Intracellular Fluid Research Articles

Identifikasi Tipe Dehidrasi dan Profil Elektrolit Mayor pada Pasien Kucing di Rumah Sakit Hewan Prof. Soeparwi dan Beberapa Klinik Hewan di Wilayah Yogyakarta

Dehydration is defined as a lack of body fluids followed by loss of electrolytes, and changes in acid-base balance. The type of dehydration is limited based on the concentration of sodium in serum at the time of dehydration. Maintenance of osmotic pressure and distribution of several compartments of body fluids are the main functions of the four major electrolytes, namely sodium (Na +), potassium (K +), chloride (Cl‾), and bicarbonate (HCO3‾). Sodium is the most cation in extracellular fluid, most potassium cation in intracellular fluid and chloride is the most anion in extracellular fluid. The purpose of this study was to identify the type of dehydration and to determine the major electrolyte profile in cats in Yogyakarta and its surroundings. This study used 18 sick cats that were thought to be dehydrated, marked by decreased skin turgor, CRT> 2 seconds, and 12 cats that were suspected of having electrolyte balance disorders with symptoms of ascites, uropoetic disorders. Blood was drawn for all cats to measure Pack Cells Volume (PCV) levels. Patient clinical data and patient diagnosis were recorded, cats with changes in serum PCV levels were separated for examination of levels of sodium, chloride, potassium using Seamaty SMT-120V. The type of dehydration is identified based on the sodium level in the serum of a dehydrated cat. The results showed that most of the cat patients were dehydrated had low serum sodium levels (hyponatremia). There was 1 cat patient had low chloride levels. Potassium levels in cats with UT obstruction increased, which led to a decrease in the Na: K ratio. Cat bicarbonate levels did not show any change. From the results of the study it was concluded that dehydration in cats at Prof. Soeparwi is hypotonic dehydration (71%). The sodium profile mostly decreased, chloride and bicarbonate levels did not change, while there were changes in potassium levels in patients with UT disorders. The advice given is to check electrolytes before doing fluid therapy. Prior to electrolyte testing, dehydrated cats can be given a sodium solution.

The interaction between stress and metabolic disruption in student population – preliminary study

Abstract Introduction: Approximately 26% of individuals between 18 and 24 years old are overweight or obese, and the number of persons with excessive body mass index (BMI) is growing. Obesity increases the risk of metabolic disruptions, which is well connected with mental health problems. Stressful situations, including entering adulthood and starting university education, affect food choices negatively. The aim of the study was to examine the relationship between psychological stress and body composition in the student population. Materials and methods: The study group consisted of 80 students (76% of women and 24% of men) between 19 and 28 years old from universities in Lublin. To determine anthropometric measurement (fat-free mass (FFM), fat mass (FM), total body water (TBW), intracellular (ICF) and extracellular (ECF) fluids), bioelectrical impedance analysis (BIA) method was applied. The severity of stress symptoms was measured using Perceived Stress Scale (PSS-10). Results: When it comes to 41.25% of participants, they used relaxation techniques, mainly meditation, yoga practice and walking. Most students had optimal body weight. While 60% of individuals had high stress levels. The perceived stress was not related to using the relaxation methods. Individuals with the high stress severity were characterized by lower: TBW, ECF and ICF expressed in liters, and lower FFM represented in kilograms. The inverse relationship between the severity of stress and the aforementioned parameters was also detected (p<0.05). Conclusions: Implementing appropriate healt h education programs to prevent negat ive changes in ant hropometric measurements, psychological stress, and their health-related consequences in the student population should be considered.

PEGylated Doxorubicin Prodrug-Forming Reduction-Sensitive Micelles With High Drug Loading and Improved Anticancer Therapy.

Significant efforts on the design and development of advanced drug delivery systems for targeted cancer chemotherapy continue to be a major challenge. Here, we reported a kind of reduction-responsive PEGylated doxorubicin (DOX) prodrug via the simple esterification and amidation reactions, which self-assembled into the biodegradable micelles in solutions. Since there was an obvious difference in the reduction potentials between the oxidizing extracellular milieu and the reducing intracellular fluids, these PEG–disulfide–DOX micelles were localized intracellularly and degraded rapidly by the stimulus to release the drugs once reaching the targeted tumors, which obviously enhanced the therapeutic efficacy with low side effects. Moreover, these reduction-sensitive micelles could also physically encapsulate the free DOX drug into the polymeric cargo, exhibiting a two-phase programmed drug release behavior. Consequently, it showed a potential to develop an intelligent and multifunctional chemotherapeutic payload transporter for the effective tumor therapy.

