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Journal of Clinical Anesthesia Sep 2024The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain.
Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China.
STUDY OBJECTIVE
The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain.
DESIGN
A retrospective cohort study.
SETTING
This study was conducted at one tertiary care hospital in China.
PATIENTS
We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs).
INTERVENTIONS
Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid.
MEASUREMENTS
The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered.
MAIN RESULTS
After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes.
CONCLUSIONS
Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.
Topics: Humans; Acute Kidney Injury; Hydroxyethyl Starch Derivatives; Retrospective Studies; Female; Male; Middle Aged; China; Propensity Score; Crystalloid Solutions; Aged; Postoperative Complications; Incidence; Plasma Substitutes; Adult; Renal Replacement Therapy; Length of Stay; Surgical Procedures, Operative
PubMed: 38723416
DOI: 10.1016/j.jclinane.2024.111493 -
Translational Vision Science &... May 2024The blood-retinal barrier (BRB) restricts the delivery of intravenous therapeutics to the retina, necessitating innovative approaches for treating retinal disorders....
PURPOSE
The blood-retinal barrier (BRB) restricts the delivery of intravenous therapeutics to the retina, necessitating innovative approaches for treating retinal disorders. This study sought to explore the potential of focused ultrasound (FUS) to non-invasively deliver intravenously administered gold nanoparticles (AuNPs) across the BRB. FUS-BRB modulation can offer a novel method for targeted retinal therapy.
METHODS
AuNPs of different sizes and shapes were characterized, and FUS parameters were optimized to permeate the BRB without causing retinal damage in a rodent model. The delivery of 70-kDa dextran and AuNPs to the retinal ganglion cell (RGC) layer was visualized using confocal and two-photon microscopy, respectively. Histological and statistical analyses were conducted to assess the effectiveness and safety of the procedure.
RESULTS
FUS-BRB modulation resulted in the delivery of dextran and AuNPs to the RGC and inner nuclear layer. Smaller AuNPs reached the retinal layers to a greater extent than larger ones. The delivery of dextran and AuNPs across the BRB with FUS was achieved without significant retinal damage.
CONCLUSIONS
This investigation provides the first evidence, to our knowledge, of FUS-mediated AuNP delivery across the BRB, establishing a foundation for a targeted and non-invasive approach to retinal treatment. The results contribute to developing promising non-invasive therapeutic strategies in ophthalmology to treat retinal diseases.
TRANSLATIONAL RELEVANCE
Modifying the BRB with ultrasound offers a targeted and non-invasive delivery strategy of intravenous therapeutics to the retina.
Topics: Animals; Gold; Retinal Ganglion Cells; Metal Nanoparticles; Blood-Retinal Barrier; Dextrans; Drug Delivery Systems; Rats; Microscopy, Confocal; Male
PubMed: 38713474
DOI: 10.1167/tvst.13.5.5 -
Journal of the American Academy of... May 2024Graft materials available to supplement hindfoot and ankle arthrodesis procedures include autologous (autograft) or allogeneic bone graft (allograft) but also bone graft... (Review)
Review Comparative Study
Graft materials available to supplement hindfoot and ankle arthrodesis procedures include autologous (autograft) or allogeneic bone graft (allograft) but also bone graft substitutes such as demineralized bone matrix, calcium sulfate, calcium phosphate, and tricalcium phosphate/hydroxyapatite. In addition, biologic agents, such as recombinant human bone morphogenetic protein-2 or recombinant human platelet derived growth factor-BB (rhPDGF-BB), and preparations, including platelet-rich plasma or concentrated bone marrow aspirate, have been used to facilitate bone healing in ankle or hindfoot arthrodesis. The purpose of this review was to summarize the available clinical evidence surrounding the utilization and efficacy of the above materials and biological agents in ankle or hindfoot arthrodesis procedures, with emphasis on the quality of the existing evidence to facilitate clinical decision making.
Topics: Humans; Arthrodesis; Bone Transplantation; Bone Substitutes; Ankle Joint; Calcium Phosphates
PubMed: 38704857
DOI: 10.5435/JAAOSGlobal-D-23-00216 -
European Journal of Pharmaceutical... Jul 2024Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of...
Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR) and 60 min (COMDR) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR (R = 0.82 and Q = 0.77) and COMDR (R = 0.87 and Q = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R = 0.83 (COMDR) and R = 0.84 (COMDR). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.
Topics: Drug Liberation; Solubility; Drug Compounding; Povidone; Computer Simulation; Pharmaceutical Preparations; Least-Squares Analysis
PubMed: 38697312
DOI: 10.1016/j.ejps.2024.106780 -
Molecules (Basel, Switzerland) Apr 2024This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct...
