Regulation Of Fluid Balance Research Articles

RhoprCAPA-2 acts as a gonadotropin regulating reproduction in adult female, Rhodnius prolixus

CAPA peptides play diverse roles in insects, modulating muscle contraction, regulating fluid balance, and reproduction. In Rhodnius prolixus, a hematophagous insect and a vector for human Chagas disease, three CAPA peptides are encoded by the capability gene, including RhoprCAPA-1, RhoprCAPA-2, and RhoprCAPA-PK-1. RhoprCAPA-2 is an anti-diuretic hormone in R. prolixus. Here, we explore the involvement of RhoprCAPA-2 in reproduction in adult female R. prolixus. Double-label immunohistochemistry reveals co-localization of RhoprCAPA-2-like and the glycoprotein hormone (GPA2/GPB5) subunit GPB5-like immunoreactivity in neurosecretory cells in the mesothoracic ganglionic mass and in their neurohemal sites, suggesting these peptides can be co-released to regulate physiological processes. qPCR analysis reveals changes in transcript expression levels of the RhoprCAPA receptor (CAPAR) in the fat body and reproductive tissues after feeding in adult female R. prolixus. RNA interference-mediated knockdown of CAPAR transcript decreases egg production and reduces hatching rate and survival rate in female R. prolixus. Downregulation of CAPAR decreases vitellogenin RhoprVg1 transcript expression in the fat body and deceases its receptor RhoprVgR transcript level in the ovaries; accompanied by a reduction in vitellogenin content in the fat body and hemolymph. Incubation of fat body and ovaries in vitro with RhoprCAPA-2 increases RhoprVg1 transcript expression in the fat body, vitellogenin content in the fat body culture medium, and increases RhoprVgR transcript in the ovaries. These findings implicate the CAPA signaling pathway in reproduction, with RhoprCAPA-2 acting as a gonadotropin in adult female R. prolixus.

Primerjava ultrazvočnega merjenja premera spodnje votle vene in merjenja sestave telesa z metodo bioelektrične impedance za oceno tekočinskega stanja pri novorojenčkih

Background: Neonatal medical conditions often disrupt the physiological processes that regulate fluid balance, so assessing fluid status in sick neonates is important for clinical management. In clinical practice we use clinical signs, which, however, on their own, do not provide a reliable assessment of fluid status. We aimed to compare two methods: i) diameters and collapsibility index of vena cava inferior (VCI) measured by ultrasonography and ii) analysis of body composition by bioelectrical impedance (BIA) and to evaluate their relation to changes in body mass. Methods: In a cohort-prospective clinical trial we included 27 neonates aged 1–7 days with various pathologies. Ultrasound measurements of VCI transversely and longitudinally, measurements of body composition by BIA and measurements of body mass were performed in each subject at least three times with an interval of 24–72 hours. Simultaneous measurements of the same subject were then analysed and evaluated. Results: The average proportion of total body water (TBW) decreased in the first days after birth, from 80.3% (Day 1) to 73.1% (Day 8) (p = 0.006). The decrease in the average proportion of extracellular water (ECW) in the first days after birth was not statistically significant. The association between ECW and body mass over time was statistically significant (p < 0.001). The association between transversely measured large VCI diameter during inspiration, body mass, and ECW was statistically significant (p = 0.024). No statistically significant association with ECW or body mass was proven for the other ultrasound-measured variables. Conclusions: By measuring body composition with BIA, we confirmed the reduction of the average proportions of TBW after birth and the association between body mass, ECW, and transversely measured maximal diameter of VCI during inspiration. BIA is an appropriate method for monitoring fluid status in a newborn. Additional research on a larger number of subjects is needed to define the significance of VCI measurements for assessing fluid status.

Association of Sleep Problems With Dialysis Shifts in Patients Undergoing Hemodialysis in Tbilisi, Georgia.