Abstract 10782: Optimization of Preservation Solution and Temperature of Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch for Regenerative Therapy

Background: Regenerative therapy for heart failure is being practical as a new treatment. Since cell products contain living cells, it is important to apply the storage method according to the characteristics of the product in order to maintain its structure and function. A lot of studies have been done on suitable storage solutions for organs, and organ storage solutions may also be effective for cell product preservation, especially tissues with three-dimensional structures. In this study, we investigated the optimal storage conditions for human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) patches. Methods and Results: We evaluated the properties of iPSC-CM patches after storage in cell culture buffer solution (BS), intracellular fluid type organ preservation solution A (PSA), and extracellular fluid type organ preservation solution B (PSB) and under room temperature or 4°C. Although the patches maintained their sheet-like morphology up to 120hrs , the sarcomere structure was disrupted, and the viability decreased over time after 48hrs of storage in BS at room temperature. Myocardial contraction/relaxation velocity and cytokine production after reculture of the stored patches showed a significant decrease after 96hrs of storage in BS at room temperature. We tested whether PSA and PSB improve the preservation of the patches compared to the BS in 48hrs storage. As a result, contraction velocity after reculture was comparable for PSA (17.1±4.4 μm/sec), PSB (10.0±0.9 μm/sec) and BS (12.9±1.4μm/sec). However, cell viability after storage was significantly decreased in PSA (13.9±19.9%) and PSB (68.4±26.1%) compared to BS (90.6±4.1%). Although sarcomere structure was maintained in BS, it was disrupted in PSA and PSB. No improvement was observed in contraction velocity, cell viability and sarcomere structure in PSA at 4°C compared to BS at room temperature. Conclusions: The iPSC-CM patches maintained their structure and function for up to 48 hrs under storage conditions in BS at room temperature. The buffer solution, intracellular or extracellular fluid type organ preservation solution have different ionic balances, suggesting that the optimal storage conditions differ according to tissue structure and cell type.

Abstract PO-027: Investigating unfolded protein responses in pancreatic ductal adenocarcinoma under lipid imbalance

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death with a five-year survival rate of only 10%. A major feature of PDAC tumor microenvironment (TME) is desmoplasia, which are dense fibrotic and inflammatory stromal regions constituting the PDAC TME. This desmoplastic reaction results in poor intratumoral perfusion and elevated interstitial fluid pressure, creating regions with severe oxygen and nutrient deprivation. One result is a significant deficiency in unsaturated fatty acids (UFAs) because the de novo synthesis of UFAs requires molecular oxygen. Our data indicate that PDAC cells experience endoplasmic reticulum (ER) stress and trigger a subsequent unfolded protein response (UPR) under tumor-like stress, which can be mitigated by UFAs. The UPR regulates an intricate signaling network mediated by three major stress sensors: Inositol-requiring enzyme 1a (IRE1a), PKR-like ER kinase (PERK) and activating transcription factor 6a (ATF6a). UPR output can be either cytoprotective or cytotoxic depending on tumor types and the severity of stress. Our data suggest that B-I09, a selective IRE1 RNase inhibitor, impairs PDAC cell viability under stress conditions, indicating a pro-survival role for IRE1a. Previous studies showed that MYC-driven cancer cells are highly reliant on UPR pathways. Therefore, we hypothesize that the two major PDAC transcriptional subtypes “Classical” and “Basal-like” may have distinct dependencies on UPR pathways, with the Basal-like subtype being more dependent due to an enrichment of MYC gene signatures. Overall, we hypothesize that IRE1a, PERK and/or ATF6a play(s) an oncogenic role in PDAC tumorigenesis due to lipid saturation abnormalities, and the Basal-like PDAC subtype is more sensitive to inhibition of UPR pathway(s). We are evaluating the role of IRE1a, PERK and ATF6a using pharmacologic inhibition and genetic knockdown in vitro and in vivo under UFA deprived conditions. We will also evaluate PDAC intracellular and interstitial fluid lipidomics using LC-MS. In addition, we will assess whether hypoxic PDAC cells experience ER stress in vivo due to UFA deprivation using Stimulated Raman scattering (SRS) microscopy. To explore the subtype-specific dependency on the UPR pathways, we are querying a UPR gene signature in different tumor cell clusters using single cell RNA-seq datasets of patient samples. In addition, we will employ an isogenic system for PDAC subtypes and examine subtype-specific responses to UPR inhibition in vitro and in vivo. Our goal is to better understand UPR pathways in PDAC cells as a survival mechanism in response to the “lipotoxicity” induced by ER membrane saturation, with a consideration of intratumoral heterogeneity of PDAC cell subtype. Citation Format: Yanqing (Christine) Jiang, Xu Han, Michelle Burrows, Carson Poltorack, Celeste Simon, Brian Keith. Investigating unfolded protein responses in pancreatic ductal adenocarcinoma under lipid imbalance [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-027.

