Effect Of Osmolality Research Articles

Enlarged brain perivascular spaces correlate with blood plasma osmolality in the healthy population: A longitudinal study

Enlarged perivascular spaces (EPVS) are increasingly recognized as an MRI detectable feature of neuroinflammatory processes and age-related neurodegenerative changes. Understanding perivascular characteristics in healthy individuals is crucial for their applicability as a reference for pathological changes. Limited data exists on the EPVS load and interhemispheric asymmetry in distribution among young healthy subjects. Despite the known impact of hydration on brain morphometric studies, blood plasma osmolality's effect on EPVS remains unexplored.This study investigated the influence of age, total intracranial volume (TIV), and blood plasma osmolality on EPVS characteristics in 59 healthy adults, each undergoing MRI and osmolality assessment twice within 14.8 months (mean ± 4 months). EPVS analysis was conducted in the centrum semiovale using high-resolution automated segmentation, followed by an optimization algorithm to enhance EPVS segmentation accuracy. Linear Mixed Effects model was used for the statistical analysis, which unveiled significant inter-individual variability in EPVS load and inter-hemispheric asymmetry. EPVS volume increased with age, higher TIV and lower blood plasma osmolality levels. Our findings offer valuable insights into EPVS characteristics among the healthy population, establishing a foundation to further explore age-related and pathological changes.

Overloading effect on the osmo-viscoelastic and recovery behavior of the intervertebral disc.

In vitro studies investigating the effect of high physiological compressive loads on the intervertebral disc mechanics as well as on its recovery are rare. Moreover, the osmolarity effect on the disc viscoelastic behavior following an overloading is far from being studied. This study aims to determine whether a compressive loading-unloading cycle exceeding physiological limits could be detrimental to the cervical disc, and to examine the chemo-mechanical dependence of this overloading effect. Cervical functional spine units were subjected to a compressive loading-unloading cycle at a high physiological level (displacement of 2.5 mm). The overloading effect on the disc viscoelastic behavior was evaluated through two relaxation tests conducted before and after cyclic loading. Afterward, the disc was unloaded in a saline bath during a rest period, and its recovery response was assessed by a third relaxation test. The chemo-mechanical coupling in the disc response was further examined by repeating this protocol with three different saline concentrations in the external fluid bath. It was found that overloading significantly alters the disc viscoelastic response, with changes statistically dependent on osmolarity conditions. The applied hyper-physiological compressive cycle does not cause damage since the disc recovers its original viscoelastic behavior following a rest period. Osmotic loading only influences the loading-unloading response; specifically, increasing fluid osmolarity leads to a decrease in disc relaxation after the applied cycle. However, the disc recovery is not impacted by the osmolarity of the external fluid.

Effect of tear osmolarity on postoperative refractive error after cataract surgery

Purpose: To analyze the effects of tear osmolarity on postoperative refractive error and patient satisfaction after cataract surgery. Methods: The patients were divided into two groups based on the tear osmolarity (group Nr 1-normal tear osmolarity, <310 mOsm/L; group Nr 2-hyperosmolar, >310 mOsm/L). Preoperative and postoperative (1 month after surgery) visual acuities (VAs), refractions, and best corrected VAs (BCVAs) were measured. The postoperative refractive error was measured as the spherical equivalent (SE) (SE = sphere + [0.5 × cylinder]). The postoperative VA, BCVA, and SE were compared between groups. Results: Eighty-one patients were included in the study (group Nr 1=40 patients and group Nr 2=41 patients). The hyperosmolar group had a statistically significant higher postoperative refractive error (p<0.01, mean SE for group Nr 1=0.284; mean SE for group Nr 2=0.604) and lower VA after surgery (p<0.01, mean VA for group Nr 1=0.891; mean VA for group Nr 2=0.762). Conclusions: Increased tear osmolarity can affect the planned outcome of cataract surgery as an unexpected refractive error. Measuring tear osmolarity before routine cataract surgery would help achieve accurate results and improve postoperative patient satisfaction.

Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway.

Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway.

Increased ICU mortality in septic shock patients with hypo- or hyper- serum osmolarity: A retrospective study.

