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Ferroptosis has emerged as a promising strategy for cancer treatment. Nevertheless, the efficiency of ferroptosis-mediated therapy remains a challenge due to high glutathione (GSH) levels and insufficient endogenous hydrogen peroxide in the tumor microenvironment. Herein, we presented a nitric-oxide (NO) boost-GSH depletion strategy for enhanced ferroptosis therapy through a multifunctional nanoplatform with near-infrared (NIR) triggered NO release. The nanoplatform, IS@ATF, was designed that self-assembled by loading the NO donor L-arginine (L-Arg), ferroptosis inducer sorafenib (SRF), and indocyanine green (ICG) onto tannic acid (TA)-Fe3+‒metal-phenolic networks (MPNs) modified with hydroxyethyl starch. Inside the tumor, SRF could inhibit GSH biosynthesis, impair the activation of glutathione peroxidase 4, and disrupt the ferroptosis defensive system. In conjunction with TA-Fe3+‒MPNs, which has cascaded Fenton catalytic activity, it could navigate the lethal ferroptosis to cancer cells. Upon NIR laser irradiation, the ICG-generated ROS oxidated L-Arg to a substantial quantity of NO, which further depleted the intracellular GSH and caused LPO accumulation, enhancing cell ferroptosis. Moreover, ICG also serves as a photothermal agent that can produce hyperthermia when exposed to irradiation, further potentiating ferroptosis therapy. In addition, the nanoplatform showed significantly improved tumor therapeutic efficacy and anti-metastasis efficiency. This work thus demonstrated that utilizing NO boost-GSH depletion to enhance ferroptosis induction is a feasible and promising strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Endothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES). Results: Male rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44–5.25] vs. 5.33 [5.06–6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41–4.75] vs. 4.51 [4.47–4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1–7] vs. 14 [12–16] vessels per recording, p = 0.008; HES: 4 [2–6] vs. 12 [10–13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1–9] vs. HES: 1 [0–4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0–5.0] mL vs. 9 [4.5–10.0], p < 0.001) and phenylephrine (20 [0–40] µg vs. 90 [40–200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1), glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13–25] vs. 33 [24–51] ng/mL, p = 0.006), interleukin-10 (434 [295–782] vs. 2120 [1309–3408] pg/ml, p < 0.0001), syndecan-1 (5 [3–7] vs. 15 [11–16] ng/mL, p < 0.001) and NGAL (555 [375–1078] vs. 2200 [835–3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES. Conclusion: CPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming. [ABSTRACT FROM AUTHOR]

OBJCETIVE: To systematically review the efficacy and safety of hydroxyethyl starch combined with atorvastatin in the treatment of elderly patients with cerebral watershed infarction. METHODS: Randomized controlled trials on the clinical efficacy and safety of hydroxyethyl starch combined with atorvastatin (observation group) versus atorvastatin alone (control group) in the treatment of elderly patients with cerebral watershed infarction based on basic treatment were retrieved from PubMed, CBM, CNKI, Wanfang Data and VIP databases (the retrieval time was from database establishment to Jan. 2024), RevMan 5. 3 statistical software was adopted to conduct Meta-analysis after data extraction and quality evaluation on the clinical researches that matched the inclusion criteria. RESULTS: A total of 18 RCT including 1 632 patients were enrolled. Meta-analysis indicated that the total effective rate (RR =1. 25, 95%CI = 1. 20-1. 31, P<0. 000 01), Barthel index (MD =10. 42, 95%CI =8. 93-11. 90, P<0. 000 01) and ADL score (MD = 12. 25, 95%CI =11. 02-13. 48, P<0. 000 01) of the observation group were significantly higher than those of the control group, the NIHSS score (MD = -3. 11, 95%CI = -3. 52--2. 70, P<0. 000 01) and incidence of three major adverse drug reactions (upper gastrointestinal hemorrhage, pulmonary infection and depression after cerebrovascular disease) were significantly lower than those of the control group (P<0. 000 01), the differences were statistically significant. CONCLUSIONS: The clinical efficacy and safety of hydroxyethyl starch combined with atorvastatin in the treatment of elderly patients with cerebral watershed infarction are better than atorvastatin alone. [ABSTRACT FROM AUTHOR]

