Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota.

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Redox-sensitive self-assembling polymer micelles based on oleanolic modified hydroxyethyl starch: Synthesis, characterisation, and oleanolic release.

Our study aimed at developing polymer micelles that possess redox sensitivity and excellent controlled release properties. 3,3'-dithiodipropionic acid (DTDPA, Abbreviation in synthetic polymers: SS) was introduced as ROS (Reactive oxygen species)response bond and connecting arm to couple hydroxyethyl starch (HES) with oleanolic acid (OA), resulting in the synthesis of four distinct grafting ratios of HES-SS-OA. FTIR (Fourier Transform infrared spectroscopy) and 1H NMR (1H Nuclear magnetic resonance spectra) were used to verify the triumphant combination of HES-SS-OA. Polymer micelles were found to encapsulate OA in an amorphous form, as indicated by the results of XRD (X-ray diffraction) and DSC (Differential scanning calorimetry). When the OA grafting rate on HES increased from 7.72 % to 11.75 %, the particle size decreased from 297.79 nm to 201.39 nm as the polymer micelles became compact due to enhanced hydrophobicity. In addition, the zeta potential changed from -16.42 mv to -25.78 mv, the PDI (polydispersity index) decreased from 0.3649 to 0.2435, and the critical micelle concentration (CMC) decreased from 0.0955 mg/mL to 0.0123 mg/mL. Results of erythrocyte hemolysis, cytotoxicity and cellular uptake illustrated that HES-SS-OA had excellent biocompatibility and minimal cytotoxicity for AML-12 cells. Disulfide bond breakage of HES-SS-OA in the presence of H2O2 and GSH confirmed the redox sensitivity of the HES-SS-OA micelles and their excellent controlled release properties for OA. These findings suggest that HES-SS-OA can be potentially used in the future as a healthcare drug and medicine for the prevention or adjuvant treatment of inflammation.

Perioperative management of kidney transplantation in China: A national survey in 2021.

Perioperative anaesthesia management has an important significance for kidney transplantation; however, the related consensus remains limited. An electronic survey with 44 questions was developed and sent to the chief anaesthesiologist at 115 non-military medical centres performing kidney transplantation in China through WeChat. A response rate of 81.7% was achieved from 94 of 115 non-military medical centres, where 94.4% of kidney transplants (10404 /11026) were completed in 2021. The result showed an overview of perioperative practice for kidney transplantations in China, identify the heterogeneity, and provide evidence for improving perioperative management of kidney transplantation. Some controversial therapy, such as hydroxyethyl starch, are still widely used, while some recommended methods are not widely available. More efforts on fluid management, hemodynamical monitoring, perioperative anaesthetics, and postoperative pain control are needed to improve the outcomes. Evidence-based guidelines for standardizing clinical practice are needed.

Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion.

OBJECTIVE: Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. METHODS: This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. RESULTS: Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage. CONCLUSIONS: Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Feasibility and safety of non-contrast optical coherence tomography imaging using hydroxyethyl starch in coronary arteries.

Intracoronary optical coherence tomography (OCT) requires injection of flushing media for image acquisition. Alternative flushing media needs to be investigated to reduce the risk of contrast-induced renal dysfunction. We investigated the feasibility and safety of pentastarch (hydroxyethyl starch) for clinical OCT imaging. We prospectively enrolled 43 patients with 70 coronary lesions (46-stented; 24-native). Total 81 OCT pullback pairs were obtained by manual injection of iodine contrast, followed by pentastarch. Each pullback was assessed frame-by-frame using an automated customized lumen contour/stent strut segmentation algorithm. Paired images were compared for the clear image segments (CIS), blood-flushing capability, and quantitative morphometric measurements. Overall image quality, as assessed by the proportion of CIS, was comparable between the contrast- and pentastarch-flushed images (97.1% vs. 96.5%; p = 0.160). The pixel-based blood-flushing capability was similar between the groups (0.951 [0.947-0.953] vs. 0.950 [0.948-0.952], p = 0.125). Quantitative two- and three-dimensional morphometric measurements of the paired images correlated well (p < 0.001) with excellent inter-measurement variability. All patients safely underwent OCT imaging using pentastarch without resulting in clinically relevant complications or renal deterioration. Non-contrast OCT imaging using pentastarch is clinically safe and technically feasible with excellent image quality and could be a promising alternative strategy for patients at high risk of renal impairment.

Effect of hydroxypropyl distarch phosphate on the retrogradation properties of sterilized pea starch jelly and its possible mechanism.