Introduction According to a 2023 poll by the International Society of Nephrology, 850 million individuals worldwide suffer from chronic kidney disease (CKD) andhemodialysis (HD) is the primary treatment for 69% of the patients with CKD. While HD effectively regulates fluid balance and electrolyte levels, patients often face challenges such as weakness, exhaustion, and cognitive changes, which impact their quality of life. Sleep-related issues, including poor quality, excessive morning sleepiness, insomnia, and restless leg syndrome (RLS), are particularly common among HD patients. These disturbances stem from various factors, including psychological discomfort and biochemical imbalances. Dialysis shifts, despite their importance, remain poorly studied regarding their impact on sleep and biochemical parameters. Our study aims to address these gaps, exploring how different dialysis shifts affect sleep quality and biochemical parameters.Our hypothesis suggests that the particular dialysis shift that hemodialysis patients undergo has an impact on the quality of sleep, with various groups exhibiting varying degrees of sleep disturbance. Simultaneously, we believe that the time of dialysis shifts could influence biochemical parameter variations, which in turn could affect the quality of sleep in hemodialysis patients. Methodology This cross-sectional study focuses on assessing sleep problems and analyzing biochemical variables among hemodialysis (HD) patients in Georgia. A total of 150 participants were selected from morning, afternoon, and evening dialysis shifts, with strict inclusion criteria and exclusion criteria. Assessment procedures involved questionnaires on sleep quality, restless leg syndrome (RLS), daytime sleepiness, and severity of insomnia. Biochemical variables were obtained from the hospital records. Statistical analyses were performed using Graph Pad Prism software (GraphPad,San Diego, USA), including ANOVA and Chi-square tests for association between biochemical variables and dialysis shifts, as well as logistic regression for assessing the influence of biochemical variables on insomnia and poor sleep quality. The significance level was set at 95%. Results Results showed that patients in the afternoon shift undergo longer sessions of hemodialysis compared to other shifts. Notably, a larger proportion of morning shift patients reported poor sleep quality, while a smaller fraction of evening shift patients experienced insomnia. There were no significant associations between dialysis shift and excessive morning sleepiness or restless leg syndrome.Potassium emerged as the sole biochemical variable exhibiting an association with all three dialysis shifts. Biochemical parameters showed no discernible impact on insomnia or poor sleep quality. Conclusion Our findings suggest an association between poor sleep quality and insomnia with dialysis shifts. Hemodialysis does influence potassium levels. However, biochemical variables like sodium, potassium, calcium, phosphorus, vitamin D3, parathyroid gland hormone (PTH), and hemoglobin do not seem to affect poor sleep quality and insomnia. Further research is needed to explore potential sleep issues with nocturnal shifts and to assess if creatinine and chloride have any influence on poor sleep quality.It is important to acknowledge dialysis shift as a contributor to sleep problems, emphasizing the need for targeted interventions to enhance the quality of life for these patients.

PVN predisposes microglia to be susceptible to hemodynamic signals and promote sympathetic excitation in hypertension

Hypertension is usually accompanied with an elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not fully understood. Recent advances reveal that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels, and found that microglia in the hypothalamic paraventricular nucleus (PVN) were early responders to hypertensive challenges. PVN is the central hub for maintaining cardiovascular function via regulation of fluid balance and sympathetic outflow. Comprehensive vasculature analyses unveiled that PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology among brain regions. As such, PVN is susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. ATP ligation to microglial P2Y12 receptor is responsible for the microglial accumulation and activation in the PVN. Both pharmacological blockade and genetic ablation of microglial P2Y12 could substantially restrain blood pressure increase under hypertensive challenge. Together, these findings disclose that a unique vasculature pattern results in the vulnerability of PVN pre-sympathetic neurons to hypertension-associated inflammatory insults, which is mediated by microglia. NSFC82170441. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lymphatic System and the Kidney: From Lymphangiogenesis to Renal Inflammation and Fibrosis Development.

The lymphatic kidney system plays a crucial role in managing interstitial fluid removal, regulating fluid balance, and tuning immune response. It also assists in the reabsorption of proteins, electrolytes, cytokines, growth factors, and immune cells. Pathological conditions, including tissue damage, excessive interstitial fluid, high blood glucose levels, and inflammation, can initiate lymphangiogenesis-the formation of new lymphatic vessels. This process is associated with various kidney diseases, including polycystic kidney disease, hypertension, ultrafiltration challenges, and complications post-organ transplantation. Although lymphangiogenesis has beneficial effects in removing excess fluid and immune cells, it may also contribute to inflammation and fibrosis within the kidneys. In this review, we aim to discuss the biology of the lymphatic system, from its development and function to its response to disease stimuli, with an emphasis on renal pathophysiology. Furthermore, we explore how innovative treatments targeting the lymphatic system could potentially enhance the management of kidney diseases.

