Local variation in brain temperature explains gender-specificity of working memory performance.

Introduction: Exploring gender differences in cognitive abilities offers vital insights into human brain functioning. Methods: Our study utilized advanced techniques like magnetic resonance thermometry, standard working memory n-back tasks, and functional MRI to investigate if gender-based variations in brain temperature correlate with distinct neuronal responses and working memory capabilities. Results: We observed a significant decrease in average brain temperature in males during working memory tasks, a phenomenon not seen in females. Although changes in female brain temperature were significantly lower than in males, we found an inverse relationship between the absolute temperature change (ATC) and cognitive performance, alongside a correlation with blood oxygen level dependent (BOLD) signal change induced by neural activity. This suggests that in females, ATC is a crucial determinant for the link between cognitive performance and BOLD responses, a linkage not evident in males. However, we also observed additional female specific BOLD responses aligned with comparable task performance to that of males. Discussion: Our results suggest that females compensate for their brain's heightened temperature sensitivity by activating additional neuronal networks to support working memory. This study not only underscores the complexity of gender differences in cognitive processing but also opens new avenues for understanding how temperature fluctuations influence brain functionality.

Antidepressant effects of selective adenosine receptor antagonists targeting the A1 and A2A receptors administered jointly with NMDA receptor ligands: behavioral, biochemical and molecular investigations in mice.

BACKGROUND: The objective of the study was to ascertain the antidepressant potential of the co-administration of NMDA receptor ligands and selective adenosine A1 and A2A receptor antagonists. METHODS: The forced swim test (FST) and spontaneous locomotor activity test were carried out in adult male naïve mice. Before the behavioral testing, animals received DPCPX (a selective adenosine A1 receptor antagonist, 1 mg/kg) or istradefylline (a selective adenosine A2A receptor antagonist, 0.5 mg/kg) in combination with L-701,324 (a potent NMDA receptor antagonist, 1 mg/kg), D-cycloserine (a partial agonist at the glycine recognition site of NMDA receptor, 2.5 mg/kg), CGP 37849 (a competitive NMDA receptor antagonist, 0.3 mg/kg) or MK-801 (a non-competitive NMDA receptor antagonist, 0.05 mg/kg). Additionally, serum BDNF level and the mRNA level of the Adora1, Comt, and Slc6a15 genes in the murine prefrontal cortex were determined. RESULTS: The obtained results showed that DPCPX and istradefylline administered jointly with NMDA receptor ligands (except for DPCPX + D-cycloserine combination) produced an antidepressant effect in the FST in mice without enhancement in spontaneous motility of animals. An elevation in BDNF concentration was noted in the D-cycloserine-treated group. Adora1 expression increased with L-701,324, DPCPX + D-cycloserine, and DPCPX + CGP 37849, while D-cycloserine, CGP 37849, and MK-801 led to a decrease. Comt mRNA levels dropped with DPCPX + L-701,324, istradefylline + L-701,324/CGP 37849 but increased with D-cycloserine, MK-801, CGP 37849 and DPCPX + MK-801/ CGP 37849. Slc6a15 levels were reduced by D-cycloserine, DPCPX + L-701,324 but rose with DPCPX + CGP 37849/MK-801 and istradefylline + D-cycloserine/MK-801/CGP 37849. CONCLUSION: Our study suggests that selective antagonists of adenosine receptors may enhance the antidepressant efficacy of NMDA receptor ligands highlighting a potential synergistic interaction between the adenosinergic and glutamatergic systems. Wherein, A2A receptor antagonists are seen as more promising candidates in this context. Given the intricate nature of changes in BDNF levels and the expression of Adora1, Comt, and Slc6a15 seen after drug combinations exerting antidepressant properties, further research and integrative approaches are crucial understand better the mechanisms underlying their antidepressant action.

Can We Go beyond Pathology? The Prognostic Role of Risk Scoring Tools for Cancer-Specific Survival of Patients with Bladder Cancer Undergoing Radical Cystectomy.

