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Farmacia Hospitalaria : Organo Oficial... May 2024To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops...
OBJECTIVE
To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome.
METHOD
The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5±3 °C), at room temperature (25±2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones.
RESULTS
The eye drops stored at 5 °C were the most stable; in the 1 mg/mL eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/mL eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/mL, presented a white precipitate from day 14 and 28, respectively. Non-refrigerated 1 mg/mL eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers.
CONCLUSIONS
1 mg/mL MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/mL eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.
PubMed: 38782645
DOI: 10.1016/j.farma.2024.04.021 -
Nature May 2024Higher plants survive terrestrial water deficiency and fluctuation by arresting cellular activities (dehydration) and resuscitating processes (rehydration). However, how...
Higher plants survive terrestrial water deficiency and fluctuation by arresting cellular activities (dehydration) and resuscitating processes (rehydration). However, how plants monitor water availability during rehydration is unknown. Although increases in hypo-osmolarity-induced cytosolic Ca concentration (HOSCA) have long been postulated to be the mechanism for sensing hypo-osmolarity in rehydration, the molecular basis remains unknown. Because osmolarity triggers membrane tension and the osmosensing specificity of osmosensing channels can only be determined in vivo, these channels have been classified as a subtype of mechanosensors. Here we identify bona fide cell surface hypo-osmosensors in Arabidopsis and find that pollen Ca spiking is controlled directly by water through these hypo-osmosensors-that is, Ca spiking is the second messenger for water status. We developed a functional expression screen in Escherichia coli for hypo-osmosensitive channels and identified OSCA2.1, a member of the hyperosmolarity-gated calcium-permeable channel (OSCA) family of proteins. We screened single and high-order OSCA mutants, and observed that the osca2.1/osca2.2 double-knockout mutant was impaired in pollen germination and HOSCA. OSCA2.1 and OSCA2.2 function as hypo-osmosensitive Ca-permeable channels in planta and in HEK293 cells. Decreasing osmolarity of the medium enhanced pollen Ca oscillations, which were mediated by OSCA2.1 and OSCA2.2 and required for germination. OSCA2.1 and OSCA2.2 convert extracellular water status into Ca spiking in pollen and may serve as essential hypo-osmosensors for tracking rehydration in plants.
Topics: Arabidopsis; Arabidopsis Proteins; Calcium; Calcium Channels; Calcium Signaling; Escherichia coli; Germination; Mutation; Osmolar Concentration; Pollen; Water; HEK293 Cells; Humans; Dehydration
PubMed: 38778102
DOI: 10.1038/s41586-024-07445-6 -
Nature Communications May 2024Biotic-abiotic hybrid photocatalytic system is an innovative strategy to capture solar energy. Diversifying solar energy conversion products and balancing photoelectron...
Biotic-abiotic hybrid photocatalytic system is an innovative strategy to capture solar energy. Diversifying solar energy conversion products and balancing photoelectron generation and transduction are critical to unravel the potential of hybrid photocatalysis. Here, we harvest solar energy in a dual mode for CuSe nanoparticles biomineralization and seawater desalination by integrating the merits of Shewanella oneidensis MR-1 and biogenic nanoparticles. Photoelectrons generated by extracellular Se nanoparticles power CuSe synthesis through two pathways that either cross the outer membrane to activate periplasmic Cu(II) reduction or are directly delivered into the extracellular space for Cu(I) evolution. Meanwhile, photoelectrons drive periplasmic Cu(II) reduction by reversing MtrABC complexes in S. oneidensis. Moreover, the unique photothermal feature of the as-prepared CuSe nanoparticles, the natural hydrophilicity, and the linking properties of bacterium offer a convenient way to tailor photothermal membranes for solar water production. This study provides a paradigm for balancing the source and sink of photoelectrons and diversifying solar energy conversion products in biotic-abiotic hybrid platforms.
Topics: Solar Energy; Shewanella; Copper; Seawater; Biomineralization; Salinity; Water Purification; Nanoparticles; Catalysis
PubMed: 38778052
DOI: 10.1038/s41467-024-48660-z -
Clinical Nutrition ESPEN Jun 2024Patients with an ileostomy often have impaired quality of life, sodium depletion, secondary hyperaldosteronism, and other organ-specific pathologies. The osmolality of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with an ileostomy often have impaired quality of life, sodium depletion, secondary hyperaldosteronism, and other organ-specific pathologies. The osmolality of oral supplements influences ileostomy output and increases sodium loss. We hypothesized the existence of an osmolality range in which fluid absorption and secondary natriuresis are optimal.