This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (M) and co-precipitation at controlled pH (M), were explored, including the assessment of the coating's influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from M consist of approximately 11-13% of Fe present in magnetite, while samples obtained from M have higher contents of 33-45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SP-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.
Topics: Theranostic Nanomedicine; Magnetic Iron Oxide Nanoparticles; Magnetic Resonance Imaging; Contrast Media; Magnetite Nanoparticles; Humans; Gold; Dextrans; Gadolinium; Surface Properties; Hyperthermia, Induced; Particle Size
PubMed: 38675647
DOI: 10.3390/molecules29081824 -
Food and Chemical Toxicology : An... Jun 2024Consumption of rice-based foods provides essential nutrients required for infants and toddlers' growth. However, they could contain toxic and excess essential elements...
Consumption of rice-based foods provides essential nutrients required for infants and toddlers' growth. However, they could contain toxic and excess essential elements that may affect human health. The study aims to determine the composition of rice-based baby foods in the USA and outside and conduct a multiple-life stages probabilistic exposure and risk assessment of toxic and essential elements in children. Elemental concentrations were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in thirty-three rice-based baby foods. This includes 2 infant formulas, 11 rice baby cereals, and 20 rice snacks produced primarily in the United States, China, and other countries. A probabilistic risk assessment was conducted to assess risks of adverse health effects. Results showed that infant formula had higher median concentrations of selenium (Se), copper (Cu), zinc (Zn), sodium (Na), magnesium (Mg), calcium (Ca), and potassium (K) compared to rice baby cereal and rice snacks. On the contrary, rice snacks had the highest median concentration of Arsenic (As) (127 μg/kg) while rice baby cereals showed the highest median concentration of Cd (7 μg/kg). A higher lifetime estimated daily intake was observed for samples manufactured in the USA compared to those from China and other countries. Hazard quotient (HQ < 1) values were suggestive of minimal adverse health effects. However, lifetime carcinogenic risk analysis based on total As indicated an unacceptable cancer risk (>1E-04). These findings show a need for ongoing monitoring of rice-based foods consumed by infants and toddlers as supplementary and substitutes for breast milk or weaning food options. This can be useful in risk reduction and mitigation of early life exposure to improve health outcomes.
Topics: Oryza; Humans; United States; Infant Food; Risk Assessment; Infant; Food Contamination; Trace Elements; China; Infant Formula
PubMed: 38641042
DOI: 10.1016/j.fct.2024.114677 -
PloS One 2024Diffusion within extracellular matrix is essential to deliver nutrients and larger metabolites to the avascular region of the meniscus. It is well known that both...
Diffusion within extracellular matrix is essential to deliver nutrients and larger metabolites to the avascular region of the meniscus. It is well known that both structure and composition of the meniscus vary across its regions; therefore, it is crucial to fully understand how the heterogenous meniscal architecture affects its diffusive properties. The objective of this study was to investigate the effect of meniscal region (core tissue, femoral, and tibial surface layers) and molecular weight on the diffusivity of several molecules in porcine meniscus. Tissue samples were harvested from the central area of porcine lateral menisci. Diffusivity of fluorescein (MW 332 Da) and three fluorescence-labeled dextrans (MW 3k, 40k, and 150k Da) was measured via fluorescence recovery after photobleaching. Diffusivity was affected by molecular size, decreasing as the Stokes' radius of the solute increased. There was no significant effect of meniscal region on diffusivity for fluorescein, 3k and 40k dextrans (p>0.05). However, region did significantly affect the diffusivity of 150k Dextran, with that in the tibial surface layer being larger than in the core region (p = 0.001). Our findings contribute novel knowledge concerning the transport properties of the meniscus fibrocartilage. This data can be used to advance the understanding of tissue pathophysiology and explore effective approaches for tissue restoration.
Topics: Animals; Swine; Dextrans; Meniscus; Menisci, Tibial; Fibrocartilage; Fluoresceins
PubMed: 38626169
DOI: 10.1371/journal.pone.0301432 -
PloS One 2024The nucleus preserves the genomic DNA of eukaryotic organisms and maintains the integrity of the cell by regulating the transport of molecules across the nuclear...
