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Clinical Chemistry and Laboratory... Jul 2023Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be... (Review)
Review
Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be aware of these pitfalls since they often lead to medical overconsumption or incorrect diagnosis. Pre-analytical issues (use of vacuum tubes or urine tubes containing preservatives) can affect test results. In routine clinical laboratories, hematuria can be assayed using either chemical (test strips) or particle-counting techniques. In cases of doubtful results, Munchausen syndrome or adulteration of the urine specimen should be excluded. Pigmenturia (caused by the presence of dyes, urinary metabolites such as porphyrins and homogentisic acid, and certain drugs in the urine) can be easily confused with hematuria. The peroxidase activity (test strip) can be positively affected by the presence of non-Hb peroxidases (e.g. myoglobin, semen peroxidases, bacterial, and vegetable peroxidases). Urinary pH, haptoglobin concentration, and urine osmolality may affect specific peroxidase activity. The implementation of expert systems may be helpful in detecting preanalytical and analytical errors in the assessment of hematuria. Correcting for dilution using osmolality, density, or conductivity may be useful for heavily concentrated or diluted urine samples.
Topics: Humans; Hematuria; Peroxidase; Hemoglobins; Erythrocytes; Osmolar Concentration
PubMed: 37079906
DOI: 10.1515/cclm-2023-0260 -
Nature Nov 2023Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular...
Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions. Reciprocally, macromolecules restrict the movement of 'structured' water molecules within their hydration layers, reducing the available 'free' bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function.
Topics: Cell Death; Cytosol; Homeostasis; Macromolecular Substances; Osmolar Concentration; Pressure; Proteins; Solvents; Temperature; Thermodynamics; Time Factors; Water
PubMed: 37853127
DOI: 10.1038/s41586-023-06626-z -
Deutsches Arzteblatt International Oct 2023Hydration disturbances are common in old age: the reported prevalence of dehydration in elderly patients ranges from 19% to 89%, depending on the definition and the... (Review)
Review
BACKGROUND
Hydration disturbances are common in old age: the reported prevalence of dehydration in elderly patients ranges from 19% to 89%, depending on the definition and the population in question. However, the clinical assessment of patients' hydration status is difficult. In this review, we discuss the diagnostic value of currently used methods that may or may not be suitable for assessing older patients' hydration status.
METHODS
We conducted a selective literature search for relevant studies concerning patients aged 65 and above. Of the 355 articles retrieved by the initial search, a multistep selection process yielded 30 that were suitable for inclusion in this review.
RESULTS
107 different methods for the diagnostic assessment of dehydration in older persons were evaluated on the basis of the reviewed publications. High diagnostic value, especially for the determination of hyperosmolar dehydration, was found for serum osmolality, serum sodium concentration, inferior vena cava ultrasonography, a history (from the patient or another informant) of not drinking between meals, and axillary dryness. On the other hand, a variety of clinical signs such as a positive skin turgor test, sunken eyes, dry mouth, tachycardia, orthostatic dysregulation, and dark urine were found to be of inadequate diagnostic value.
CONCLUSION
Only five of the 107 methods considered appear to be suitable for determining that a patient is dehydrated. Thus, the available scientific evidence indicates that all clinicians should critically reconsider their own techniques for assessing hydration status in elderly patients. To optimize the clinical assessment of patients' hydration status, there seems to be a need for the rejection of unsuitable methods in favor of either newly developed criteria or of a combination of the best criteria already in use.
Topics: Aged; Humans; Aged, 80 and over; Dehydration; Osmolar Concentration
PubMed: 37583084
DOI: 10.3238/arztebl.m2023.0182 -
ELife Feb 2024Experiments involving periodic stimuli shed light on the interplay between hyper-osmotic stress and glucose starvation in yeast cells.
Experiments involving periodic stimuli shed light on the interplay between hyper-osmotic stress and glucose starvation in yeast cells.
Topics: Humans; Glucose; Osmotic Pressure; Saccharomyces cerevisiae; Starvation
PubMed: 38416131
DOI: 10.7554/eLife.91717 -
Contact Lens & Anterior Eye : the... Oct 2023To demonstrate how the likelihood of making a correct diagnosis of dry eye disease varies according to the clinical test methods used. (Review)
Review
PURPOSE
To demonstrate how the likelihood of making a correct diagnosis of dry eye disease varies according to the clinical test methods used.
METHODS
The probability of a person having dry eye, given that they return a positive test, was calculated for a range of standard tests, using the Bayes-Price rule. Global specificity and sensitivity values for each test were estimated by employing the Beta distribution to combine all relevant data obtained from a literature review.
RESULTS
At an assumed prevalence of 11.6%, the single test with the highest probability of a correct diagnosis was corneal staining (probability = 0.28) and the lowest was the ocular surface disease index - OSDI (0.14). The best combination of symptoms with a single test of tear film homeostasis was the 5-item dry eye questionnaire (DEQ-5) + corneal staining (0.42) while OSDI + tear film break up time (TBUT) was the worst (0.23). The simultaneous observation of conjunctival and corneal staining was associated with a probability of 0.49. The probability of a correct diagnosis increased with the number of positive tests, up to a maximum of 0.90 when all of DEQ-5, conjunctival and corneal staining, osmolarity and TBUT were positive.
