Search Results (138)

The kidney plays a critical role in maintaining the homeostasis of body fluid by filtration of metabolic wastes and reabsorption of nutrients. Due to the overload, a vast of energy is required through aerobic metabolism, which inevitably leads to the generation of reactive oxygen species (ROS) in the kidney. Under unstressed conditions, ROS are counteracted by antioxidant systems and maintained at low levels, which are involved in signal transduction and physiological processes. Accumulating evidence indicates that the reduction–oxidation (redox) system interacts with renal tubular transport. Redox imbalance or dysfunction of tubular transport leads to renal disease. Here, we discuss the ROS and antioxidant systems in the kidney and outline the metabolic dysfunction that is a common feature of renal disease. Importantly, we describe the key molecules involved in renal tubular transport and their relationship to the redox system and, finally, summarize the impact of their dysregulation on the pathogenesis and progression of acute and chronic kidney disease. Full article

Acute kidney injury (AKI) describes a condition associated with elevated serum creatinine levels and decreased glomerular filtration rate. AKI can develop as a result of sepsis, the nephrotoxic properties of several drugs, and ischemia/reperfusion injury. Renal damage can be associated with metabolic acidosis, fluid overload, and ionic disorders. As the molecular background of the pathogenesis of AKI is insufficiently understood, more studies are needed to identify the key signaling pathways and molecules involved in the progression of AKI. Consequently, future treatment methods may be able to restore organ function more rapidly and prevent progression to chronic kidney disease. MicroRNAs (miRNAs) are small molecules that belong to the non-coding RNA family. Recently, numerous studies have demonstrated the altered expression profile of miRNAs in various diseases, including inflammatory and neoplastic conditions. As miRNAs are major regulators of gene expression, their dysregulation is associated with impaired homeostasis and cellular behavior. The aim of this article is to discuss current evidence on the involvement of miRNAs in the pathogenesis of AKI. Full article

Sepsis is a complex syndrome with heterogeneous clinical presentation and outcome, characterized by an abnormal inflammatory response, potentially leading to multiorgan damage and hemodynamic instability. Early resuscitation with fluids and timely control of the source of sepsis are key treatment targets in septic patients. Recommendations on when to add vasopressors and inotropes are mostly empirical and anecdotal, therefore remaining a topic of debate. This narrative review was developed to present and discuss current options in the early management of hemodynamic derangement induced by sepsis. We discuss the strengths and drawbacks of the recommended treatment with fluids and how to optimize volume resuscitation in order to avoid fluid overload or under-resuscitation. The choice and timing of vasopressor use represent hot topics in the early management of septic patients. We describe the advantages and limitations of the early introduction of vasopressors and new catecholamine-sparing strategies. We conclude with a description of the inotropes, considering that the heart plays a key role in the pathophysiology of septic shock. Full article

Background and Objectives: The use of a bipolar resectoscope has become popular due to the lower risk of hyponatremia. However, gynecologists might overlook the risk of water intoxication. Water intoxication is associated with the infusion of distending fluid. We were interested in the prediction of the infused distending fluid volume in the era of bipolar hysteroscopy. Thus, the aim of this study was to identify the predictors of the infused distending fluid volume for hysteroscopic myomectomy. Materials and Methods: All consecutive women who underwent monopolar (n = 45) or bipolar (n = 137) hysteroscopic myomectomy were reviewed. Results: Myoma diameter (cm, coefficient = 680 mL, 95% confidence interval (CI) = 334–1025 mL, p <0.001) and bipolar hysteroscopy (coefficient = 1629 mL, 95% CI = 507–2752 mL, p = 0.005) were independent predictors of infused distending fluid volume. A myoma diameter ≥4.0 cm was the optimal cutoff value to predict the presence of >5000 mL of infused distending fluid. One woman in the bipolar group developed life-threatening water intoxication. Conclusions: Myoma diameter is associated with an increase in infused distending fluid volume, especially for myomas ≥4 cm. Meticulous monitoring of the infused distension fluid volume is still crucial to avoid fluid overload during bipolar hysteroscopic myomectomy. Full article

Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat’s striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl₂/kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson’s disease and other copper dysregulation states. Full article