The nucleus preserves the genomic DNA of eukaryotic organisms and maintains the integrity of the cell by regulating the transport of molecules across the nuclear membrane. It is hitherto assumed that small molecules having a size below the passive permeability limit are allowed to diffuse freely to the nucleus while the transport of larger molecules is regulated via an active mechanism involving energy. Here we report on the kinetics of nuclear import and export of dextran molecules having a size below the passive permeability limit. The studies carried out using time-lapse confocal fluorescence microscopy show a clear deviation from the passive diffusion model. In particular, it is observed that the steady-state concentration of dextran molecules inside the nucleus is consistently less than the concentration outside, in contradiction to the predictions of the passive diffusion model. Detailed analysis and modeling of the transport show that the nuclear export rates significantly differ from the import rates, and the difference in rates is dependent on the size of the molecules. The nuclear export rates are further confirmed by an independent experimental study where we observe the diffusion of dextran molecules from the nucleus directly. Our experiments and transport model would suggest that the nucleus actively rejects exogenous macromolecules even below the passive permeability limit. This result can have a significant impact on biomedical research, especially in areas related to targeted drug delivery and gene therapy.
Topics: Nuclear Envelope; Cell Nucleus; Dextrans; Active Transport, Cell Nucleus; Diffusion
PubMed: 38626108
DOI: 10.1371/journal.pone.0297738 -
Journal of Colloid and Interface Science Jul 2024There has been an increasing demand for simultaneous detection of multiple analytes in one sample. Microbead-based platforms have been developed for multiplexed assays....
There has been an increasing demand for simultaneous detection of multiple analytes in one sample. Microbead-based platforms have been developed for multiplexed assays. However, most of the microbeads are made of non-biodegradable synthetic polymers, leading to environmental and human health concerns. In this study, we developed an environmentally friendly dextran microbeads as a new type of multi-analyte assay platform. Biodegradable dextran was utilized as the primary material. Highly uniform magnetic dextran microspheres were successfully synthesized using the Shirasu porous glass (SPG) membrane emulsification technique. To enhance the amount of surface functional groups for ligand conjugation, we coated the dextran microbeads with a layer of dendrimers via a simple electrostatic adsorption process. Subsequently, a unique and efficient click chemistry coupling technique was developed for the fluorescence encoding of the microspheres, enabling multiplexed detection. The dextran microbeads were tested for 3-plex cytokine analysis, and exhibited excellent biocompatibility, stable coding signals, low background noise and high sensitivity.
Topics: Dextrans; Microspheres; Particle Size; Surface Properties; Humans; Cytokines; Click Chemistry; Porosity; Mice; Animals; Green Chemistry Technology
PubMed: 38613982
DOI: 10.1016/j.jcis.2024.04.061 -
Nutrients Mar 2024The goblet cells of the gastrointestinal tract (GIT) produce glycoproteins called mucins that form a protective barrier from digestive contents and external stimuli....
The goblet cells of the gastrointestinal tract (GIT) produce glycoproteins called mucins that form a protective barrier from digestive contents and external stimuli. Recent evidence suggests that the milk fat globule membrane (MFGM) and its milk phospholipid component (MPL) can benefit the GIT through improving barrier function. Our objective was to compare the effects of two digested MFGM ingredients with or without dextran sodium sulfate (DSS)-induced barrier stress on mucin proteins. Co-cultured Caco-2/HT29-MTX intestinal cells were treated with in vitro digests of 2%, 5%, and 10% (/) MFGM or MPL alone for 6 h or followed by challenge with 2.5% DSS (6 h). Transepithelial electrical resistance and fluorescein isothiocyanate (FITC)-dextran (FD4) permeability measurements were used to measure changes in barrier integrity. Mucin characterization was performed using a combination of slot blotting techniques for secreted (MUC5AC, MUC2) and transmembrane (MUC3A, MUC1) mucins, scanning electron microscopy (SEM), and periodic acid Schiff (PAS)/Alcian blue staining. Digested MFGM and MPL prevented a DSS-induced reduction in secreted mucins, which corresponded to the prevention of DSS-induced increases in FD4 permeability. SEM and PAS/Alcian blue staining showed similar visual trends for secreted mucin production. A predictive bioinformatic approach was also used to identify potential KEGG pathways involved in MFGM-mediated mucosal maintenance under colitis conditions. This preliminary in silico evidence, combined with our in vitro findings, suggests the role of MFGM in inducing repair and maintenance of the mucosal barrier.
Topics: Humans; Dextrans; Caco-2 Cells; Alcian Blue; Glycoproteins; Epithelial Cells; Mucins; Glycolipids; Fluorescein-5-isothiocyanate; Lipid Droplets
PubMed: 38612988
DOI: 10.3390/nu16070954