While many factors that are associated with increased mortality in septic shock patients have been identified, the effects of serum osmolarity on the outcomes of ICU patients with septic shock have not yet been studied. The present study was designed to examine the association of serum osmolarity with ICU 28-day mortality in ICU patients with septic shock. Adult patients diagnosed with septic shock from the MIMIC-IV database were selected in this study. The serum osmolarity was calculated synchronously according to the serum concentrations of Na+, K+, glucose, and urea nitrogen. In the present study, a significant difference was observed between the 28-day mortality of septic shock patients with hypo-osmolarity, hyper-osmolarity, and normal osmolarity (30.8%, 34.9%, and 23.0%, respectively, p < 0.001), which were detected at ICU admission. After propensity score matching (PSM) for basic characteristics, the relatively higher mortality was still observed in the hypo-osmolarity and hyper-osmolarity groups, compared to normal osmolarity group (30.6%, 30.0% vs. 21.7%, p = 0.009). Furthermore, we found that transforming the hyper-osmolarity into normal osmolarity by fluid therapy on day 2 and 3 decreased this mortality. The serum osmolarity disorder is markedly associated with increased 28-day mortality in septic shock patients.

Development of a diluent storage media and effect of cryoprotectants on semen collected from white spotted bamboo sharks (Chiloscyllium plagiosum) and cooled to 5 ºC

Three experiments were performed to evaluate the effects of osmolarity, temperature, media and cryoprotectants on white spotted bamboo shark (Chiloscyllium plagiosum) spermatozoa. Semen was collected from 7 different males using a massage technique with the animals held in tonic immobilization with gills submerged. A Computer Assisted Sperm Analysis (CASA) system was used to assess sperm motility. Experiment one evaluated the effects of Hank’s balanced salt solution (HBSS) with different osmolarities (200, 400, 800 and 1000 mOsm Kg1) and incubation temperatures (5 °C and 24 °C [room temperature]) over time (6 h, 12 h and 24 h). Membrane integrity and morphology were degraded (P < 0.05) over time; however, sperm extended with HBSS 1000 and HBSS 800 were least affected. Higher total motility (TM) and average path velocity (VAP, P > 0.05) sperm parameters were observed with HBSS 1000 and HBSS 800, respectively. In addition, TM, VAP, and curvilinear velocity (VCL) were all reduced (P < 0.05) compared to sperm held at 5 °C. Experiment two compared the effects of sperm diluted in crystal reef water (CRW), elasmobranch ringers (ER) or raw held at 5 °C. Results indicated that CRW had improved viability, TM, VAP, VSL, VCL, and straightness (STR) when compared to sperm diluted in ER or Raw at 5 °C. The final experiment compared different cryoprotectants (dimethyl sulfoxide [DMSO] 10%, DMSO 20%, Ethylene-glycol [EG] 10%, EG 20%, and Trehalose [Tre] 10%, Tre 20%) during incubation at 5 °C. Across all time points, sperm incubated in Tre (10 or 20%) had increased (P < 0.05) membrane integrity and normal morphology compared to all other media and raw. Across all time points, sperm exposed to Tre (10% and 20%) and 10% DMSO had significantly improved TM (P < 0.05) compared to EG (10% and 20%) and 20% DMSO which were similar to raw. Although sperm collected from WSBS are robust and appear to tolerate a wide range of osmotic conditions and media, media made at 1000 mOsm Kg1 should provide the best in-vitro osmotic pressure, while storing at cooler temperatures should improve storage survival. For future cryopreservation studies, media using TRE and DMSO as cryoprotectants should be evaluated.

Effects of Osmolarity on Ultrasound-Induced Membrane Depolarization in Isolated Crayfish Motor Axon.