Approach to Decompensated Right Heart Failure in the Acute Setting

Acute right heart failure (ARHF) arises when the right ventricle fails to pump blood efficiently to the pulmonary circulation. This inefficiency leads to a decreased blood supply to various organs. ARHF is a significant health concern, often leading to increased hospital admissions and being associated with a higher risk of mortality. This condition underscores the importance of effective cardiac care and timely intervention to manage its complications and improve patient outcomes. Diagnosing ARHF involves a comprehensive approach that includes a physical examination to evaluate the patient’s fluid status and heart-lung function, blood tests to identify potential triggers and help forecast patient outcomes and various imaging techniques. These imaging techniques include electrocardiograms, point-of-care ultrasounds, computed tomography, cardiac magnetic resonance imaging, and other advanced monitoring methods. These diagnostic tools collectively aid in a detailed assessment of the patient’s cardiac and pulmonary health, essential for effective management of ARHF. The management of ARHF focuses on addressing the underlying causes, regulating fluid balance, and enhancing cardiac function through pharmacological treatments or mechanical support aimed at boosting right heart performance. This management strategy includes the use of medications that modulate preload, afterload, and inotropy; vasopressors; anti-arrhythmic drugs; ensuring proper oxygenation and ventilation; and the utilization of heart and lung assist devices as a bridge to potential transplantation. This review article is dedicated to exploring the pathophysiology of ARHF, examining its associated morbidity and mortality, evaluating the various diagnostic tools available, and discussing the diverse treatment modalities. The article seeks to provide a comprehensive understanding of ARHF, its impact on health, and the current strategies for its management.

Mitochondrial Signaling, the Mechanisms of AKI-to-CKD Transition and Potential Treatment Targets.

Acute kidney injury (AKI) is increasing in prevalence and causes a global health burden. AKI is associated with significant mortality and can subsequently develop into chronic kidney disease (CKD). The kidney is one of the most energy-demanding organs in the human body and has a role in active solute transport, maintenance of electrochemical gradients, and regulation of fluid balance. Renal proximal tubular cells (PTCs) are the primary segment to reabsorb and secrete various solutes and take part in AKI initiation. Mitochondria, which are enriched in PTCs, are the main source of adenosine triphosphate (ATP) in cells as generated through oxidative phosphorylation. Mitochondrial dysfunction may result in reactive oxygen species (ROS) production, impaired biogenesis, oxidative stress multiplication, and ultimately leading to cell death. Even though mitochondrial damage and malfunction have been observed in both human kidney disease and animal models of AKI and CKD, the mechanism of mitochondrial signaling in PTC for AKI-to-CKD transition remains unknown. We review the recent findings of the development of AKI-to-CKD transition with a focus on mitochondrial disorders in PTCs. We propose that mitochondrial signaling is a key mechanism of the progression of AKI to CKD and potential targeting for treatment.

The Prescribing Patterns of Diuretics in Intensive Care Retrospective Study About 64 Cases

Diuretics are commonly recommended in medical practice, utilized for both chronic management and emergency interventions in intensive care units., due to their powerful pharmacological effect. However, their use in the intensive care setting is sometimes inappropriate and excessive, leading to errors in indication and significantly increased iatrogenic harm. Our study aims to evaluate the use of diuretics in intensive care units by examining the indications for prescription as well as their clinical and biological impacts, in order to elucidate practical guidelines for optimal use ensuring relevant and safe employment while eliminating harmful practices that could have serious consequences for the health of intensive care patients. To achieve this, we conducted a retrospective descriptive case series study involving patients hospitalized in the medical intensive care unit of CHU Ibn Rochd in Casablanca from January 1, 2022, to December 31, 2022. Demographic, clinical, paraclinical, therapeutic, and evolutionary data were collected. Out of the 292 patients hospitalized in the medical intensive care unit during the year 2022, 64 cases of diuretic use were collected, with an incidence of 21.91%. The most frequent indications for diuretic use in our series were acute renal failure and inadequate diuresis, followed by acute respiratory distress syndrome and heart failure. Furosemide was the only diuretic prescribed in our series. Following diuretic administration, hemodynamic, metabolic, and organic complications were observed. The most frequently encountered complications were arterial hypotension requiring the use of vasoactive drugs in some cases, hypokalemia, and impaired renal function. Mortality was high in our series, with death occurring in 77% of our patients. The indications for diuretics in intensive care have changed over the last decade. They are no longer recommended in cases of acute renal failure to maintain diuresis or to preserve renal function, nor in hepatorenal syndrome as this can worsen renal perfusion and acute renal injury. However, as part of fluid balance regulation by the intensivist, diuretic administration may be considered in organ congestion, particularly pulmonary, and in various situations such as ventilatory weaning, acute heart failure, and acute respiratory distress syndrome, provided that this use is carefully evaluated and associated with precise administration modalities, in addition to appropriate compensatory treatments to prevent their adverse effects.

