Association between serum osmolality and deteriorating renal function in patients with acute myocardial infarction: analysis of the MIMIC- IV database.

BACKGROUND: To investigate the association between serum osmolality and deteriorating renal function in patients with acute myocardial infarction (AMI). METHODS: Three thousand eight hundred eighty-five AMI patients from the Medical Information Mart for Intensive Care IV were enrolled for this study. The primary outcome was deteriorating renal function. Secondary outcomes included the new-onset of acute kidney injury (AKI) and progress of AKI. < 293.2725 mmol/L was defined as low serum osmolality, and ≥ 293.2725 mmol/L as high serum osmolality based on upper quartile. Univariate and multivariate logistic regression models were used to explore the associations between serum osmolality and the development of deteriorating renal function, the new-onset of AKI and progress of AKI among AMI patients. Subgroup analysis was also conducted. RESULTS: One thousand three hundred ninety-three AMI patients developed deteriorating renal function. After adjusting all confounding factors, high serum osmolality was associated with increased risk of deteriorating renal function [odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.22-1.78], new-onset of AKI (OR = 1.31, 95% CI: 1.01-1.69), and progress of AKI risk (OR = 1.26, 95% CI: 1.01-1.59) among AMI patients. In addition, when the stratified analysis was performed for age, AMI type, cardiogenic shock, and estimated glomerular filtration rate (eGFR), high serum osmolality was risk factor for the risk of deteriorating renal function among patients aged 65 years or older, without cardiogenic shock, and with an eGFR ≥ 60 mL/min/1.73m2. CONCLUSION: Higher serum osmolality increased the risk of deteriorating renal function among AMI patients.

The association between renal medullary and cortical fibrosis, stiffness, and concentrating capacity: an observational, single-center cross-sectional study.

BACKGROUND: Fibrosis is a common final pathway leading to end-stage renal failure. As the renal medulla and cortex contain different nephron segments, we analyzed the factors associated with the progression of renal medullary and cortical fibrosis. METHODS: A total of 120 patients who underwent renal biopsy at Kawashima Hospital between May 2019 and October 2022 were enrolled in this retrospective study. Renal medullary and cortical fibrosis and stiffness were evaluated using Masson's trichrome staining and shear wave elastography, respectively. Maximum urine osmolality in the Fishberg concentration test was also examined. RESULTS: Medullary fibrosis was positively correlated with cortical fibrosis (p < 0.0001) and log-converted urinary ß2-microglobulin (MG) (log urinary ß2-MG) (p = 0.022) and negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.0002). Cortical fibrosis also correlated with log urinary ß2-MG, eGFR, and maximum urine osmolality. Multivariate analysis revealed that cortical fibrosis levels (odds ratio [OR]: 1.063) and medullary stiffness (OR: 1.089) were significantly associated with medullar fibrosis (≧45%). The severe fibrosis group with both medullary fibrosis (≧45%) and cortical fibrosis (≧25%) had lower eGFR and maximum urine osmolality values and higher urinary ß2-MG levels than the other groups. CONCLUSIONS: Patients with disorders involving both renal medullary and cortical fibrosis had decreased maximum urine osmolality but had no abnormalities in the urinary concentrating capacities with either condition. Renal medullary and cortical fibrosis were positively correlated with urinary ß2-MG, but not with urinary N-acetyl-beta-D-glucosaminidase.

Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model.