We have previously identified a novel non-selective membrane conductance (g_US) opened by focused ultrasound (FUS) in crayfish motor axons. In the work described here, we studied g_US properties further by comparing FUS-evoked depolarization (FUSD) in control and hypotonic saline with 75% of control osmolarity. The FUS was a train of 20 FUS bursts (2.1 MHz and 50 µs per burst) delivered at 1 kHz. The amplitude, onset latency, frequency of occurrence and duration of FUSD were compared in a 15-min time window before and after switching to hypotonic saline. Significant increases were observed for amplitude (p &lt; 0.001) and frequency of occurrence (p &lt; 0.01) while the onset latency exhibited a significant decrease (p &lt; 0.001). FUSD duration did not significantly differ. These results support predictions based on our hypothesis that g_US is mediated by opening of nanopores in the lipid bilayer and that stretching of axonal membrane caused by swelling at low osmolarity should increase the probability of nanopore formation under FUS. The FUSD parameters, in addition, exhibited time-dependent trends when the window of observation was expanded to 45 min in each saline. The statistical significance of amplitude and duration differed between 15- and 45-min time windows, indicating the presence of adaptive responses of axonal membrane to osmotic manipulation.

Guilty by association: Importers, exporters and MscS-type mechanosensitive channels encoded in biosynthetic gene clusters for the stress-protectant ectoine.

Ectoine and its derivative hydroxyectoine are widely synthesized or imported by bacteria to fend off the detrimental effects of high osmolarity on cellular hydration and growth. Genes that are connected to a particular physiological process are often found in the same genomic context. We exploited this feature in a comprehensive bioinformatical analysis of 1103 ectoine biosynthetic gene clusters from Bacteria and Archaea through which we identified 415 ect operons that colocalize with genes encoding potential osmolyte transporters. These belong to various importer families. Focusing on the complex ect gene clusters of the alpha-proteobacteria Hyphomonas neptunium and Novoshingobium sp. LH128, we analysed several transporters with respect to their substrate specificities through physiological, molecular and modelling approaches. Accordingly, we identified an MFS-type uptake system specific for ectoines (EctU) and a novel SSS-type ectoine/hydroxyectoine importer (EctI) with a broader substrate profile for osmostress protectants. Furthermore, some ect gene clusters encode a MscS/YbdG-type mechanosensitive channel protein, whose functionality was assessed through down-shock assays. Moreover, our analysis identified the gene for the first putative ectoine/hydroxyectoine-specific efflux system (EctX), a member of the MFS superfamily. Our findings make substantial contributions to the understanding of the ecophysiology of ectoines, key players in microbial osmostress adjustment systems.

Effect of osmolarity and displacement rate on cartilage microfracture clusters failure into two regimes

Articular cartilage is a poroviscoelastic (PVE) material with remarkable resistance to fracture and fatigue failure. Cartilage failure mechanisms and material properties that govern failure are incompletely understood. Because cartilage is partially comprised of negatively charged glycosaminoglycans, altering solvent osmolarity can influence PVE relaxations. Therefore, this study aims to use osmolarity as a tool to provide additional data to interpret the role of PVE relaxations and identify cartilage failure regimes. Cartilage fracture was induced using a 100 μm radius spheroconical indenter at controlled displacement rates under three different osmolarity solvents. Secondarily, contact pressure (CP) and strain energy density (SED) were estimated to cluster data into two failure regimes with an expectation maximization algorithm. Critical displacement, critical load, critical time, and critical work to fracture increased with increasing osmolarity at a slow displacement rate whereas no significant effect was observed at a fast displacement rate. Clustering provided two distinct failure regimes, with regime (I) at lower normalized thickness (contact radius divided by sample thickness), and regime (II) at higher normalized thickness. Varied CP and SED in regime (I) suggest that failure in the regime is strain-governed. Constant CP and SED in regime (II) suggests that failure in the regime is dominantly governed by stress. These regimes can be interpreted as ductile versus brittle, or using a pressurized fragmentation interpretation. These findings demonstrated fundamental failure properties and postulate failure regimes for articular cartilage.