Role of Herbal Medicine in Cardiovascular Activities

Herbal medicine has gained substantial attention for its potential role in supporting cardiovascular health. This chapter explores the intricate interplay between herbal compounds and cardiovascular activities, shedding light on their mechanisms of action and therapeutic applications. With a historical backdrop of traditional herbal medicine, the prevalence of cardiovascular diseases serves as a compelling backdrop for the investigation. The chapter delves into the multifaceted mechanisms by which herbal compounds influence the cardiovascular system. Notably, herbs exhibit vasodilatory effects, contributing to blood pressure regulation, and harbor potent antioxidant and anti-inflammatory properties that collectively mitigate oxidative stress and inflammation within the cardiovascular milieu. Furthermore, certain herbs intricately modulate lipid metabolism, holding promise in the management of dyslipidemia. A thorough analysis of well-known herbal treatments clarifies each one's unique contributions to cardiovascular health. Hawthorn is revealed to be the champion of heart health, and garlic demonstrates its mastery of cholesterol reduction. Ginkgo Biloba is notable for its capacity to improve circulation, and turmeric demonstrates powerful anti-inflammatory properties. The chapter also looks at herbal medicine's potential as an intervention for regulating fluid balance, arrhythmias, and hypertension. Examined is the potential for resveratrol-rich plants and green tea to protect against heart disease. Along with considerations for safety, interactions, and future study, the symbiotic relationship between stress reduction, adaptogenic herbs, and heart health is also discussed in this article. This chapter concludes with a thorough examination of the crucial part herbal medicine plays in cardiovascular health. The complex interaction between herbal substances and circulatory functions, from mechanisms of action to clinical applications, shows promise for a more integrative and holistic approach to cardiovascular care

The impact of vascular endothelial glycocalyx on the pathogenesis and treatment of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a complex disorder characterized by widespread activation of blood clotting mechanisms throughout the body. Understanding the role of vascular endothelial glycocalyx in the pathogenesis and treatment of DIC is crucial for advancing our knowledge in this field. The vascular endothelial glycocalyx is a gel-like layer that coats the inner surface of blood vessels. It plays a significant role in maintaining vascular integrity, regulating fluid balance, and preventing excessive clotting. In the pathogenesis of DIC, the disruption of the vascular endothelial glycocalyx is a key factor. Pathological conditions trigger the activation of enzymes, including heparanase, hyaluronase, and matrix metalloproteinase. This activation leads to glycocalyx degradation, subsequently exposing endothelial cells to procoagulant stimuli. Additionally, the ANGPTs/Tie-2 signaling pathway plays a role in the imbalance between the synthesis and degradation of VEG, exacerbating endothelial dysfunction and DIC. Understanding the mechanisms behind glycocalyx degradation and its impact on DIC can provide valuable insights for the development of targeted therapies. Preservation of the glycocalyx integrity may help prevent the initiation and propagation of DIC. Strategies such as administration of exogenous glycocalyx components, anticoagulant agents, or Tie-2 antibody agents have shown promising results in experimental models. In conclusion, the vascular endothelial glycocalyx plays a crucial role in the pathogenesis and treatment of DIC. Further research in this field is warranted to unravel the complex interactions between the glycocalyx and DIC, ultimately leading to the development of novel therapies.

Strategies in activating lymphatic system on symptom distress and health-related quality of life in patients with heart failure: secondary analysis of a pilot randomized controlled trial.