Objective: To compare the ability of bioreactance noninvasive cardiac output (BR‐NICO) with thermodilution cardiac output (TDCO) for the measurement of cardiac output (CO) in healthy adult horses receiving 2 different IV volume replacement solutions. Design: Prospective randomized crossover study from September to November 2021. Setting: University teaching hospital. Animals: Six university‐owned adult horses. Interventions: Horses were randomly assigned to receive 7.2% hypertonic saline solution (HSS) or 6% hydroxyethyl starch (130/0.4) solution (HETA). BR‐NICO and TDCO were measured simultaneously at baseline, 10, 20, 30, 40, 50, 60, 90, and 120 minutes before fluid administration and again at the same times after starting a bolus infusion of IV volume replacers. All solutions were administered within 10 minutes. Measurements and Main Results: BR‐NICO and TDCO were strongly correlated (Pearson r2 = 0.93; P < 0.01). Regression analysis showed the relationship between TDCO and BR‐NICO was BR‐NICO = 0.48 × TDCO + 0.6. For the corrected BR‐NICO values, the Bland–Altman agreement mean bias and lower/upper limits of agreement were −0.62 and −5.3 to 3.9 L/min, respectively. Lin's concordance (95% confidence interval) between methods was 0.894 (0.825–1.097). Compared with baseline, HSS increased the CO at 10 and 20 minutes (TDCO and BR‐NICO). Compared with baseline, HETA decreased the CO at 10 and 20 minutes (TDCO and BR‐NICO) and increased the CO at 90 (TDCO only) and 120 minutes (TDCO and BR‐NICO). Conclusions: BR‐NICO strongly agreed with TDCO in the measurement of CO in healthy unsedated adult horses. HSS administration significantly increased CO in the first 30 minutes, while HETA initially decreased CO at 10 minutes but increased CO to above baseline values by 90 minutes. [ABSTRACT FROM AUTHOR]

Microbioreactors increase information output in biopharmaceutical screening applications because they can be operated in parallel without consuming large quantities of the pharmaceutical formulations being tested. A capillary wave microbioreactor (cwMBR) has recently been reported, allowing cost-efficient parallelization in an array that can be activated for mixing as a whole. Although impedance spectroscopy can directly distinguish between dead and viable cells, the monitoring of cells in suspension within bioreactors is challenging because the signal is influenced by the potentially varying properties of the culture medium. In order to address this challenge, an impedance sensor consisting of two sets of microelectrodes in a cwMBR is presented. Only one set of electrodes was covered by a two-photon cross-linked hydrogel to become insensitive to the influence of cells while remaining sensitive to the culture medium. With this impedance sensor, the biomass of Saccharomyces cerevisiae could be measured in a range from 1 to 20 g L−1. In addition, the sensor can compensate for a change in the conductivity of the suspension of 5 to 15 mS cm−1. Moreover, the two-photon cross-linking of hydroxyethyl starch methacrylate hydrogel, which has been studied in detail, recommends itself for even much broader sensing applications in miniaturized bioreactors and biosensors. [ABSTRACT FROM AUTHOR]

Han Luo,1,&ast; Xiaofei Wang,1,&ast; Mengqi Fang,1 Huifan Yu,1 Lili Gui,1 Zhengkun Wu,1 Jianyong Sheng,2 Fei Li1 1Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Hubei University of Medicine, 30 Renmin South Road, Shiyan, Hubei, 442000, People’s Republic of China, Email piaopodexinlifei@163.comIntroduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1± 16.8 nm, zeta potential of about − 23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.Keywords: Hydroxyethyl starch, nanocrystals, stabilizer, luteolin, oral bioavailability, anti-hyperuricemia

Background: Respiratory variations in arterial pulse pressure (APP) are accurate predictors of fluid responsiveness in mechanically ventilated patients. Aim and Objective: To evaluate the ability of SVV obtained by the vigileo-flo trac device to predict fluid responsiveness in mechanically ventilated patients and to correlate it to the calculated ivc distensibility index. Method and material: We conducted a prospective study on 36 septic shock patients. SVV, PPV, and other hemodynamic data were recorded before and after the fluid administration of 500 ml of 6% hydroxyethyl starch. Responders were defined as patients with an increase in stroke volume index of at least 15% after fluid loading. Results: The correlation between baseline SVV and PPV was strong (P < 0.001). Twenty (55.56%) patients were classified as responders to fluid administration. The hemodynamic variables in responders and nonresponders are shown in Table 2. Volume infusion produced an increase in MAP, CVP, SVI, CI, and DO2I. In contrast, the intravenous fluid significantly decreased HR, SVRI, SVV, and PPV. Both baseline SVV and PPV were significantly higher in responders than in nonresponders, 14.75±1.37 vs. 8.4±0.72% and 16.7±2.23 vs. 8.7±0.8, respectively (P < 0.013 for both). Conclusion: In patients in passively ventilated septic shock with a regular cardiac rhythm and a tidal volume of at least 8 ml kg-1, the SVV, obtained by FloTrac/Vigileo, and the automated PPV, obtained by the IntelliVue MP monitor, performed similarly well in terms of anticipating fluid responsiveness. [ABSTRACT FROM AUTHOR]