Due to the high content of amylose in pea starch (PS), PS jelly is prone to retrogradation during storage and its quality reduces subsequently. Hydroxypropyl distarch phosphate (HPDSP) shows a potential inhibitory effect on the retrogradation of starch gel. Based on this, five retrograded PS-HPDSP blends containing 1 %, 2 %, 3 %, 4 % and 5 % (w/w, based on the weight of PS) of HPDSP were prepared, and their long-range, short-range ordered structure and retrogradation properties, and the possible interaction between PS and HPDSP were investigated. The addition of HPDSP significantly reduced the hardness of PS jelly and maintained its springiness during cold storage, and this effect was enhanced with HPDSP dosage being from 1 % to 4 %. The presence of HPDSP destroyed both short-range ordered structure and long-range ordered structure. Rheological results indicated that all the gelatinized samples were typical non-Newtonian fluids with shear-thinning characteristics and HPDSP increased their viscoelasticity in a dose-dependent manner. In conclusion, HPDSP delays the retrogradation of PS jelly mainly by combining with amylose in PS through hydrogen bonds and steric hindrance.

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch.

BACKGROUND: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. STUDY DESIGN AND METHODS: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. RESULTS: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. CONCLUSION: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.

Characteristics of New Oxygen-Carrying Plasma and Its Application Prospects in the Treatment of Severe Acute Pancreatitis.

ABSTRACT: Oxygen-carrying plasma, a new type of colloid substitute, is composed of hydroxyethyl starch and acellular hemoglobin-based oxygen carriers. It can supplement colloidal osmotic pressure and rapidly improve the body's oxygen supply. The resuscitation effect of the new oxygen-carrying plasma in animal shock models is better than that of hydroxyethyl starch or hemoglobin-based oxygen carriers alone. It can reduce the histopathological damage and mortality associated with severe acute pancreatitis, and it is expected to become an interesting treatment method for severe acute pancreatitis. This article reviews the characteristics of the new oxygen-carrying plasma, its role in fluid resuscitation, and its application prospects in the treatment of severe acute pancreatitis.

Slow Intravenous Infusion of a Novel Damage Control Cocktail Decreases Blood Loss in a Pig Polytrauma Model.

BACKGROUND: Our objective was to optimize a novel damage control resuscitation (DCR) cocktail composed of hydroxyethyl starch, vasopressin, and fibrinogen concentrate for the polytraumatized casualty. We hypothesized that slow intravenous infusion of the DCR cocktail in a pig polytrauma model would decrease internal hemorrhage and improve survival compared with bolus administration. METHODS: We induced polytrauma, including traumatic brain injury (TBI), femoral fracture, hemorrhagic shock, and free bleeding from aortic tear injury, in 18 farm pigs. The DCR cocktail consisted of 6% hydroxyethyl starch in Ringer's lactate solution (14mL/kg), vasopressin (0.8U/kg), and fibrinogen concentrate (100mg/kg) in a total fluid volume of 20mL/kg that was either divided in half and given as two boluses separated by 30 minutes as control or given as a continuous slow infusion over 60 minutes. Nine animals were studied per group and monitored for up to 3 hours. Outcomes included internal blood loss, survival, hemodynamics, lactate concentration, and organ blood flow obtained by colored microsphere injection. RESULTS: Mean internal blood loss was significantly decreased by 11.1mL/kg with infusion compared with the bolus group (p = .038). Survival to 3 hours was 80% with infusion and 40% with bolus, which was not statistically different (Kaplan Meier log-rank test, p = .17). Overall blood pressure was increased (p < .001), and blood lactate concentration was decreased (p < .001) with infusion compared with bolus. There were no differences in organ blood flow (p > .09). CONCLUSION: Controlled infusion of a novel DCR cocktail decreased hemorrhage and improved resuscitation in this polytrauma model compared with bolus. The rate of infusion of intravenous fluids should be considered as an important aspect of DCR.

Hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanocrystals for cancer therapy.

Cancer stem cells (CSCs) have been recognized as the culprit for tumor progression, treatment resistance, metastasis, and recurrence while redox homeostasis represents the Achilles' Heel of CSCs. However, few drugs or formulations that are capable of elevating oxidative stress have achieved clinical success for eliminating CSCs. Here, we report hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@HES NPs), which conspicuously suppress CSCs not only in vitro but also in numerous tumor models in vivo. Furthermore, CuET@HES NPs effectively inhibit CSCs in fresh tumor tissues surgically excised from hepatocellular carcinoma patients. Mechanistically, we uncover that hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanocrystals via copper­oxygen coordination interactions, thereby promoting copper-diethyldithiocarbamate colloidal stability, cellular uptake, intracellular reactive oxygen species production, and CSCs apoptosis. As all components are widely used in clinics, CuET@HES NPs represent promising treatments for CSCs-rich solid malignancies and hold great clinical translational potentials. This study has critical implications for design of CSCs targeting nanomedicines.