CONCLUSION
A significant risk of misdiagnosis is associated with using any single test for dry eye disease, or the minimum TFOS DEWS II criterion of symptoms plus any single test of tear film homeostasis. To minimize this risk, the maximum number of tests available should be performed and the results used to inform diagnosis. The simultaneous occurrence of conjunctival and corneal staining should be considered a key outcome and be specified in future guidelines.
Topics: Humans; Dry Eye Syndromes; Bayes Theorem; Tears; Osmolar Concentration; Diagnostic Errors
PubMed: 37544866
DOI: 10.1016/j.clae.2023.102048 -
International Journal of Molecular... Mar 2024Gaining insight into osmotic pressure and its biological implications is pivotal for revealing mechanisms underlying numerous fundamental biological processes across... (Review)
Review
Gaining insight into osmotic pressure and its biological implications is pivotal for revealing mechanisms underlying numerous fundamental biological processes across scales and will contribute to the biomedical and pharmaceutical fields. This review aims to provide an overview of the current understanding, focusing on two central issues: (i) how to determine theoretically osmotic pressure and (ii) how osmotic pressure affects important biological activities. More specifically, we discuss the representative theoretical equations and models for different solutions, emphasizing their applicability and limitations, and summarize the effect of osmotic pressure on lipid phase separation, cell division, and differentiation, focusing on the mechanisms underlying the osmotic pressure dependence of these biological processes. We highlight that new theory of osmotic pressure applicable for all experimentally feasible temperatures and solute concentrations needs to be developed, and further studies regarding the role of osmotic pressure in other biological processes should also be carried out to improve our comprehensive and in-depth understanding. Moreover, we point out the importance and challenges of developing techniques for the in vivo measurement of osmotic pressure.
Topics: Osmotic Pressure; Solutions; Temperature
PubMed: 38542282
DOI: 10.3390/ijms25063310 -
Nature Communications Nov 2023The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various...
The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.
Topics: Animals; Mice; Cryoelectron Microscopy; Calcium; Calcium Channels; Osmolar Concentration
PubMed: 37945568
DOI: 10.1038/s41467-023-42956-2 -
Liver International : Official Journal... Sep 2023PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium-permeable channels. The aim of this study was to determine the relevance and relationship of these...
BACKGROUND & AIMS
PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium-permeable channels. The aim of this study was to determine the relevance and relationship of these channels in the contractile tone of the hepatic portal vein, which experiences mechanical and osmotic variations as it delivers blood to the liver from the intestines, gallbladder, pancreas and spleen.
METHODS
Wall tension was measured in freshly dissected portal veins from adult male mice, which were genetically unmodified or modified for either a non-disruptive tag in native PIEZO1 or endothelial-specific PIEZO1 deletion. Pharmacological agents were used to activate or inhibit PIEZO1, TRPV4 and associated pathways, including Yoda1 and Yoda2 for PIEZO1 and GSK1016790A for TRPV4 agonism, respectively.
RESULTS
PIEZO1 activation leads to nitric oxide synthase- and endothelium-dependent relaxation of the portal vein. TRPV4 activation causes contraction, which is also endothelium-dependent but independent of nitric oxide synthase. The TRPV4-mediated contraction is suppressed by inhibitors of phospholipase A and cyclooxygenases and mimicked by prostaglandin E , suggesting mediation by arachidonic acid metabolism. TRPV4 antagonism inhibits the effect of agonising TRPV4 but not PIEZO1. Increased wall stretch and hypo-osmolality inhibit TRPV4 responses while lacking effects on or amplifying PIEZO1 responses.
CONCLUSIONS
The portal vein contains independently functioning PIEZO1 channels and TRPV4 channels in the endothelium, the pharmacological activation of which leads to opposing effects of vessel relaxation (PIEZO1) and contraction (TRPV4). In mechanical and osmotic strain, the PIEZO1 mechanism dominates. Modulators of these channels could present important new opportunities for manipulating liver perfusion and regeneration in disease and surgical procedures.
Topics: Animals; Male; Mice; Endothelium; Nitric Oxide; Nitric Oxide Synthase; Osmotic Pressure; Portal Vein; TRPV Cation Channels; Vasodilation; Ion Channels
PubMed: 37349903
DOI: 10.1111/liv.15646 -
Cell Reports Aug 2023Volume-regulated anion channels (VRACs) are hexamers of LRRC8 proteins that are crucial for cell volume regulation. N termini (NTs) of the obligatory LRRC8A subunit...
Volume-regulated anion channels (VRACs) are hexamers of LRRC8 proteins that are crucial for cell volume regulation. N termini (NTs) of the obligatory LRRC8A subunit modulate VRACs activation and ion selectivity, but the underlying mechanisms remain poorly understood. Here, we report a 2.8-Å cryo-electron microscopy structure of human LRRC8A that displays well-resolved NTs. Amino-terminal halves of NTs fold back into the pore and constrict the permeation path, thereby determining ion selectivity together with an extracellular selectivity filter with which it works in series. They also interact with pore-surrounding helices and support their compact arrangement. The C-terminal halves of NTs interact with intracellular loops that are crucial for channel activation. Molecular dynamics simulations indicate that low ionic strength increases NT mobility and expands the radial distance between pore-surrounding helices. Our work suggests an unusual pore architecture with two selectivity filters in series and a mechanism for VRAC activation by cell swelling.
Topics: Humans; Cryoelectron Microscopy; Membrane Proteins; Anions; Cell Size; Osmolar Concentration
PubMed: 37543949
DOI: 10.1016/j.celrep.2023.112926