Composition Of Extracellular Fluid Research Articles

Serum apolipoprotein H determines ferroptosis resistance by modulating cellular lipid composition

Ferroptosis is a regulated cell death process dependent on iron, triggered by the accumulation of lipid peroxidation. The environmental context significantly impacts cellular sensitivities to ferroptosis. Serum, constituting the extracellular fluid composition in vivo, provides crucial environmental biomolecules. In this study, we investigated the influence of sera on ferroptosis induction, pinpointing the serum protein apolipoprotein H (APOH) as a pivotal inhibitor of ferroptosis. Moreover, we elucidated that APOH suppresses ferroptosis by activating the phosphoinositide 3-kinase (PI3K)-AKT-sterol regulatory element-binding proteins (SREBPs) pathway, thereby elevating stearoyl-CoA desaturase (SCD) levels and augmenting cellular monounsaturated fatty acid-containing phospholipids (MUFA-PLs). Furthermore, ApoHinfer, the peptide derivative of the active region of APOH, mimics its ferroptosis inhibitory activity. Our findings underscore the critical role of serum protein APOH in the inhibition of ferroptosis and indicates potential therapeutic applications in treating cancer and diseases associated with ferroptosis.

The ex vivo perfused mouse adrenal gland—a new model to study aldosterone secretion

Aldosterone is a steroid hormone that is important for maintaining the volume and ionic composition of extracellular fluids and is produced in the zona glomerulosa of the adrenal cortex. The basic mechanisms controlling aldosterone secretion are known. However, more detailed studies on the regulation of aldosterone secretion often fail due to the lack of suitable models: although secretion can be studied in cultured adrenocortical cells under defined conditions, the differentiation status of the cells is difficult to control and the complex anatomy of the adrenal cortex is lost. In living animals, the physiological context is intact, but the influences are manifold and the examination conditions cannot be sufficiently controlled. One method that closes the gap between cell models and studies in living animals is the isolated perfused adrenal gland. In the past, this method has provided important data on the pathophysiology of adrenal glands from larger animals, but the technique was not used in mice. Here, we developed a method for isolation and perfusion of the mouse adrenal gland to study aldosterone secretion. This technique preserves the complex anatomical and functional context of the mouse adrenal cortex, to ensure defined experimental conditions and to minimize extra-adrenal influences. Initial series of experiments with the ex vivo perfused mouse adrenal gland show that this model offers the possibility for unique insights into pathophysiological regulatory principles and is suitable for the use of genetically modified mouse models.

Long-term health outcomes associated with hydration status.

Body water balance is determined by fundamental homeostatic mechanisms that maintain stable volume, osmolality and the composition of extracellular and intracellular fluids. Water balance is maintained by multiple mechanisms that continuously match water losses through urine, the skin, the gastrointestinal tract and respiration with water gains achieved through drinking, eating and metabolic water production. Hydration status is determined by the state of the water balance. Underhydration occurs when a decrease in body water availability, due to high losses or low gains, stimulates adaptive responses within the water balance network that are aimed at decreasing losses and increasing gains. This stimulation is also accompanied by cardiovascular adjustments. Epidemiological and experimental studies have linked markers of low fluid intake and underhydration - such as increased plasma concentration of vasopressin and sodium, as well as elevated urine osmolality - with an increased risk of new-onset chronic diseases, accelerated aging and premature mortality, suggesting that persistent activation of adaptive responses may be detrimental to long-term health outcomes. The causative nature of these associations is currently being tested in interventional trials. Understanding of the physiological responses to underhydration may help to identify possible mechanisms that underlie potential adverse, long-term effects of underhydration and inform future research to develop preventative and treatment approaches to the optimization of hydration status.

An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity.