Utility of 6% hydroxyethyl starch 130/0.4 in oral cancer surgeries with a duration of over 6 hours: A retrospective case-control study.

To evaluate the utility of 6% hydroxyethyl starch (HES) 130/0.4 in oral cancer surgeries with durations over 6 hours. Using a case-control study design, the investigators enrolled patients who underwent oral cancer surgery involving osteotomy or manipulation near the major blood vessels at the Department of Orofacial Surgery in our hospital between 2017 and 2020. The predictor variable was 6% HES130/0.4. Outcomes included in-out balance and other postoperative parameters pertaining to circulatory maintenance (blood loss, urine volume, infusion volume, blood transfusion volume, albumin dose, hemoglobin levels, blood albumin levels, and doses of vasopressors used to maintain blood pressure), as well as pre- and postoperative renal function, pH, bicarbonate levels, and base excess. Changes in renal function were evaluated by assessing blood urea nitrogen and creatinine levels before surgery and at 1 and 7 days postoperatively. The Mann-Whitney U test was used for between-group comparisons, and Student t test was used for intragroup comparisons. The statistical significance was set at P < .05. A total of 65 patients underwent oral cancer surgery with a duration over 6 hours during the study period. The administration of 6% HES130/0.4 at 22.1 ± 7.5 mL/kg/day did not increase blood loss or the blood transfusion volume. Moreover, patients who were administered 6% HES130/0.4 had a significantly larger mean urine volume and infusion volume than those who were not administered 6% HES130/0.4. The infusion therapy could maintain the urine volume and did not worsen renal function. The results of this study showed that administration of 6% HES130/0.4 at a dose lower than 25 mL/kg in patients undergoing oral cancer surgery over 6 hours was effective for circulation maintenance but did not increase the intraoperative blood loss or transfusion volume. This treatment did not cause any dilutional metabolic acidosis or renal dysfunction.

Characterization of Combined Blast- and Fragment-Induced Pelvic Injuries and Hemostatic Resuscitation in Rabbits.

INTRODUCTION: To establish a blast- and fragment-induced pelvic injury animal model in rabbits, observe its injury characteristics, and explore the effects of hemostatic resuscitation combined with damage control surgery (DCS) with respect to this injury model. METHODS: Forty-eight rabbits were randomly allocated to four groups: group A rabbits were subjected to pelvic injury, group B rabbits to pelvic injury + DCS, group C rabbits to pelvic injury + DCS + resuscitation with Hextend, and group D rabbits to pelvic injury + DCS + Hextend + hemostatic resuscitation with tranexamic acid, fibrinogen concentrate, and prothrombin complex concentrate. Simulated blast and fragment-induced pelvic injury was produced by a custom-made machine. We implemented CT scanning and necropsy to assess the injury state and calculated the coefficient of variation (CV) of the cumulative abbreviated injury scale (AIS) to assess the reproducibility of the animal model. Immediately after instrumentation (0 h), and 1 h, 2 h, 4 h, and 8 h after injury, blood samples were taken for laboratory tests. RESULTS: We found that severe pelvic injury was produced with an AIS CV value of 10.32%, and the rabbits demonstrated severe physiologic impairment and coagulo-fibrinolytic derangements with high mortality. In rabbits of group D, however, physiologic and coagulo-fibrinolytic parameters were significantly enhanced with improved organ function and lowered mortality when compared with the other three groups. CONCLUSIONS: We herein established in rabbits a blast- and fragment-induced pelvic injury animal model that exhibited high reproducibility, and we demonstrated that hemostatic resuscitation plus DCS was effective in improving the outcome.

The effect of tetrastarch on the endothelial glycocalyx layer in early hemorrhagic shock using fluorescence intravital microscopy: a mouse model.

