Hydroxyethyl Starch Research Articles

The effect of 6% hydroxyethyl starch 130/0.4 preloading on the blood glucose levels in diabetic patients undergoing orthopedic surgery with spinal anesthesia: a randomized pilot study.

Perioperative hyperglycemia can occur in surgical patients and may increase postoperative morbidity and mortality, especially in patients with diabetes. Therefore, we conducted the present study to evaluate whether the administration of 6% hydroxyethyl starch (HES)-130/0.4 increases blood glucose levels in patients with diabetes. Forty patients undergoing lower limb surgery under spinal anesthesia were randomly allocated into two groups according to the fluids administered 20 min before spinal anesthesia (Group L, lactated Ringer's solution; Group H, 6% HES-130/0.4). Patient characteristics, intraoperative variables, blood glucose levels, mean blood pressure (MBP), and heart rate (HR) were recorded at five time-points (0, 20, 60, 120, and 240 min). A total of 39 patients were analyzed (Group L, n = 20; Group H, n = 19). The amount of intraoperative fluid was significantly higher in Group L than in Group H (718.2 ml vs. 530.0 ml, P = 0.010). There were no significant differences in the changes in blood glucose levels, HR, or MBP between the two groups (P = 0.737, P = 0.896, and P = 0.141, respectively). Serial changes in mean blood glucose levels from baseline also showed no significant differences between the groups (P = 0.764). There were no significant changes in blood glucose levels when lactated Ringer's solution or 6% HES-130 was used. When compared to the lactated Ringer's solution, no evidence that 6% HES-130/0.4 produces hyperglycemia in diabetic patients could be found. Further evaluation of larger populations is needed.

Hyperbaric Oxygen Activates Enzyme-Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination.

Tumor starvation induced by intratumor glucose depletion emerges as a promising strategy for anticancer therapy. However, its antitumor potencies are severely compromised by intrinsic tumor hypoxia, low delivery efficiencies, and undesired off-target toxicity. Herein, a multifunctional cascade bioreactor (HCG), based on the self-assembly of pH-responsive hydroxyethyl starch prodrugs, copper ions, and glucose oxidase (GOD), is engineered, empowered by hyperbaric oxygen (HBO) for efficient cooperative therapy against aggressive breast cancers. Once internalized by tumor cells, HCG undergoes disassembly and releases cargoes in response to acidic tumor microenvironment. Subsequently, HBO activates GOD-catalyzed oxidation of glucose to H2 O2 and gluconic acid by ameliorating tumor hypoxia, fueling copper-catalyzed •OH generation and pH-responsive drug release. Meanwhile, HBO degrades dense tumor extracellular matrix, promoting tumor accumulation and penetration of HCG. Moreover, along with the consumption of glucose and the redox reaction of copper ions, the antioxidant capacity of tumor cells is markedly reduced, collectively boosting oxidative stress. As a result, the combination of HCG and HBO can not only remarkably suppress the growth of orthotopic breast tumors but also restrain pulmonary metastases by inhibiting cancer stem cells. Considering the clinical accessibility of HBO, this combined strategy holds significant translational potentials for GOD-based therapies.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Optimizing of the isolation of hematopoietic stem cell in bone marrow transplantation in children

Most of collected hematopoietic stem cell (HSCs) products need processing in order to isolate stem cells, squeeze out of plasma and erythrocytes. There are two main aims for bone marrow (BM) enrichment: reduction of immunogenicity of AB0 incompatible transplants and/or preventing toxicity of hemolysis during cryopreservation. In our center we have implemented two methods for BM enrichment: manual technic using 10 % HAES (hydroxyethyl starch) and automatic cell separator. In order to optimize the process, we examined retrospectively the parameters which could have a great impact on final efficiency of engraftment, such as reduction of hematocrit, CD34 + , WBC recovery and cell viability. This study was a retrospective analysis of 46 pediatric patients (pts) who underwent autologous or allogeneic HSCT. There were performed 27 procedures using cell separator and 19 with HAES technique. This study showed that cell separator processing is significantly less damaging for stem cells than widely longer, manual HAES technique. Comparing RBC depletion and WBC recovery both used techniques are same efficient and good enough but we found out a significant difference in the efficiency of CD34 + recovery which was much higher in a technique of cell separator. We examined also the effect of addition of packed red blood cells (PRBCs) to the BM on purifying and efficiency of HSCs isolation. Doing so it decreased only the WBC recovery during sell separator processing. To sum up after series of analyzes we found out that cell separator is more convenient than HAES technique in most of considered aspects. Furthermore, cell separator use is cheaper and needs less time for processing.

