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Biological & Pharmaceutical Bulletin 2023Extravasations are common manifestations of iatrogenic injuries associated with intravenous therapy. Cytotoxic agents are already subject to a relatively well-defined... (Review)
Review
Extravasations are common manifestations of iatrogenic injuries associated with intravenous therapy. Cytotoxic agents are already subject to a relatively well-defined management strategy in healthcare institutions and classified into three groups according to the extent of damage from extravasation: vesicants, irritants, and non-tissue-damaging agents. Therefore, careful monitoring and initial treatment according to the severity of the skin injury decreases the incidence of extravasation injury. In contrast, high osmolarity, acidic or alkaline, and/or vasoconstrictive activity have all been suggested as possible causes of tissue injury due to the extravasation of noncytotoxic agents. However, the severity of the injuries has not been classified. Therefore, due to a lack of awareness, case reports of severe extravasation injury caused by noncytotoxic agents are increasing. In this paper, we review case reports and animal experiments and classify the severity of extravasation injury by noncytotoxic agents into three categories. Parallel to cytotoxic agents, the classification provides appropriate warning of possible injury severity, helping medical personnel better understand the severity of tissue damage and prevent injury severity during extravasation.
Topics: Animals; Extravasation of Diagnostic and Therapeutic Materials; Cytotoxins; Irritants; Osmolar Concentration; Antineoplastic Agents
PubMed: 37258139
DOI: 10.1248/bpb.b22-00850 -
Fluids and Barriers of the CNS Jun 2022The etiology of idiopathic normal pressure hydrocephalus (iNPH) is currently unknown. With no visible obstructions, altered cerebrospinal fluid (CSF) dynamics may...
BACKGROUND
The etiology of idiopathic normal pressure hydrocephalus (iNPH) is currently unknown. With no visible obstructions, altered cerebrospinal fluid (CSF) dynamics may explain the accumulation of ventricular fluid. We hypothesized that elevated osmolality in the CSF of iNPH patients could potentiate formation of ventricular fluid and thereby cause the disease progression and/or predict the surgical outcome. To address this hypothesis, we determined the lumbar and ventricular CSF osmolality of iNPH patients at different disease stages and compared with lumbar CSF samples obtained from control subjects.
METHODS
The osmolality of CSF was determined on a total of 35 iNPH patients at diagnosis and at the subsequent treatment with shunt surgery (n = 20) and compared with the CSF osmolality from 20 control subjects. Simultaneously collected lumbar and ventricular CSF samples from experimental pigs were used to evaluate the compatibility between CSF from different compartments.
RESULTS
We found no evidence of increased osmolality in the CSF of iNPH patients upon diagnosis or at the time of shunt treatment months after the diagnosis, compared with control individuals. CSF tapped from the lumbar space could be used as a read-out for ventricular CSF osmolality, as these were similar in both the patient group and in experimental pigs. We further observed no correlation between the CSF osmolality in iNPH patients and their responsiveness to shunt surgeries.
CONCLUSIONS
The osmolality of lumbar CSF is a reliable reflection of the ventricular CSF osmolality, and is not elevated in iNPH patients. iNPH therefore does not appear to arise as a function of osmotic imbalances in the CSF system and CSF osmolality cannot serve as a biomarker for iNPH or as a predictive tool for shunt responsiveness.
Topics: Animals; Biomarkers; Cerebrospinal Fluid Shunts; Humans; Hydrocephalus, Normal Pressure; Osmolar Concentration; Swine; Treatment Outcome
PubMed: 35761330
DOI: 10.1186/s12987-022-00349-5 -
Biochimica Et Biophysica Acta.... Nov 2019We investigated melting transitions in native biological membranes containing their membrane proteins. The membranes originated from E. coli, B. subtilis, lung...