Background and Objectives: Left ventricular hypertrophy (LVH) represents a significant cardiovascular risk in patients undergoing chronic hemodialysis (CHD). A large inferior vena cava diameter (IVCD), potentially indicative of fluid overload and a contributing factor to elevated cardiovascular risk, has not been sufficiently explored. Therefore, our study aims to gain further insights into this aspect. Materials and Methods: A retrospective cohort study enrolled patients receiving CHD in a single medical center with available echocardiography from October to December 2018. They were categorized into four groups based on LVH geometry and IVCD. Cox proportional hazard models assessed the risk of major adverse cardiovascular effects (MACEs) and cardiovascular and overall mortality after multivariate adjustments. Kaplan–Meier analysis depicted MACE-free events and survival during the follow-up time. Results: Of the 175 CHD patients, 38, 42, 45, and 50 exhibited small IVCD with eccentric and concentric LVH and large IVCD with eccentric and concentric LVH, respectively. Compared to small IVCD and eccentric LVH, large IVCD and eccentric LVH had the highest risk of MACEs, followed by large IVCD and concentric LVH (aHR: 4.40, 3.60; 95% CI: 1.58–12.23, 1.28–10.12, respectively). As for cardiovascular mortality, large IVCD and concentric LVH had the highest risk, followed by large IVCD and eccentric LVH, and small IVCD and concentric LVH. (aHR: 14.34, 10.23, 8.87; 95% CI: 1.99–103.35, 1.41–74.33; 1.01–77.87). The trend in overall mortality risk among the groups was similar to that of cardiovascular mortality. Conclusions: LVH geometry and IVCD co-modify the risk of MACEs and cardiovascular and overall mortality in CHD patients. The highest risk of MACEs is associated with large IVCD and eccentric LVH, while the highest risk of cardiovascular and overall mortality is linked with large IVCD and concentric LVH. Full article

Ovalbumin (OVA), a protein vital for chick embryo nutrition, hydration, and antimicrobial protection, together with other egg-white proteins, migrates to the amniotic fluid and is orally absorbed by the embryo during embryogenesis. Recently, it has been shown that for optimal eggshell quality, the hen diet can be supplemented with manganese. Although essential for embryonic development, manganese in excess causes neurotoxicity. This study investigates whether OVA may be involved in the regulation of manganese levels. The binding of Mn(II) to OVA was investigated using electron paramagnetic resonance (EPR) spectroscopy. The results show that OVA binds a maximum of two Mn(II) ions, one with slightly weaker affinity, even in a 10-fold excess, suggesting it may have a protective role from Mn(II) overload. It seems that the binding of Mn(II), or the presence of excess Mn(II), does not affect OVA’s tertiary structure, as evidenced from fluorescence and UV/vis measurements. Comparative analysis with bovine and human serum albumins revealed that they exhibit higher affinities for Mn(II) than OVA, most likely due to their essentially different physiological roles. These findings suggest that OVA does not play a role in the transport and storage of manganese; however, it may be involved in embryo protection from manganese-induced toxicity. Full article

Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting. Full article

Background: The prediction of fluid responsiveness in critical patients helps clinicians in decision making to avoid either under- or overloading of fluid. This study was designed to determine whether lung recruitment maneuver (LRM) would have an effect on the predictability of fluid responsiveness by the changes of hemodynamic parameters in pediatric patients who were receiving lung-protective ventilation and one-lung ventilation (OLV). Methods: A total of 34 children, aged 1–6 years old, scheduled for heart surgeries via right thoracotomy were enrolled. Patients were anesthetized and OLV with lung-protection ventilation settings was established, and then, positioned on left lateral decubitus. LRM and volume expansion (VE) were performed in sequence. Heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP) diastolic arterial pressure (DAP), stroke volume (SV), stroke volume variation (SVV), and pulse pressure variation (PPV) were recorded via an A-line based monitor system at the following time points: before and after LRM (T1 and T2) and before and after VE (T3 and T4). An increase in stroke volume (SV) or mean arterial pressure (MAP) of ≥10% following fluid loading identified fluid responders. The predictability of fluid responsiveness by the changes of SV (ΔSV_LRM) and MAP (ΔMAP_LRM) after LRM and VE were statistically evaluated by receiver operating characteristic curves [area under the curves (AUC)]. Results: SVs in all patients were significantly decreased after LRM (p < 0.01) and then, increased and returned to baseline after VE (p < 0.01). In total, 16 out of 34 patients who were fluid responders had significantly lower SV after LRM compared to that in fluid non-responders. The area under the receiver operating characteristic curves for ΔSV_LRM was 0.828 (95% confidence interval [CI], 0.660 to 0.935; p < 0.001) and it indicated that ΔSV_LRM was able to predict the fluid responsiveness of pediatric patients. MAPs in all patients were also decreased significantly after LRM, and 12 of them fell into the category of fluid responders after VE. Statistically, ΔMAP_LRM did not predict fluid responsiveness when LRM was considered as an influential factor (p = 0.07). Conclusions: ΔSV_LRM, but not ΔMAP_LRM, showed great reliability in the prediction of the fluid responsiveness following VE in children during one-lung ventilation with lung-protective settings. Trial registration: ChiCTR2300070690. Full article