Radical cystectomy (RC) remains a mainstay surgical treatment for non-metastatic muscle-invasive and BCG-unresponsive bladder cancer. Various perioperative scoring tools assess comorbidity burden, complication risks, and cancer-specific mortality (CSM) risk. We investigated the prognostic value of these scores in patients who underwent RC between 2015 and 2021. Cox proportional hazards were used in survival analyses. Risk models' accuracy was assessed with the concordance index (C-index) and area under the curve. Among 215 included RC patients, 63 (29.3%) died, including 53 (24.7%) cancer-specific deaths, with a median follow-up of 39 months. The AJCC system, COBRA score, and Charlson comorbidity index (CCI) predicted CSM with low accuracy (C-index: 0.66, 0.65; 0.59, respectively). Multivariable Cox regression identified the AJCC system and CCI > 5 as significant CSM predictors. Additional factors included the extent of lymph node dissection, histology, smoking, presence of concomitant CIS, and neutrophil-to-lymphocyte ratio, and model accuracy was high (C-index: 0.80). The internal validation of the model with bootstrap samples revealed its slight optimism of 0.06. In conclusion, the accuracy of the AJCC staging system in the prediction of CSM is low and can be improved with the inclusion of other pathological data, CCI, smoking history and inflammatory indices.

Intensification of anxiety, symptoms of depression, and level of social support among women in pathological pregnancy - a cross-sectional preliminary study.

INTRODUCTION AND OBJECTIVE: Women in pathological pregnancy are a group of patients especially exposed to the risk of occurrence of psychological complications. The aim of the study was assessment of the risk of depressive and anxiety disorders, and the relationship between the intensity of symptoms and social support. MATERIAL AND METHODS: The study group were 300 patients hospitalized in the Department of Pathology of Pregnancy. The study was conducted using the State-Trait Anxiety Inventory (STAI), the Hospital Anxiety and Depression Scale (HADS), the Inventory of Socially Supportive Behaviours (ISSB), and an author-constructed socio-demographic questionnaire. RESULTS: The level of State Anxiety (STAI) was higher in respondents from the study group, compared to the control group. The level of anxiety (HADS-A) was higher in the control group than in women from the study group. The level of social informational support was higher in those from the control group, compared to those from the study group. The level of emotional support was lower in respondents from the study group, compared to those from the control group. Instrumental support negatively correlated with the symptoms of depression among women in physiological pregnancy. The lack of evaluative support statistically significantly correlated with anxiety among women hospitalized before labour. CONCLUSIONS: The results obtained suggest the necessity for the substantive preparation of medical and psychological staff employed in departments of pathology of pregnancy to provide proper emotional and informational support for hospitalized women.

Environmental Factors as the Main Hormonal Disruptors of Male Fertility.

INTRODUCTION AND OBJECTIVE: Many scientific reports confirm a systematic decline in male semen parameters over the last decades. This phenomenon has been observed in all parts of the world, and its occurrence is associated, among others, with the hazardous effects of some environmental factors. The environmental factors for which the adverse effect on male fertility has been proven include water, air, and soil pollution, as well as electromagnetic fields and ionizing radiation. The aim of this article was the evaluation of the effect of selected environmental factors on male reproductive capacity based on an analysis of the current scientific reports. REVIEW METHODS: A systematic literature review was carried out using three databases: PubMed, EMBASE, and Scopus. The search was limited to the period from 2015 until the end of December 2023. Brief description of the state of knowledge: Environmental factors, such as heavy metals, tobacco smoke, pesticides, dioxins, furans, phthalates, and bisphenols, are well-tested substances that exert an adverse effect on male fertility. A harmful effect of electromagnetic fields and water and air pollution on reproductive functions may be expected; however, this has not been fully proven. SUMMARY: Results obtained by many researchers published to date should evoke great concern regarding the quality of the environment in which we live, as well as fears about the effect of environmental factors not only on male fertility, but also on all aspects of human health. The majority of environmental pollutants affect the male body by causing oxidative stress and through their effect on the endocrine system.

Pelvic Organ Prolapse Reconstruction with the Chitosan-Based Novel Haemostatic Agent in Ovine Model-Preliminary Report.