We investigated melting transitions in native biological membranes containing their membrane proteins. The membranes originated from E. coli, B. subtilis, lung surfactant and nerve tissue from the spinal cord of several mammals. For some preparations, we studied the pressure, pH and ionic strength dependence of the transition. For porcine spine, we compared the transition of the native membrane to that of the extracted lipids. All preparations displayed melting transitions of 10-20° below physiological or growth temperature, independent of the organism of origin and the respective cell type. We found that the position of the transitions in E. coli membranes depends on the growth temperature. We discuss these findings in the context of the thermodynamic theory of membrane fluctuations close to transition that predicts largely altered elastic constants, an increase in fluctuation lifetime and in membrane permeability. We also discuss how to distinguish lipid melting from protein unfolding transitions. Since the feature of a transition slightly below physiological temperature is conserved even when growth conditions change, we conclude that the transitions are likely to be of major biological importance for the survival and the function of the cell.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Cell Membrane; Lipids; Mammals; Osmolar Concentration; Phase Transition; Temperature; Thermodynamics; Transition Temperature
PubMed: 31465764
DOI: 10.1016/j.bbamem.2019.07.014 -
FEBS Open Bio Sep 2019α-Conotoxin (CTx) TxID is a potent α3β4 nicotinic acetylcholine receptor (nAChR) antagonist that has been suggested as a potential drug candidate to treat addiction...
α-Conotoxin (CTx) TxID is a potent α3β4 nicotinic acetylcholine receptor (nAChR) antagonist that has been suggested as a potential drug candidate to treat addiction and small cell lung cancer. The function and structure of TxID have been well-studied, but analyses of its stability have not previously been reported. The purpose of this study was to analyze the stability and forced degradation of TxID under various conditions: acid, alkali, water hydrolysis, oxidation, light, thiols, temperature, ionic strength and buffer pH. Different degradation products were formed under various conditions, and the degradation patterns of TxID showed pseudo-first-order kinetics. TxID degraded slowest at pH 3 within a pH range of 2-8. The major degradation products were analyzed using liquid chromatography-tandem mass spectrometry and the activity of the main product with α3β4 nAChR was analyzed using electrophysiological methods. Our analysis of TxID stability may aid the selection of appropriate conditions for peptide production, packaging and storage.
Topics: Animals; Conotoxins; Conus Snail; Hydrogen-Ion Concentration; Kinetics; Osmolar Concentration; Protein Folding; Temperature
PubMed: 31278882
DOI: 10.1002/2211-5463.12697 -
FEMS Yeast Research Mar 2022Cells coordinate intracellular activities in response to changes in the extracellular environment to maximize their probability of survival and proliferation. Eukaryotic... (Review)
Review
Cells coordinate intracellular activities in response to changes in the extracellular environment to maximize their probability of survival and proliferation. Eukaryotic cells need to adapt to constant changes in the osmolarity of their environment. In yeast, the high-osmolarity glycerol (HOG) pathway is responsible for the response to high osmolarity. Activation of the Hog1 stress-activated protein kinase (SAPK) induces a complex program required for cellular adaptation that includes temporary arrest of cell cycle progression, adjustment of transcription and translation patterns, and the regulation of metabolism, including the synthesis and retention of the compatible osmolyte glycerol. Hog1 is a member of the family of p38 SAPKs, which are present across eukaryotes. Many of the properties of the HOG pathway and downstream-regulated proteins are conserved from yeast to mammals. This review addresses the global view of this signaling pathway in yeast, as well as the contribution of Dr Hohmann's group to its understanding.
Topics: Animals; Glycerol; Mammals; Mitogen-Activated Protein Kinases; Osmolar Concentration; Osmotic Pressure; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35254447
DOI: 10.1093/femsyr/foac013 -
International Journal of Molecular... Jul 2019Crop yield improvement is necessary to keep pace with increasing demand for food. Due to climatic variability, the incidence of drought stress at crop growth stages is... (Review)
Review
Crop yield improvement is necessary to keep pace with increasing demand for food. Due to climatic variability, the incidence of drought stress at crop growth stages is becoming a major hindering factor to yield improvement. New techniques are required to increase drought tolerance along with improved yield. Genetic modification for increasing drought tolerance is highly desirable, and genetic engineering for drought tolerance requires the expression of certain stress-related genes. Genes have been identified which confer drought tolerance and improve plant growth and survival in transgenic wheat. However, less research has been conducted for the development of transgenic wheat as compared to rice, maize, and other staple food. Furthermore, enhanced tolerance to drought without any yield penalty is a major task of genetic engineering. In this review, we have focused on the progress in the development of transgenic wheat cultivars for improving drought tolerance and discussed the physiological mechanisms and testing of their tolerance in response to inserted genes under control or field conditions.