Background: Shiga toxin-producing Escherichia coli–haemolytic uremic syndrome (STEC-HUS) can result in kidney and neurological complications. Early volume-expansion therapy has been shown to improve outcomes, but caution is required to avoid fluid overload. Lung ultrasound scanning (LUS) can be used to detect fluid overload and may be useful in monitoring hydration therapy. Methods: This prospective observational pilot study involved children with STEC-HUS who were recruited from a regional paediatric nephrology centre. B-line quantification by LUS was used to assess fluid status at the emergency department (ED) admission and correlated with the decrease in patient weight from the target weight. A control group of children on chronic dialysis therapy with episodes of symptomatic fluid overload was also enrolled in order to establish a B-line threshold indicative of severe lung congestion. Another cohort of “healthy” children, without renal or lung-related diseases, and without clinical signs of fluid overload was also enrolled in order to establish a B-line threshold indicative of euvolemia. Results: LUS assessment was performed in 10 children with STEC-HUS at ED admission, showing an average of three B-lines (range 0–10). LUS was also performed in 53 euvolemic children admitted to the ED not showing kidney and lung disease (healthy controls), showing a median value of two B-lines (range 0–7), not significantly different from children with STEC-HUS at admission (p = 0.92). Children with STEC-HUS with neurological involvement during the acute phase and those requiring dialysis presented a significantly lower number of B-lines at admission compared to patients with a good clinical course (p < 0.001). Patients with long-term renal impairment also presented a lower number of B-lines at disease onset (p = 0.03). Conclusions: LUS is a useful technique for monitoring intravenous hydration therapy in paediatric patients with STEC-HUS. A low number of B-lines at ED admission (<5 B-lines) was associated with worse short-term and long-term outcomes. Further studies are needed to determine the efficacy and safety of an LUS-guided strategy for reducing complications in children with STEC-HUS. Full article

Hemodialysis (HD) is a life-sustaining membrane-based therapy that is essential for managing kidney failure. However, it can have significant physical and psychological effects on patients due to chronic or acute consequences related to membrane bioincompatibility. End-stage renal disease (ESRD) patients on hemodialysis have a high incidence of psychiatric illness, particularly depression and anxiety disorders, and poor quality of life has been observed. Dialysis can also lead to physical symptoms of its own, such as fatigue, loss of appetite, anemia, low blood pressure, and fluid overload, in addition to the symptoms associated with kidney failure. Therefore, this critical review aims to comprehensively understand the impact of dialysis membrane bioincompatibility and the use of varying molecular weight cut-off membranes on the physical and psychological symptoms experienced by dialysis patients. We analyzed the latest research on the correlation between major inflammatory biomarkers released in patients’ blood due to membrane incompatibility, as well as the critical influence of low levels of hemoglobin and vital proteins such as human serum albumin due to the use of high-cut-off membranes and correlated these factors with the physical and psychological symptoms experienced by dialysis patients. Furthermore, our study aims to provide valuable insights into the impact of dialysis on critical symptoms, higher hospitalization rates, and the quality of life of First Nations, as well as child and youth dialysis patients, in addition to diabetic dialysis patients. Our goal is to identify potential interventions aiming to optimize the dialysis membrane and minimize its negative effects on patients, ultimately improving their well-being and long-term outcomes. Full article