BACKGROUND: Syringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand local fluid osmoregulation in post-traumatic SM (PTSM) to highlight important pathways for future molecular interventions. METHODS: A rat PTSM model consisting of a laminectomy at the C7 to T1 level followed by a parenchymal injection of 2 µL quisqualic acid (QA) and an injection of 5 µL kaolin in the subarachnoid space was utilized 6 weeks after initial surgery, parenchymal fluid and cerebrospinal fluid (CSF) were collected, and the osmolality of fluids were analyzed. Immunohistochemistry (IHC), metabolomics analysis using LC-MS, and mass spectrometry-based imaging (MSI) were performed on injured and laminectomy-only control spinal cords. RESULTS: We demonstrated that the osmolality of the local parenchymal fluid encompassing syrinxes was higher compared to control spinal cords after laminectomy, indicating a local osmotic imbalance due to SM injury. Moreover, we also found that parenchymal fluid is more hypertonic than CSF, indicating establishment of a local osmotic gradient in the PTSM injured spinal cord (syrinx site) forcing fluid into the spinal cord parenchyma to form and/or expand syrinxes. IHC results demonstrated upregulation of betaine, ions, water channels/transporters, and enzymes (BGT1, AQP1, AQP4, CHDH) at the syrinx site as compared to caudal and rostral sites to the injury, implying extensive local osmoregulation activities at the syrinx site. Further, metabolomics analysis corroborated alterations in osmolality at the syrinx site by upregulation of small molecule osmolytes including betaine, carnitine, glycerophosphocholine, arginine, creatine, guanidinoacetate, and spermidine. CONCLUSIONS: In summary, PTSM results in local osmotic disturbance that propagates at 6 weeks following initial injury. This coincides with and may contribute to syrinx formation/expansion.

Elevated Osmolal Gap in a Case of Multiple Myeloma.

BACKGROUND: The estimated serum osmolality is a measurement of solutes in the blood, including sodium, glucose, and urea, but also includes ethanol and toxic alcohols (e.g., methanol, ethylene glycol, diethylene glycol, isopropyl alcohol, propylene glycol) when present. These rarely measured toxic alcohols can elevate the serum osmolality, giving the true measured osmolality. The difference between that and a calculated osmolality is the osmolal gap, which can be elevated in many clinical scenarios such as renal failure, ingestion of toxic alcohols, diabetic ketoacidosis, shock, and others. CASE REPORT: We report a patient with a history of alcohol use disorder who came to the Emergency Department with an abnormally elevated osmolal gap in the setting of altered mental status. The patient's increased osmolal gap was further investigated while he was promptly treated with fomepizole, thiamine, and urgent hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss the differential diagnosis for substances that increase the osmolal gap with respective ranges of elevation. This case demonstrates that although osmolal gap elevation is often attributed to the presence of toxic alcohols, other common etiologies may account for the gap, including acute renal failure and multiple myeloma.

An experimental and theoretical study on cell swelling for osmotic imbalance induced by electroporation.

The cellular membrane serves as a pivotal barrier in regulating intra- and extracellular matter exchange. Disruption of this barrier through pulsed electric fields (PEFs) induces the transmembrane transport of ions and molecules, creating a concentration gradient that subsequently results in the imbalance of cellular osmolality. In this study, a multiphysics model was developed to simulate the electromechanical response of cells exposed to microsecond pulsed electric fields (µsPEFs). Within the proposed model, the diffusion coefficient of the cellular membrane for various ions was adjusted based on electropore density. Cellular osmolality was governed and described using Van't Hoff theory, subsequently converted to loop stress to dynamically represent the cell swelling process. Validation of the model was conducted through a hypotonic experiment and simulation at 200 mOsm/kg, revealing a 14.2% increase in the cell's equivalent radius, thereby confirming the feasibility of the cell mechanical model. With the transmembrane transport of ions induced by the applied µsPEF, the hoop stress acting on the cellular membrane reached 179.95 Pa, and the cell equivalent radius increased by 11.0% when the extra-cellular medium was supplied with normal saline. The multiphysics model established in this study accurately predicts the dynamic changes in cell volume resulting from osmotic imbalance induced by PEF action. This model holds theoretical significance, offering valuable references for research on drug delivery and tumor microenvironment modulation.

Serum osmolality measured in fingertip capillary blood is comparable to serum osmolality measured in venous blood.