This prospective study aimed to assess the feasibility of chitosan biomaterial and subcutaneous gel implantation in an ovine model, with implications for women with genital prolapse. Twenty-four ewes were divided into four groups (n = 6 per group): chitosan type B, chitosan type C, chitosan unmodified injections, and polypropylene mesh. Ovine models were chosen due to their morphological resemblance to human reproductive organs. Animals were sacrificed after 90 days for macroscopic, pathomorphological, and immunohistochemical analysis. In the chitosan type B group, IL-6 and IL-10 levels decreased after 28 days, while chitosan type C and injection groups exhibited higher IL-6 than IL-10 levels. The polypropylene group displayed the highest IL-6 and lowest IL-10 levels. Histological examination of the polypropylene group revealed no degenerative changes or inflammation, whereas chitosan injection induced local inflammation. Other groups exhibited no degenerative changes. Ewes implanted with chitosan displayed reduced inflammation compared to polypropylene-implanted ewes. Chitosan implantation facilitated vaginal tissue healing, in contrast to polypropylene mesh, which led to extrusion. While chitosan holds promise as an alternative to polypropylene mesh, further research is imperative for comprehensive evaluation. This study suggests the potential of a chitosan biomaterial in pelvic organ prolapse treatment, warranting additional investigation.

Frequency-dependent dynamics of steady-state visual evoked potentials under sustained flicker stimulation.

Steady-state visual evoked potentials (SSVEP) are electroencephalographic signals elicited when the brain is exposed to a visual stimulus with a steady frequency. We analyzed the temporal dynamics of SSVEP during sustained flicker stimulation at 5, 10, 15, 20 and 40 Hz. We found that the amplitudes of the responses were not stable over time. For a 5 Hz stimulus, the responses progressively increased, while, for higher flicker frequencies, the amplitude increased during the first few seconds and often showed a continuous decline afterward. We hypothesize that these two distinct sets of frequency-dependent SSVEP signal properties reflect the contribution of parvocellular and magnocellular visual pathways generating sustained and transient responses, respectively. These results may have important applications for SSVEP signals used in research and brain-computer interface technology and may contribute to a better understanding of the frequency-dependent temporal mechanisms involved in the processing of prolonged periodic visual stimuli.

Optical imaging of the intrinsic signal as a tool to characterize orientation sensitivity in the primary visual cortex of the young mouse.

We employed intrinsic signal optical imaging (ISOI) to investigate orientation sensitivity bias in the visual cortex of young mice. Optical signals were recorded in response to the moving light gratings stimulating ipsi­, contra­ and binocular eye inputs. ISOI allowed visualization of cortical areas activated by gratings of specific orientation and temporal changes of light scatter during visual stimulation. These results confirmed ISOI as a reliable technique for imaging the activity of large populations of neurons in the mouse visual cortex. Our results revealed that the contralateral ocular input activated a larger area of the primary visual cortex than the ipsilateral input, and caused the highest response amplitudes of light scatter signals to all ocular inputs. Horizontal gratings moved in vertical orientation induced the most significant changes in light scatter when presented contralaterally and binocularly, surpassing stimulations by vertical or oblique gratings. These observations suggest dedicated integration mechanisms for the combined inputs from both eyes. We also explored the relationship between point luminance change (PLC) of grating stimuli and ISOI time courses under various orientations of movements of the gratings and ocular inputs, finding higher cross-correlation values for cardinal orientations and ipsilateral inputs. These findings suggested specific activation of different neuronal assemblies within the mouse's primary visual cortex by grating stimuli of the corresponding orientation. However, further investigations are needed to examine this summation hypothesis. Our study highlights the potential of optical imaging as a valuable tool for exploring functional­anatomical relationships in the mouse visual system.

Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates - Harnessing the potential in the construction of materials for skin regeneration processes.