Abnormal interstitial fluid accumulation remains the major cause for patients with heart failure (HF) to endure a myriad of distressing symptoms and a decline in their health-related quality of life (HRQoL). The lymphatic system is essential in regulating fluid balance within the interstitial compartment and has recently been recognized as an important target for the prevention and mitigation of congestion. This study aimed to investigate the effects of exercises in activating lymphatic system on symptom distress and HRQoL among patients with HF. This was a pre-determined, secondary analysis of the TOLF-HF [The-Optimal-Lymph-Flow for Heart Failure (TOLF-HF)] study, a two-arm pilot randomized controlled trial evaluating the preliminary effects of the lymphatic exercise intervention in enhancing interstitial decongestion among patients with HF. Participants were randomized to receive either a four-week TOLF-HF program in addition to standard care or standard care alone. The Chinese version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was employed to measure symptom distress and HRQoL before and after the intervention. Data analyses included descriptive statistics, the independent sample t-test, Pearson's chi-square test, the Mann-Whitney U test, and covariance analysis. Of the 66 patients enrolled, 60 completed the study. The study results exhibited that the TOLF-HF intervention were effective in alleviating both physical and psychological symptom distress. The intervention group yielded significantly lower MLHFQ total scores in comparison to the control group. The odd ratio of achieving meaningful improvement in HRQoL in TOLF-HF group was 2.157 times higher than those in the control group. The TOLF-HF program focusing on activating lymphatic system was effective in alleviating physical and psychological symptom distress as well as improving HRQoL for patients with HF. The tolerability, feasibility, and effectiveness of the TOLF-HF intervention make it a promising intervention for patients to manage HF. http://www.chictr.org.cn/index.aspx, identifier (ChiCTR2000039121).

A randomised trial to assess fluid and electrolyte balance responses following ingestion of different beverages in young and older men

BackgroundOlder adults are susceptible to dehydration and fluid overload due to a reduced ability to maintain homeostatic control of fluid and electrolyte balance.PurposeTo assess fluid and electrolyte balance responses in young and older men following ingestion of commonly consumed beverages differing in composition.Methods12 young and 11 older men were recruited. Euhydrated body mass was recorded. Participants consumed 1L (250 ml every 15 min) of water, fruit juice, a sports drink or low-fat milk in a randomized cross-over design. Urine and blood samples were obtained before and after the drinking period and every hour thereafter for 3-h. Samples were used to determine osmolality, electrolytes (Na+ and K+), water clearance, and glomerular filtration rate.ResultsFree water clearance was significantly higher in Young than Older at 1 and 2 h after the ingestion of W and S (p < 0.05). Net Na+ and K+ balance were not different between Young and Older (p = 0.91 and p = 0.65) adults, respectively. At 3 h Na+ balance was negative after ingesting water and fruit juice, but neutral after sport drink and milk. Net K+ balance was neutral at 3 h after ingesting milk, but negative after water, fruit juice and sport drink.ConclusionsMilk was retained longer than other beverages in Young, but not in Older, despite similar net electrolyte balance responses. Older had higher fluid retention in the first 2 h after the ingestion of all beverages, except for milk when compared to Young, indicating an age-related loss of ability to regulate fluid balance under current study conditions.

RENAL9: REDIEM 2.0: Renal Extremity Device to Measure Impedance, Edema, Movement

Background: Renal failure due to chronic kidney disease (CKD) is a leading cause of global mortality. CKD disrupts fluid balance regulation, inducing comorbidities such as excessive swelling of the extremities (edema) and restless leg syndrome (RLS). Clinical limitations impede the ability to quantitatively track edema and RLS in variable settings. We report on the development of a wearable device capable of continuously measuring and analyzing: 1. leg edema, 2. water content, and 3. RLS-specific leg movements. Methods: An enhanced system (2.0) was designed through integration of flex sensors, accelerometry, electromyography (EMG) and impedance biosensors into a flexible stocking that transmits data to a smartphone application for graphical interpretation. Assessment of components was performed through simulations of RLS and edema. EMG and accelerometry were assessed for identification accuracy by applying sensors to a subject performing movements of set type/frequency to simulate RLS. Subject’s plantar reflex was induced to verify increased EMG response to sudden reflexive motion. Flex sensors were assessed on simulated edema via a measured-fill hydration system with compressed sponges, measuring resistance in relation to circumference during expansion. Results: RLS sensor trials were able to differentiate RLS movement with EMG using peak detection software (Figure A). This was verified using accelerometry, which identified leg movement at >95% recognition accuracy. Edema sensor trials were able to accurately measure linear change in resistance during circumference expansion with an R2 value of 0.949 (Figure B). Further assessment will be performed to confirm water content using impedance sensors. Conclusion: Preliminary data demonstrates measurement and recognition accuracy in all components tested. Correlations identified between circumference expansion and resistance change allow for accurate quantification of swelling via resistance measurements. Motion differentiation/identification allows for tracking of RLS movement incidence and frequency. Ability to perform condition progression analysis on an aggregation of this data over time indicates future utility of the integrated device in CKD treatment. Continued work is intended to demonstrate this viability and conclude with a complete and comprehensive system for use by clinicians and patients.Figure 1. A. Representative EMG demonstrating RLS motion. Peaks identified by detection software are associated with sudden or jerk-like motions. B. Detection of circumference change (edema) via change in resistance using sensor.