Blood osmolality is considered the gold standard hydration assessment, but has limited application for technical and invasive reasons. Paired antecubital-venous blood and fingertip-capillary blood were collected pre- and 30 min post-drinking 600 mL water in 55 male/female participants. No bias (0.2 mOsmo/kg, limits of agreement = -2.5 to 2.8 mOsmo/kg) was found between sampling methods, with high linear correlation (Spearman's r = 0.95, P < 0.001). Capillary blood sampling offers an accurate less-invasive method for determining serum osmolality than venous blood sampling.

Alteration of the maximal renal water excretion capacity with kidney function and age in human.

PURPOSE: The kidney's capability to concentrate and dilute urine is crucial to maintaining body fluid compartments and plasma osmolality. Advanced age and chronic kidney disease (CKD) result in decreased maximal urine concentration. Less is known regarding urine dilution ability. The primary purpose of this study was to determine the relationship between maximal renal water excretion and renal function, age, and gender in humans. METHODS: This monocentric retrospective study includes patients referred to the Department of Clinical Physiology in Toulouse University Hospital to measure the glomerular filtration rate (mGFR) between April 2013 and February 2018. mGFR was assessed using inulin renal clearance and required ample hydration. We quantified the effects of age, gender and mGFR have on water excretion ability, which was assessed by minimal urinary osmolality (minUosm) and maximal free water clearance (maxCH2O). RESULTS: 666 patients were included (mean age 51 ± 14 years, 53% female). Mean mGFR was 82 ± 25 mL/min/1.73m2. MinUosm after hydration was higher in patients with renal insufficiency while maxCH2O was markedly lower. Age was also, with a weaker effect, associated with decreased in water excretion, independently of mGFR. MaxCH2O clearance was similar in both genders, whereas minUosm was lower in women, possibly resulting from a lower osmotic load. DISCUSSION: This study shows a decrease in maximal urinary dilution capacity and free water clearance with CKD and age, without gender difference. These alterations are mild but must be considered when a significant water intake is required or in the case of hyponatremia.

The Content of Bioactive Compounds and Technological Properties of Matcha Green Tea and Its Application in the Design of Functional Beverages.

Matcha is a powdered green tea obtained from the Camellia sinensis L. plant intended for both "hot" and "cold" consumption. It is a rich source of bioactive ingredients, thanks to which it has strong antioxidant properties. In this research, an organoleptic evaluation was carried out, and the physical characteristics (i.e., instrumental color measurement (L*a*b*), water activity, water solubility index (WSI), water holding capacity (WHC) of 10 powdered Matcha green teas, and in the 2.5% Matcha water solutions, pH, °Brix and osmolality were tested. Also, the content of phenolic ingredients, i.e., selected phenolic acids, flavonoids and total polyphenols, was assessed. The content of chlorophyll, vitamin C and antioxidant potential were also examined. Matcha M-4 was used to design two functional model beverages, in the form of ready-to-use powdered drinks, consisting of Matcha green tea, protein preparations, inulin, maltodextrin and sugar. The obtained powdered drink, when dissolved in the preferred liquid (water, milk, juice), is regenerative, high-protein and rich in bioactive ingredients from the Matcha drink, with prebiotic properties derived from the added inulin. The beverage is also characterized by low osmolality. It can be recommended as a regenerating beverage for a wide group of consumers, athletes and people with deficiencies, among others protein, and elderly people, as well as in the prevention and supportive treatment of bone and joint tissue diseases.

Hypoosmolar and hyperosmolar COVID-19 patients are predisposed to dismal clinical outcomes.

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

Tissue metal concentrations and antioxidant enzyme activity in western north Atlantic white sharks (Carcharodon carcharias).

