) in relation to the thiol groups and malondialdehyde concentration. Acrylamide was injected intraperitoneally (20 and 40 mg/kg, i.e. 0.52 and 1.04 mg per animal). The hypothalamus and muscles were taken 24, 48, and 192 h after the injection. Acetylcholinesterase activity was significantly lower (P < 0.001 to P < 0.05) in all structures. It was accompanied by the statistically significant (P < 0.001 to P < 0.05) increase in malondialdehyde concentrations in most of the studied structures time periods and ACR doses. -SH groups concentrations were significantly depleted in selected structures (P < 0.001 to P < 0.05). The AChE activity evaluation in mice muscles and hypothalamus was very important because there are many evidences that acrylamide affects directly on the peripheral nerves. Thus, it causes structural damages and physiological changes. The results obtained in the present study provide evidence for the occurrence of oxidative stress after intraperitoneal injection of acrylamide to hypothalamus, heart muscle, skeletal muscles of the thigh and smooth muscle of the small intestine.

Prostaglandin-targeting agents and spectral heart rate variability in experimental partial bladder outlet obstruction in rats.

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.

The role of sensory C-fibers in response of vagal afferent stimulation by gastric distension in rats with experimental chronic gastric ulcer.

There is growing evidence that gastric vagal afferent input may contribute to the altered sensations associated with gastrointestinal disorders. The aim of our study was to evaluate gastric vagal afferents (VA) activity in rats with experimental gastric ulcer and ulcer healing. The study was carried out on rats with gastric ulcer (GU), including, a group with perivagal capsaicin pretreatment (CAP), a group with capsaicin administration in gastric ulcer (CAP+GU) animals and control rats. In all rats electrical VA activity was recorded and analysed. In GU rats recordings were carried out in chronic ulcer and ulcer healing. In GU and CAP+GU groups gastric balloon distensions with vagal recording was performed on 3(rd) day after ulcer induction. Usually, experimental GU healed spontaneously within 2 weeks. Three days after acetic acid application when GU fully develop, the frequency of the basal VA activity was almost 3-times higher than in the control intact rats and remained elevayed until 4(th) week after ulcer induction. VA response to gastric distension increased concomitantly with increased balloon volume in both GU and control animals, but it was several times higher in GU rats. Perivagal capsaicin application decreased the frequency of spontaneous VA activity and decreased the response of VA to gastric distension. In CAP+GU, spontaneous activity as well as the response to gastric distension were higher than in CAP rats. Our study shows that GU induced inflammatory changes increase sensitivity of gastric VA. Capsaicin-sensitive vagal afferent fibers may play some role in this phenomenon. Peripheral sensitization of VA persists even when gastric ulcer is completely healed.

Disturbances of the parasympathetic branch of the autonomic nervous system in patients with gastroesophageal reflux disease (GERD) estimated by short-term heart rate variability recordings.

Gastro-esophageal reflux disease (GERD) is the result of the acid contents regurgitation back from the stomach into the esophagus. According to the endoscopic findings, GERD can be divided into two main forms: non-erosive (NERD) and erosive reflux esophagitis. The pathogenesis of GERD is associated with the impaired function of the antireflux barrier. Disturbances of the autonomic nervous system (ANS), especially parasympathetic part of the ANS, may be also involved in the pathogenesis of this disease. The aim of our study was to establish the parasympathetic activity in patients with reflux esophagitis and in patients with symptomatic endoscopically negative reflux. Working hypothesis was the question, whether the possible parasympathetic activity disturbances, which are observed in all GERD patients, may be regarded as the primary or secondary to the esophagitis. All the participants (20 pts. with NERD, 20 pts. with reflux esophagitis and 20 healthy controls) underwent esophageal manometry, 24-hour ambulatory pH-monitoring, resting heart rate variability (HRV) recording and the deep breathing (DB) test with the continuous HRV recording. The results of the spectral analysis both of the short-term, resting HRV recordings and DB-evoked revealed the disturbances of the main power spectra components - LF and HF in both groups of patients in comparison with the control group. In our opinion, the observed HRV spectra changes in both groups of patients support the hypothesis that not only is the parasympathetic activity impairment associated with the pathogenesis of GERD but it is also the primary factor contributing to the pathophysiological mechanism of reflux.