METHODS
This was a single-center, quasi-randomized crossover intervention study, including patients with an ileostomy and no home parenteral support. After an 8-h fasting period, each patient ingested 500 mL of 3-18 different oral supplements and a standardized meal during the various intervention periods, followed by a 6-h collection of ileostomy and urine outputs. The primary outcome was 6-h ileostomy output.
RESULTS
A total of 14 ileostomy patients with a median age of 65 years (interquartile range 38-70 years) were included. The association between osmolalities (range 5-1352 mOsm/kg) and ileostomy output forecasted an S-curve. A linear association between osmolality of oral supplements (range 290-600 mOsm/kg) and ileostomy output was identified and assessed with a mixed-effects model. Ileostomy output increased by 57 g/6 h (95% confidence interval (CI) 21-94) when the oral supplement osmolality increased by 100 mOsm/kg (p = 0.005).
CONCLUSION
Osmolality in oral supplements correlated with ileostomy output. Our results indicate that patients with an ileostomy may benefit from increased ingestion of oral supplements with osmolalities between 100 and 290 mOsm/kg. We define this range as the Goldilocks zone, equivalent to optimal fluid and electrolyte absorption.
Topics: Humans; Ileostomy; Middle Aged; Aged; Male; Female; Dietary Supplements; Adult; Osmolar Concentration; Cross-Over Studies; Administration, Oral; Sodium
PubMed: 38777478
DOI: 10.1016/j.clnesp.2024.03.003 -
Environmental Microbiology Reports Jun 2024The pathogenic fungus Batrachochytrium dendrobatidis has caused declines of amphibians worldwide. Yet our understanding of how water quality influences fungal...
The pathogenic fungus Batrachochytrium dendrobatidis has caused declines of amphibians worldwide. Yet our understanding of how water quality influences fungal pathogenicity is limited. Here, we reviewed experimental studies on the effect of water quality on this pathogen to determine which parameters impacted disease dynamics consistently. The strongest evidence for protective effects is salinity which shows strong antifungal properties in hosts at natural levels. Although many fungicides had detrimental effects on the fungal pathogen in vitro, their impact on the host is variable and they can worsen infection outcomes. However, one fungicide, epoxiconazole, reduced disease effects experimentally and likely in the field. While heavy metals are frequently studied, there is weak evidence that they influence infection outcomes. Nitrogen and phosphorous do not appear to impact pathogen growth or infection in the amphibian host. The effects of other chemicals, like pesticides and disinfectants on infection were mostly unclear with mixed results or lacking an in vivo component. Our study shows that water chemistry does impact disease dynamics, but the effects of specific parameters require more investigation. Improving our understanding of how water chemistry influences disease dynamics will help predict the impact of chytridiomycosis, especially in amphibian populations affected by land use changes.
Topics: Animals; Batrachochytrium; Amphibians; Water Quality; Mycoses; Salinity; Fungicides, Industrial; Chytridiomycota; Pesticides; Disinfectants; Antifungal Agents
PubMed: 38775382
DOI: 10.1111/1758-2229.13274 -
PeerJ 2024The aim of the current study was to assess the potency of the exopolymeric substances (EPS)-secreting purple non-sulfur bacteria (PNSB) on rice plants on acidic...
The aim of the current study was to assess the potency of the exopolymeric substances (EPS)-secreting purple non-sulfur bacteria (PNSB) on rice plants on acidic salt-affected soil under greenhouse conditions. A two-factor experiment was conducted following a completely randomized block design. The first factor was the salinity of the irrigation, and the other factor was the application of the EPS producing PNSB ( EPS18, EPS37, and EPS54), with four replicates. The result illustrated that irrigation of salt water at 3-4‰ resulted in an increase in the Na accumulation in soil, resulting in a lower rice grain yield by 12.9-22.2% in comparison with the 0‰ salinity case. Supplying the mixture of EPS18, EPS37, and EPS54 increased pH by 0.13, NH by 2.30 mg NH kg, and available P by 8.80 mg P kg, and decreased Na by 0.348 meq Na 100 g, resulting in improvements in N, P, and K uptake and reductions in Na uptake, in comparison with the treatment without bacteria. Thus, the treatments supplied with the mixture of EPS18, EPS37, and EPS54 resulted in greater yield by 27.7% than the control treatment.