Angiotensin-Related Peptides and Their Role in Pain Regulation.

Angiotensin (Ang)-generating system has been confirmed to play an important role in the regulation of fluid balance and blood pressure and is essential for the maintenance of biological functions. Ang-related peptides and their receptors are found throughout the body and exhibit diverse physiological effects. Accordingly, elucidating novel physiological roles of Ang-generating system has attracted considerable research attention worldwide. Ang-generating system consists of the classical Ang-converting enzyme (ACE)/Ang II/AT1 or AT2 receptor axis and the ACE2/Ang (1-7)/MAS1 receptor axis, which negatively regulates AT1 receptor-mediated responses. These Ang system components are expressed in various tissues and organs, forming a local Ang-generating system. Recent findings indicate that changes in the expression of Ang system components under pathological conditions are involved in the development of neuropathy, inflammation, and their associated pain. Here, we summarized the effects of changes in the Ang system on pain transmission in various organs and tissues involved in pain development process.

Chronic aldosterone administration alters aquaporin expression and localization in the murine kidney

The steroid hormone aldosterone is an important regulator of fluid balance and electrolyte homeostasis. While acute aldosterone signaling is canonically associated with fluid retention due to its role in promoting sodium reabsorption through ENaC in the distal nephron, chronic aldosterone exposure has been shown to exacerbate urine production in a rat model of diabetes insipidus through its actions on aquaporin 2 (AQP2) localization and expression. In our studies, we aimed to characterize not only the effect of chronic aldosterone administration on AQP2 expression and localization, but also its effect on the basolateral water channels, AQP3 and AQP4. Given the large urinary output we observed in our animals following chronic aldosterone treatments, we hypothesized all three of these channels would show reduced expression.Aldosterone was administered to male C57Bl/6 mice at a dose of 200 μg/kg/day for 28 days via subcutaneous minipumps. Aldosterone treatment caused a significant diuresis as compared to control animals by day 15 (Ctl 4.8 ± 1.6 ml; Aldo 8.4 ± 2.4 ml), and this difference persisted for the remainder of the experiment. Mice given aldosterone also consumed more water as compared to their control counterparts (Ctl 4.0 ± 1.2 ml; Aldo 9.6 ± 2.3 ml). Urine osmolality was measured by freeze-point depression, with a significant decrease in urinary concentration being noted during the daytime by day 4 (Ctl 1219.8 ± 473.4 mOsm/kg; Aldo 638.8 ± 143.8 mOsm/kg) and during the night by day 17 (Ctl 905.3 ± 175.1 mOsm/kg; Aldo 522.2 ± 127.3 mOsm/kg). At the end of the 28 days of aldosterone administration, mice receiving aldosterone had a higher whole blood [Na + ] (Ctl 146 ± 1.9mmol/l; Aldo 152 ± 1.3mmol/l) and lower whole blood [K+] (Ctl 4.8 ± 0.56mmol/l; Aldo 3.0 ± 0.34mmol/l) as measured by iSTAT cartridge with terminal cardiac blood draw.Kidneys were examined by Western blot and immunofluorescent staining for expression and localization of the three AQPs. AQP2 expression decreased after both 14 and 28 days of aldosterone administration, with line scan analysis showing a decreased signal present at the apical membrane. AQP3 expression was decreased in the basolateral membranes of principal cells within the cortex of the kidney but increased in cells within the inner medulla after 28 days of aldosterone. AQP4 levels were significantly increased in AQP2-positive cells of the inner stripe of the outer medulla and the inner medulla, suggesting that this channel may be upregulated to compensate for changes in the other two aquaporins. Potassium supplementation to separate the effects of aldosterone administration from hypokalemia did not rescue the expression of these channels.Overall, our studies reveal that chronic aldosterone administration in healthy mice leads to polyuria and polydipsia, with decreased apical expression of AQP2 and variable changes in AQP3 and AQP4 dependent on location within in the kidney. This study was funded by NIH grants R01 DK130901 (to SS), R01 HL147818 and R01 DK129285 (to TRK), and P30 DK079307 (the Pittsburgh Center for Kidney Research). SMM was supported by T32 DK061296, T32 DK007052, and a grant from Relypsa. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Roles of EP Receptors in the Regulation of Fluid Balance and Blood Pressure.