PURPOSE: To investigate vascular endothelial dysfunction based on glycocalyx impairment in massive hemorrhage and to evaluate fluid therapy. METHODS: In this randomized controlled animal study, we withdrew 1.5 mL blood and administered 1.5 mL resuscitation fluid. Mice were divided into six groups according to the infusion type and administration timing: NS-NS (normal saline), NS-HES ([hydroxyethyl starch]130), HES-NS, NS-ALB (albumin), ALB-NS, and C (control) groups. RESULTS: The glycocalyx index (GCXI) of a 40-µm artery was significantly larger in group C than in other groups (P < 0.01). Similarly, the GCXI for a 60-µm artery was significantly higher in group C than in NS-NS (P ≤ 0.05), NS-HES (P ≤ 0.01), and NS-ALB groups (P ≤ 0.05). The plasma syndecan-1 concentration, at 7.70 ± 5.71 ng/mL, was significantly lower in group C than in group NS-NS (P ≤ 0.01). The tetramethylrhodamine-labeled dextran (TMR-DEX40) fluorescence intensity in ALB-NS and HES-NS groups and the fluorescein isothiocyanate-labeled hydroxyethyl starch (FITC-HES130) fluorescence intensity in NS-HES and HES-NS groups were not significantly different from those of group C at any time point. FITC-HES130 was localized on the inner vessel wall in groups without HES130 infusion but uniformly distributed in HES130-treated groups in intravital microscopy. FITC-FITC-HES130 was localized remarkably in the inner vessel walls in group HES-NS in electron microscopy. CONCLUSIONS: In an acute massive hemorrhage mouse model, initial fluid resuscitation therapy with saline administration impaired glycocalyx and increased vascular permeability. Prior colloid-fluid administration prevented the progression of glycocalyx damage and improve prognosis. Prior HES130 administration may protect endothelial cell function.

Manipulation of Nitric Oxide Levels via a Modified Hydroxyethyl Starch Molecule.

INTRODUCTION: Although the improving effect of nitric oxide (NO) donors has experimentally been demonstrated in shock, there are still no NO donor medications clinically available. Thiol-nitrosothiol-hydroxyethyl starch (S-NO-HES) is a novel molecule consisting of NO coupled to a thiolated derivative of hydroxyethyl starch (HES). It was aimed to assess the ability of S-NO-HES to serve as an NO donor under a variety of in vitro simulated physiologic conditions, which might be the first step to qualify this molecule as a novel type of NO donor-fluid. METHODS: We studied the effect of temperature on NO-releasing properties of S-NO-HES in blood, at 34°C, 37°C, and 41°C. Ascorbic acid (Asc) and amylase were also tested in a medium environment. In addition, we evaluated the activity of S-NO-HES in the isolated aortic ring and Langendorff-perfused heart setup. RESULTS: The NO release property of S-NO-HES was found at any temperature. Asc led to a significant increase in the production of NO compared to S-NO-HES incubation (P < 0.05). The addition of amylase together with Asc to the medium further increased the release of NO (P < 0.05). S-NO-HES exerted significant vasodilatory effects on phenylephrine precontracted aortic rings that were dose-dependent (P < 0.01). Furthermore, S-NO-HES significantly increased the heart rate and additionally reduced the duration of the cardiac action potential, as indicated by a reduction of QTc-B values (P < 0.01). CONCLUSIONS: We demonstrated for the first time that the S-NO-HES molecule exhibited its NO-releasing effects. The effectiveness of this new NO donor to substitute NO deficiency under septic conditions or in other indications needs to be studied.

Impact of colloids or crystalloids in renal function assessed by NGAL and KIM-1 after hysterectomy: randomized controlled trial

Abstract Background Hydroxyethyl starches are colloids used in fluid therapy that may reduce volume infusion compared with crystalloids, but they can affect renal function in critical care patients. This study aims to assess renal effects of starches using renal biomarkers in the perioperative setting. Methods This prospective, controlled, randomized study compared Hydroxyethyl starch 6% (HES) with Ringer's lactate (RL) in hysterectomy. Each episode of mean arterial pressure (MAP) below 60 mmHg guided the fluid replacement protocol. The RL group received 300 mL bolus of RL solution while the HES group received 150 mL of HES solution. All patients received RL (2 mL.kg−1.h−1) intraoperatively to replace insensible losses. Blood and urine samples were collected at three time points (preoperatively, 24 hours, and 40 days postoperatively) to assess urinary NGAL and KIM-1, as primary outcome, and other markers of renal function. Results Seventy patients were randomized and 60 completed the study. The RL group received a higher crystalloid volume (1,277 ± 812.7 mL vs. 630.4 ± 310.2 mL; p= 0.0002) with a higher fluid balance (780 ± 720 mL vs. 430 ± 440 mL; p= 0.03) and fluid overload (11.7% ± 10.4% vs. 7.0% ± 6.3%; p= 0.04) compared to the HES group. NGAL and KIM-1 did not differ between groups at each time point, however both biomarkers increased 24 hours postoperatively and returned to preoperative levels after 40 days in both groups. Conclusion HES did not increase renal biomarkers following open hysterectomy compared to RL. Moreover, HES provided better hemodynamic parameters using less volume, and reduced postoperative fluid balance and fluid overload.

