Prevalence and Management of Chronic Pain, Including Neuropathic Pain, in Dialysis Patients with End-Stage Renal Disease.

BACKGROUND Chronic kidney disease (CKD) is a growing global health concern. Chronic pain, as a common symptom of CKD, particularly among patients with end-stage renal disease (ESRD), is influenced by complications, dialysis procedures, and comorbidities. We aimed to evaluate chronic pain and probable neuropathic pain in 96 dialysis patients with ESRD using the Douleur Neuropathique 4 (DN4) questionnaire. MATERIAL AND METHODS A total of 96 patients from a single dialysis center were enrolled for the purpose of this study. ESRD was caused by diseases causing kidney damage, such as diabetes. The average duration of maintenance dialysis was 4.6±5.67 years. Comorbidities, functional and mental assessment, and pharmacological treatment data were collected using a questionnaire. The satisfaction with life scale was also used. Chronic pain was defined as lasting more than 3 months. The DN4 was used to determine the neuropathic component of pain. RESULTS Chronic pain was observed in 63.5% of the study participants, with 47.5% of them reporting the presence of neuropathic pain accompanied by a neuropathic component. Significantly more patients with chronic pain reported mood disorders and reduced life satisfaction, but there was no difference in their activities of daily living-assessed functional status or duration of dialysis. Patients experiencing chronic pain received non-steroidal anti-inflammatory drugs, paracetamol, and opioids. CONCLUSIONS Chronic pain, especially with a neuropathic component, is highly prevalent in patients with CKD, and its treatment remains ineffective. Undiagnosed components of pain can contribute to underdiagnosis and inadequate therapy. Further studies and staff education are needed to address this important issue.

Copper and Zinc Particles as Regulators of Cardiovascular System Function-A Review.

Copper and zinc are micronutrients that play a crucial role in many cellular pathways, act as cofactors in enzymatic systems, and hence, modulate enzyme activity. The regulation of these elements in homeostasis is precisely controlled by various mechanisms. Superoxide dismutase (SOD) is an enzyme requiring both copper and zinc for proper functioning. Additionally, there is an interaction between the concentrations of copper and zinc. Dietary ingestion of large amounts of zinc augments intestinal absorption of this trace element, resulting in copper deficiency secondary to zinc excess. The presence of an overabundance of copper and zinc has a detrimental impact on the cardiovascular system; however, the impact on vascular contractility varies. Copper plays a role in the modulation of vascular remodeling in the cardiac tissue, and the phenomenon of cuproptosis has been linked to the pathogenesis of coronary artery disease. The presence of copper has an observable effect on the vasorelaxation mediated by nitric oxide. The maintenance of proper levels of zinc within an organism influences SOD and is essential in the pathogenesis of myocardial ischemia/reperfusion injury. Recently, the effects of metal nanoparticles have been investigated due to their unique characteristics. On the other hand, dietary introduction of metal nanoparticles may result in vascular dysfunction, oxidative stress, and cellular DNA damage. Copper and zinc intake affect cardiovascular function, but more research is needed.

The In Vitro Effect of Steroid Hormones, Arachidonic Acid, and Kinases Inhibitors on Aquaporin 1, 2, 5, and 7 Gene Expression in the Porcine Uterine Luminal Epithelial Cells during the Estrous Cycle.

Aquaporins (AQPs) are integral membrane proteins, which play an important role in water homeostasis in the uterus. According to the literature, the expression of aquaporins in reproductive structures depends on the local hormonal milieu. The current study investigated the effect of selected PKA kinase inhibitor H89 and MAPK kinase inhibitor PD98059, on the expression of AQP1, 2, 5, and 7, and steroid hormones (E2), progesterone (P4), and arachidonic acid (AA) in the porcine endometrium on days 18-20 and 2-4 of the estrous cycle (the follicular phase where estrogen and follicle-stimulating hormone (FSH) are secreted increasingly in preparation for estrus and the luteal phase where the ovarian follicles begin the process of luteinization with the formation of the corpus luteum and progesterone secretion, respectively). The luminal epithelial cells were incubated in vitro in the presence of the aforementioned factors. The expression of mRNA was determined by the quantitative real-time PCR technique. In general, in Experiment 1, steroid hormones significantly increased expression of AQP1, 2, and 5 while arachidonic acid increased expression of AQP2 and AQP7. On the other hand, MAPK kinase inhibitor significantly decreased the expression of AQP1 and 5. In Experiment 2, E2, P4, or AA combined with kinase inhibitors differentially affected on AQPs expression. E2 in combination with PKA inhibitor significantly decreased expression of AQP1 but E2 or P4 combined with this inhibitor increased the expression of AQP5 and 7. On the contrary, E2 with PD98059 significantly increased AQP5 and AQP7 expression. Progesterone in combination with MAPK kinase inhibitor significantly downregulated the expression of AQP5 and upregulated AQP7. Arachidonic acid mixed with H89 or PD98059 caused a decrease in the expression of AQP5 and an increase of AQP7. The obtained results indicate that estradiol, progesterone, and arachidonic acid through PKA and MAPK signaling pathways regulate the expression of AQP1 and AQP5 in the porcine luminal epithelial cells in the periovulatory period.