Prostaglandin E2 (PGE2) is an important prostanoid expressing throughout the kidney and cardiovascular system. Despite the diverse effects on fluid metabolism and blood pressure, PGE2 is implicated in sustaining volume and hemodynamics homeostasis. PGE2 works through four distinct E-prostanoid (EP) receptors which are G protein-coupled receptors. To date, pharmacological specific antagonists and agonists of all four subtypes of EP receptors and genetic targeting knockout mice for each subtype have helped in uncoupling the diverse functions of PGE2 and discriminating the respective characteristics of each receptor. In this review, we summarized the functions of individual EP receptor subtypes in the renal and blood vessels and the molecular mechanism of PGE2-induced fluid metabolism and blood pressure homeostasis.

Myostatin Deletion Protects Against Renal Dysfunction During a High Salt Diet

Chronic Kidney Disease (CKD) afflicts ~15% of U.S. adults and occurs when the kidneys are ineffective in filtering the blood of waste products. CKD is irreversible and current interventions are focused on protecting and preserving renal function. Risk factors for CKD are multifactorial but growing evidence suggest that a key risk factor is dietary salt intake. A diet high in sodium will increase fluid retention, blood pressure, proteinuria, and ultimately drive the progression of kidney damage. Currently, it is estimated that 90% of the U.S. population consumes excess dietary sodium. As such, it is a medical necessity that interventions focus on ways to optimize renal sodium excretion and protect kidney function over time.Exercise is a key therapy to improve kidney function but a large amount of people are unable to exercise due to disability, lack of time or money, or a pandemic. Our lab has previously discovered that when myostatin, a negative regulator of skeletal muscle mass, is deleted from lean mice it also improves kidney function in diabetes. However, it is unknown whether myostatin deletion will also improve renal sodium handling. Thus, the hypothesis is that myostatin deletion improves sodium handling and protects against renal damage during a high salt diet.The experiment used adult lean mice with and without myostatin constitutively deleted. Both groups of mice were placed on a high salt (HS) diet (4% NaCl) for 14 days. Food consumption, water intake, and urine production was assessed at baseline, acutely (first 3 days on HS diet) and at the end of the experiment using metabolic cages. Blood pressure studies (in vivo) are ongoing and markers of renal (dys)function are currently being assessed, along plasma hormones that regulate fluid balance. Significance was determined at P&lt;0.05.The results showed that myostatin deletion protects against kidney dysfunction during a high salt diet, as the myostatin KO mice consumed significantly more food, but maintained fluid balance (drank and urinated similar amounts to the lean control). Blood pressure remained lower in the myostatin KO compared to control. Importantly, myostatin deletion significantly blunted renal hypertrophy (68% less mass) compared to the control. Taken together, myostatin deletion improves the efficiency of the kidney in handling sodium and maintains fluid balance during a high salt diet. Thus, pharmaceutical inhibition of myostatin may prove an effective target for long‐term protection against high salt diets and preserving kidney function during CKD.

Vasopressin, Cortisol, and Osmotic Regulation in Non‐hospitalized SARS‐CoV‐2 Infected Patients

Vasopressin (AVP) has been implicated in the inflammatory response to SARS‐CoV‐2 infection as increased disease severity has been reported to be associated with elevated levels of copeptin. Elevated AVP and cortisol levels seen in systemic inflammatory responses may be associated with severe pulmonary edema and dilutional hyponatremia caused be dysregulation of neurohormonal control of fluid and electrolyte balance. Early and effective regulation of fluid balance before acute respiratory failure spirals into hypoxemia‐induced septic shock and multisystem organ failure, may be needed to prevent progression to severe disease.We hypothesized that control of osmotic homeostasis in non‐severe cases of COVID‐19 is an outcome of cortisol and AVP stimulation arising from an appropriate stress response. In an observational study of asymptomatic to moderately symptomatic non‐hospitalized individuals (n = 45; 14 to 71 years of age) positive for SARS‐CoV‐2 (confirmed by PCR test), we assessed osmotic regulation by measuring circulating AVP (by radioimmunoassay), cortisol (by enzyme linked immunoassay), plasma osmolality (pOsm), plasma sodium (pNa) and plasma potassium (pK). Two plasma specimens from each person were collected between 2 and 32 days from onset of symptoms or confirmed positive test. Inflammatory stimulation of the immune response was verified by quantitative measurement of IgG targeted to the SARS‐Cov‐2 spike protein (Epitope Diagnostics, Dynex Agility).Plasma osmolality (293+1 mOsm/L) remained stable even at the peak of IgG immune response. Multiple regression analyses showed pOsm was directly related to AVP and inversely related to cortisol (p<0.001). Examination of electrolyte levels over time from positive SARS‐CoV‐2 test week 1 vs week 3 (7+1 vs 18+1 days) revealed a slight decrease in pNa (139.7+0.8 to 136.9+0.5 mEq/l p<0.05, but there was no evidence of hyponatremia or inappropriate levels of AVP (SIADH) which was 1.9+0.2 uU/ml at week 1 and 2.2+0.3 uU/ml at week 3. Vasopressin regulation was appropriately positively correlated with pOsm and cortisol and negatively related to pK (p<0.001). Cortisol levels increased from week 1 to 3 (14.7+1.2 to 22.2+2.2 ug/dL), and positively correlated with AVP and negatively correlated with pNa.Results demonstrated that the stimulated immune response to SARS‐CoV‐2 infection in mild to moderate cases of COVID‐19 does not disrupt osmotic regulation by AVP. Thus, reports of dysregulation of osmotic homeostasis and SIADH observed in severe pneumonia and coronavirus sepsis in hospitalized patients is likely due to the dominating non‐osmotic stimulation of AVP to pathophysiological levels needed to maintain blood pressure and renal perfusion. In mild to moderate COVID‐19 cases, control of fluid and electrolyte balance at physiological levels of AVP appears to be maintained.