This paper presents an experimental study on preparation of tramadol hydrochloride (TrH) loaded nanoparticles, and stability determination in various infusion solutions. In this study, various nanoparticle preparation parameters based on w/o/w emulsification solvent evaporation method, including stabilizer type, stabilizer concentration, polymer concentration, homogenization speed and initial drug amount were systematically tested to verify their versatility for preparing nanoparticles. Initially both particle size and encapsulation efficiency of nanoparticles were changed significantly with the change in surfactant and polymer ratio (p<0.05). However, homogenization speed only changed particle size (average size 339.3±1.8 nm for 15000 rpm, 318.9±6.4 nm for 20000 rpm and 237.2±7.8 nm for 25000 rpm) (p<0.05) and initial drug concentration is only affected the encapsulation efficiency (34.2±0.7% for 4 mg/mL and 33.2±0.9 for 1.6 mg/mL) (p<0.05). Storage at room temperature for 3 months resulted in an increase in particle size and polydispersity index. Prepared nanoparticles showed the best stability after storage at – 20 °C for in 3 months. Finally, storage of nanoparticles in various infusion solutions resulted an undesirable changes for 6% Hydroxyethyl starch in 0.9% sodium chloride injection, 10% Dextran 40 and 4% Succinyl gelatin solutions. It was shown that an appropriate delivery of TrH loaded PLGA nanoparticles as infusion can be prepared only in water for injection, 20% Mannitol, 0.9% Sodium chloride and 5% Dextrose solutions. [ABSTRACT FROM AUTHOR]

In this work, for the first time, the specific impedances of various injection solutions as well as the surface and tissue impedance after injection of these solutions were analyzed and compared regarding the radio-frequency surgical cutting process. The impedances of 0.9% NaCl, 4% gelatine, 6% hydroxyethyl starch, 10% glycerol/5% fructose, 10% glucose, 5% and 20% albumin, blood, and blood plasma as well as aqua destillata have been tested in vitro. Even if EMR and ESD are routinely used in clinical practice, there is so far no easy, fast, and safe method to remove larger lesions en bloc. We show that the impedance of the injected solution shows to be a crucial factor for safe removal, especially of larger lesions (Ø > 20 mm) and more importantly in accordance with the requirements of oncology and pathology. Key messages: Impedance is playing a crucial factor in the radio-frequency (RF)-surgery. With a higher Impedance there will be less current necessary to reach the aimed voltage. Injection solution Aqua destillata and 10% Glucose, show significantly higher Impedances. Higher impedances lead to less surgical related complications. Minor changes in existing method to improve patent safety. [ABSTRACT FROM AUTHOR]