Hetastarch induced volume changes of starving adenoma and suggested mechanism of action.

Submucosal injection is often required step during endoscopic mucosal resection (EMR). In clinical practice we have observed that the EMR injection solution containing hetastarch (HES) lead to selective increase of the neoplasms volume, facilitating their resection. The aim of this study was to explore the possible mechanisms of such behaviour, which was not reported elsewhere. The HCT116 cell line of human colon cancer was exposed to the same EMR solution in vitro. The significant volume increase of HCT116 cells was observed, but only for starving cell culture, suggesting that the starving is essential for the neoplasms-specific volume change. We suggest, that for the iso-oncotic composition of the EMR submucosa injection solution the HES component is crucial, as it can be subject of the starch hydrolysis followed by facilitated transport of resulting monosaccharides from the submucosa into the neoplastic tissue.

Measurement of solution properties and molecular weight of hydroxyethyl starches using multi-angle laser light scattering: An interlaboratory comparison.

The solution properties of hydroxyethyl starch (HES) vary significantly owing to different measurement parameters adopted and sample structures. Here, a round-robin study was conducted to compare inter-laboratory measurements of solution properties, weight-average molecular weight (Mw), and molecular weight distribution of four HES candidates covering the low- and medium-molecular-weight range, and 50 commercially available HES 130/0.4 drug samples. Analysis was performed using size exclusion chromatography (SEC) combined with multi-angle laser light scattering (MALLS) and differential refractive index (dRI) detectors. The results indicate that HES molecules in the Mw range of 17,000-130,000, with varying degrees of substitution (between 0.4 and 0.8), yielded a refractive index increment (dn/dc) value of 0.145 ± 0.003 mL/g (solvent: acetic acid-sodium acetate buffer; wavelength: 658 nm) and that the second virial coefficient (A2) is correlated with Mw. The SEC-MALLS-dRI method for Mw determination of HES demonstrated good inter-laboratory reproducibility; however, the study findings suggest that column specifications should be added for HES quality standards. Comparing Mw results obtained using common and experimentally corrected dn/dc and A2 values revealed an influence of dn/dc and A2 on Mw, indicating that the Mw acceptance criteria of HES quality standards should be adjusted.

Effects of Different Types of Early Restrictive Fluid Resuscitation on Immune Function and Multiorgan Damage on Hemorrhagic Shock Rat Model in a Hypothermic Environment.

Objective: This study was aimed at investigating the effects of different types of fluid restriction fluid resuscitation on the immune dysfunction and organ injury of hemorrhagic shock rats under a hypothermic environment. Methods: SD rats were divided into sham operation group (SHAM), hemorrhagic shock model group (HS), crystal liquid limited resuscitation group (CRLLR), colloidal liquid limited resuscitation group (COLLR), and nonlimited resuscitation group (NLR); rats in each group were placed in a low-temperature environment of 0-5°C for 30 min, and then, a hemorrhagic shock rat model was prepared. Sodium lactate Ringer's restricted resuscitation solution, hydroxyethyl starch restricted resuscitation solution, and hydroxyethyl starch were used for resuscitation, and hemodynamic examination was performed. The mortality rate, inflammatory factors, oxidative stress factors, and immune function were detected by ELISA. The dysfunction and injury of the intestinal, lung, liver, and kidney were examined by histological methods. Results: Hemorrhagic shock resulted in decreased immune function and activation of inflammation. Unrestricted fluid infusion further activated the inflammatory response. The crystalloid-restricted fluid infusion performed effectively to regulate inflammatory response, promote antioxidative activity, and reduce the immunosuppressive reaction. Rehydration could regulate the coagulation. The hydroxyethyl starch reduced the expression of platelet glycoproteins Ib and IIb/IIIa and blocked the binding of fibrinogen to activated platelets, thereby inhibiting intrinsic coagulation and platelet adhesion and aggregation. Rats in the CRLLR group showed to relieve the injury of the lung, liver, kidney, and intestine from hemorrhagic shock in low-temperature environment. Conclusion: The early application of restrictive crystalloid resuscitation in hemorrhagic shock rats in hypothermic environment showed the best therapy results. Early LR-restrictive fluid replacement promotes the balance of inflammatory response and the recovery of immunosuppressive state, resists oxidative stress, stabilizes the balance of coagulation and fibrinolysis, improves coagulation function, and relieves organ injury.