Brain tumours have significant impacts on patients' quality of life, and current treatments have limited effectiveness. To improve understanding of tumour development and explore new therapies, researchers rely on experimental models. However, reproducing tumour-associated epilepsy (TAE) in these models has been challenging. Existing models vary from cell lines to in vivo studies, but in vivo models are resource-intensive and often fail to mimic crucial features like seizures. In this study, we developed a technique in which normal rat organotypic brain tissue is implanted with an aggressive brain tumour. This method produces a focal invasive lesion that preserves neural responsiveness and exhibits epileptiform hyperexcitability. It allows for real-time imaging of tumour growth and invasion for up to four weeks and microvolume fluid sampling analysis of different regions, including the tumour, brain parenchyma, and peritumoral areas. The tumour cells expand and infiltrate the organotypic slice, resembling in vivo behaviour. Spontaneous seizure-like events occur in the tumour slice preparation and can be induced with stimulation or high extracellular potassium. Furthermore, we assess extracellular fluid composition in various regions of interest. This technique enables live cell confocal microscopy to record real-time tumour invasion properties, whilst maintaining neural excitability, generating field potentials, and epileptiform discharges, and provides a versatile preparation for the study of major clinical problems of tumour-associated epilepsy.

Thirst: neuroendocrine regulation in mammals.

Animals can sense their changing internal needs and then generate specific physiological and behavioural responses in order to restore homeostasis. Water-saline homeostasis derives from balances of water and sodium intake and output (drinking and diuresis, salt appetite and natriuresis), maintaining an appropriate composition and volume of extracellular fluid. Thirst is the sensation which drives to seek and consume water, regulated in the central nervous system by both neural and chemical signals. Water and electrolyte homeostasis depends on finely tuned physiological mechanisms, mainly susceptible to plasma Na+ concentration and osmotic pressure, but also to blood volume and arterial pressure. Increases of osmotic pressure as slight as 1-2% are enough to induce thirst ("homeostatic" or cellular), by activation of specialized osmoreceptors in the circumventricular organs, outside the blood-brain barrier. Presystemic anticipatory signals (by oropharyngeal or gastrointestinal receptors) inhibit thirst when fluids are ingested, or stimulate thirst associated with food intake. Hypovolemia, arterial hypotension, Angiotensin II stimulate thirst ("hypovolemic thirst", "extracellular dehydration"). Hypervolemia, hypertension, Atrial Natriuretic Peptide inhibit thirst. Circadian rhythms of thirst are also detectable, driven by suprachiasmatic nucleus in the hypothalamus. Such homeostasis and other fundamental physiological functions (cardiocircolatory, thermoregulation, food intake) are highly interdependent.

Breaking free: endocytosis and endosomal escape of extracellular vesicles

Extracellular vesicles (EVs) are natural micro-/nanoparticles that play an important role in intercellular communication. They are secreted by producer/donor cells and subsequent uptake by recipient/acceptor cells may result in phenotypic changes in these cells due to the delivery of cargo molecules, including lipids, RNA, and proteins. The process of endocytosis is widely described as the main mechanism responsible for cellular uptake of EVs, with endosomal escape of cargo molecules being a necessity for the functional delivery of EV cargo. Equivalent to synthetic micro-/nanoparticles, the properties of EVs, such as size and composition, together with environmental factors such as temperature, pH, and extracellular fluid composition, codetermine the interactions of EVs with cells, from binding to uptake, intracellular trafficking, and cargo release. Innovative assays for detection and quantification of the different steps in the EV formation and EV-mediated cargo delivery process have provided valuable insight into the biogenesis and cellular processing of EVs and their cargo, revealing the occurrence of EV recycling and degradation, next to functional cargo delivery, with the back fusion of the EV with the endosomal membrane standing out as a common cargo release pathway. In view of the significant potential for developing EVs as drug delivery systems, this review discusses the interaction of EVs with biological membranes en route to cargo delivery, highlighting the reported techniques for studying EV internalization and intracellular trafficking, EV-membrane fusion, endosomal permeabilization, and cargo delivery, including functional delivery of RNA cargo.

Real-Time Dynamic Collection of Hippocampal Extracellular Fluid from Conscious Rats Using a Microdialysis System.

