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.

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.

Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention .

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

The effect of hyperosmolar stimuli and cyclophosphamide on the culture of normal rat urothelial cells in vitro.

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

Current management and future perspectives of overactive bladder (OAB) pharmacotherapy.

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

[Autonomic nervous system activity in IBS patients estimated by heart rate variability (HRV)]. / Aktywnosc autonomicznego ukladu nerwowego u pacjentów z zespolem jelita nadwrazliwego (IBS) oceniana metoda zmiennosci rytmu serca (HRV).

BACKGROUND: The mixed irritable bowel syndrome (IBS) is a functional disorder concerned with diarrhea and constipation without organic changes. The etiology of IBS is complex, concerning with the changing psychological factors and associated with the autonomic dysfunction ultimately. The aim of the study was the estimation of the autonomic nervous system (ANS) activity in IBS patients using time and frequency domain analysis parameters of heart rate variability. PATIENTS AND METHODS: 10 patients (47.3 +/- 12.5 years) with typical IBS symptoms in mixed form (diarrhoea and constipation) and 10 healthy persons (49.1 +/- 8 yrs) were studied. The control group was matched by age and gender. Each subject underwent 5-minutes, resting heart rate variability recording, during deep breathing (DB) test (6 breath/min) and 24-hour ECG monitoring using Holter equipment. In each case time and spectral domain analysis HRV parameters were obtained. RESULTS: Short-term HRV recording: In IBS patients we noted the decrease of the all parameters of the HRV spectral domain analysis in comparison to the control group (VLF--468.1 [ms2] vs. 906.3 [ms2]; LF--437.1 [ms2] vs. 811.6 [ms2]; HF--271.5 [ms2] vs. 854.6 [ms2]; p < 0.05 respectively). During DB test increase of LF power (2005.2 [ms2] vs. 6652.1 [ms2]; p < 0.05) and HF power (328.8 [ms2] vs. 901.7 [ms2]; p < 0.05) was observed in both group, however the response was lower in IBS patients. Circadian HRV recording: In IBS patients normalised parameter nHF was increased in both day and night periods in comparison to the control (35.5 [n.u.] and 38.5 [n.u.] vs. 22.0 [n.u.] and 25.7 [n.u.] respectively) while normalised nLF parameter was in both periods of registration lower in IBS patients of approximately 50% (the day--37.9 [n.u.] vs. 76.9 [n.u.]; the night--40.7 [n.u.] vs. 71.6 [n.u.]; p < 0.05). CONCLUSIONS: Our results indicate changes of the circadian ANS activity in patients with mixed IBS: the increase of the parasympathetic and the decrease of the sympathetic activity. However the ANS response to parasympathetic stimulation in DB test was diminished.

24-hour heart rate variability in patients with gastroesophageal reflux disease.

The GERD pathogenesis may be associated with disturbances of the autonomic nervous system (ANS), which can be revealed using heart rate variability studies (HRV). The aim of presented study was to estimate the circadian ANS activity in 24-hour HRV recordings in GERD patients, both in non-erosive form (NERD), and with erosive, inflammatory changes in the esophagus (ERD patients). Our results demonstrated disturbances in the parasympathetic ANS part, but they also delivered the proofs for possible sympathetic disorder. That is why the autonomic neuropathy in GERD patients may have mixed character.

[Motor and endocrine function disturbances of the gastrointestinal tract in patients with chronic renal failure (CRF)]. / Zaburzenia czynnosci motorycznej oraz endokrynnej przewodu pokarmowego u chorych z przewlekla niewydolnoscia nerek (PNN).

In the chronic renal failure (CRF) there are several upper gastrointestinal symptoms, which result from both disturbed motor function (associated with the delayed gastric emptying) and myoelectrical one (associated with abnormal electrogastrography registration). In patients suffering from CRF, disturbances of the endocrine digestive system function were also demonstrated, which are related to the observations of many gastrointestinal hormones increased levels.