Topics: Oryza; Soil; Soil Microbiology; Salinity; Salt Stress; Proteobacteria; Hydrogen-Ion Concentration; Sodium
PubMed: 38770100
DOI: 10.7717/peerj.16943 -
Journal of Cellular and Molecular... May 2024Farnesoid X receptor (FXR), a ligand-activated transcription factor, plays an important role in maintaining water homeostasis by up-regulating aquaporin 2 (AQP2)...
Farnesoid X receptor (FXR), a ligand-activated transcription factor, plays an important role in maintaining water homeostasis by up-regulating aquaporin 2 (AQP2) expression in renal medullary collecting ducts; however, its role in the survival of renal medullary interstitial cells (RMICs) under hypertonic conditions remains unclear. We cultured primary mouse RMICs and found that the FXR was expressed constitutively in RMICs, and that its expression was significantly up-regulated at both mRNA and protein levels by hypertonic stress. Using luciferase and ChIP assays, we found a potential binding site of nuclear factor kappa-B (NF-κB) located in the FXR gene promoter which can be bound and activated by NF-κB. Moreover, hypertonic stress-induced cell death in RMICs was significantly attenuated by FXR activation but worsened by FXR inhibition. Furthermore, FXR increased the expression and nuclear translocation of hypertonicity-induced tonicity-responsive enhance-binding protein (TonEBP), the expressions of its downstream target gene sodium myo-inositol transporter (SMIT), and heat shock protein 70 (HSP70). The present study demonstrates that the NF-κB/FXR/TonEBP pathway protects RMICs against hypertonic stress.
Topics: Animals; NF-kappa B; Signal Transduction; Mice; Kidney Medulla; Osmotic Pressure; Aquaporin 2; Transcription Factors; Male; Mice, Inbred C57BL; HSP70 Heat-Shock Proteins; Promoter Regions, Genetic; Cells, Cultured; Gene Expression Regulation; Symporters; Receptors, Cytoplasmic and Nuclear
PubMed: 38769917
DOI: 10.1111/jcmm.18409 -
The American Journal of Case Reports May 2024BACKGROUND Nephrogenic diabetes insipidus (NDI) is a rare renal disorder that can be congenital, and is caused by mutations in either aquaporin 2 or arginine vasopressin...
A Rare Case of Congenital Nephrogenic Diabetes Insipidus Associated with Aquaporin 2 Gene Mutation and Subsequent Acute Lymphoblastic Leukemia: Impact of Steroids on Kidney Function.
BACKGROUND Nephrogenic diabetes insipidus (NDI) is a rare renal disorder that can be congenital, and is caused by mutations in either aquaporin 2 or arginine vasopressin receptor 2, or it can be secondary to kidney disease or electrolyte imbalance. The clinical signs of NDI include polyuria, compensatory polydipsia, hypernatremic dehydration, and growth retardation without prompt treatment. In this report, we present the case of a patient with congenital NDI who was later diagnosed with acute lymphoblastic leukemia (ALL). With dexamethasone treatment, he had uncontrolled polyuria and polydipsia. Our aim was to concentrate on the impact of steroids on the kidneys. CASE REPORT Our patient presented at the age of 9 months with signs of severe dehydration that were associated with polyuria. His laboratory examinations revealed hypernatremia and decreased urine osmolality. He was diagnosed with NDI and his exome sequence revealed a homozygous mutation at the nucleotide position AQP2 NM_000486.6: c.374C>T (p.Thr125Met). He was treated with hydrochlorothiazide and amiloride. Then, at age 19 months, he presented with gastroenteritis and a complete blood count (CBC) showed high white blood cell count and blast cells. He was diagnosed with (ALL) and began receiving chemotherapy, during which again developed polydipsia and polyuria, which could not be controlled with an increased dosage of hydrochlorothiazide. CONCLUSIONS We report a rare case of NDI caused by a missense mutation in the aquaporin 2 gene. One year later, the child developed ALL, and treatment with dexamethasone led to an uncompensated state of polydipsia and polyuria.