Anthropogenic practices have increased metal contamination in marine ecosystems. Most sharks have long lifespans, occupy an important ecological position at the top of marine food webs, and can accumulate metals. However, reference levels of metal contaminants in the tissues of sharks, particularly, apex predators such as the white shark (Carcharodon carcharias), are lacking. In this study, concentrations of copper (Cu), cadmium (Cd), nickel (Ni), lead (Pb), silver (Ag), and zinc (Zn) were measured in the muscle tissue of white (n = 42) and tiger (Galeocerdo cuvier; n = 3) sharks. Metal exposure in various species, including sharks, has been correlated with increased oxidative stress. Therefore, the main objectives of this study were to assess metal accumulation and antioxidant enzyme activity (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) in the muscle tissue of the population of white sharks and tiger sharks inhabiting the Western North Atlantic. The measured parameters were qualitatively compared between species. The small sample size of tiger sharks (collected from only one site) limited statistical analyses, therefore, white sharks were the primary focus of this study. Differences in tissue metal (Cu, Cd, Ni, and Zn) concentrations and antioxidant enzyme activities were detected based on collection site, with significant positive correlations between Cd and enzymes, SOD and CAT, and Zn and enzymes, SOD and GPx in C. carcharias. Differences in Ni concentration were detected based on sex, with females having higher Ni levels. Additionally, plasma osmolality was not correlated with tissue metal concentrations; however, osmolality decreased with increasing length in C. carcharias. This study is the first to report baseline levels of Cu, Zn, Cd, Ni, Ag, and Pb in muscle of North Atlantic white sharks and provides new insights into oxidative stress responses of these sensitive species to metal contaminants.

Single-strain behavior predicts responses to environmental pH and osmolality in the gut microbiota.

Changes to gut environmental factors such as pH and osmolality due to disease or drugs correlate with major shifts in microbiome composition; however, we currently cannot predict which species can tolerate such changes or how the community will be affected. Here, we assessed the growth of 92 representative human gut bacterial strains spanning 28 families across multiple pH values and osmolalities in vitro. The ability to grow in extreme pH or osmolality conditions correlated with the availability of known stress response genes in many cases, but not all, indicating that novel pathways may participate in protecting against acid or osmotic stresses. Machine learning analysis uncovered genes or subsystems that are predictive of differential tolerance in either acid or osmotic stress. For osmotic stress, we corroborated the increased abundance of these genes in vivo during osmotic perturbation. The growth of specific taxa in limiting conditions in isolation in vitro correlated with survival in complex communities in vitro and in an in vivo mouse model of diet-induced intestinal acidification. Our data show that in vitro stress tolerance results are generalizable and that physical parameters may supersede interspecies interactions in determining the relative abundance of community members. This study provides insight into the ability of the microbiota to respond to common perturbations that may be encountered in the gut and provides a list of genes that correlate with increased ability to survive in these conditions. IMPORTANCE To achieve greater predictability in microbiota studies, it is crucial to consider physical environmental factors such as pH and particle concentration, as they play a pivotal role in influencing bacterial function and survival. For example, pH is significantly altered in various diseases, including cancers, inflammatory bowel disease, as well in the case of over-the-counter drug use. Additionally, conditions like malabsorption can affect particle concentration. In our study, we investigate how changes in environmental pH and osmolality can serve as predictive indicators of bacterial growth and abundance. Our research provides a comprehensive resource for anticipating shifts in microbial composition and gene abundance during complex perturbations. Moreover, our findings underscore the significance of the physical environment as a major driver of bacterial composition. Finally, this work emphasizes the necessity of incorporating physical measurements into animal and clinical studies to better understand the factors influencing shifts in microbiota abundance.

Effect of cryopreservation on post-thaw motility and viability of Grey mullet, Mugil cephalus sperm (Linnaeus, 1758).