Changes in Aquaporin 1, 5 and 9 Gene Expression in the Porcine Oviduct According to Estrous Cycle and Early Pregnancy.

Aquaporins (AQPs) are a group of small, integral membrane proteins which play an important role in fluid homeostasis in the reproductive system. In our previous study, we demonstrated AQP1, 5 and 9 protein expression and localization in the porcine oviduct. The presence of these isoforms could suggest their role in the transport of the ovum to the uterus by influencing the epithelial cells' production of oviductal fluid. The aim of this study was to evaluate the expression of AQP1, AQP5 and AQP9 in the infundibulum, ampulla and isthmus in the porcine oviduct during the estrous cycle (early luteal phase, days 2-4, medium luteal phase, days 10-12, late luteal phase days 14-16, follicular phase days 18-20) and pregnancy (period before implantation, days 14-16 and after the implantation, days 30-32) using the Real-Time PCR technique. As clearly demonstrated for the first time, AQP1, 5, and 9 gene expression is influenced by the estrus cycle and pregnancy. Furthermore, expression of AQPs in the porcine oviduct may provide the physiological medium that sustains and enhances fertilization and early cleavage-stage embryonic development. Overall, our study provides a characterization of oviduct AQPs, increasing our understanding of fluid homeostasis in the porcine oviduct to successfully establish and maintain pregnancy.

Pituitary Hormones (FSH, LH, PRL, and GH) Differentially Regulate AQP5 Expression in Porcine Ovarian Follicular Cells.

This study aimed to examine the effect of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and growth hormone (GH) on Aquaporin 5 (AQP5) expression in granulosa (Gc) and theca cells (Tc) from medium (MF) and large (LF) ovarian follicles of pigs. The results showed that GH significantly decreased the expression of AQP5 in Gc from MF in relation to the control. In the Gc of large follicles, PRL stimulated the expression of AQP5. However, the increased expression of AQP5 in the Tc of LF was indicated by GH and PRL in relation to the control. A significantly higher expression of the AQP5 protein in the Gc from MF and LF was indicated by FSH and PRL. In co-cultures, an increased expression of AQP5 was observed in the Gc from LF incubated with LH, PRL, and GH. A significantly increased expression of AQP5 was also observed in co-cultures of Tc from all type of follicles incubated with LH, whereas PRL stimulated the expression of AQP5 in Tc from MF. Moreover, AQP5 protein expression increased in the co-culture isolated from MF and LF after treatment with FSH, LH, PRL, and GH. AQP5 immunoreactivity was observed in the cytoplasm, mainly in the perinuclear region and endosomes, as well as in the cell membranes of Gc and Tc from the LF and MF.

Pituitary Gonadotropins, Prolactin and Growth Hormone Differentially Regulate AQP1 Expression in the Porcine Ovarian Follicular Cells.

The present in vitro study analyzed whether the hormones that affect the ovarian follicular steroidogenesis process also participate in the regulation of AQP1 mRNA and protein expression. Granulosa (Gc) and theca cells (Tc) of medium and large porcine ovarian follicles were exposed to follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) for 24 h in separated cells and co-cultures of these cells. Real-time PCR, Western blotting, immunofluorescence and volumetric analysis were then performed. Gonadotropins, PRL and GH had a stimulatory impact on AQP1 mRNA and protein expression in Gc and Tc of medium and large ovarian cells. Moreover, swelling assays, in response to a hypotonic environment, demonstrated the functional presence of AQPs in porcine Gc and Tc. Immunofluorescence analysis showed that AQP1 protein was mainly localized in the perinuclear region of the cytoplasm, endosomes and cell membranes of Gc and Tc from medium and large follicles. It seems possible that AQP1 present in Gc and Tc cells may be implicated not only in the regulation of water homeostasis required for follicle development but also in cell proliferation and migration.