Uniwersalność i personalizacja modelowania ścieżkowego w badaniu procesów lojalnościowych

W dobie rewolucji informacyjnej można dostrzec silny wzrost znaczenia zasobów niematerialnych przedsiębiorstw zarówno w procesie wyznaczania ich wartości rynkowej, jak również określania pozycji konkurencyjnej względem innych graczy rynkowych. W niniejszym artykule autor skoncentrował się na prezentacji głównych cech niematerialnych zasobów firmy wraz z ograniczeniami ich pomiaru, wynikającymi z ich specyficznego charakteru. Ponadto zostały szczegółowo omówione w perspektywie trzech różnych sektorów gospodarczych trzy modele ścieżkowe służące do pomiaru jednego z obszarów omawianej grupy zasobów, tj. satysfakcji i lojalności klientów

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

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

The influence of montelukast on the autonomic nervous system activity in rats with cyclophosphamide-induced hemorrhagic cystitis

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

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 toHRV 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

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

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

Resting heart rate variability and plasma noradrenaline level as a measurement of autonomic nervous system activity in mature, aging rats

Introduction and objective. Aging is a process that also affects the autonomic nervous system (ANS) making it less adaptable to environmental and intrinsic stimuli and affecting its ability to maintain body homeostasis. The aim of this study was to estimate the resting ANS function using heart rate variability (HRV) method and by noradrenaline measurement in aging, 2–12-months-old rats. Materials and method. Resting 15-minute-long ECG recordings were performed in anaesthetized rats with a subsequent spectral HRV analysis. Basic non-normalized HRV components in the range of very low (VLF), low (LF) and high (HF) frequency, along with the total HRV spectrum power (TP) were estimated. Moreover, normalized LF (nLF) and normalized HF (nHF) were calculated. Blood samples were also collected to assay plasma noradrenaline (NA) level. Results. In the overall assessment, plasma noradrenaline level as well as both TP and all non-normalized HRV components demonstrated a tendency for reduction when compared the first (2nd) and last (12th) months. In the case of nLF and nHF, a trend of nLF predominance in the 2nd and 3rd month was revealed while an inverse relation was observed from the 6th month on, with nHF superiority. Overall, males reached comparable or slightly higher NA and non-normalized HRV values compared to females, although most differences were not statistically significant. A parallel decline of LF (starting from the 10th month) and HF (from the 6th month) was demonstrated in both male and female animals. Female rats had a little more stable nLF and nHF course in the study time. Conclusions. Rat ANS aging is associated with global HRV decrease with parallel plasma NA decline, although without selective impairment of individual (sympathetic/parasympathetic) ANS components

Nephrotoxicity of a single dose of cyclophosphamide and ifosfamide in rats

Oxazaphosphorines (cyclophosphamide ñ CP, ifosfamide ñ IF) are alkylating cytostatics used in chemotherapy of cancer and autoimmune diseases. They have numerous adverse effects, including uro- and nephrotoxic, dependent of the type of drug, time of therapy and presence of any coexistent nephrotoxic factors in a treated patient. Purpose of this study was to estimate the renal function and the level of urinary bladder dysfunction occurring in rats following administration of a single, large CP/IF dose. The experiment involved 30 rats who were administered a single intraperitoneal dose of 150 mg/kg b.w. of CP (group 1) or IF (group 2) or normal saline (group 3 ñ control), respectively. Following the administration animals were placed in individual metabolic cages. 24 h later rats were sacrificed, blood collected and nephrectomy and cystectomy performed in order to prepare specimens for histopathological analysis. Circadian diuresis was also assessed, along with a qualitative urine assessment with strip tests and laboratory renal function parameters in plasma and urine: sodium, urea, creatinine and uric acid levels, and circadian elimination of sodium, potassium, urea, creatinine, uric acid and protein. Creatinine clearance, urea clearance and fractionated sodium elimination (FENa) and renal failure index (RFI) were also calculated. An increased diuresis and acidification of urine with reduced circadian elimination of potassium and a significant proteinuria, as well as increased plasma levels of creatinine and urea were found in the group of rats that received a single dose of CP, compared to control animals. Rats treated with IF also demonstrated acidification of urine, reduced circadian potassium elimination, a significant proteinuria and increased plasma creatinine and urea levels, but their diuresis was comparable to that observed in control animals. IF-treated animals were also characterized by reduced urea clearance, FENa and RFI. Histopathological analysis confirmed presence of inflammatory changes in urinary bladders in both groups 1 and 2, and absence of any significant morphological disorders in kidneys. Obtained results suggest a dysfunction of distal tubules and collective tubules developing as a result of administration of a single nephrotoxic dose of IF/CP. FENa and RFI results indicate also a higher nephrotoxic potential of IF administered as a single dose

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 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

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

A syndrome with urgency, with or without associated urine incontinence and usually accompanied by higher urinary frequency and nocturia has been named “overactive bladder; OAB”. OAB is an entity with complex pathophysiology, involving both myogenic and neurogenic (afferent / efferent bladder innervation) disturbances. OAB symptoms accompany benign prostatic hypertrophy - BPH (“obstructive OAB”). The aim of the study was to estimate the autonomic nervous system activity (ANS) in the experimental bladder outlet obstruction (BOO) which was an animal model of the human BPH. The study was conducted using 30 female rats, divided into two groups: BOO animals (n=15), with surgically induced BOO (by partial ligation of the proximal urethra) and control ones (n=15), which underwent sham procedure (without urethral ligation). Two weeks after the surgery, in both groups, ANS activity was estimated using time- and spectral analysis of the heart rate variability recordings. The bladder overactivity in BOO animals was confirmed using urodynamic recordings and bladder histological assessment, juxtaposed against the results of the control group. The key finding of our study was the development of autonomic disturbances in bladder outlet obstruction (BOO) rats. Our study revealed that BOO animals were characterised by diminished rMSSD and spectral HRV parameters: TP, LF and HF, in comparison with the control group. The normalised nLF and nHF parameters did not differ significantly in both groups, although slight changes in the nLF (increased) and nHF (decreased) were noted in BOO group. The absolute VLF value was almost the same in both studied populations, however, the percentage part of this component in the appropriate HRV spectrum differed considerably in both studied groups. In BOO animals, VLF percentage amounted to about 90�20whereas in control animals this parameter reached only about 53�0of the total power spectrum.Thus, to sum up, our findings suggest autonomic imbalance with decreased global autonomic tension and diminished parasympathetic activity with relatively sympathetic overactivity.