A variety of central nervous system (CNS) diseases are associated with changes in the composition of hippocampal extracellular fluid (HECF). However, difficulty in obtaining HECF in real time from conscious rats has long restricted the evaluation of CNS disease progression and the effectiveness of ethnomedicine therapy. Encouragingly, a brain microdialysis technique can be used for continuous sampling with the advantages of dynamic observation, quantitative analysis, and a small sampling size. This allows the monitoring of changes in the extracellular fluid content for compounds from traditional herbs and their metabolites in the brain of living animals. The aim of this study was thus to accurately implant a cerebrospinal fluid microdialysis probe into the hippocampal region of Sprague Dawley (SD) rats with a three-dimensional brain stereotaxic apparatus, cutting off molecular weights greater than 20 kDa. The high-quality HECF was then obtained from conscious rats using a microdialysis sampling control system with an adjustable sampling rate from 2.87 nL/min - 2.98 mL/min. In conclusion, our protocol provides an efficient, rapid, and dynamic method to obtain HECF in awake rats with the help of microdialysis technology, which provides us with unlimited possibilities to further explore the pathogenesis of CNS-related diseases and evaluate drug efficacy.

Clinical factors within a week of birth influencing sodium level difference between an arterial blood gas analyzer and an autoanalyzer in VLBWIs: A retrospective study.

Neonatologists often experience sodium ion level difference between an arterial blood gas analyzer (direct method) and an autoanalyzer (indirect method) in critically ill neonates. We hypothesize that clinical factors besides albumin and protein in the blood that cause laboratory errors might be associated with sodium ion level difference between the 2 methods in very-low-birth-weight infants during early life after birth. Among very-low-birth-weight infants who were admitted to Jeonbuk National Hospital Neonatal Intensive Care Units from October 2013 to December 2016, 106 neonates were included in this study. Arterial blood sample was collected within an hour after birth. Blood gas analyzer and biochemistry autoanalyzer were performed simultaneously. Seventy-six (71.7%) were found to have sodium ion difference exceeding 4 mmol/L between 2 methods. The mean difference of sodium ion level was 5.9 ± 6.1 mmol/L, exceeding 4 mmol/L. Based on sodium ion level difference, patients were divided into >4 and ≤4 mmol/L groups. The sodium level difference >4 mmol/L group showed significantly (P < .05) higher sodium level by biochemistry autoanalyzer, lower albumin, lower protein, and higher maximum percent of physiological weight than the sodium level difference ≤4 mmol/L group. After adjusting for factors showing significant difference between the 2 groups, protein at birth (odds ratio: 0.835, 95% confidence interval: 0.760–0.918, P < .001) and percent of maximum weight loss (odds ratio: 1.137, 95% confidence interval: 1.021–1.265, P = .019) were factor showing significant associations with sodium level difference >4 mmol/L between 2 methods. Thus, difference in sodium level between blood gas analyzer and biochemistry autoanalyzer in early stages of life could reflect maximum physiology weight loss. Based on this study, if the study to predict the body's composition of extracellular and intracellular fluid is proceeded, it will help neonatologist make clinical decisions at early life of preterm infants.

Characterization of Aspergillus tamarii Strains From Human Keratomycoses: Molecular Identification, Antifungal Susceptibility Patterns and Cyclopiazonic Acid Producing Abilities.

Aspergillus tamarii appears to be an emerging aetiological agent of human keratomycoses in South India. The investigated strains were isolated from six suspected fungal keratitis patients attending a tertiary care eye hospital in Coimbatore (Tamil Nadu, India), and were initially identified by the microscopic examinations of the scrapings and the cultures. Our data suggest that A. tamarii could be easily overlooked when identification is carried out based on morphological characteristics alone, while the sequence analysis of the calmodulin gene can be used successfully to recognize this species accurately. According to the collected clinical data, ocular trauma is a common risk factor for the infection that gradually developed from mild to severe ulcers and could be healed with an appropriate combined antifungal therapy. Antifungal susceptibility testing revealed that A. tamarii strains are susceptible to the most commonly used topical or systemic antifungal agents (i.e., econazole, itraconazole and ketoconazole) except for natamycin. Moreover, natamycin proved to be similarly less effective than the azoles against A. tamarii in our drug interaction tests, as the predominance of indifferent interactions was revealed between natamycin and econazole and between natamycin and itraconazole as well. Four and five isolates of A. tamarii were confirmed to produce cyclopiazonic acid (CPA) in RPMI-1640 – which is designed to mimic the composition of human extracellular fluids – and in yeast extract sucrose (YES) medium, respectively, which is a widely used culture medium for testing mycotoxin production. Although a ten times lower mycelial biomass was recorded in RPMI-1640 than in YES medium, the toxin contents of the samples were of the same order of magnitude in both types of media. There might be a relationship between the outcome of infections and the toxigenic properties of the infecting fungal strains. However, this remains to be investigated in the future.