Background: The outcome of patients undergoing major surgery treated with HES for hemodynamic optimization is unclear. This post-hoc analysis of a randomized clinical pilot trial investigated the impact of low-molecular balanced HES solutions on the coagulation system, blood loss and transfusion requirements. Methods: The Trial was registered: EudraCT 2008-004175-22 and ethical approval was provided by the ethics committee of Berlin. Patients were randomized into three groups receiving either a 10% HES 130/0.42 solution, a 6% HES 130/0.42 solution or a crystalloid following a goal-directed hemodynamic algorithm. Endpoints were parameters of standard and viscoelastic coagulation laboratory, blood loss and transfusion requirements at baseline, at the end of surgery (EOS) and the first postoperative day (POD 1). Results: Fifty-two patients were included in the analysis (HES 10% (n = 15), HES 6% (n = 17) and crystalloid (n = 20)). Fibrinogen decreased in all groups at EOS (HES 10% 338 [298;378] to 192 [163;234] mg dl-1, p<0.01, HES 6% 385 [302;442] to 174 [163;224] mg dl-1, p<0.01, crystalloids 408 [325;458] to 313 [248;370] mg dl-1, p = 0.01). MCF FIBTEM was decreased for both HES groups at EOS (HES 10%: 20.5 [16.0;24.8] to 6.5 [5.0;10.8] mm, p = <0.01; HES 6% 27.0 [18.8;35.2] to 7.0 [5.0;19.0] mm, p = <0.01). These changes did not persist on POD 1 for HES 10% (rise to 16.0 [13.0;24.0] mm, p = 0.88). Blood loss was not different in the groups nor transfusion requirements. Conclusion: Our data suggest a stronger but transient effect of balanced, low-molecular HES on the coagulation system. Despite the decline of the use of artificial colloids in clinical practice, these results may help to inform clinicians who use HES solutions. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary bypass (CPB) can adversely affect coagulation and systemic inflammatory response. Given that the optimal strategy for priming CPB in cardiac surgery remains a matter of debate, this study aimed to investigate the effects of albumin 20% and hydroxyethyl starch 6% as priming solutions on bleeding and interleukin-6 (IL-6) levels during CPB. Methods: This randomized clinical trial involved 40 patients undergoing coronary artery bypass surgery at Shahid Chamran Hospital between July 2021 and July 2022. Participants were assigned to 2 groups: the first group received 50 mL of albumin 20% as the priming solution for the CPB circuit, while the second group received 500 mL of hydroxyethyl starch 6%. Bleeding and IL-6 levels were assessed before and after the intervention. Results: The albumin group comprised 80.0% men and 20.0% women, with a mean age of 66.45±5.84 years. The hydroxyethyl starch 6% group consisted of 85.0% men and 15.0% women, with a mean age of 63.05±5.92 years (P>0.05). The findings revealed that 12 hours after CPB, the IL-6 level in the hydroxyethyl starch 6% group (mean: 171.6±77.71 pg/mL) was significantly higher than that in the albumin group (mean: 105.8±36.45 pg/mL; P=0.002). At 48 hours after CPB, the mean bleeding was not significantly different between the groups (P=0.950). Conclusion: Albumin 20% was more effective than hydroxyethyl starch 6% concerning IL-6 levels. However, no significant differences in bleeding were observed between the groups at 48 hours post-CPB. [ABSTRACT FROM AUTHOR]

Objective: To describe and compare prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG), HCT, and platelet count measurements in a hemorrhage/over‐resuscitation model. Design: Randomized crossover study. Setting: University teaching hospital. Animals: Six cats. Interventions: Anesthetized cats underwent 3 treatments at 2‐month intervals. The treatments were as follows: NHR—no controlled hemorrhage and sham resuscitation; LRS—controlled hemorrhage and lactated Ringer's solution (LRS) for resuscitation; and Voluven—controlled hemorrhage and 6% tetrastarch 130/0.4 for resuscitation. The LRS and Voluven were administered at 60 and 20 mL/kg/h, respectively, for 120 minutes. Blood samples were drawn for PT, aPTT, TEG, HCT, and platelet count measurements at a healthy check (T − 7d), after controlled hemorrhage (T0), at 60 and 120 minutes of resuscitation (T60 and T120), and at 24 hours after completion of resuscitation (T24h). Data were analyzed using a general linear mixed model approach (significance was P < 0.05). Measurements and Main Results: Total median blood loss (controlled hemorrhage and blood sampling from T0 to T120) at T120 was 11.4, 31.0, and 30.8 mL/kg for NHR, LRS, and Voluven, respectively. PT and aPTT during LRS and Voluven were prolonged at T60 and T120 compared to NHR (P < 0.001). On TEG, the reaction time, kinetic time, and alpha‐angle were within reference intervals for cats at all time points in all treatments, while maximum amplitude was less than the reference interval (40 mm) at T0, T60, and T120 during Voluven and at T60 and T120 during LRS compared to NHR (both P < 0.001). The HCT and platelet count were significantly lower at T60 and T120 during LRS and Voluven compared to NHR (P < 0.001). Conclusions: Hypocoagulopathy was observed during hemorrhage and liberal fluid resuscitation. Prolongation of PT and aPPT and decreased clot strength may have been caused by hemodilution and platelet loss. [ABSTRACT FROM AUTHOR]

Polysaccharide-based nanoformulations with tailored hydrophobic properties have become a frontier in nanomedicine applications. Herein, highly hydrophobicized hydroxyethyl starch (HES) conjugates were synthesized by grafting stearic acid (SA) with HES via a carbodiimide-mediated reaction. A detailed NMR characterization of HES and the conjugates was studied to obtain structural information. The grafting ratio of the stearate-HES (St-HES) conjugates was determined from 1H NMR spectra as 29.4% (St-HES29.4) and 60.3% (St-HES60.3). Thermal analyses and X-ray diffractograms suggested an entire transition from amorphous HES to a semicrystalline (St-HES60.3) character upon increasing the degree of grafting. Both conjugates, St-HES29.4 and St-HES60.3, were able to form self-assembled particles with a diameter of 130.7 nm and 152.5 nm, respectively. SEM images showed that the self-aggregates were mostly spherical in shape. These conjugates can be employed to entrap highly hydrophobic drugs with an increased encapsulation efficiency and loading capacity. [ABSTRACT FROM AUTHOR]