This study involved creating oligomeric conjugates of 3-hydroxy fatty acids and diclofenac, named Dic-oligo(3HAs). Advanced NMR techniques confirmed no free diclofenac in the mix. We tested diclofenac release under conditions resembling healthy and chronic wound skin. These oligomers were used to make P(3HO) blends, forming patches for drug delivery. Their preparation used the solvent casting/porogen leaching (SCPL) method. The patches' properties like porosity, roughness, and wettability were thoroughly analysed. Antimicrobial assays showed that Dic-oligo(3HAs) exhibited antimicrobial activity against reference (S. aureus, S. epidermis, S. faecalis) and clinical (Staphylococcus spp.) strains. Human keratinocytes (HaCaT) cell line tests, as per ISO 10993-5, showed no toxicity. A clear link between material roughness and HaCaT cell adhesion was found. Deep cell infiltration was verified using DAPI and phalloidin staining, observed under confocal microscopy. SEM also confirmed HaCaT cell growth on these scaffolds. The strong adhesion and proliferation of HaCaT cells on these materials indicate their potential as wound dressing layers. Additionally, the successful diclofenac release tests point to their applicability in treating both normal and chronic wounds.

The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms.

Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I-control, II-rats with rapamycin (RA)-induced OAB, III-rats administered IMP at a dose of 10 mg/kg/day, and IV-rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB.

The clinical efficacy and safety of outside-in transobturator sling with additional paraurethral fixation - The prospective longitudinal study.

Stress urinary incontinence (SUI) is a common condition that affect 30-40% of women in their lifetime. Midurethral slings (MUS) either suprapubic or transobturator can be safely used in the surgical treatment of SUI. The aim of this study was to collect clinical long-term data regarding safety and performance of transobturator sling with an additional tape fixation in women with urinary incontinence. This prospective longitudinal study was conducted on a group of 2086 female patients diagnosed with stress urinary incontinence. Follow up visits where scheduled 6 weeks, 6 and 12 months after surgery followed by annual checking when possible. Patients underwent transobturator sling procedure from 01.01.2011 to 31.12.2021. All patients had a monofilament tape inserted at the mid-urethra using outside-in technique (TOT) with 2 absorbable sutures parallel to the urethra. Success of surgery was defined as lack of any leakage during cough stress test whereas the subjective cure rate was determined by Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF). 87% of patients who were operated at least 10 years before assessment reported ICIQ -SF < 6. Main postoperative complications were storage symptoms - de novo urgency and voiding difficulties. TOT is safe and highly effective surgical treatment for (SUI) in a long-term observation.

Evaluation of Antidepressive-like Behaviours and Oxidative Stress Parameters in Mice Receiving Imipramine-Zinc Complex Compound.

The study aimed to evaluate the antidepressant-like effects of an imipramine-zinc (IMI-Zn) complex compound on mice and assess the level of oxidative stress parameters. The research also investigated whether the IMI-Zn complex showed superior antidepressant activity compared to individual treatments of both compounds at effective doses and their joint administration at subtherapeutic doses. The study was conducted on mice. Forced swim (FST), tail suspension (TST), and locomotor activity tests were used for behavioral studies. The results demonstrated the IMI-Zn complex's dose-dependent antidepressant potential when orally administered to mice. Its efficacy was similar to the separate administration of therapeutic doses of imipramine (IMI) and zinc (Zn) and their joint administration at subtherapeutic doses. Moreover, subjecting mice to acute stress did not significantly affect the activity of on glutathione peroxidase (GPX), glutathione reductase (GR), and total antioxidant status (TAS), possibly due to the short exposure time to the stress stimulus. By developing the IMI-Zn complex, it might be possible to simplify the treatment approach, potentially improving patient compliance by combining the therapeutic effects of both IMI and Zn within a single compound, thus addressing one of the contributing factors to non-compliance in depression therapy. The IMI-Zn complex could be a valuable strategy to optimize therapeutic outcomes and balance efficacy and tolerability.

Matrix metalloproteinase-3 in preeclamptic and normotensive pregnancies complicated by foetal growth restriction.