Aether, Fields & Energy Dynamics in Living Bodies - Part II

In this article, we examine dynamics of the three primary aether modalities in the water-body: first, the magnetic, which takes origin in the cardiovascular system; secondly, the radiant, related to ambient light-fall upon the body from the outside or that generated internally, and flows as organized currents in interstitial water; and the dielectric, which predominates in the intracellular fluid spaces, mediated by ion currents, and is involved in the generation and maintenance of cell structure and molecular energy metabolism.

Perturbed body fluid distribution and osmoregulation in response to high salt intake in patients with hereditary multiple exostoses

SummaryBackgroundHereditary Multiple Exostoses (HME) is a rare autosomal disorder characterized by the presence of multiple exostoses (osteochondromas) caused by a heterozygous loss of function mutation in EXT1 or EXT2; genes involved in heparan sulfate (HS) chain elongation. Considering that HS and other glycosaminoglycans play an important role in sodium and water homeostasis, we hypothesized that HME patients have perturbed whole body volume regulation and osmolality in response to high sodium conditions.MethodsWe performed a randomized cross-over study in 7 male HME patients and 12 healthy controls, matched for age, BMI, blood pressure and renal function. All subjects followed both an 8-day low sodium diet (LSD, <50 mmol/d) and high sodium diet (HSD, >200 mmol/d) in randomized order. After each diet, blood and urine samples were collected. Body fluid compartment measurements were performed by using the distribution curve of iohexol and 125I-albumin.ResultsIn HME patients, HSD resulted in significant increase of intracellular fluid volume (ICFV) (1.2 L, p = 0.01). In this group, solute-mediated water clearance was significantly lower after HSD, and no changes in interstitial fluid volume (IFV), plasma sodium, and effective osmolality were observed. In healthy controls, HSD did not influence ICFV, but expanded IFV (1.8 L, p = 0.058) and increased plasma sodium and effective osmolality.ConclusionHME patients show altered body fluid distribution and osmoregulation after HSD compared to controls. Our results might indicate reduced interstitial sodium accumulation capacity in HME, leading to ICFV increase. Therefore, this study provides additional support that HS is crucial for maintaining constancy of the internal environment.

Mislocalization of CFTR expression in acute pancreatitis and the beneficial effect of VX-661+VX-770 treatment on disease severity.