Objective To compare the efficiency of 3 different processing methods (Sepax, AutoXpress [AXP], and manual processing with hydroxyethyl starch [HES] sedimentation) used at Stemlab during a 10-year period. Methods Historical data were compiled and the analytical results obtained for the 3 different methods were compared. Results The manual processing (HES) method yielded the highest level of total nucleated cell recovery after processing, and the AXP system yielded the highest CD34+ cell number. The red blood cell reduction was also significantly higher with the HES method. Also, HES showed comparable results to Toticyte technology for umbilical cord blood (UCB) processing. Conclusion These results show that the HES method is as effective as automated technologies for UCB volume reduction; hence, it is a suitable methodology for private and public UCB banks. The HES method also proved to be superior to Toticyte technology for medical applications, with higher recovery yields of total nucleated cells after thawing and equivalent CD34+ cell recovery and functionality. [ABSTRACT FROM AUTHOR]

Cancer is one of the most lethal diseases all over the world. Despite that many drugs have been developed for cancer therapy, they still suffer from various limitations including poor treating efficacy, toxicity to normal human cells, and the emergence of multidrug resistance. In this study, the amphiphilic LHES polymers were prepared using hydroxyethyl starch (HES) and linoleic acid as starting materials. The content and substitution degree of linoleic acid groups in LHES polymers were analyzed. The LHES polymers were used for fabricating LHES-B nanoparticles carrying a linoleic acid modified berberine derivative (L-BBR). The LHES-B nanoparticles showed high drug loading efficiency (29%) and could quickly release L-BBR under acidic pH condition (pH = 4.5). Biological investigations revealed that LHES-B nanoparticles significantly inhibited the proliferation of HepG2 cells and exhibited higher cytotoxicity than L-BBR. In a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasv12) zebrafish model, LHES-B nanoparticles obviously inhibited the expression of krasv12 oncogene. These results indicated that LHES carriers could improve the anticancer activity of L-BBR, and the synthesized LHES-B nanoparticles showed great potential as anticancer drug.

Islet transplantation is the most effective treatment strategy for type 1 diabetes. Long-term storage at ultralow temperatures can be used to prepare sufficient islets of good quality for transplantation. For freezing islets, dimethyl sulfoxide (DMSO) is a commonly used penetrating cryoprotective agent (CPA). However, the toxicity of DMSO is a major obstacle to cell cryopreservation. Hydroxyethyl starch (HES) has been proposed as an alternative CPA. To investigate the effects of two types of nonpermeating CPA, we compared 4 % HES 130 and HES 200 to 10 % DMSO in terms of mouse islet yield, viability, and glucose-stimulated insulin secretion (GSIS). After one day of culture, islets were cryopreserved in each solution. After three days of cryopreservation, islet recovery was significantly higher in the HES 130 and HES 200 groups than in the DMSO group. Islet viability in the HES 200 group was also significantly higher than that in the DMSO group on Day 1 and Day 3. Stimulation indices determined by GSIS were higher in the HES 130 and 200 groups than in the DMSO group on Day 3. After three days of cryopreservation, HES 130 and HES 200 both reduced the expression of apoptosis- and necrosis-associated proteins and promoted the survival of islets. In conclusion, the use of HES as a CPA improved the survival and insulin secretion of cryopreserved islets compared with the use of a conventional CPA.

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. [ABSTRACT FROM AUTHOR]

Massive burn patients are at risk of developing intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as a complication of resuscitation. This study aimed to evaluate the effect of Hydroxyethyl starch (HES) versus 5% albumin solution on intra-abdominal pressure (IAP) in massive burn patients. This was a prospective randomized clinical trial carried on at Ain Shams University (ASU) burn unit for 2 years. Where adult patients with burns more than 20% of TBSA were equally randomized into HES group or albumin group. Fifty-two patients were equally randomized into 2 groups. We found no difference in age, sex, weight, type of burn, and TBSA between the two groups. The mean t otal resuscitation fluid volume in the first 48 h was 213 ml/kg and 206.2 ml/kg for the HES group and the albumin group respectively (p = 0.674). IAP statistically was non-significantly higher in the HES group. We found no statistical difference between the two groups as regards the renal function tests. Both HES and 5% albumin solution are effective and safe colloids for burn resuscitation. As regards the IAP, it seems that both 5% albumin and HES have comparable effect regarding IAH in severely burn patients. Both HES and 5% albumin were partially equal in terms of renal involvement and vital data stability. • Adding colloids to resuscitation fluid help to avoid over resuscitation complication in burn patients. • Abdominal compartment syndrome is an avoidable complication in sever burn patients. • Monitoring intra-abdominal pressure is very important in sever burn cases. [ABSTRACT FROM AUTHOR]