Superfluidity of trapped dipolar fermi gases.

We derive the phase diagram for ultracold trapped dipolar Fermi gases. Below the critical value of the dipole-dipole interaction energy, the BCS transition into a superfluid phase ceases to exist. The critical dipole strength is obtained as a function of the trap aspect ratio. Alternatively, for a given dipole strength there is a critical value of the trap anisotropy for the BCS state to appear. The order parameter exhibits a novel nonmonotonic behavior at the criticality.

[Disturbances of the autonomic nervous system in gastroesophageal reflux disease]. / Zaburzenia ukladu autonomicznego w chorobie refluksowej przelyku.

GERD (Gastroesophageal Reflux Disease) is a common clinical problem, which affects the upper part of the gastrointestinal tract. The pathophysiology of GERD is associated with dysfunction of the various mechanisms called "the anti-reflux barrier". Lately, the disturbances of the autonomic nervous system (ANS) have been stressed in the pathogenesis of the different diseases (including GERD). The HRV examination (Heart Rate Variability) seems to be the best non-invasive method to evaluate the disturbances of ANS. The aim of our study was to detect possible ANS disturbances in GERD patients. 23 persons (healthy volunteers and GERD patients) took part in the examinations. 24-h-esophageal pH-metry and the resting, "deep breathing" (DB) test, as a short-term measurement of heart rate variability, were performed in every person. The results proved that the GERD patients have abnormal low values of the basic components that make up the HRV spectrum (LF and HF obtained from rest record and HF from record during DB). We demonstrated the evidence of functional ANS disturbances, which may be responsible for the changing the HRV parameters of the frequency domain analysis in GERD patients. The disturbances mentioned above are supposed to influence the normal modulation of the X (vagus) nerve, which plays an important role in the maintaining the physiological LES function.

The role of vagal efferents in regulation of gastric emptying and motility in rats.

UNLABELLED: Nonpharmacologic regulation of gastrointestinal motility may become competitive to actually applied methods in the nearest future. The Aim of this study was to evaluate effect of vagal stimulation on gastric motility and emptying. Experiments were performed on 30 male Wistar rats in vivo. Electrodes (120 um O Cr/Mo Microfil Industries) were placed on right vagal trunk below diaphragm without affecting its integrity. The fistula was implanted in gastric antrum. Stimulation parameters were: 0.3 V; 0.5 Hz, impulse duration--10 msec, time stimulation--5 min. Gastric pressure (balloon, Synectics pressure transducer, Sweden) and gastric emptying (red phenol method) were measured subsequently during and between stimulations. RESULTS: Stimulation significantly decreased amplitude of gastric contractions about 14% (52.7 +/- +/- 24.5 vs control 66.8 +/- 15.0; p < 0.05) and increased liquid gastric emptying from isotonic solution about 10% (87.35 +/- 4.75 vs control 75.31 +/- 11.24; p < 0.001), hypertonic liquid about 15% (49.05 +/- 12.16 vs control 34.1 +/- 13.68; p < 0.001) and hypotonic liquid about 7% (83.05 +/- 8.8 vs control 76.29 +/- 11.88). The frequency of gastric contractions did not change significantly in Fast Fourier Analysis of the period of stimulations and in control group. CCK concentrations were not significantly different between stimulated and control group (0.3 +/- 0.08 vs control 0.27 +/- 0.06 pmol/L). L-NAME infusion abolished completely acceleration of gastric emptying of isotonic solution (50.38 +/- 12.66 vc control 87.82 +/- 5.49; p < 0.05), hypertonic solution (32.17 +/- 15.09 vs control 51.65 +/- 10.74; p < 0.05) and hypotonic solution (60.42 +/- 12.05 vs control 82.67 +/- 8.06; p < 0.05) during electrical stimulation. DISCUSSION: In this experiment efferent stimulation of abdominal vagal nerve release neuromediators from afferent and efferent fibers. The main regulator seems to be nitric oxide. These results indicate the effective vagal nerve stimulation affects gastric motility and emptying. It is likely that observed effects reflect integrated response with activating vago-vagal reflexes and neurohumoral factors.