The aim of the present study was to assess the interrelationships between the level of matrix metalloproteinase-3 in the blood serum of pregnant women and the occurrence of pregnancy complications in the form of foetal growth restriction, idiopathic or in the course of preeclampsia. Methods: A total of 245 patients were included in the study. 65 of them are normotensive patients with idiopathic foetal growth restriction (FGR group). 115 women were diagnosed with severe preeclampsia. In the group of women with preeclampsia, there were 51 patients with adequate for gestational age foetal growth and 64 patients with the foetal growth restriction in the course of severe preeclampsia. The control group consisted of 65 healthy patients with normal pregnancy course, with no cardiovascular disorders at the present and in the history, normal blood pressure and normal intrauterine foetal growth. Matrix metalloproteinase-3 (MMP-3) in maternal circulation were determined by ELISA method. Results: In our studies, we observed elevated levels of matrix metalloproteinase-3 in preeclamptic women with pregnancies complicated by FGR and significantly lower in the group of normotensive women with idiopathic FGR. The mean values of MMP-3 were 33.50 ± 65.74 ng/mL [Median (min-max) 19.19 (2.05-454.53)] in the Control group, 21.22 ± 23.28 ng/mL [Median (min-max) 16.39 (3.45-156.29)] in the FGR group, 35.96 ± 46.14 ng/mL [Median (min-max) 25.21 (4.16-253.05)] in the P group and 52.81 ± 61.61 ng/mL [Median (min-max) 32.83 (5.06-314.14)] in preeclamptic women with FGR (group PI) respectively.The assessment of MMP-3 in the serum of women with pregnancies complicated by intrauterine foetal growth restriction with normal values of blood pressure and in the group of preeclamptic patients in relation to healthy pregnant women with uncomplicated pregnancies and in relation to preeclamptic patients with normal intrauterine foetal growth is the novelty of this study. Such a strict definition of each research group seems to allow for the assessment of each pregnancy complication separately. Conclusion: It seems that higher levels of MMP-3 in preeclamptic women may suggest the need for observation towards the risk of lower birth weight of newborns. This necessitates further research and a better integration in the clinical practice.

Women's Knowledge about Pharmacological and Non-Pharmacological Methods of Pain Relief in Labor.

This study aimed to assess knowledge about non-pharmacological pain-relief methods in labor among women who have given birth at least once. This cross-sectional study was conducted using an online survey among 466 adult women. The minimum sample size was estimated based on the number of labor admissions in the year before the study in Poland. The survey included questions about respondents' sociodemographics and knowledge of pain-relief methods. The knowledge score was calculated using the sum of correct answers. Non-parametric Spearman's correlation, Kruskal-Wallis and Wilcoxon variance tests were used. Antenatal classes (313/68.9%) and the Internet (248/54.6%) were the most common sources of knowledge. The most popular pharmacological pain-relief methods included epidural anesthesia (386/85.0%) and nitrous oxide (301/66.3%). Massage and breathing techniques were the most commonly known non-pharmacological methods (405/89.2% and 400/88.1%, respectively). The knowledge score about non-pharmacological methods was significantly higher as compared to the pharmacological methods score (rc = 0.85; p < 0.001). Respondents' age correlated with knowledge about non-pharmacological methods (rs = -0.10,p = 0.026) but did not correlate with knowledge about pharmacological methods. Educational level correlated with knowledge about pharmacological (rs = -0.13,p = 0.007) and non-pharmacological (rs = 0.14, p = 0.003) methods concerning pain relief in labor. No correlation was found between respondents' knowledge and gravidity, number of vaginal or cesarean deliveries, and hospital referral levels for previous deliveries. Our findings support the need to implement educational programs to increase evidence-based knowledge about pain-relief methods during labor in women.

Efficacy of Fractional CO2 Laser Treatment for Genitourinary Syndrome of Menopause in Short-Term Evaluation-Preliminary Study.

The postmenopausal state covers 40% of modern women's lives and 50-70% of postmenopausal women report GSM symptoms such as vaginal dryness, itching, frequent inflammations, lack of elasticity, or dyspareunia. Consequently, a safe and effective method of treatment is crucial. In a group of 125 patients, a prospective observational study was performed. The aim was to evaluate the clinical effectiveness of fractional CO2 laser in the treatment of GSM symptoms using a protocol of three procedures in 6-week intervals. The vaginal pH, VHIS, VMI, FSFI, and treatment satisfaction questionnaire were used. The fractional CO2 laser treatment was effective in improving all the objective forms of evaluation: vaginal pH (from 5.61 ± 0.50 at the baseline up to 4.69 ± 0.21 in the 6-week follow-up after the third procedure); VHIS (12.02 ± 1.89 at the baseline vs. 21.50 ± 1.76); VMI (21.5 ± 5.66 vs. 48.4 ± 4.46). Similar results were obtained for FSFI: 12.79 ± 5.351 vs. 24.39 ± 2.733, where 79.77% of patients were highly satisfied. Fractional CO2 laser therapy increases the quality of life by having a beneficial effect on the sexual function of women with GSM symptoms. This effect is obtained by restoring the correct structure and proportions of the cellular composition of the vaginal epithelium. This positive effect was confirmed by both objective and subjective forms of evaluating GSM symptom severity.