Objective. To investigate the mechanisms of cryoprotection with compositions that were supplemented with polymers (dextran [Dex], hydroxyethyl starch [HES], polyethylene glycol [PEG]) or fetal bovine serum [FBS]). Methods. Differential scanning calorimetry (DSC) and thermomechanical analysis (TMA) of cryoprotective media containing serum, as well as media that do not contain serum or its components but include polymers. Results. The combinations of dimethyl sulfoxide with FBS or polymers in cryoprotective media were able to promote the formation of amorphous phase and suppress salt eutectic crystallization/melting and recrystallization. The medium supplemented with 0.7 M Me2SO and 100 mg/ml Dex (0.7Me2SO+Dex) was somewhat superior compared to other compositions. It also had an optimal glass transition temperature (-26...-21 °C). The feature correlated with an adequate cell recovery when the medium was utilized to preserve testicular cells. Conclusions. The mechanism of cryoprotection depends not only on the concentrations of cryoprotective agents such as Me2SO, polymers or FBS, but also on the composition of the cryoprotective media. The 0.7Me2SO+Dex medium can be the basis for the creation of commercial serum-free cryoprotective media with a defined stable composition that does not require removal of Me2SO before using the cryopreserved cells or tissues for cultivation, transplantation and transfusion. [ABSTRACT FROM AUTHOR]

Background and Objectives: Granulocyte transfusion (GTX) is a treatment option for severe infections in patients with neutropenia. In previous studies, hydroxyethyl starch (HES) was used to enhance red blood cell sedimentation for granulocyte collection (GC). However, there are safety concerns about HES, and HES is not readily available in some countries. Therefore, we compared the granulocyte counts and GC efficiency achieved by two apheresis systems without HES. Materials and Methods: All consecutive GC procedures performed between July 2011 and March 2018 at our hospital were analysed. COBE Spectra was used until 5 February 2016, and Spectra Optia was used afterwards. HES was not used. Results: Twenty‐six GC procedures were performed, including 18 performed using COBE Spectra and 8 using Spectra Optia. When Spectra Optia was used, >1 × 1010 neutrophils were collected from seven of the eight (88%) procedures. Although there was no significant difference in the granulocyte yield between COBE Spectra‐based and Spectra Optia‐based GC procedures, the collection efficiency of Spectra Optia was significantly higher than that of COBE Spectra (p = 0.021). Furthermore, the granulocyte yields of Spectra Optia‐based GC tended to be more strongly correlated with the peripheral blood neutrophil count on the day of apheresis than those of COBE Spectra‐based GC. Conclusion: Our results suggest that Spectra Optia achieves greater GC efficiency than COBE Spectra, even without HES. GTX may be a therapeutic option for severe neutropenia, even in places where HES is not available. [ABSTRACT FROM AUTHOR]

In the last decade, hydrogels for hydraulic fracturing based on viscoelastic surfactants have been actively studied. Interest in these systems is justified by their unique qualities: good viscoelasticity and the ability to form stable suspensions of proppant or sand, destruction without the formation of bridging agents, hydrophobization of the rock surface and metal of technological equipment, as well as oil-cleaning properties. These qualities are most often provided by a minimum set of components—a surfactant and an electrolyte. However, the absence of a polymer limits the use of these gels in formations where fluid leakoff is possible. In this article, a liquid was studied, based on a pseudo gemini surfactant (PGVES) with the addition of a water-soluble polysaccharide. The objects of study were selected based on the assumption of interactions between PGVES and the polymer; interactions which favorably influence the technological characteristics of the fracturing fluid. To confirm the hypothesis, rheological studies were carried out. These included rotational viscometry and oscillatory studies at various temperatures. The settling velocity of particles of various proppant fractions was studied and tests were carried out to assess fluid leakoff. The performed experiments show an improvement in the characteristics of the PGVES-based gel under the influence of the polysaccharide. In particular, the rheological properties increase significantly, the stability of proppant suspensions improves, and the fluid leakoff of systems decreases, all of which expands the possibility of using these fracturing fluids and makes this area of experimentation promising. [ABSTRACT FROM AUTHOR]