Effect of Serum Osmolarity on Prognosis of Traumatic Brain Injury

Introduction: Road traffic accident has been a significant cause of mortality in today's fast paced world. Metabolic and intracranial parameters have affected the outcome of traumatic brain injury. Countless analysis on biomechanical injury and tissue damage has substantiated additional treatment strategies. Laboratory values have been less investigated to predict the outcome of brain injury.&#x0D; Aims: This study was done to find out the association between the serum osmolarity with severity of head injury and the outcome in traumatic brain injury.&#x0D; Methods: This study was conducted at Department of Neurosurgery, Nepalgunj Medical college, Kohalpur, Banke from July 2020 to June 2021. 106 patients were included in the study. Clinical profile of the patients and calculated plasma osmolarity were monitored daily.&#x0D; Results: 106 patients were enrolled with mean age of 39±18.6 and male study population being on the higher side. 62(58.49%) patients with Traumatic Brain Injury accounted for road traffic accident with mild head injury as the commonest presentation. In about 40.57% of the patients osmolarity ranged between 285 to 295 milliosmole/ litre with mean osmolarity of 290.99±10.60. There was no significant association between severity of head injury and serum osmolarity (p value=0.45).&#x0D; Conclusion: There is no association between the severity of head injury with serum osmolarity.

Physosmotic Induction of Chondrogenic Maturation Is TGF-β Dependent and Enhanced by Calcineurin Inhibitor FK506.

Increasing extracellular osmolarity 100 mOsm/kg above plasma level to the physiological levels for cartilage induces chondrogenic marker expression and the differentiation of chondroprogenitor cells. The calcineurin inhibitor FK506 has been reported to modulate the hypertrophic differentiation of primary chondrocytes under such conditions, but the molecular mechanism has remained unclear. We aimed at clarifying its role. Chondrocyte cell lines and primary cells were cultured under plasma osmolarity and chondrocyte-specific in situ osmolarity (+100 mOsm, physosmolarity) was increased to compare the activation of nuclear factor of activated T-cells 5 (NFAT5). The effects of osmolarity and FK506 on calcineurin activity, cell proliferation, extracellular matrix quality, and BMP- and TGF-β signaling were analyzed using biochemical, gene, and protein expression, as well as reporter and bio-assays. NFAT5 translocation was similar in chondrocyte cell lines and primary cells. High supraphysiological osmolarity compromised cell proliferation, while physosmolarity or FK506 did not, but in combination increased proteoglycan and collagen expression in chondrocytes in vitro and in situ. The expression of the TGF-β-inducible protein TGFBI, as well as chondrogenic (SOX9, Col2) and terminal differentiation markers (e.g., Col10) were affected by osmolarity. Particularly, the expression of minor collagens (e.g., Col9, Col11) was affected. The inhibition of the FK506-binding protein suggests modulation at the TGF-β receptor level, rather than calcineurin-mediated signaling, as a cause. Physiological osmolarity promotes terminal chondrogenic differentiation of progenitor cells through the sensitization of the TGF-β superfamily signaling at the type I receptor. While hyperosmolarity alone facilitates TGF-β superfamily signaling, FK506 further enhances signaling by releasing the FKBP12 break from the type I receptor to improve collagenous marker expression. Our results help explain earlier findings and potentially benefit future cell-based cartilage repair strategies.

Effects of solvent osmolarity and viscosity on cartilage energy dissipation under high-frequency loading

Articular cartilage is a spatially heterogeneous, dissipative biological hydrogel with a high fluid volume fraction. Although energy dissipation is important in the context of delaying cartilage damage, the dynamic behavior of articular cartilage equilibrated in media of varied osmolarity and viscosity is not widely understood. This study investigated the mechanical behaviors of cartilage when equilibrated to media of varying osmolarity and viscosity. Dynamic moduli and phase shift were measured at both low (1 Hz) and high (75–300 Hz) frequency, with cartilage samples compressed to varied offset strain levels. Increasing solution osmolarity and viscosity both independently resulted in larger energy dissipation and decreased dynamic modulus of cartilage at both low and high frequency. Mechanical property alterations induced by varying osmolarity are likely due to the change in permeability and fluid volume fraction within the tissue. The effects of solution viscosity are likely due to frictional interactions at the solid-fluid interface, affecting energy dissipation. These findings highlight the significance of interstitial fluid on the energy dissipation capabilities of the tissue, which can influence the onset of cartilage damage.

The Association Between Plasma Osmolarity and In-hospital Mortality in Cardiac Intensive Care Unit Patients.