An Assessment of Serum Selenium Concentration in Women with Ovarian Cancer.

BACKGROUND: Available studies on the effect of serum selenium levels on the risk of malignancies show some conflicting results. In this study, we investigated the correlation between serum selenium levels and ovarian cancer occurrence. METHODS: 314 women (157 diseased patients and 157 healthy ones) matched in terms of age and BMI were included in the study. The measurements of selenium in the collected blood samples were performed using an ICP mass spectrometer. Univariable and multivariable analyzes were performed to determine the relationship between the factors under the study and the occurrence of ovarian cancer. RESULTS: The mean concentration of selenium was lower among diseased ones than among controls (53.31 µg/L vs. 78.99 µg/L). A decrease in selenium concentration was noticed with the advancement of ovarian cancer. In univariable and multivariable analyzes, a clear relationship between low selenium concentration and the occurrence of ovarian cancer was found (35.3 (95% CI: 11.2-111; p < 0.001) and 45.8 (95% CI: 12.8-164; p < 0.001)). CONCLUSION: The studied patients with ovarian cancer are characterized by statistically significant lower serum selenium levels than patients from the control group. Among the study group, a decrease in selenium concentration was observed with an increase in the FIGO stage. The determination of the role of selenium as a prophylactic factor in ovarian cancer requires further prospective studies.

The Cannabinoid Ligand Arachidonyl-2'-Chloroethylamide (ACEA) Ameliorates Depressive and Overactive Bladder Symptoms in a Corticosterone-Induced Female Wistar Rat Model.

There is growing need to increase the knowledge on the cannabinoid ligands in the treatment of overactive bladder. Among potential candidates, arachidonyl-2'-chloroethylamide (ACEA), a selective cannabinoid CB1 receptor agonist is proposed. The aim of this paper was to determine if ACEA, a selective cannabinoid CB1 receptor agonist, could reverse the effects of corticosterone (CORT), characteristic of depressive and bladder overactivity potential. The animals (48 female rats) were divided into four groups: I-control, II-received CORT, III-received ACEA, and IV-received the combination of CORT and ACEA. The conscious cystometry, forced swim test (FST), and locomotor activity measurements were performed 3 days after the last dose of ACEA, followed by ELISA measurements. In group IV, ACEA restored urodynamic parameters that were altered by CORT. CORT prolonged the immobility time in FST and the values were lowered by ACEA. ACEA normalized the expression of c-Fos in all the analyzed central micturition centers (group IV vs. group II). ACEA restored the CORT-induced changes in the biomarkers in urine (BDNF, NGF), bladder detrusor (VAChT, Rho kinase), bladder urothelium (CGRP, ATP, CRF, OCT-3, TRPV1), and hippocampus (TNF-α, IL-1ß and Il-6, CRF, IL-10, BDNF, NGF). In conclusion, ACEA was proven to reverse CORT-induced changes in both cystometric and biochemical parameters that are determinants of OAB/depression, which represents an example of an existing link between OAB and depression via cannabinoid receptors.

The role of the L-arginine-NO-cGMP-dependent pathway in the development of sensitization to mephedrone effects on the locomotor activity in mice.