Cardiopulmonary bypass (CPB) is frequently employed for cardiac surgery, and selecting a suitable priming fluid is a prerequisite for CPB. Currently, the commonly used priming fluids in clinics are classified as crystalloids and colloids, including balanced crystalloids, albumin, dextran, gelatin and hydroxyethyl starch (HES). This network meta-analysis compared the effects of eight fluids used during CPB in adults to determine optimal priming fluid during CPB surgery. Randomised controlled trials assessing priming fluids for CPB in adult cardiac surgery published before 13 April 2023 were searched across Ovid MEDLINE(R) ALL, OVID EMbase, and Cochrane Central Register of Controlled Trials. Various priming fluids were classified into eight categories, including balanced crystalloids, 0.9% NaCl, iso-oncotic human albumin, hyperoncotic human albumin, HES with molecular weight 130k, HES with molecular weight 200k, gelatin and dextran. The NMA of platelet counts revealed no significant differences in any result. In direct comparison results, only the comparison of HES with molecular weight 130k vs. gelatin (standard mean difference = −0.40, 95% confidence interval [95%CI: −0.63, −0.16) revealed a significant difference. According to the SUCRA, balanced crystalloids had the highest platelet count, followed by gelatin, and HES with a molecular weight of 130k had the lowest platelet, followed by HES with a molecular weight of 200k. Patients using dextran have a low mortality rate and a short mean CPB time, the use of balanced crystalloids is beneficial in terms of platelet count, and HES with molecular weight 130k is beneficial for postoperative urine volume at 24h. However, all priming fluids have pros and cons quite, and the optimal choice of priming fluids remains unsupported by current evidences. When performing CPB surgery, the type of priming fluid should be selected according to the actual situation in CPB for adult cardiac surgery. When dextran was used as the CPB priming fluid, patients had the lowest mortality and shortest mean CPB time. With iso-oncotic HA, patients had the shortest length of ICU stay, the least blood loss 24h after surgery, and the lowest chest tube output 24h after surgery. The use of balanced crystalloids was beneficial for platelet count, the use of L-HES was beneficial for urine output 24h after surgery, and the use of H-HES resulted in the shortest hospital stay. In summary, each of these fluids has pros and cons quite, and an optimal choice of priming fluids during CPB surgery remains unsupported by current evidence. When performing CPB surgery, the type of priming fluids should be selected according to the actual condition of the patient's body. [ABSTRACT FROM AUTHOR]

The intracellular protein corona has not been fully investigated in the field of nanotechnology-biology (nano-bio) interactions. To effectively understand intracellular protein corona formation and dynamics, we established a workflow to isolate the intracellular protein corona at different uptake times of two nanoparticles - magnetic hydroxyethyl starch nanoparticles (HES-NPs) and magnetic human serum albumin nanocapsules (HSA-NCs). We performed label-free quantitative LC-MS proteomics to analyze the composition of the intracellular protein corona and correlated our findings with results from conventional methods for intracellular trafficking of nanocarriers, such as flow cytometry, transmission electron microscopy (TEM), and confocal microscopy (cLSM). We determined the evolution of the intracellular protein corona. At different time stages the protein corona of the HES-NPs with a slower uptake changed, but there were fewer changes in that of the HSA-NCs with a more rapid uptake. We identified proteins that are involved in macropinocytosis (RAC1, ASAP2) as well as caveolin. This was confirmed by blocking experiments and by TEM studies. The investigated nanocarrier predominantly trafficked from early endosomes as determined by RAB5 identification in proteomics and in cLSM to late endosomes/lysosomes (RAB7, LAMP1, cathepsin K and HSP 90-beta) We further demonstrated differences between nanoparticles with slower and faster uptake kinetics and determined the associated proteome at different time points. Analysis of the intracellular protein corona provides us with effective data to examine the intracellular trafficking of nanocarriers used in efficient drug delivery and intracellular applications. Many research papers focus on the protein corona on nanoparticles formed in biological fluids, but there are hardly any articles dealing with proteins that come in contact with nanoparticles inside cells. The "intracellular protein corona" studied here is a far more complex and highly demanding field. Most nanocarriers are designed to be taken up into cells. Given this, we chose two different nanocarriers to reveal changes in the proteins in dendritic cells during contact at specific times. Further studies will allow us to examine molecular target proteins using these methods. Our research is a significant addition towards the goal of understanding and thus improving the efficacy of drug nanocarriers. [Display omitted] [ABSTRACT FROM AUTHOR]