Can Sweat Sensors Detect Common Diseases? A Simple Sweat Patch May Soon Achieve It.

Diseases, infections, and hazardous chemicals alter the physiology of the human body and result in changes in the composition of extracellular and intracellular fluids. Given the difficulty in collecting extracellular and intracellular fluids, blood is typically analyzed to diagnose pathological conditions. Blood supplies oxygen and nutrients to every cell of the body and also carries away waste products; therefore, the assumption that blood composition depicts the cellular environment as closely as possible is reasonable. Blood collection, however, requires invasive procedures (such as phlebotomy or a fingerprick) and is not pleasant for the majority of the population, in some cases deterring individuals from seeking medical assistance and having blood tests. If the composition of another biofluid that could be easily tested using a noninvasive sampling technology and portable detectors would be proven to accurately depict the cellular environment, then new disease diagnostic tests could be developed, and health-testing procedures would become easier, cheaper, and appealing to almost everybody. Sweat is a biofluid that can be collected noninvasively, and some research studies suggest that sweat composition might reveal pathological conditions, chemical and biochemical exposures, and psychological stress. There are also articles in popular media that have gone even further and claimed that “sweat is the new blood” and sweat analyses will soon substitute traditional blood tests. The fact is that sweat is analyzed in medical practice in only a few specific cases (e.g., diagnosis of cystic fibrosis, hyperhidrosis, and hematohidrosis, and to optimize fluid and electrolyte intake strategies in athletes), and normal and pathological concentrations of biomarkers in sweat have not been established yet (1). It is also true that the wealth of chemical information present in the sweat has been undervalued for decades and that sweat has not been thoroughly studied for clinical diagnostic purposes. Sweat collection and analysis using conventional …

Effects of oxytocin administration on the hydromineral balance of median eminence-lesioned rats.

In the clinical setting, acute injuries in hypothalamic mediobasal regions, along with polydipsia and polyuria, have been observed in patients with cerebral salt wasting (CSW). CSW is also characterised by hypovolaemia and hyponatraemia as a result of an early increase in natriuretic peptide activity. Salt and additional amounts of fluid are the main treatment for this disorder. Similarly, experimental lesions to these brain regions, which include the median eminence (ME), produce a well-documented neurological model of polydipsia and polyuria in rats, which is preceded by an early sodium excretion of unknown cause. In the present study, oxytocin (OT) was used to increase the renal sodium loss and prolong the hydroelectrolyte abnormalities of ME-lesioned animals during the first few hours post-surgery. The objective was to determine whether OT-treated ME-lesioned animals increase their sodium appetite and water intake to restore the volume and composition of extracellular body fluid. Electrolytic lesion of the ME increased water intake, urinary volume and sodium excretion of food-deprived rats and also decreased urine osmolality and estimated plasma sodium concentration. OT administration at 8hours post-surgery reduced water intake, urine output and plasma sodium concentration and also increased urine osmolality and urine sodium excretion between 8 and 24hours post-lesion. From 24 to 30hours, more water and hypertonic NaCl was consumed by OT-treated ME-lesioned rats than by physiological saline-treated-ME-lesioned animals. Food availability from 30 to 48hours reduced the intake of hypertonic saline solution by ME/OT animals, which increased their water and food intake during this period. OT administration therefore appears to enhance the natriuretic effect of ME lesion, producing hydroelectrolyte changes that reduce the water intake of food-deprived animals. Conversely, the presence of hypertonic NaCl increases the fluid intake of these animals, possibly as a result of the plasma sodium depletion and hypovolaemic states previously generated. Finally, the subsequent increase in food intake by ME/OT animals reduces their need for hypertonic NaCl but not water, possibly in response to osmotic thirst. These results are discussed in relation to a possible transient activation of the ME with the consequent secretion of natriuretic peptides stored in terminal swellings, which would be augmented by OT administration. Electrolytic lesion of the ME may therefore represent a useful neurobiological model of CSW.