Submucosal tunneling endoscopic resection for rectal gastrointestinal stromal tumor.

A 60-year-old man was referred for evaluation of a rectal submucosal tumor located 5 cm proximal to the anus ([Video 1, ] [Fig. 1]). Endoscopic ultrasonography revealed a 3-cm hypoechoic lesion originating from the muscular layer. The patient underwent submucosal tunneling endoscopic resection (STER) under sedation with propofol for diagnosis and treatment ([Fig. 2]). A small horizontal incision was made at the anus and a submucosal pocket was created with injection of a mixture of hydroxyethyl starch and indigo carmine into the submucosal layer (GIF 190TH1; Olympus, Tokyo, Japan; and Flush Knife BTs 1.5 mm, FujiFilm, Tokyo, Japan). The tip of the tumor was enucleated ([Fig. 3]), and then the intramuscular portion of the tumor was dissected with a square-tip knife (Square Knife; Endoaccess, Garbsen, Germany) using spray coagulation (VIO 3; Erbe, Tübingen, Germany). Dissection was advanced up to the level of the perirectal fat, while paying attention to avoid damage to the tumor capsule. The tumor was removed en bloc ([Fig. 4]) and the mucosal entrance was closed with two clips. The procedure lasted for 1 hour. The patient was hospitalized for 1 night, received oral amoxicillin/clavulanic acid for 5 days, and had an uneventful recovery. Histology showed a benign gastrointestinal stromal tumor ([Fig. 4]). STER is mainly applied in the stomach and esophagus [1]. This case report demonstrates the feasibility of this technique in the rectum.

Effectiveness of 2‐dimensional shear wave elastography for noninvasive and reliable estimation of right atrial pressure in dogs with induced volume overload

Two-dimensional shear wave elastography (2D-SWE) provides information on hepatic elastic modulus as shear wave velocity (SWV). To assess SWV using 2D-SWE in dogs with induced volume overload, investigate the relationship between this information and right atrial pressure (RAP) measured by invasive right heart catheterization, and also evaluate the difference in SWV before and after diuretic administration. Six healthy beagles. Prospective experimental study. Right heart catheterization and 2D-SWE were performed in 6 anesthetized beagles at baseline and after the induction of volume overload. Volume overload was induced by IV hydroxyethyl starch 70/0.5 infusion (100 mL/kg/h). Furosemide (4-6 mg/kg, IV) was administered, and the SWVs were measured. Shear wave velocity showed a significant gradual increase during acute volume overload compared to baseline. SWV was significantly positively correlated with RAP (P < .0001, ρ = 0.9729). The area under the curve of SWV to predict RAP at >10, >15, and >20 mm Hg was 0.9896 (95% confidence interval [95% CI], 0.9690-1.000), 0.9907 (95% CI, 0.9701-1.000), and 0.9722 (95% CI, 0.9280-1.000), respectively. The SWV after diuretic use decreased significantly. Two-dimensional shear wave elastography might be useful for noninvasive and reliable estimation of RAP in dogs with acute volume overload and has potential as a quantitative biomarker for evaluating therapeutic response in dogs with right sided congestive heart failure.