Cystic fibrosis transmembrane conductance regulator (CFTR) has an essential role in maintaining pancreatic ductal function. Impaired CFTR function can trigger acute pancreatitis (AP) and exacerbate disease severity. We aimed to investigate the localization and expression of CFTR during AP, and determined the effects of a CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. AP was induced in FVB/n mice by 6-10 hourly intraperitoneal injections of 50μg/kg cerulein. Some mice were pre-treated with five to six daily injections of 2mg/kg VX-661+VX-770. Control animals were administered physiological saline instead of cerulein and dimethyl sulfoxide instead of VX compounds. AP severity was determined by measuring laboratory and histological parameters; CFTR and CK19 expression was measured. Activity of ion transporters was followed by intracellular pH or fluid secretion measurement of isolated pancreatic intra-/interlobular ducts. Cerulein-induced AP severity was greatest between 12 and 24h. CFTR mRNA expression was significantly increased 24h after AP induction. Immunohistochemistry demonstrated disturbed staining morphology of CFTR and CK19 proteins in AP. Mislocalization of CFTR protein was observed from 6h, while expression increased at 24h compared to control. Ductal HCO3- transport activity was significantly increased 6h after AP induction. AP mice pre-treatment with VX-661+VX-770 significantly reduced the extent of tissue damage by about 20-30%, but other parameters were unchanged. Interestingly, VX-661+VX-770 in vitro administration significantly increased the fluid secretion of ducts derived from AP animals. This study described the course of the CFTR expression and mislocalization in cerulein-induced AP. Our results suggest that the beneficial effects of CFTR correctors and potentiators should be further investigated in AP. KEY POINTS: Cystic fibrosis transmembrane conductance regulator (CFTR) is an important ion channel in epithelial cells. Its malfunction has several serious consequences, like developing or aggravating acute pancreatitis (AP). Here, the localization and expression of CFTR during cerulein-induced AP in mice were investigated and the effects of CFTR corrector (VX-661) and a potentiator (VX-770) on disease severity were determined. CFTR mRNA expression was significantly increased and mislocalization of CFTR protein was observed in AP compared to the control group. Interestingly, pre-treatment of AP mice with VX-661+VX-770 significantly reduced the extent of pancreatic tissue damage by 20-30%. In vitro administration of VX-661+VX-770 significantly increased the fluid secretion of ducts derived from AP animals. Based on these results, the utilization of CFTR correctors and potentiators should be further investigated in AP.

Screening of zearalenone-degrading bacteria and analysis of degradation conditions

Zearalenone(ZEN) is a mycotoxin produced by Fusarium, possessing estrogen-like effects, carcinogenicity, and multiple toxicities. To seek more efficient and practical agents for biological detoxification and broaden their application, this study isolated 194 bacterial strains from the moldy tuberous root of Pseudostellaria heterophylla, which were co-cultured with ZEN. An efficient ZEN-degrading strain H4-3-C1 was screened out by HPLC and identified as Acinetobacter calcoaceticus by morphological observation and molecular identification. The effects of culture medium, inoculation dose, culture time, pH, and temperature on the degradation of ZEN by H4-3-C1 strain were investigated. The mechanism of ZEN degradation and the degrading effect in Coicis Semen were discussed. The degradation rate of 5 μg·mL~(-1) ZEN by H4-3-C1 strain was 85.77% in the LB medium(pH 6) at 28 ℃/180 r·min~(-1) for 24 h with the inoculation dose of 1%. The degradation rate of ZEN in the supernatant of strain culture was higher than that in the intracellular fluid and thalli. The strain was inferred to secret extracellular enzymes to degrade ZEN. In addition, the H4-3-C1 strain could also degrade ZEN in Coicis Semen. If the initial content of ZEN in Coicis Semen was reduced from 90 μg·g~(-1) to 40.68 μg·g~(-1), the degradation rate could reach 54.80%. This study is expected to provide a new strain and application technology for the biological detoxification of ZEN in food processing products and Chinese medicinal materials.

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Yes Is No

Utilization of Chemical Compounds in Cocoa Peel Waste as a Healthy Drink

West Sumatra Province is one of the largest cocoa pod (Theobroma cacao L) producing areas in Indonesia. It was recorded that from 2004 to 2007 the area of cocoa plantations increased by around 33,340 ha from 13,197 ha to 46,627 ha. As long as only the seeds are used from cocoa pods, while the skin is only used as animal feed or compost and the rest is left to rot around the plantation area. Whereas cocoa skin waste contains chemical compounds that are beneficial to the body. Based on XRF analysis, it was found that the cocoa husk contained the most K and Ca elements. K is important cation in the intracellular fluid that plays a role in balance pH and osmolality and the element Ca is an essential nutrient needed for various body functions. Cocoa peel contains polysaccharides (hemicellulose 36.23％ and cellulose 1.14％) and lignin around 20-27.95％ and contains flavonoids which can act as antioxidants against free radicals. Free radicals that enter the body cause cell damage that results in the emergence of several diseases such as heart disease, Alzheimer's disease, cancer, and other diseases. Therefore, cocoa shell waste is very suitable to be processed into natural health drinks because of the many chemical compounds in it.