Effect of tissue thickness and liquid composition on the penetration of long-lifetime reactive oxygen and nitrogen species (RONS) generated by a plasma jet

Two of the key questions in plasma medicine are how deep the reactive oxygen and nitrogen species (RONS) generated by a plasma can penetrate into tissue and how the liquid (extracellular and intracellular fluid) composition affects the concentration of RONS. In this paper, different thicknesses of pig muscle tissue are used as a tissue mode to investigate the effect of tissue thickness on the penetration of RONS through tissue. Six different types of liquid (inorganic group: double-distilled water (DDW), 1% phosphate-buffered saline, 0.9% NaCl; organic group: 5% glucose, 2% serum and 10% serum solution) are used in the receiving chamber under the tissue in order to try to understand the effect of liquid composition on the penetration of RONS (H2O2, and ) generated by the plasma. It is found that when a tissue thickness of 500 µm is used the H2O2 concentrations in organic liquids are about 20–30 times higher than in DDW. The and concentrations in serum liquid are much higher than in all other liquids, which might be due to the plasma reacting with amino acids and proteins. Besides, the concentration in organic solution is higher than the concentration for the same experimental conditions. Furthermore, when the serum percentage is increased from 2% to 10%, the concentration increases dramatically but the concentration decreases significantly. This is especially true for a tissue thickness of 500 µm. One novel discovery is the RONS do not only penetrate the tissue by diffusion—there are also reactions between the plasma and the liquid which affect the final RONS concentration.

Plasma-Sprayed Hydroxylapatite Coatings as Biocompatible Intermediaries Between Inorganic Implant Surfaces and Living Tissue

The present contribution discusses critical aspects of the thermal alteration that HAp particles undergo when passing along the extremely hot plasma jet. This heat treatment leads to dehydroxylated phases such as oxyhydroxylapatite/oxyapatite as well as thermal decomposition products such as tri- and tetracalcium phosphates, and quenched phases in the form of amorphous calcium phosphate (ACP) of variable composition. The contribution also includes studying the influence bioinert TiO2 bond coats have on adhesion, crystallinity, and composition of HAp coatings. Moreover, the question is being addressed whether oxyapatite might exist as a (meta)stable phase or whether its occurrence is merely an ephemeral event. In addition, the article deals with the role that HAp coatings are playing during in vitro interaction with simulated body fluid (SBF) resembling the composition of extracellular fluid (ECF). The biological and biomechanical advantages of using HAp coatings for medical implants as well as salient aspects of their biomineralization and osseointegration will be discussed in some detail.

Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq

Prior RNA sequencing (RNA-seq) studies have identified complete transcriptomes for most renal epithelial cell types. The exceptions are the cell types that make up the renal collecting duct, namely intercalated cells (ICs) and principal cells (PCs), which account for only a small fraction of the kidney mass, but play critical physiological roles in the regulation of blood pressure, extracellular fluid volume, and extracellular fluid composition. To enrich these cell types, we used FACS that employed well-established lectin cell surface markers for PCs and type B ICs, as well as a newly identified cell surface marker for type A ICs, c-Kit. Single-cell RNA-seq using the IC- and PC-enriched populations as input enabled identification of complete transcriptomes of A-ICs, B-ICs, and PCs. The data were used to create a freely accessible online gene-expression database for collecting duct cells. This database allowed identification of genes that are selectively expressed in each cell type, including cell-surface receptors, transcription factors, transporters, and secreted proteins. The analysis also identified a small fraction of hybrid cells expressing aquaporin-2 and anion exchanger 1 or pendrin transcripts. In many cases, mRNAs for receptors and their ligands were identified in different cells (e.g., Notch2 chiefly in PCs vs. Jag1 chiefly in ICs), suggesting signaling cross-talk among the three cell types. The identified patterns of gene expression among the three types of collecting duct cells provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.