Dimethylglycine Can Enhance the Cryopreservation of Red Blood Cells by Reducing Ice Formation and Oxidative Damage

The cryopreservation of red blood cells (RBCs) holds great potential for ensuring timely blood transfusions and maintaining an adequate RBC inventory. The conventional cryoprotectants (CPAs) have a lot of limitations, and there is an obvious need for novel, efficient, and biocompatible CPAs. Here, it is shown for the first time that the addition of dimethylglycine (DMG) improved the thawed RBC recovery from 11.55 ± 1.40% to 72.15 ± 1.22%. We found that DMG could reduce the mechanical damage by inhibiting ice formation and recrystallization during cryopreservation. DMG can also scavenge reactive oxygen species (ROS) and maintain endogenous antioxidant enzyme activities to decrease oxidative damage during cryopreservation. Furthermore, the properties of thawed RBCs were found to be similar to the fresh RBCs in the control. Finally, the technique for order performance by similarity to ideal solution (TOPSIS) was used to compare the performance of glycerol (Gly), hydroxyethyl starch (HES), and DMG in cryopreservation, and DMG exhibited the best efficiency. This work confirms the use of DMG as a novel CPA for cryopreservation of RBCs and may promote clinical transfusion therapy.

TCTAP A-059 Comparison of Contrast Media Versus Hydroxyethyl Starch for Frequency-Domain Optical Coherence Tomography Imaging in Coronary Artery Disease

TCTAP A-059 Comparison of Contrast Media Versus Hydroxyethyl Starch for Frequency-Domain Optical Coherence Tomography Imaging in Coronary Artery Disease

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 copper‑oxygen 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.

Combined therapy with methotrexate nanoconjugate and dendritic cells with downregulated IL-10R expression modulates the tumor microenvironment and enhances the systemic anti-tumor immune response in MC38 murine colon carcinoma.

Understanding the negative impact of the tumor microenvironment on the creation of an effective immune response has contributed to the development of new therapeutic anti-cancer strategies. One such solution is combined therapy consisting of chemotherapeutic administration followed by dendritic cell (DC)-based vaccines. The use of cytostatic leads to the elimination of cancer cells, but can also modulate the tumor milieu. Moreover, great efforts are being made to increase the therapeutic outcome of immunotherapy, e.g. by enhancing the ability of DCs to generate an efficient immune response, even in the presence of immunosuppressive cytokines such as IL-10. The study aimed to determine the effectiveness of combined therapy with chemotherapeutic with immunomodulatory potential - HES-MTX nanoconjugate (composed of methotrexate (MTX) and hydroxyethyl starch (HES)) and DCs with downregulated expression of IL-10 receptor stimulated with tumor antigens (DC/shIL-10R/TAg) applied in MC38 murine colon carcinoma model. With the use of lentiviral vectors the DCs with decreased expression of IL-10R were obtained and characterized. During in vivo studies MC38-tumor bearing mice received MTX or HES-MTX nanoconjugate as a sole treatment or combined with DC-based immunotherapy containing unmodified DCs or DCs transduced with shRNA against IL-10R (or control shRNA sequence). Tumor volume was monitored during the experiment. One week after the last injection of DC-based vaccines, tumor nodules and spleens were dissected for ex vivo analysis. The changes in the local and systemic anti-tumor immune response were estimated with the use of flow cytometry and ELISA methods. In vitro studies showed that the downregulation of IL-10R expression in DCs enhances their ability to activate the specific anti-tumor immune response. The use of HES-MTX nanoconjugate and DC/shIL-10R/TAg in the therapy of MC38-tumor bearing mice resulted in the greatest tumor growth inhibition. At the local anti-tumor immune response level a decrease in the infiltration of cells with suppressor activity and an increase in the influx of effector cells into MC38 tumor tissue was observed. These changes were crucial to enhance the effective specific immune response at the systemic level, which was revealed in the greatest cytotoxic activity of spleen cells against MC38 cells.

Hydroxyethyl Starch-Bovine Hemoglobin Conjugate as an Effective Oxygen Carrier with the Ability to Expand Plasma.