In this study, we optimized a simple method of cryopreservation for Mugil cephalus sperm based on post-thaw motility and viability. A series of experiments were conducted by changing the extender, cryoprotectant and freezing height above the liquid nitrogen (LN) surface. First, we carried out the cryopreservation using the extender V2E and cryoprotective agents (CPAs) namely, propylene glycol (PG), methanol (MeOH), glycerol (GLY), ethylene glycol (EG), dimethylsulfoxide (Me2SO) and dimethylacetamide (DMA) at a final concentration of 5% and 10%. We found that 10% of GLY, EG and Me2SO were more suitable compared to other CPAs. Then, different freezing heights (6, 8, 10 and 12 cm) above the LN surface were experimented with extender V2E and optimized CPAs. Then, 0.3 M of glucose, sucrose and trehalose were tested as extender along with optimized CPAs and freezing height. Additionally, the effect of fast-rate freezing and storage days (7, 30 and 180) on post-thaw sperm quality was documented using the factors optimized in earlier experiments. For all experiments, the fresh sperm was diluted at a ratio of 1:1 with cryomedium (CPA + extender), loaded into cryovials (2.0 mL) and frozen. The cryopreserved sperm was thawed at 30 °C for 90-120 s and their quality was evaluated. Among the experimented factors, sperm diluted in cryomedium (0.3 M glucose + 10% EG) and frozen at 4 cm above the LN surface registered significantly (P < 0.05) highest post-thaw motility (73 ± 2%) and (71 ± 1%) viability. Fast-rate freezing has resulted in lower (about 30%) post-thaw motility and viability of sperm. The storage days (7, 30 and 180) did not have a significant effect on post-thaw sperm quality. Overall results show that using the factors optimized through this study, high-quality sperm can be obtained after cryopreservation.

Characterizing Hydration Practices in Healthy Young Recreationally Active Adults-Is There Utility in First Morning Urine Sampling?

First morning urine (FMU) assessment would be a practical and convenient solution for clinically acceptable detection of underhydration prior to competition/training, and for the general public. Thus, we thus sought to determine the diagnostic accuracy of FMU as a valid indicator of recent (previous 24 hr, 5 days average) hydration practices. For 5 consecutive days and one final morning, 67 healthy women (n = 38) and men (n = 29; age: 20 [1] years, body mass index: 25.9 [5.5]) completed 24-hr diet logs for total water intake (from beverages and foods, absolute and relative to body mass), 24-hr urine and FMU collection (last morning only) for osmolality (Osm), specific gravity (SG), and color (Col), and morning blood sampling for plasma osmolality and copeptin. Correlations determined significance and relationship strength among FMU and all other variables. Area under the receiver operating characteristic curves, sensitivity, specificity, and positive likelihood ratios were employed using previously reported values to indicate underhydration (total water intake < 30 ml/kg, osmolality > 500, and >800 mOsm/kg, specific gravity > 1.017, and copeptin > 6.93 pmol/L). FMU_Osm and FMU_SG were significantly correlated (p < .05) to all variables except the previous 5-day plasma osmolality. FMU_Col was only significantly correlated with other color time intervals and total water intake per gram. FMU_Osm held greatest utility (area under the receiver operating characteristic curve, sensitivity, and specificity >80%) overall, with the best outcome being FMU_Osm indicating a previous 24-hr osmolality threshold of 500 mOsm/kg (FMU_Osm criterion >710 mOsm/kg and positive likelihood ratio = 5.9). With less effort and cost restriction, FMU is a viable metric to assess underhydration.

Is a hyperosmolar pump prime for cardiopulmonary bypass a risk factor for postoperative delirium? A double blinded randomised controlled trial.