The characteristic of the component body composition of athletes involved in game-based and cyclic kinds of sports

Objective:to determine a component body composition of students specializing in volleyball and athletics and to conduct a comparative analysis of the results.Materials and methods:the study was conducted at the Department of physical training and sports at the Yaroslavl State Medical University of the Ministry of Health of the Russian Federation. The study included students from different groups of physical training: volleyball (10 men and 10 women), athletics (10 women) (experimental groups), and first­year students that attended physical training classes (14 men and 16 women) (control group).Results:significant differences were revealed between the anthropometric measurements in the experimental groups of the studied women and between the results of anthropometric measurements in the female volleyball players, female athletes, and students from the control group. Significant differences were revealed in the component body composition of the studied women from the experimental and control groups. The analysis of the results of anthropometric measurements in the experimental and control groups of men did not reveal any significant differences between the parameters. Bioimpedancemetry revealed significant differences in the composition of the internal milieu of volleyball players in comparison with the control group.Conclusions:1. differences were revealed in the component composition of the body of female athletes involved in game­based and cyclic kinds of sport as well as in the parameters of bio­impedance of female volleyball players and the control group. Female volleyball players had higher parameters of total body fluids, intracellular and extracellular fluids, fat­free, fat, and active cell mass in comparison with female light athletes and the control group. The differences in the obtained results were more significant in the experimental groups. 2. Bio­impendance analysis of men showed significant differences in the component body composition of volleyball players in comparison with untrained students. The parameters of total body fluids, fat­free, fat, and active cell mass in sportsmen exceeded the same parameters in the control group. 3. Differences were established in the anthropometric parameters depending on the sport­oriented specialization of female students. Female volleyball players had higher values of mass, length, body weight index, and body surface area, the circumferences of the pelvis, thighs, and wrists in comparison with the results obtained in female light athletes. Similar differences were revealed in the anthropometric parameters of female volleyball players and students from the control group. Significantly lower values of the body weight index, circumference of the chest and pelvis of female athletes were registered in comparison with students from the control group. Male volleyball players did not have significant differences in the anthropometric parameters. They tended to have an increase in the body mass, length and surface area of the body, circumference of the chest, thighs, and wrists.

Genotoxin-responsive DNA capsules for the detection of styrene oxide

Environmental genotoxins cause DNA damage and lead to gene dysfunction and mutation, posing a serious threat to health. In this article, a styrene-7,8-oxide–responsive DNA capsule (SODC) was designed and synthesized to respond to styrene-7,8-oxide (SO) (0–2%) within 10 min. The SODC was constructed by assembling three DNA oligos in a layer-by-layer structure and forming crosslinked hybridized DNA with segmented duplexes in 7–8 bp. The duplexes contained numerous guanine–cytosine pairs that were susceptible to electrophilic attack of SO. The resulting SO–purine adducts caused duplex dehybridization, which led to collapse of the SODC and release of fluorescent cargo. The size, number, zeta potential, and morphology of the SODC were evaluated. The melting curve indicated integrity of the crosslinked hybridization, which was evident from a substantial increase in melting temperature. SO-triggered transformation of the DNA capsules was tracked using a confocal microscope. To maximize the unlocking efficiency of the SODC, the effects of incubation time, temperature, pH, and ionic concentration on the outputted fluorescence were also studied. The response yielded by styrene and toluene (2%) was minimal. The interference caused by a high concentration of K3PO4 (50 mM)—a mimicking condition of intracellular fluid—was negligible. This system presented promising DNA-encoded sensing elements in the surveillance of the effect caused by environmental genotoxins.

Long range electromagnetic field nature of nerve signal propagation in myelinated axons

The nature of saltatory conduction in myelinated axon described by equivalent circuit and circuit theory is still contentious. Recent experimental observations of action potentials transmitting through disjointed nerve fibers strongly suggest an electromagnetic wave propagation mechanism of the nerve signals. In this paper, we employ the electromagnetic wave model of the myelinated axon to describe action potential signal propagation. We use the experimental frequency-dependent conductivity and permittivity values of the nerve tissues in order to reliably calculate the electromagnetic modes by using electromagnetic mode solvers. We find that the electromagnetic waves above 10 kHz can be well confined in extracellular fluid–myelin sheath–intracellular fluid waveguide and propagate a distance of 7 mm without much attenuation. Our study may serve as one of the fundamental researches for the better understanding of the nervous system.