ACTIVE PRINCIPLES APPLIED ON BIOMATERIALS FOR THE CURATIVE THERAPY OF INFLAMMATORY SKIN DISEASES - A REVIEW

Every year, millions of peoples are affected by skin injuries of either an acute or chronic nature. Worldwide 300,000 people die every year in lower-middle-income countries due to chronic wounds and burn injuries. Wounds are described as the disruption in the skin integrity and function, which arises from different causes such as trauma, surgery, diabetes, and burns. Skin provides a mechanical barrier against the external environment and has further roles in thermoregulation, metabolism and regulation of fluid balance. Skin diseases can affect each of these regions and they can be influenced by body size, sex, age, medications, diet, and microenvironment. Also, they can manifest whether the skin is healthy or diseased. Wound dressings are critical to wound care, providing a physical barrier between the wound and the external environment to prevent further damage or infection. The most promising wound dressings are biocompatible, enable physical protection of the wound milieu against penetration of bacteria and are highly porous. The use of natural biocompatible drugs is highly desirable in wound dressing compared to synthetic chemicals. To achieve an adequate therapeutic effect, different polymeric systems are used for drug delivery. To improve drug efficacy, safety, patient compliance and convenience a drug delivery system is modified to enhance drug release profile, absorption, distribution and elimination of the drug. The present review is an attempt to brief readers about the engineering of wound dressing materials from natural and synthetic sources upfront using active principles, such as bee products, drugs, essential oils, metallic nanoparticles and vitamins.

The (pro)renin receptor ((P)RR) and soluble (pro)renin receptor (s(P)RR) in pregnancy.

The (pro)renin receptor ((P)RR) is a multi-functional protein that can be proteolytically cleaved and released in a soluble form (s(P)RR). Recently, the (P)RR and s(P)RR have become of interest in pregnancy and its associated pathologies. This is because the (P)RR not only activates tissue renin angiotensin systems, but it is also an integral component of vacuolar-ATPase, activates the wingless/integrated (Wnt)/β-catenin and extracellular signal regulated kinases 1 and 2/mitogen-activated protein kinase signalling pathways, and stabilises the β subunit of pyruvate dehydrogenase. Additionally, s(P)RR is detected in plasma and urine, and maternal plasma levels are elevated in pregnancy complications including fetal growth restriction, preeclampsia and gestational diabetes mellitus. Therefore, s(P)RR has potential as a biomarker for these pregnancy pathologies. Preliminary functional findings suggest that s(P)RR may be important for regulating fluid balance, inflammation and blood pressure, all of which contribute to a successful pregnancy. The (P)RR and s(P)RR regulate pathways that are known to be important in maintaining pregnancy, however their role in the physiological context of pregnancy is poorly characterised. This review summarises the known and potential functions of the (P)RR and s(P)RR in pregnancy, and how their dysregulation may contribute to pregnancy complications. It also highlights the need for further research into the source and function of s(P)RR in pregnancy. Soluble (P)RR levels could be indicative of placental, kidney or liver dysfunction and therefore be a novel clinical biomarker, or therapeutic target, to improve the detection and treatment of pregnancy pathologies.