Objective: Postoperative delirium (POD) is common after cardiac surgery. We have previously identified plasma sodium concentration and the volume of infused fluids during surgery as possible risk factors. Both are linked to the selection and composition of the pump prime used for cardiopulmonary bypass (CPB). Present study aims to examine whether hyperosmolality increases the risk for POD. Design: Patients ≥65 years (n = 195) scheduled for cardiac surgery were prospectively enrolled into this double blinded randomised clinical trial. Study group received a pump prime containing mannitol and ringer-acetate (966 mOsmol) (n = 98) vs. ringer-acetate (388 mOsmol) (n = 97) in the control group. Postoperative delirium was defined according to DSM-5 criteria based on a test-battery pre- and postoperatively (days 1-3). Plasma osmolality was measured on five occasions and coordinated with the POD assessments. The primary outcome was the POD incidence related to hyperosmolality as the secondary outcome. Results: The incidence of POD was 36% in the study group and 34% in the control group, without intergroup difference (p=.59). The plasma osmolality was significantly higher in the study group, both on days 1 and 3 and after CPB (p<.001). Post hoc analysis indicated that high osmolality levels increased the risk for delirium on day 1 by 9% (odds ratio (OR) 1.09, 95% CI 1.03-1.15) and by 10% on day 3 (OR 1.10, 95% CI 1.04-1.16). Conclusions: Use of a prime solution with high osmolality did not increase the incidence of POD. However, the influence of hyperosmolality as a risk factor for POD warrants further investigation.

Impact of urine cyclic AMP relative to plasma arginine vasopressin on response to tolvaptan in patients with chronic kidney disease and heart failure.

BACKGROUND: The clinical utility of tolvaptan in chronic kidney disease (CKD) patients with heart failure remains uncertain. The level of urine cyclic adenosine monophosphate (AMP) relative to plasma arginine vasopressin (AVP) indicates the residual function of the collecting ducts in response to AVP stimulation and might be a key to predicting response of tolvaptan. METHODS: CKD patients who were hospitalized to treat their congestive heart failure refractory to conventional loop diuretics were considered to receive tolvaptan and included in this prospective study. The impact of urine cyclic AMP/plasma AVP ratio for prediction of response to tolvaptan, which was defined as any increase in urine volume at day 7 from day 0, was investigated. RESULTS: A total of 30 patients (median 75 years old, 24 men, and median estimated glomerular filtration rate 14.4 mL/min/1.73 m2) were included. As compared to baseline, urine volume increased at day 7 in 17 responders, whereas urine volume decreased at day 7 in 13 non-responders. Baseline urine cyclic AMP/plasma AVP ratio distributed between 0.25 and 4.01 with median 1.90. The urine cyclic AMP/plasma AVP ratio was a significant predictor of response to tolvaptan, which was adjusted for 6 potential confounders with a cutoff of 1.24. CONCLUSIONS: Baseline urine cyclic AMP/plasma AVP ratio is an independent predictor of response to tolvaptan in advanced CKD patients with heart failure. CLINICAL TRIAL REGISTRATION: UMIN000022422.

A Highly Translatable Dual-arm Local Delivery Strategy To Achieve Widespread Therapeutic Coverage in Healthy and Tumor-bearing Brain Tissues.

Drug delivery nanoparticles (NPs) based entirely on materials generally recognized as safe that provide widespread parenchymal distribution following intracranial administration via convection-enhanced delivery (CED) are introduced. Poly(lactic-co-glycolic acid) (PLGA) NPs are coated with various poloxamers, including F68, F98, or F127, via physical adsorption to render particle surfaces non-adhesive, thereby resisting interactions with brain extracellular matrix. F127-coated PLGA (F127/PLGA) NPs provide markedly greater distribution in healthy rat brains compared to uncoated NPs and widespread coverage in orthotopically-established brain tumors. Distribution analysis of variously-sized F127/PLGA NPs determines the average rat brain tissue porosity to be between 135 and 170 nm while revealing unprecedented brain coverage of larger F127/PLGA NPs with an aid of hydraulic pressure provided by CED. Importantly, F127/PLGA NPs can be lyophilized for long-term storage without compromising their ability to penetrate the brain tissue. Further, 65- and 200-nm F127/PLGA NPs lyophilized-reconstituted and administered in a moderately hyperosmolar infusate solution show further enhance particle dissemination in the brain via osmotically-driven enlargement of the brain tissue porosity. Combination of F127/PLGA NPs and osmotic tissue modulation provides a means with a clear regulatory path to maximize the brain distribution of large NPs that enable greater drug loading and prolong drug release.