Chemical Sensing Systems that Utilize Soft Electronics on Thin Elastomeric Substrates with Open Cellular Designs.

A collection of materials and device architectures are introduced for thin, stretchable arrays of ion sensors that mount on open cellular substrates to facilitate solution exchange for use in biointegrated electronics. The results include integration strategies and studies of fundamental characteristics in chemical sensing and mechanical response. The latter involves experimental measurements and theoretical simulations that establish important considerations in the design of low modulus, stretchable properties in cellular substrates, and in the realization of advanced capabilities in spatiotemporal mapping of chemicals' gradients. As the chemical composition of extracellular fluids contains valuable information related to biological function, the concepts introduced here have potential utility across a range of skin- and internal-organ-integrated electronics where soft mechanics, fluidic permeability, and advanced chemical sensing capabilities are key requirements.

MDCK cells are capable of water secretion and reabsorption in response to changes in the ionic environment.

A prerequisite for tissue electrolyte homeostasis is highly regulated ion and water transport through kidney or intestinal epithelia. In the present work, we monitored changes in the cell and luminal volumes of type II Madin-Darby canine kidney (MDCK) cells grown in a 3D environment in response to drugs, or to changes in the composition of the basal extracellular fluid. Using fluorescent markers and high-resolution spinning disc confocal microscopy, we could show that lack of sodium and potassium ions in the basal fluid (tetramethylammonium chloride (TMACl) buffer) induces a rapid increase in the cell and luminal volumes. This transepithelial water flow could be regulated by inhibitors and agonists of chloride channels. Hence, the driving force for the transepithelial water flow is chloride secretion, stimulated by hyperpolarization. Chloride ion depletion of the basal fluid (using sodium gluconate buffer) induces a strong reduction in the lumen size, indicating reabsorption of water from the lumen to the basal side. Lumen size also decreased following depolarization of the cell interior by rendering the membrane permeable to potassium. Hence, MDCK cells are capable of both absorption and secretion of chloride ions and water; negative potential within the lumen supports secretion, while depolarizing conditions promote reabsorption.

Plasma-Sprayed Hydroxylapatite-Based Coatings: Chemical, Mechanical, Microstructural, and Biomedical Properties

This contribution discusses salient properties and functions of hydroxylapatite (HA)-based plasma-sprayed coatings, including the effect on biomedical efficacy of coating thickness, phase composition and distribution, amorphicity and crystallinity, porosity and surface roughness, cohesion and adhesion, micro- and nano-structured surface morphology, and residual coating stresses. In addition, it will provide details of the thermal alteration that HA particles undergo in the extremely hot plasma jet that leads to dehydroxylated phases such as oxyhydroxylapatite (OHA) and oxyapatite (OA) as well as thermal decomposition products such as tri-(TCP) and tetracalcium phosphates (TTCP), and quenched phases such as amorphous calcium phosphate (ACP). The contribution will further explain the role of ACP during the in vitro interaction of the as-deposited coatings with simulated body fluid resembling the composition of extracellular fluid (ECF) as well as the in vivo responses of coatings to the ECF and the host tissue, respectively. Finally, it will briefly describe performance profiles required to fulfill biological functions of osteoconductive bioceramic coatings designed to improve osseointegration of hip endoprostheses and dental root implants. In large parts, the content of this contribution is a targeted review of work done by the author and his students and coworkers over the last two decades. In addition, it is considered a stepping stone toward a standard operation procedure aimed at depositing plasma-sprayed bioceramic implant coatings with optimum properties.