Hemorrhagic shock leads to intravasal volume deficiency, tissue hypoxia, and cellular anaerobic metabolism. Hemoglobin (Hb) could deliver oxygen for hypoxic tissues but is unable to expand plasma. Hydroxyethyl starch (HES) could compensate for the intravasal volume deficiency but cannot deliver oxygen. Thus, bovine Hb (bHb) was conjugated with HES (130 kDa and 200 kDa) to develop an oxygen carrier with the ability to expand plasma. Conjugation with HES increased the hydrodynamic volume, colloidal osmotic pressure, and viscosity of bHb. It slightly perturbed the quaternary structure and heme environment of bHb. The partial oxygen pressures at 50% saturation (P 50) of the two conjugates (bHb-HES130 and bHb-HES200) were 15.1 and 13.9 mmHg, respectively. The two conjugates showed no apparent side effects on the morphology and rigidity, hemolysis, and platelet aggregation of red blood cells of Wistar rats. Thus, bHb-HES130 and bHb-HES200 were expected to function as an effective oxygen carrier with the ability to expand plasma.

Preparation of temperature-pH dual-responsive hydrogel from hydroxyethyl starch for drug delivery

Preparation of temperature-pH dual-responsive hydrogel from hydroxyethyl starch for drug delivery

Diselenide-triggered hydroxyethyl starch conjugate nanoparticles with cascade drug release properties for potentiating chemo-photodynamic therapy

A novel type of diselenide bond-bridged hydroxyethyl starch-doxorubicin conjugate, HES-SeSe-DOX, was synthesized via a specially designed multistep synthetic route. The optimally achieved HES-SeSe-DOX was further combined with photosensitizer, chlorin E6 (Ce6), to self-assemble into HES-SeSe-DOX/Ce6 nanoparticles (NPs) for potentiating chemo-photodynamic anti-tumor therapy via diselenide-triggered cascade actions. HES-SeSe-DOX/Ce6 NPs were observed to disintegrate through the cleavage or oxidation of diselenide-bridged linkages in response to the stimuli arising from glutathione (GSH), hydrogen peroxide and Ce6-induced singlet oxygen, respectively, as evidenced by the enlarged size with irregular shapes and cascade drug release. In vitro cell studies exhibited that HES-SeSe-DOX/Ce6 NPs in combination with laser irradiation effectively consumed intracellular GSH and promoted a large rise in levels of reactive oxygen species in tumor cells, actuating the disruption of intracellular redox balance and the enhanced chemo-photodynamic cytotoxicity against tumor cells. The in vivo investigations revealed that HES-SeSe-DOX/Ce6 NPs were inclined to accumulate in tumors with persistent fluorescence emission, inhibited tumor growth with high efficacy and had good safety. These findings demonstrate the potential of HES-SeSe-DOX/Ce6 NPs for use in chemo-photodynamic tumor therapy and suggest their viability for clinical translation.

Combining targeted chemotherapy of hydroxyethyl starch prodrug and photothermal therapy of MoS2 for treatment of bladder cancer

Combining targeted chemotherapy of hydroxyethyl starch prodrug and photothermal therapy of MoS2 for treatment of bladder cancer

Hydroxyethyl starch solution for infusion: risk of kidney injury, reminder of risk minimisation measures

Hydroxyethyl starch solution for infusion: risk of kidney injury, reminder of risk minimisation measures

Novel amphiphilic hydroxyethyl starch-based nanoparticles loading camptothecin exhibit high anticancer activity in HepG2 cells and zebrafish

Camptothecin is a naturally occurred anticancer drug but exhibits limitations including poor aqueous solubility, low bioavailability, and high level of adverse drug reactions on normal organs. To overcome these problems, this paper developed a novel amphiphilic Lau-Leu-HES carrier using hydroxyethyl starch, lauric acid, and L-leucine as starting materials. The carrier was successfully applied to prepare Lau-Leu-HES nanoparticles loading camptothecin. The drug loading efficiency and encapsulation efficiency of the nanoparticles were calculated to be 29.04% and 81.85%, respectively. The nanoparticles exhibited high zeta potential (–15.51 mV) and small hydrodynamic diameter (105.4 nm). Camptothecin in nanoparticles could be rapidly released under acidic condition (pH = 4.5), thereby indicating the high sensitivity under cancer microenvironments. Anticancer investigation revealed that the nanoparticles could inhibit the proliferation of HepG2 cells in vitro. Compared with commercial available drug doxorubicin, the nanoparticles could significantly inhibit the expression of krasv12 oncogene in transgenic Tg (EGFP-krasV12) zebrafish. These results indicate that the camptothecin-loaded Lau-Leu-HES nanoparticles are expected to be a potential candidate for cancer therapy.