Objectives: Plasma osmolarity is a common marker used for evaluating the balance of fluid and electrolyte in clinical practice, and it has been proven to be related to prognosis of many diseases. The purpose of this study was to identify the association between plasma osmolarity and in-hospital mortality in cardiac intensive care unit (CICU) patients.Method: All of the patients were divided into seven groups stratified by plasma osmolarity, and the group with 290–300 mmol/L osmolarity was used as a reference group. Primary outcome was in-hospital mortality. The local weighted regression (Lowess) smoothing curve was drawn to determine the “U”-shaped relationship between plasma osmolarity and in-hospital mortality. Binary logistic regression analysis was performed to determine the effect of plasma osmolarity on the risk of in-hospital mortality.Result: Overall, 7,060 CICU patients were enrolled. A “U”-shaped relationship between plasma osmolarity and in-hospital mortality was observed using the Lowess smoothing curve. The lowest in-hospital mortality (7.2%) was observed in the reference group. whereas hyposmolarity (<280 mmol/L vs. 290–300 mmol/L: 13.0 vs. 7.2%) and hyperosmolarity (≥330 mmol/L vs. 290–300 mmol/L: 31.6 vs. 7.2%) had higher in-hospital mortality. After adjusting for possible confounding variables with binary logistic regression analysis, both hyposmolarity (<280 mmol/L vs. 290–300 mmol/L: OR, 95% CI: 1.76, 1.08–2.85, P = 0.023) and hyperosmolarity (≥330 mmol/L vs. 290–300 mmol/L: OR, 95% CI: 1.65, 1.08–2.52, P = 0.021) were independently associated with an increased risk of in-hospital mortality. Moreover, lengths of CICU and hospital stays were prolonged in patients with hyposmolarity or hyperosmolarity.Conclusion: A “U”-shaped relationship between plasma osmolarity and in-hospital mortality was observed. Both hyposmolarity and hyperosmolarity were independently associated with the increased risk of in-hospital mortality.

A multiscale and multiaxial model for anisotropic damage and failure of human annulus fibrosus

This article presents a multiscale model to predict deformation-induced damage and failure of human annulus fibrosus under multiaxial loading. In the modeling approach, formulated within the framework of nonlinear continuum mechanics, the hierarchical structure of the soft tissue is considered from the nano-sized collagen fibrils to the micro-sized oriented collagen fibers. At the macroscale, the multi-layered lamellar/inter-lamellar organization of the soft tissue is introduced by considering the effective interactions between adjacent layers. The stochastic process of progressive damage events operating at different scales of the solid phase is introduced for the extracellular matrix and the network of nano-sized fibrils/micro-sized fibers. The damage is made anisotropic due to lamellar oriented collagen fibers and special orientation distribution of the inter-fibrillar and inter-lamellar network of fibrils. The chemical-induced volumetric strain is also considered in our modeling approach to take into account the osmolarity effects along with the anisotropic time-dependent transversal deformations. The capacity of the model is discussed using a few available stretching datasets till failure along circumferential and radial directions. Model predictions under tilted stretching, biaxial stretching and shearing are also presented to illustrate further the efficiencies of our modeling approach. This work shows for the first time the directional effects on annulus mechanics and failure in relation to external loading mode, structure features, damage events and hydration.

Refractive Index Sensing for Measuring Single Cell Growth.