End-Stage Renal Disease (ESRD): Physical Activity and Elucidation of Its Effects on Biochemical and Haematological Parameters in Haemodialysis Patients

End-stage renal disease (ESRD) is a progressive disorder for which there is no prospect of recovery, and for which patients receive regular haemodialysis. In ESRD the ability of the kidneys to excrete metabolic waste products and to regulate the composition of extracellular fluid is compromised. Symptoms of ESRD also include cardiovascular dysfunction, anaemia, malnutrition, muscle wasting, muscle weakness, glucose intolerance and reduced bone density. Patients with ESRD are likely to be challenged by participation in exercise whilst undergoing a HD regimen. Nevertheless there is a case for prescribing exercise in patients who struggle to become active. Some benefits of exercise In patients receiving haemodialysis, the benefits of physical exercise, which include: 1) Reduction of toxins and fluid overload in the circulatory system, permitting improved tolerance to the HD regimen and 2) Increased heart rate, which improves cardiovascular performance, 3) a reduction in comorbidities and an increase in well-being, and 4) the facilitation of positive coping strategies. An understanding how exercise can be of clinical advantage in ESRD patients is unique and challenging given the variety of nutritional and clinical conditions with which they present. The haematological and biochemical parameters which should be monitored in these patients (including blood potassium, urea, calcium and hemoglobin levels) need to be prioritized, and this prioritization depends in turn upon general patient well-being. More research is also required in the understanding of physiology and importance of good nutrition in this population. The aim of this work is to provide some background of the key parameters in HD patients and to identify literature on biochemical parameters which are affected during physical activity in HD patients. The results help to emphasize that closer attention should be paid to monitoring HD efficacy and Kt/V, a measure of dialysis adequacy.

On the role of the extracellular space on the holistic behavior of the brain.

Multiple players are involved in the brain integrative action besides the classical neuronal and astrocyte networks. In the past, the concept of complex cellular networks has been introduced to indicate that all the cell types in the brain can play roles in its integrative action. Intercellular communication in the complex cellular networks depends not only on well-delimited communication channels (wiring transmission) but also on diffusion of signals in physically poorly delimited extracellular space pathways (volume transmission). Thus, the extracellular space and the extracellular matrix are the main players in the intercellular communication modes in the brain. Hence, the extracellular matrix is an 'intelligent glue' that fills the brain and, together with the extracellular space, contributes to the building-up of the complex cellular networks. In addition, the extracellular matrix is part of what has been defined as the global molecular network enmeshing the entire central nervous system, and plays important roles in synaptic contact homeostasis and plasticity. From these premises, a concept is introduced that the global molecular network, by enmeshing the central nervous system, contributes to the brain holistic behavior. Furthermore, it is suggested that plastic 'brain compartments' can be detected in the central nervous system based on the astrocyte three-dimensional tiling of the brain volume and on the existence of local differences in cell types and extracellular space fluid and extracellular matrix composition. The relevance of the present view for neuropsychiatry is discussed. A glossary box with terms and definitions is provided.

Key Controversies in Colloid and Crystalloid Fluid Utilization.

Nearly 2 centuries have passed since the use of intravenous fluid became a foundational component of clinical practice. Despite a steady stream of published investigations on the topic, questions surrounding the choice, dose, timing, targets, and cost-effectiveness of various fluid options remain insufficiently answered. In recent years, 2 of the most debated topics reference the role of albumin in acute care and the safety of normal saline. Although albumin has a place in therapy for specific patient populations, its high cost relative to other fluids makes it a less desirable option for hospitals and health systems with escalating formulary scrutiny. Pharmacists bear responsibility for reconciling this disparity and supporting the rational use of albumin in acute care through a careful evaluation of recently published literature. In parallel, it has become clear that crystalloids should no longer be considered a homogenous class of fluids. The past reliance on normal saline has been questioned due to recent findings of renal dysfunction attributable to the solution's supraphysiologic chloride concentration. These safety concerns with 0.9% sodium chloride may result in a practice shift toward more routine use of "balanced crystalloids," such as lactated Ringer's or Plasma-Lyte, that mimic the composition of extracellular fluid. The purpose of this review is to summarize the evidence regarding these 2 important fluid controversies that are likely to affect hospital pharmacists in the coming decades - the evidence-based use of human albumin and the rising role of balanced salt solutions in clinical practice.