Topics: Adaptation, Biological; Carbon; Droughts; Energy Metabolism; Gene Expression Regulation, Plant; Osmolar Concentration; Plant Proteins; Plants, Genetically Modified; Stress, Physiological; Transcription Factors; Triticum
PubMed: 31288392
DOI: 10.3390/ijms20133350 -
International Journal of Molecular... Aug 2022One of the commonly accepted approaches to estimate protein-protein interactions (PPI) in aqueous solutions is the analysis of their translational diffusion. The present... (Review)
Review
One of the commonly accepted approaches to estimate protein-protein interactions (PPI) in aqueous solutions is the analysis of their translational diffusion. The present review article observes a phenomenological approach to analyze PPI effects via concentration dependencies of self- and collective translational diffusion coefficient for several spheroidal proteins derived from the pulsed field gradient NMR (PFG NMR) and dynamic light scattering (DLS), respectively. These proteins are rigid globular α-chymotrypsin (ChTr) and human serum albumin (HSA), and partly disordered α-casein (α-CN) and β-lactoglobulin (β-Lg). The PPI analysis enabled us to reveal the dominance of intermolecular repulsion at low ionic strength of solution (0.003-0.01 M) for all studied proteins. The increase in the ionic strength to 0.1-1.0 M leads to the screening of protein charges, resulting in the decrease of the protein electrostatic potential. The increase of the van der Waals potential for ChTr and α-CN characterizes their propensity towards unstable weak attractive interactions. The decrease of van der Waals interactions for β-Lg is probably associated with the formation of stable oligomers by this protein. The PPI, estimated with the help of interaction potential and idealized spherical molecular geometry, are in good agreement with experimental data.
Topics: Biophysical Phenomena; Caseins; Diffusion; Humans; Osmolar Concentration; Protein Processing, Post-Translational; Static Electricity
PubMed: 36012504
DOI: 10.3390/ijms23169240 -
Cardiorenal Medicine 2022Determination of adequacy of decongestion remains a significant challenge in the management of acute heart failure (AHF).
BACKGROUND
Determination of adequacy of decongestion remains a significant challenge in the management of acute heart failure (AHF).
METHODS
This is a prospective single center cohort study of patients (>18 years old) admitted for AHF on intravenous diuretics, with BNP >100 pg/mL or echocardiographic findings of reduced ejection fraction or diastolic dysfunction, and at least 1 clinical sign of volume overload. Patients with eGFR ≤45 mL/min or on dialysis, and with exposure to contrast dye or nephrotoxins were excluded. Serum and spot urine osmolality were obtained in the early morning simultaneously daily for 5 days or until discharge. Receiver operating characteristic curves were used to analyze the optimal cutoffs for the osmolality values in the prediction of heart failure (HF) readmissions Results: Of the total 100 patients, 62% were male and 59% were Black American. The mean age was 64.41 ± 12.53 and 34% had preserved ejection fraction. Patients with 30-day readmission had higher serum osmolality (mOsm/kg) on admission (305 [299-310] vs. 298 [294-303]; p = 0.044) and had higher drop in serum osmolality between admission and discharge (-7.5 [-9.0, -1.25] vs. -1.0 [-4.0, 4.0]; p = 0.044). Serum osmolality on admission of >299 mOsm/kg (sensitivity: 83%, specificity: 61%) and drop in serum osmolality between admission and discharge of >2 mOsm/kg (sensitivity: 83%, specificity: 65%) was associated with 30-day HF readmissions. No patients discharged with urine osmolality more than 500 mOsm/kg had 30-day readmissions, but this was not statistically significant, p = 0.334.
CONCLUSION
Measurement of serum osmolality and urine osmolality may have some utility in AHF, but interpretation should consider baseline values and dynamic changes to account for individual differences in sodium and water handling.
Topics: Male; Humans; Middle Aged; Aged; Adolescent; Female; Prospective Studies; Cohort Studies; Heart Failure; Diuresis; Osmolar Concentration
PubMed: 35760046
DOI: 10.1159/000525730 -
MBio Aug 2020Bacteria must maintain a cytosolic osmolarity higher than that of their environment in order to take up water. High-osmolarity environments therefore present formidable...