Fluid Shifts With Acute Exposure To Normobaric And Hypobaric Hypoxia

PURPOSE: To determine the body fluid shifts that occur with exposure to normobaric hypoxia (NH) and hypobaric hypoxia (HH) compared to normobaric normoxia (NN). METHODS: Eighteen males and females (male = 10, female = 8, age 35 ± 7 yrs) completed three trials on back to back days in a randomized order. NN was conducted at sea level, NH was conducted at sea level but breathing a gas mixture to simulate 4,617 m of elevation, and HH was conducted at 4,617 m of terrestrial elevation. The time and rate of hypoxia exposure was consistent between NN and HH (0 m to 4,617 m in 90 minutes). Finger-stick blood samples were taken after the 90 minute intervention and analyzed for hemoglobin and hematocrit to calculate plasma volume shifts and urine was collected to measure urine specific gravity. After 10 minutes of supine resting, body water was analyzed via BIA. RESULTS: Plasma volume change was not altered by NH relative to NN (-3.77 ± 8.36%, p = 0.073), but lower in HH relative to NN (-16.610 ± 7.84%, p < 0.001). Urine specific gravity was similar between all trials (p = 0.120, main effect). Total body water was not different between NN (43.8 ± 7.6 L) and NH (43.7 ± 7.7 L, p = 0.492), but was lower in HH (43.0 ± 7.6 L) than NN (p < 0.001) and NH (p < 0.001). Extracellular fluid was not different between NN (16.35 ± 2.85 L) and NH (16.32 ± 2.84 L, p = 0.696), but was lower in HH (16.08 ± 2.78 L) than NN (p < 0.001) and NH (p = 0.006). Intracellular Fluid was not different between NN (27.41 ± 4.81 L) and NH (27.33 ± 4.89 L, p = 0.420) but was lower in HH (26.97 ± 4.80 L) than NN (p < 0.001) and NH (p = 0.016). CONCLUSIONS: Body fluid shifts are stimulated by an alteration of barometric pressure and not by hypoxia. Caution should be made when applying data from studies conducted in NH to HH.

Pre-loading large volume oral electrolytes: tracing fluid and ion fluxes in horses during rest, exercise and recovery.

Exercise results in rapid and large extracellular to intracellular fluid shifts, as well as significant sweating losses of water and ions. It is unknown whether ions within oral electrolyte supplements are taken up by muscle (and other soft tissues) and whether oral supplementation can effectively offset sweating losses. Pre-loading with 8L of a balanced hypotonic electrolyte supplement attenuated extracellular fluid losses, increased exercise duration and increased sweating fluid and ion losses during submaximal exercise. Supplemented electrolytes appear in skeletal muscle within 1h after administration. Electrolyte supplementation increased exercise performance, improved maintenance of extracellular fluid volumes, and attenuated body fluid losses while maintaining sweating rates. This study used radioactive sodium (24 Na) and potassium (42 K) in a balanced, hypotonic electrolyte supplement to trace their appearance in skeletal muscle, and also quantified extracellular and whole-body fluid and ion changes during electrolyte supplementation, exercise and recovery. In a randomized crossover design, 1h after administration of 1 to 3L of water or electrolyte supplement with 24 Na, horses were exercised at 35% VO2max to voluntary fatigue or, after administration of 8L of water or electrolyte supplement with 42 K were exercised at 50% peak VO2 for 45 min (n = 4 in each trial). Pre-exercise electrolyte supplementation was associated with decreased loss of fluid and electrolytes from the extracellular fluid compartments during exercise and recovery compared with water alone. The improved fluid and ion balance during prolonged exercise was associated with increased exercise duration, despite continuing sweating losses of fluid and ions. Nasogastric administration of radiotracer 24 Na+ and 42 K+ showed rapid absorption into the blood with plasma levels peaking 45min after administration, followed by distribution into the extracellular space and intracellular fluid of muscle within 1h. Following exercise, virtually all Na+ remained within the extracellular compartment, while the majority of K+ underwent intracellular uptake by 2h of recovery. It is concluded that pre-loading with a large volume, balanced electrolyte supplement helps maintain whole-body fluid and ion balance and support muscle function during periods of prolonged sweat ion losses.

Exploratory Metabolomic Analysis Based on Reversed-Phase Liquid Chromatography-Mass Spectrometry to Study an In Vitro Model of Hypoxia-Induced Metabolic Alterations in HK-2 Cells.

Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography–mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided.

Combination of DXA and BIS Predicts Jump Power Better Than Traditional Measures of Sarcopenia.

