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.

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.

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.

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.

[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.

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.

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.

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.

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.

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.

The non-motor complications in Parkinson's disease - what can we learn from animal models?

Sporadic Parkinson's disease is a widespread human disease that has never been reported in non-human vertebrates. The etiopathogenesis of the non-motor symptoms in the disease is not well understood and it is difficult to interpret the roles of affected neurotransmitters in currently available animal models. Most of the non-motor symptoms do not correlate with the stage of motor deficits and precede the development of motor symptoms by many years, before the permanent loss of dopaminergic neurons in the basal ganglia. The aim of this review is to briefly summarize the advantages and limitations of the well-recognized mammalian animal models with special regard to the non-motor complications of the prodromal and early stage Parkinson's disease.

Spectral heart rate variability in rats with cyclophosphamide-induced hemorrhagic cystitis treated with cyclooxygenase inhibitors.

The pathogenesis of cyclophosphamide-induced hemorrhagic cystitis (CP-HC) is complex, involving the im- pact of many systemically and locally released agents on autonomic nervous system (ANS) activity, that affects bladder functioning. The purpose of our study was to provide an indirect evaluation of ANS functional status in experimental CP-HC model, involving prostaglandin synthesis block resulting from administration of cyclooxygenase inhibitors. The ANS activity was estimated through the spectral analysis of heart rate variability (HRV) in CP-HC rats divided into three study groups: 1-control, 2-treated with meloxicam (MLX) that preferentially blocks COX-2, and 3-treated with piroxicam (PRX) that inhibits COX1 and 2 activity. In animals treated either with MLX or PRX, the percent distribution of the spectrum in relation to components of very low (VLF) and low (LF) frequency was not different from the control group. PRX-treated group displayed nearly two times lower percent share of the high frequency (HF) component compared to the control. Moreover, an increase of the normalized LF (nLF) value with simultaneous reduction of the normalized HF (nHF) value were noted in PRX-treated rat with no change of these parameters for MLX-treated rats. The HRV analysis in CP-HC rats receiving PRX, indicated a functional reorganization manifested by reduced parasym- pathetic activity and increased sympathetic tonus. A partial prostaglandin synthesis block caused by COX-2 inhibitor (meloxicam) caused no significant changes of evaluated HRV parameters compared to the control. Assessing functional changes of the ANS caused by prostaglandin synthesis block it should be stated that prostaglandins synthesized by the constitutive COX-1 isoform seem to maintain the parasympathetic activity, which may be associated with the cholinergic anti-inflammatory pathway and resolution of inflammation in course of cyclophosphamide-induced cystitis.

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.

Electromagnetic field induced biological effects in humans.

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).

[Evaluation of heart rate and blood pressure variability in Parkinson's disease patients after bilateral subthalamic deep brain stimulation]. / Ocena zmiennosci rytmu serca i cisnienia tetniczego u osób z choroba Parkinsona po obustronnej glebokiej stymulacji jadra niskowzgórzowego.

INTRODUCTION: Autonomic dysfunctions are the most common non-motor symptoms of Parkinson's disease (PD) and often precede the motor symptoms of the disease. Autonomic dysfunction may be a dominant symptom of the advanced stages of PD as well as a major cause of patient disability. Despite the wide use of neurostimulation in clinical practice, the effect of deep brain stimulation of subthalamic nucleus (STN DBS) on autonomic symptoms of PD still remains only partially understood. The aim of the study is evaluation of heart rate variability (HRV) and blood pressure variability (BPV) in patients with PD before STN DBS and following bilateral STN DBS. MATERIAL AND METHODS: The study included 25 subjects aged between 31 and 71 years, diagnosed with the idiopathic PD and selected for treatment with STN DBS. All the patients were in advanced stages of PD, disease duration ranged from 5 to 22 years. The patients enrolled into this study underwent STN DBS. Neurological examination including assessment of the severity of parkinsonism according to UPDRS scale, a psychological examination and an electrophysiological examination of autonomic disturbances based on heart rate and blood pressure variability were conducted on all patients two weeks before and three months after STN DBS. RESULTS: After STN DBS an improvement in terms of the analyzed parts of the UPDRS has been shown. The improvement of motor disorders assessed by III part UPDRS during the "off" medication/stimulation "on" was 67.8%. Orthostatic hypotension before the STN DBS procedure was observed in 56% of patients and after STN DBS in 53% of them. Before STN DBS the imbalance of the sympathetic--parasympathetic components with the predominance of the sympathetic based on HRV parameters--the ratio LF/HF-RRI (2.5) and a higher rate of LFnu (61.3%) than HFnu (38.6%) has been shown. Three months post STN DBS an increase parameters of spectral analysis of HRV in the low frequency LF-RRI, and high-frequency HF-RRI and the total power spectrum PSD-RRI was observed. After STN DBS an increase of parameters of spectral analysis of systolic BPV, very low frequency VLF-sBP, low frequency LF-sBP and total power spectrum PSD-sBP was noted. CONCLUSIONS: Results of the study suggest that STN DBS is an effective treatment method of both motor symptoms and autonomic dysfunctions. The disturbances of HRV and BPV before and after STN DBS indicate the increase of autonomic system activity with sympathetic dominance.

Indirect autonomic nervous system activity assessment with heart rate variability in rats with cyclophosphamide-induced hemorrhagic cystitis treated with melatonin or agomelatine.

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.

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.

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--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.