Accessing cell growth on adhesive substrates is critical for identifying biophysical properties of cells and their therapeutic response to drug therapies. However, optical techniques have low sensitivity, and their reliability varies with cell type, whereas microfluidic technologies rely on cell suspension. In this paper, we introduced a plasmonic functional assay platform that can precisely measure cell weight and the dynamic change in real-time for adherent cells. Possessing this ability, our platform can determine growth rates of individual cells within only 10 min to map the growth profile of populations in short time intervals. The platform could successfully determine heterogeneity within the growth profile of populations and assess subpopulations exhibiting distinct growth profiles. As a proof of principle, we investigated the growth profile of MCF-7 cells and the effect of two intracellular metabolisms critical for their proliferation. We first investigated the negative effect of serum starvation on cell growth. We then studied ornithine decarboxylase (ODC) activity, a key enzyme which is involved in proliferation, and degraded under low osmolarity that inhibits cell growth. We successfully determined the significant distinction between growth profiles of MCF-7 cells and their ODC-overproducing variants that possess strong resistance to the negative effects of low osmolarity. We also demonstrated that an exogenous parameter, putrescine, could rescue cells from ODC inhibition under hypoosmotic conditions. In addition to the ability of accessing intracellular activities through ex vivo measurements, our platform could also determine therapeutic behaviors of cancer cells in response to drug treatments. Here, we investigated difluoromethylornithine (DFMO), which has antitumor effects on MCF-7 cells by inhibiting ODC activity. We successfully demonstrated the susceptibility of MCF-7 cells to such drug treatment, while its DFMO-resistant subpopulation could survive in the presence of this antigrowth agent. By rapidly determining cell growth kinetics in small samples, our plasmonic platform may be of broad use to basic research and clinical applications.

Author Response: Clinical Characterization of Delayed Alcohol-Induced Headache: A Study of 1,108 Participants

We appreciate Dr. Gupta's comment on our article.1 The study of the effects of alcohol is challenging. Ethical concerns would not allow a “randomized controlled hangover,” in which participants would consume a controlled amount of alcohol. The goal of gaining new knowledge should never surpass the need to protect the rights and health of our patients.2 Some of the mentioned confounders3 were controlled in our study.1 We excluded participants who did consume other drugs. In addition, no patients declared prior history of hepatic, endocrinologic, or renal disorders. However, we agree that the observational nature of the study implies that all the hypotheses are merely speculative. To properly associate the clinical presentation of alcohol-induced headache (AIH) with the effect and degree of dehydration, blood and urine osmolarity and sodium levels should be measured regularly during the study.4 Measurement of plasma arginine vasopressin (AVP) concentration is technically difficult.

The potential for salt toxicity: Can the trans-epithelial potential (TEP) across the gills serve as a metric for major ion toxicity in fish?

An emerging Multi-Ion Toxicity (MIT) model for assessment of environmental salt pollution is based on the premise that major ion toxicity to aquatic organisms is related to a critical disturbance of the trans-epithelial potential across the gills (ΔTEP), which can be predicted by electrochemical theory. However, the model has never been evaluated physiologically. We directly tested key assumptions by examining the individual effects of eight different salts (NaCl, Na2SO4, MgCl2, MgSO4, KCl, K2SO4, CaCl2, and CaSO4) on measured TEP in three different fish species (fathead minnow, Pimephales promelas = FHM; channel catfish, Ictalurus punctatus = CC; bluegill, Lepomis macrochirus = BG). A geometric concentration series based on previously reported 96-h LC50 values for FHM was used. All salts caused concentration-dependent increases in TEP to less negative/more positive values in a pattern well-described by the Michaelis-Menten equation. The ΔTEP responses for different salts were similar to one another within each species when concentrations were expressed as a percentage of the FHM LC50. A plateau was reached at or before 100 % of the LC50 where the ΔTEP values were remarkably consistent, with only 1.4 to 2.2-fold variation. This relative uniformity in the ΔTEP responses contrasts with 28-fold variation in salt concentration (in mmol L−1), 9.6-fold in total dissolved solids, and 7.9-fold in conductivity at the LC50. The Michaelis-Menten Km values (salt concentrations causing 50 % of the ΔTEPmax) were positively related to the 96-h LC50 values. ΔTEP responses were not a direct effect of osmolarity in all species and were related to specific cation rather than specific anion concentrations in FHM. These responses were stable for up to 24 h in CC. The results provide strong physiological support for the assumptions of the MIT model, are coherent with electrochemical theory, and point to areas for future research.

Whole-Body Imaging of Neural and Muscle Activity during Behavior in Hydra vulgaris: Effect of Osmolarity on Contraction Bursts.