Bacteria must maintain a cytosolic osmolarity higher than that of their environment in order to take up water. High-osmolarity environments therefore present formidable stress to bacteria. To explore the evolutionary mechanisms by which bacteria adapt to high-osmolarity environments, we selected in media with a variety of osmolytes and concentrations for 250 generations. Adaptation was osmolyte dependent, with sorbitol stress generally resulting in increased fitness under conditions with higher osmolarity, while selection in high concentrations of proline resulted in increased fitness specifically on proline. Consistent with these phenotypes, sequencing of the evolved populations showed that passaging in proline resulted in specific mutations in an associated metabolic pathway that increased the ability to utilize proline for growth, while evolution in sorbitol resulted in mutations in many different genes that generally resulted in improved growth under high-osmolarity conditions at the expense of growth at low osmolarity. High osmolarity decreased the growth rate but increased the mean cell volume compared with growth on proline as the sole carbon source, demonstrating that osmolarity-induced changes in growth rate and cell size follow an orthogonal relationship from the classical Growth Law relating cell size and nutrient quality. Isolates from a sorbitol-evolved population that captured the likely temporal sequence of mutations revealed by metagenomic sequencing demonstrated a trade-off between growth at high osmolarity and growth at low osmolarity. Our report highlights the utility of experimental evolution for dissecting complex cellular networks and environmental interactions, particularly in the case of behaviors that can involve both specific and general metabolic stressors. For bacteria, maintaining higher internal solute concentrations than those present in the environment allows cells to take up water. As a result, survival is challenging in high-osmolarity environments. To investigate how bacteria adapt to high-osmolarity environments, we maintained in a variety of high-osmolarity solutions for hundreds of generations. We found that the evolved populations adopted different strategies to improve their growth rates depending on the osmotic passaging condition, either generally adapting to high-osmolarity conditions or better metabolizing the osmolyte as a carbon source. Single-cell imaging demonstrated that enhanced fitness was coupled to faster growth, and metagenomic sequencing revealed mutations that reflected growth trade-offs across osmolarities. Our study demonstrated the utility of long-term evolution experiments for probing adaptation occurring during environmental stress.
Topics: Adaptation, Physiological; Colony Count, Microbial; Culture Media; Environment; Escherichia coli; Evolution, Molecular; Mutation; Osmolar Concentration; Phenotype; Stress, Physiological
PubMed: 32753494
DOI: 10.1128/mBio.01191-20 -
PloS One 2020Ty1 is one of the many transposons in the budding yeast Saccharomyces cerevisiae. The life-cycle of Ty1 shows numerous similarities with that of retroviruses, e.g. the...
Ty1 is one of the many transposons in the budding yeast Saccharomyces cerevisiae. The life-cycle of Ty1 shows numerous similarities with that of retroviruses, e.g. the initially synthesized polyprotein precursor undergoes proteolytic processing by the protease. The retroviral proteases have become important targets of current antiretroviral therapies due to the critical role of the limited proteolysis of Gag-Pol polyprotein in the replication cycle and they therefore belong to the most well-studied enzymes. Comparative analyses of retroviral and retroviral-like proteases can help to explore the key similarities and differences which may help understanding how resistance is developed against protease inhibitors, but the available information about the structural and biochemical characteristics of retroviral-like, and especially retrotransposon, proteases is limited. To investigate the main characteristics of Ty1 retrotransposon protease of Saccharomyces cerevisiae, untagged and His6-tagged forms of Ty1 protease were expressed in E. coli. After purification of the recombinant proteins, activity measurements were performed using synthetic oligopeptide and fluorescent recombinant protein substrates, which represented the wild-type and the modified forms of naturally occurring cleavage sites of the protease. We investigated the dependence of enzyme activity on different reaction conditions (pH, temperature, ionic strength, and urea concentration), and determined enzyme kinetic parameters for the studied substrates. Inhibitory potentials of 10 different protease inhibitors were also tested. Ty1 protease was not inhibited by the inhibitors which have been designed against human immunodeficiency virus type 1 protease and are approved as antiretroviral therapeutics. A quaternary structure of homodimeric Ty1 protease was proposed based on homology modeling, and this structure was used to support interpretation of experimental results and to correlate some structural and biochemical characteristics with that of other retroviral proteases.
Topics: Endopeptidases; Enzyme Stability; Fusion Proteins, gag-pol; Hot Temperature; Kinetics; Osmolar Concentration; Protease Inhibitors; Proteolysis; Retroelements; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 31917798
DOI: 10.1371/journal.pone.0227062