Mephedrone, a popular psychostimulating substance widely used illegally in recreational purposes, exerts in rodents that regularly and intermittently were exposed to it a sensitized response to the drug. Behavioral sensitization is one of experimental models of drug dependency/abuse liability. In the present study we evaluated a potential involvement of the L-arginine-NO-cGMP pathway in the development of sensitization to the mephedrone-induced hyperlocomotion. Locomotor activity was measured automatically and experiments were performed on male Albino Swiss mice. We demonstrated that a 5-day administration of 7-nitroindazole (10 or 20 mg/kg/day) and L-NAME (50 mg/kg/day) suppressed the development of sensitization to the mephedrone-induced hyperlocomotion. As for L-arginine (125 or 250 mg/kg/day) and methylene blue (5 or 10 mg/kg/day) the obtained outcomes are inconclusive. Furthermore, the lower dose of L-NAME (25 mg/kg/day) surprisingly potentiated the development of sensitization to the mephedrone-induced effects on the spontaneous locomotor activity in mice. In conclusion, our data demonstrated that modulators of the L-arginine-NO-cGMP pathway may differently affect the development of sensitization to the locomotor stimulant effects of mephedrone. Inhibition of neuronal nitric oxide synthase (NOS) seems to prevent this process quite profoundly, non-selective inhibition of NOS may have a dual effect, whereas inhibition of soluble guanylate cyclase may only partially suppress the development of sensitization to the mephedrone-induced effects.

Study of Serum Copper and Zinc Levels and Serum Cu/Zn Ratio among Polish Women with Endometrial Cancer.

BACKGROUND: Micronutrients are important components for the homeostasis of the human body. The studies available in the literature of the subject on their impact on the risk of population diseases, including malignant neoplasms, are ambiguous. In this paper, the relationship between Cu and Zn serum levels and the occurrence of endometrial cancer have been analyzed. METHODS: 306 patients (153 test group and 153 control group) matched for age were analyzed for Cu and Zn levels. Microelements levels were determined for sera collected during the hospitalization of patients by means of an inductively coupled plasma mass spectrometry. In addition, the Cu/Zn ratio in the population included in the study was analyzed. Univariable and multivariable analyzes were used to examine the relationship between the factors under study and the incidence of endometrial cancer. RESULTS: Lower levels of elements were observed in the study group compared with the control group (Cu: 959.39 µg/L vs. 1176.42 µg/L, p < 0.001; Zn: 707.05 µg/L vs. 901.67 µg/L, p < 0.001). A statistically significant relationship with the occurrence of endometrial cancer was observed for Cu and Zn. The patients with the lowest Cu level had a significantly higher occurrence of endometrial cancer compared with reference tertile (OR 8.54; p < 0.001). Similarly, compared with the reference tertile, the patients with the lowest Zn levels had a significantly greater incidence of endometrial cancer (OR 15.0; p < 0.001). CONCLUSION: The results of the study suggest an association of endometrial cancer occurrence with lower Cu and Zn serum levels.

The efficacy of nebivolol on spontaneously hypertensive rats with overactive bladder - an experimental study.

Introduction: Overactive bladder (OAB) is a disease that significantly decreases quality of life. Adverse effects of the drugs currently used in OAB treatment limit their use in patients with hypertension. Nebivolol (a ß1-adrenergic receptor blocker) is approved for hypertension treatment, but also shows agonistic activity on ß3-adrenergic receptor, located in the urinary bladder. The aim of this study was to assess the impact of nebivolol on OAB symptoms and cardiovascular parameters in spontaneously hypertensive rats (SHR) - an animal model of OAB and hypertension. Material and methods: Female Wistar-Kyoto (WHY) and SHR rats were used in the experiments. Nebivolol was administered intra-arterially at a single daily dose of 0.05 mg/kg for 14 days. Subsequently, cystometry and bladder blood flow assessment were performed. Then, 24-hour measurement of heart rate, blood pressure, and urine production was carried out. In addition, the bladders of experimental rats were removed and processed to conduct biochemical analyses. Results: The main finding of this study is that the treatment with nebivolol resulted in an improvement of cystometric parameters characteristic for OAB in SHR. Nebivolol normalised blood pressure in SHR, while in WHY the cardiovascular parameters remained unchanged. Biomarkers characteristic for OAB were elevated in SHR compared to WHY, and nebivolol decreased their values in SHR while it had no influence on WHY. Conclusions: Nebivolol alleviates OAB symptoms and normalises blood pressure in SHRs. These results suggest that nebivolol may be a useful treatment alternative for OAB patients with pre-existing hypertension.