Topics: Humans; Male; Diabetes Insipidus, Nephrogenic; Aquaporin 2; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Infant; Dexamethasone; Mutation; Glucocorticoids
PubMed: 38769718
DOI: 10.12659/AJCR.943597 -
Nature Communications May 2024The identification of genes involved in salinity tolerance has primarily focused on model plants and crops. However, plants naturally adapted to highly saline...
The identification of genes involved in salinity tolerance has primarily focused on model plants and crops. However, plants naturally adapted to highly saline environments offer valuable insights into tolerance to extreme salinity. Salicornia plants grow in coastal salt marshes, stimulated by NaCl. To understand this tolerance, we generated genome sequences of two Salicornia species and analyzed the transcriptomic and proteomic responses of Salicornia bigelovii to NaCl. Subcellular membrane proteomes reveal that SbiSOS1, a homolog of the well-known SALT-OVERLY-SENSITIVE 1 (SOS1) protein, appears to localize to the tonoplast, consistent with subcellular localization assays in tobacco. This neo-localized protein can pump Na into the vacuole, preventing toxicity in the cytosol. We further identify 11 proteins of interest, of which SbiSALTY, substantially improves yeast growth on saline media. Structural characterization using NMR identified it as an intrinsically disordered protein, localizing to the endoplasmic reticulum in planta, where it can interact with ribosomes and RNA, stabilizing or protecting them during salt stress.
Topics: Chenopodiaceae; Plant Proteins; Salt Tolerance; Gene Expression Regulation, Plant; Vacuoles; Salinity; Sodium Chloride; Endoplasmic Reticulum; Salt Stress; Proteomics; Nicotiana; Transcriptome
PubMed: 38769297
DOI: 10.1038/s41467-024-48595-5 -
PeerJ 2024Genetic variation for salt tolerance remains elusive in jamun ().
BACKGROUND
Genetic variation for salt tolerance remains elusive in jamun ().
METHODS
Effects of gradually increased salinity (2.0-12.0 dS/m) were examined in 20 monoembryonic and 28 polyembryonic genotypes of jamun. Six genotypes were additionally assessed for understanding salt-induced changes in gas exchange attributes and antioxidant enzymes.
RESULTS
Salt-induced reductions in leaf, stem, root and plant dry mass (PDM) were relatively greater in mono- than in poly-embryonic types. Reductions in PDM relative to control implied more adverse impacts of salinity on genotypes CSJ-28, CSJ-31, CSJ-43 and CSJ-47 (mono) and CSJ-1, CSJ-24, CSJ-26 and CSJ-27 (poly). Comparably, some mono- (CSJ-5, CSJ-18) and poly-embryonic (CSJ-7, CSJ-8, CSJ-14, CSJ-19) genotypes exhibited least reductions in PDM following salt treatment. Most polyembryonic genotypes showed lower reductions in root than in shoot mass, indicating that they may be more adept at absorbing water and nutrients when exposed to salt. The majority of genotypes did not exhibit leaf tip burn and marginal scorch despite significant increases in Na and Cl, suggesting that tissue tolerance existed for storing excess Na and Cl in vacuoles. Jamun genotypes were likely more efficient in Cl exclusion because leaf, stem and root Cl levels were consistently lower than those of Na under salt treatment. Leaf K was particularly little affected in genotypes with high leaf Na. Lack of discernible differences in leaf, stem and root Ca and Mg contents between control and salt treatments was likely due to their preferential uptake. Correlation analysis suggested that Na probably had a greater inhibitory effect on biomass in both mono- and poly-embryonic types. Discriminant analysis revealed that while stem and root Cl probably accounted for shared responses, root Na, leaf K and leaf Cl explained divergent responses to salt stress of mono- and poly-embryonic types. Genotypes CSJ-18 and CSJ-19 seemed efficient in fending off oxidative damage caused by salt because of their stronger antioxidant defences.
CONCLUSIONS
Polyembryonic genotypes CSJ-7, CSJ-8, CSJ-14 and CSJ-19, which showed least reductions in biomass even after prolonged exposure to salinity stress, may be used as salt-tolerant rootstocks. The biochemical and molecular underpinnings of tissue tolerance to excess Na and Cl as well as preferential uptake of K, Ca, and Mg need to be elucidated.
Topics: Syzygium; Genotype; Salt Stress; Salt Tolerance; Plant Leaves; Plant Roots; Salinity; Antioxidants
PubMed: 38766484
DOI: 10.7717/peerj.17311