ABSTRACTTraditional diagnostic criteria for sarcopenia use dual‐energy X‐ray absorptiometry (DXA)‐measured appendicular lean mass (ALM), normalized to height (ALM/ht2) or body mass index (ALM/BMI) to define low muscle mass. However, muscle function declines with aging before the loss of muscle mass is detected by ALM. This is likely due, in part, to qualitative muscle changes such as extracellular and intracellular fluid compartment shifts uncaptured by DXA. We propose combining bioimpedance spectroscopy (BIS), which estimates extracellular and intracellular compartment volume, with DXA to more accurately predict muscle function. This combination may help incorporate muscle quality, thereby improving sarcopenia diagnosis. We cross‐sectionally analyzed data from 248 Black and White participants aged 25 to 75 years from the Midlife in the United States Refresher Cohort. We proposed two novel muscle measures: ALM corrected by the BIS‐derived whole‐body extracellular to intracellular fluid ratio (E/I) and leg lean mass (LLM) corrected by leg‐specific E/I, creating (ALM/(E/I)W) and (LLM/(E/I)L), respectively. We compared the associations of traditional muscle measures, ALM/(E/I)W, and LLM/(E/I)L, with grip strength and lower limb power using jumping mechanography. LLM/(E/I)L explained jump power best at R 2 = 0.803 compared with ALM/(E/I)W (p < 0.0001) and all other measures. ALM/(E/I)W explained jump power second best (R 2 = 0.759) but not significantly better than traditional muscle measures. No muscle measure performed better than covariates when predicting handgrip strength. LLM/(E/I)L outperformed ALM/ht2 and ALM/BMI when predicting jump power. We propose LLM/(E/I)L is a powerful and clinically relevant method that accounts for muscle quality. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

ASSESSMENT OF THE AUTOPHAGY PROCESS IN MEN OF DIFFERENT BODY WEIGHT IN DIFFERENT AGE PERIODS

The study group consisted of 20 men of various ages (14-69 years) and weight. To assess the processes of autophagy, the activity of the protein Beclin-1 was used. In individuals with normal body weight, the presence of positive reliable correlations between the level of beclin-1 and extracellular water was revealed (r = 0.96; p &lt;0.01). In the obese group, there was a significant positive relationship between beclin-1 and the amount of triglycerides&#x0D; (r = 0,57; p &lt;0,05); muscle mass (r = 0,62; p &lt;0,05); lean mass (r = 0,62; p &lt;0,05); common liquid (r = 0,62; p&#x0D; &lt;0,05). In old age, there was a direct correlation between the level of beclin-1 and intracellular fluid (r = 0,84; p &lt;0,05). In men, autophagy was less dependent on age, and to a greater extent on the content of extracellular water in persons with normal weight and muscle mass and total water content in persons with obesity.

A minimal physiologically based pharmacokinetic model for high-dose methotrexate

PurposeHigh-dose methotrexate (HDMTX) is administered for the treatment of a variety of malignant tumors. Wide intra- and inter-individual variabilities characterize the pharmacokinetics of MTX, which is mostly excreted renally. HDMTX dosages are prescribed as a function of body surface area whereas dose adjustments depending on renal function are not well defined. We develop a population pharmacokinetic model with a physiological description of renal excretion as the basis for clinical tools able to suggest model-informed dosages and support therapeutic monitoring.MethodsThis article presents a minimal physiologically based pharmacokinetic (PBPK) model for HDMTX, which specifically accounts for individual characteristics such as body weight, height, gender, age, hematocrit, and serum creatinine to provide individualized predictions. The model supplies a detailed and mechanistic description of capillary and cellular exchanges between plasma, interstitial fluid, and intracellular fluid compartments, and focuses on an individualized description of renal excretion.ResultsThe minimal PBPK model is identified and validated with a literature dataset based on Chinese patients suffering from primary central nervous system lymphoma. A comparison with a pharmacokinetic model from the literature suggests that the proposed model provides improved predictions. Remarkably, the model does not present any significant bias in a wide range of degrees of renal function.ConclusionResults show that model predictions can capture the wide intra- and inter-individual variability of HDMTX, and highlight the role played by the individual degree of renal function. The proposed model can be the basis for the development of clinical decision-support systems for individualized dosages and therapeutic monitoring.