Heart failure (HF) is a complex clinical syndrome associated with significant morbidity, mortality, and healthcare costs. It is characterized by various structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressure and/or inadequate cardiac output at rest and/or during exercise. These dysfunctions can originate from a variety of conditions, including coronary artery disease, hypertension, cardiomyopathies, heart valve disorders, arrhythmias, and other lifestyle or systemic factors. Identifying the underlying cause is crucial for detecting reversible or treatable forms of HF. Recent epidemiological studies indicate that there has not been an increase in the incidence of the disease. Instead, patients seem to experience a chronic trajectory marked by frequent hospitalizations and stagnant mortality rates. Managing these patients requires a multidisciplinary approach that focuses on preventing disease progression, controlling symptoms, and preventing acute decompensations. In the outpatient setting, patient self-care plays a vital role in achieving these goals. This involves implementing necessary lifestyle changes and promptly recognizing symptoms/signs such as dyspnea, lower limb edema, or unexpected weight gain over a few days, to alert the healthcare team for evaluation of medication adjustments. Traditional methods of HF monitoring, such as symptom assessment and periodic clinic visits, may not capture subtle changes in hemodynamics. Sensor-based technologies offer a promising solution for remote monitoring of HF patients, enabling early detection of fluid overload and optimization of medical therapy. In this review, we provide an overview of the CardioMEMS device, a novel sensor-based system for pulmonary artery pressure monitoring in HF patients. We discuss the technical aspects, clinical evidence, and future directions of CardioMEMS in HF management. Full article

A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid responsiveness via a passive leg-raising maneuver (PLR) before a spontaneous breathing trial (SBT), is associated with less extubation failure in ventilated patients with a high fluid balance admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Their postoperative fluid balance was +4476 {3697, 5722} mL. PLR maneuvers were conducted upon ICU admission (T1) and pre SBT (T2). Cardiac index (CI) changes were recorded before and after each SBT (T3). Seven patients were fluid-responsive at T1, and twelve were responsive at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between the fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 {2.8, 3.7} to 3.7 {3.4, 4.1} mL/min/m² (p = 0.045). All fluid-responsive patients at T2 were extubated after the SBTs and consolidated extubation. Two out of three of the fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post LT may start weaning earlier and achieve successful extubation despite a high postoperative fluid balance. This highlights the profound impact of personalized assessments of cardiovascular state on critical surgical patients. Full article

Chronic overloading of the cartilage can lead to its irreversible destruction, as observed in people with osteoarthritis. The floating skeleton model previously introduced postulates that overloading begins and progresses when a joint is isolated from the hydrostatical connection with other joints. Such a connection occurs via the interstitial fluid in subperiosteal space and allows for pressure transmission between synovial capsules modulating intra-articular pressure. In the current study, a simple experiment was performed to model an obstruction in the subperiosteal hydrostatic pressure conductivity between joints to illustrate the effect of that obstruction on loads borne by the joint. When the obstruction was removed, the load experienced by the joint was reduced as it was redistributed throughout the model structure. The experiment demonstrated that contact pressures can be redistributed when the conditions of Pascal’s Law are met. Full article

Fluid overload in hemodialysis patients (HD) has been proven to be associated with inflammation. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) appear to be inadequately counterbalanced by the anti-inflammatory cytokine interleukin-10 (IL-10). We initiated a cross-sectional study enrolling 40 HD patients who were categorized by a bioimpedance measurement in normovolemic (N; 23) and hypervolemic (H; 17) groups to test whether IL-10- and IL-6-related signal transduction pathways (signal transducer of transcript 3: STAT3) and/or a post-transcriptional regulating mechanism (miR-142) are impaired by hypervolemia. IL-10/IL-6 transcript and protein production by PBMCs (peripheral blood mononuclear cells) were determined. Phospho-flow cytometry was used to detect the phosphorylated forms of STAT3 (pY705 and pS727). miR-142-3p/5p levels were detected by qPCR. Hypervolemic patients were older, more frequently had diabetes, and showed higher CRP levels. IL-10 transcripts were elevated in H patients but not IL-10 protein levels. In spite of the elevated mRNA expression of the suppressor of cytokine expression 3 (SOCS3), IL-6 mRNA and protein expression were increased in immune cells of H patients. The percentage of cells staining positive for STAT3 (pY705) were comparable in both groups; in STAT3 (pS727), however, the signal needed for full transactivation was decreased in H patients. miR-142-3p, a proven target of IL-10 and IL-6, was significantly elevated in H patients. Insufficient phosphorylation of STAT3 may impair inflammatory and anti-inflammatory cytokine signaling. How far degradative mechanisms induced by elevated miR-142-3p levels contribute to an inefficient anti-inflammatory IL-10 signaling remains elusive. Full article