The neural code relates the activity of the nervous system to the activity of the muscles to the generation of behavior. To decipher it, it would be ideal to comprehensively measure the activity of the entire nervous system and musculature in a behaving animal. As a step in this direction, we used the cnidarian Hydra vulgaris to explore how physiological and environmental conditions alter simple contractile behavior and its accompanying neural and muscle activity. We used whole-body calcium imaging of neurons and muscle cells and studied the effect of temperature, media osmolarity, nutritional state, and body size on contractile behavior. In mounted Hydra preparations, changes in temperature, nutrition state, or body size did not have a major effect on neural or muscle activity, or on contractile behavior. But changes in media osmolarity systematically altered contractile behavior and foot detachments, increasing their frequency in hypo-osmolar media solutions and decreasing it in hyperosmolar media. Similar effects were seen in ectodermal, but not in endodermal muscle. Osmolarity also bidirectionally changed the activity of contraction burst (CB) neurons, but did not affect the network of rhythmic potential (RP) neurons in the ectoderm. These findings show osmolarity-dependent changes in the activity of CB neurons and ectodermal muscle, consistent with the hypothesis that CB neurons respond to media hypo-osmolarity, activating ectodermal muscle to generate CBs. This dedicated reflex could serve as an excretory system to prevent osmotic injury. This work demonstrates the feasibility of studying an entire neuronal and muscle activity in a behaving animal.

Maintenance enteral electrolyte solutions for neonatal calves: sodium acetate and osmolarity effects

ABSTRACT The use of hypotonic electrolytic solutions in enteral fluid therapy is still understudied in calves. The objective of the present study was to evaluate the effects of maintenance enteral electrolytic solutions with different concentrations of sodium acetate and different osmolarities in calves. For this, 18 Holstein calves, six male and 12 female, 20 days old and weighing around 52kg, were used. The animals were randomly divided into three groups and each group received one of the treatments. The three electrolytic solutions contained the same components in different concentrations, resulting in a hyposmotic, an isosmotic and a hyperosmotic solution. Each animal was maintained in enteral fluid therapy for 12 hours with infusion rate of 15mL kg-1 h-1. Abdominal circumference, body weight, feces consistency, glucose and plasma lactate, pH, pCO2, HCO- 3 and BE were measured at the following times: T0h, T6h, T12h and T24h. The hyposmotic solution did not generate the onset of diarrhea, while the isosmotic and the hyperosmotic did. Regardless of the dose used, acetate did not cause metabolic alkalosis in the evaluated animals. The results suggest that the use of hyposmotic solution in diarrheic calves, dehydrated and without metabolic acidosis, may be clinically important.

Hypotonic stress enhances colon cancer cell death induced by platinum derivatives and immunologically improves antitumor efficacy of intraperitoneal chemotherapy.

Colorectal cancer is a highly metastatic disease that could invade various distal organs and also the peritoneal cavity leading to peritoneal carcinomatosis. This is a terminal condition with poor prognosis and only palliative treatments such as cytoreductive surgery and intraperitoneal chemotherapy are proposed to some patients. However, clinicians use different parameters of treatments without any consensus. Here we decided to evaluate the effect of osmolarity in the efficacy of this procedure to kill colon cancer cells. We first show that a short exposure of platinum derivatives in hypotonic conditions is more efficient to decrease cell viability of human and murine colon cancer cells in vitro as compared to isotonic conditions. This is related to more important incorporation of platinum and the capacity of hypotonic stress to induce the copper transporter CTR1 oligomerization. Oxaliplatin in hypotonic conditions induces caspase-dependent cell death of colon cancer cells. Moreover, hypotonic conditions also modulate the capacity of oxaliplatin and cisplatin (but not carboplatin) to induce immunogenic cell death (ICD). In vivo, oxaliplatin in hypotonic conditions increases CD8+ T cell tumor infiltration and activation. Finally, in a murine peritoneal carcinomatosis model, oxaliplatin in hypotonic conditions is the only tested protocol which is able to slow down the appearance of tumor nodules and increase mice survival, while showing no effect in CD8+ T cells depleted mice or in immunodeficient mice. Altogether, our study provides new information both in vitro and in a preclinical model of peritoneal carcinomatosis, which highlights the importance of hypoosmolarity in intraperitoneal chemotherapy.