Pseudohyponatremia Secondary to Hypercholesterolemia in the Setting of Intrahepatic Cholestasis due to Metastatic Liver Disease: A Case Report and Review of the Literature.

OBJECTIVE: We describe a rare case of pseudohyponatremia in the setting of hypercholesterolemia caused by cholestasis due to metastatic liver disease and provide a review of the published cases in the literature. CASE REPORT: We report a case of pseudohyponatremia in a 60-year-old man with rectal cancer with extensive metastasis to the liver. While assessing the patient for hyponatremia, extremely elevated serum cholesterol with normal serum osmolality was detected leading to the diagnosis of pseudohyponatremia. This is one of very few reports of pseudohyponatremia in patients with elevated cholesterol in cholestatic liver disease. CONCLUSION: Hypercholesterolemia is an exceedingly rare cause for pseudohyponatremia. Although pseudohyponatremia per se does not carry a risk to the patient, the delay in diagnosis and treatment plans may pose additional risks. Pseudohyponatremia needs to be considered in patients with low sodium and co-existing cholestasis from metastatic liver disease.

Enhancement of effector functions of anti-CD20 monoclonal antibody by increased afucosylation in CHO cell line through cell culture medium optimization.

BACKGROUND: Recombinant therapeutic anti-CD20 monoclonal antibody (mAb) is used for the treatment of non-Hodgkin's lymphoma, a common B cell lymphoma constituting 80% of all lymphomas. Anti-CD20 mAb contains an Fc-linked biantennary glycan. Although, anti-CD20 monoclonal antibodies are being increasingly used for immunotherapy, their efficacy is limited in a section of patients with drug resistance to immunotherapy. There is a need to improve the efficacy by increasing the effector functions, such as the antibody-dependent cellular cytotoxicity (ADCC) activity of anti-CD20 monoclonal antibodies. RESULTS: We developed a simple and cost-effective approach to enhance ADCC effector activity in an in-house developed clone of anti-CD20 monoclonal antibody by increasing afucosylation in a new clone of Chinese Hamster Ovary (CHO) cells using 8X uridine, manganese, and galactose (UMG) to modulate the osmolality of the medium. The purified anti-CD20 monoclonal antibody from 8X UMG-containing medium showed a 2-fold increase in afucose content and 203% ADCC activity in comparison to control antibody. CONCLUSIONS: Our study reports enhanced ADCC activity by modulating afucosylation using osmolality by altering simple feed additives in the culture medium.

Water transport regulates nucleus volume, cell density, Young's modulus, and E-cadherin expression in tumor spheroids.

Cell volume is maintained by the balance of water and solutes across the cell membrane and plays an important role in mechanics and biochemical signaling in cells. Here, we assess the relationship between cell volume, mechanical properties, and E-cadherin expression in three-dimensional cultures for ovarian cancer. To determine the effect of water transport in multi-cellular tumors, ovarian cancer spheroids were subjected to hypotonic and hypertonic shock using water and sucrose mixtures, respectively. Increased osmolality resulted in decreased nucleus volume, increased Young's modulus, and increased tumor cell density in ovarian cancer spheroids. Next, we looked at the reversibility of mechanics and morphology after 5 min of osmotic shock and found that spheroids had a robust ability to return to their original state. Finally, we quantified the size of E-cadherin clusters at cell-cell junctions and observed a significant increase in aggregate size following 30 min of hypertonic and hypotonic osmotic shocks. Yet, these effects were not apparent after 5 min of osmotic shock, illustrating a temporal difference between E-cadherin regulation and the immediate mechanical and morphology changes. Still, the osmotically induced E-cadherin aggregates which formed at the 30-minute timepoint was reversible when spheroids were replenished with isotonic medium. Altogether, this work demonstrated an important role of osmolality in transforming mechanical, morphology, and molecular states.