Impact of Vasodilation on Oxygen-Enhanced Functional Lung MRI at 0.55 T.

Oxygen-enhanced magnetic resonance imaging (OE-MRI) can be used to assess regional lung function without ionizing radiation. Inhaled oxygen acts as a T1-shortening contrast agent to increase signal in T1-weighted (T1w) images. However, increase in proton density from pulmonary hyperoxic vasodilation may also contribute to the measured signal enhancement. Our aim was to quantify the relative contributions of the T1-shortening and vasodilatory effects of oxygen to signal enhancement in OE-MRI in both swine and healthy volunteers. We imaged 14 anesthetized female swine (47 ± 8 kg) using a prototype 0.55 T high-performance MRI system while experimentally manipulating oxygenation and blood volume independently through oxygen titration, partial occlusion of the vena cava for volume reduction, and infusion of colloid fluid (6% hydroxyethyl starch) for volume increase. Ten healthy volunteers were imaged before, during, and after hyperoxia. Two proton density-weighted (PDw) and 2 T1w ultrashort echo time images were acquired per experimental state. The median PDw and T1w percent signal enhancement (PSE), compared with baseline room air, was calculated after image registration and correction for lung volume changes. Differences in median PSE were compared using Wilcoxon signed rank test. The PSE in PDw images after 100% oxygen was similar in swine (1.66% ± 1.41%, P = 0.01) and in healthy volunteers (1.99% ± 1.79%, P = 0.02), indicating that oxygen-induced pulmonary vasodilation causes ~2% lung proton density increase. The PSE in T1w images after 100% oxygen was also similar (swine, 9.20% ± 1.68%, P < 0.001; healthy volunteers, 10.10% ± 3.05%, P < 0.001). The PSE in T1w enhancement was oxygen dose-dependent in anesthetized swine, and we measured a dose-dependent PDw image signal increase from infused fluids. The contribution of oxygen-induced vasodilation to T1w OE-MRI signal was measurable using PDw imaging and was found to be ~2% in both anesthetized swine and in healthy volunteers. This finding may have implications for patients with regional or global hypoxia or vascular dysfunction undergoing OE-MRI and suggest that PDw imaging may be useful to account for oxygen-induced vasodilation in OE-MRI.

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.

Advanced Skin Antisepsis: Application of UVA-Cleavable Hydroxyethyl Starch Nanocapsules for Improved Eradication of Hair Follicle-Associated Microorganisms.

Hair follicles constitute important drug delivery targets for skin antisepsis since they contain ≈25% of the skin microbiome. Nanoparticles are known to penetrate deeply into hair follicles. By massaging the skin, the follicular penetration process is enhanced based on a ratchet effect. Subsequently, an intrafollicular drug release can be initiated by various trigger mechanisms. Here, we present novel ultraviolet A (UVA)-responsive nanocapsules (NCs) with a size between 400 and 600 nm containing hydroxyethyl starch (HES) functionalized by an o-nitrobenzyl linker. A phase transfer into phosphate-buffered saline (PBS) and ethanol was carried out, during which an aggregation of the particles was observed by means of dynamic light scattering (DLS). The highest stabilization for the target medium ethanol as well as UVA-dependent release of ethanol from the HES-NCs was achieved by adding 0.1% betaine monohydrate. Furthermore, sufficient cytocompatibility of the HES-NCs was demonstrated. On ex vivo porcine ear skin, a strong UVA-induced release of the model drug sulforhodamine 101 (SR101) could be demonstrated after application of the NCs in cyclohexane using laser scanning microscopy. In a final experiment, a microbial reduction comparable to that of an ethanol control was demonstrated on ex vivo porcine ear skin using a novel UVA-LED lamp for triggering the release of ethanol from HES-NCs. Our study provides first indications that an advanced skin antisepsis based on the eradication of intrafollicular microorganisms could be achieved by the topical application of UVA-responsive NCs.

Precautions for use of hydroxyethyl starch revised in Japan

Precautions for use of hydroxyethyl starch revised in Japan