INTRODUCTION: Granulocyte transfusion is one of the best therapeutic modalities in prolonged neutropenic patients with severe bacterial/fungal infections. Granulocyte harvest using conventional acid citrate dextrose (ACD) anticoagulant (ACD-A) by apheresis is not satisfactory in comparison to the use of hydroxyethyl starch (HES), but the latter is associated with various adverse events, especially with high-molecular-weight HES. AIMS AND OBJECTIVE: This study aimed to assess the beneficial impact of the use of medium-molecular-weight (MMW)-HES and trisodium citrate combination over ACD-A in granulocyte apheresis when using Spectra Optia. MATERIALS AND METHODS: This was a retrospective study comparing granulocyte harvest results with the use of ACD or HES and trisodium citrate combination. All the donors in both the groups received single 600 μg of granulocyte colony-stimulating factor subcutaneous injection followed by 8 mg of dexamethasone tablet 10–12 h and omnacortil 60 mg orally 3 h before harvest. A number of adverse incidents, if any, were observed and noted. Donor/procedure parameters were compared using Mann–Whitney U-test/unpaired t-test. RESULTS: Granulocyte yield (mean: 3.29 × 1010/unit vs. 4.5 × 1010/unit in the ACD and HES groups, respectively, P ≤ 0.0001) was significantly better in the HES group. The collection efficiency was also better in the HES group (mean: 15.86% vs. 26.70% in the ACD and HES groups, respectively, P ≤ 0.0001) in the ACD and HES groups, respectively. There was no significant adverse event noted in any of these two groups. CONCLUSION: In our study, granulocytes with optimum yield can be easily harvested with Spectra Optia cell separator using 6% HES (MMW) and trisodium citrate combination with standard 12-h interval gap between mobilization and harvest. This strategy can also have no or minimal extra cost burden to patients.

AbstractBackground Cardiopulmonary bypass (CPB) is frequently employed for cardiac surgery, and selecting a suitable priming fluid is a prerequisite for CPB. Currently, the commonly used priming fluids in clinics are classified as crystalloids and colloids, including balanced crystalloids, albumin, dextran, gelatin and hydroxyethyl starch (HES). This network meta-analysis compared the effects of eight fluids used during CPB in adults to determine optimal priming fluid during CPB surgery.Methods Randomised controlled trials assessing priming fluids for CPB in adult cardiac surgery published before 13 April 2023 were searched across Ovid MEDLINE(R) ALL, OVID EMbase, and Cochrane Central Register of Controlled Trials. Various priming fluids were classified into eight categories, including balanced crystalloids, 0.9% NaCl, iso-oncotic human albumin, hyperoncotic human albumin, HES with molecular weight 130k, HES with molecular weight 200k, gelatin and dextran.Results The NMA of platelet counts revealed no significant differences in any result. In direct comparison results, only the comparison of HES with molecular weight 130k vs. gelatin (standard mean difference = −0.40, 95% confidence interval [95%CI: −0.63, −0.16) revealed a significant difference. According to the SUCRA, balanced crystalloids had the highest platelet count, followed by gelatin, and HES with a molecular weight of 130k had the lowest platelet, followed by HES with a molecular weight of 200k.Conclusion Patients using dextran have a low mortality rate and a short mean CPB time, the use of balanced crystalloids is beneficial in terms of platelet count, and HES with molecular weight 130k is beneficial for postoperative urine volume at 24h. However, all priming fluids have pros and cons quite, and the optimal choice of priming fluids remains unsupported by current evidences. When performing CPB surgery, the type of priming fluid should be selected according to the actual situation in CPB for adult cardiac surgery.

In this study, we evaluated the efficacy of tranexamic acid (TXA) and acute normovolemic hemodilution (ANH) with 6% hydroxyethyl starch (130/0.4) in minimizing blood loss during open partial liver resection. Coagulation function was assessed using thromboelastography (TEG) and hemostasis tests, while renal function changes were tracked through serum creatinine values post-surgery.Methods: Thirty patients undergoing open partial liver resection were allocated to two groups: Group T received TXA + ANH, and Group A received ANH alone. Blood was drawn from the radial artery under general anesthesia. Both groups received peripheral vein injections of 6% hydroxyethyl starch 130/0.4. Group T additionally received intravenous TXA. Primary outcomes included blood loss and allogeneic blood transfusions. TEG assessed coagulation status and renal function was monitored.Results: Group T demonstrated superior outcomes compared to Group A. Group T had significantly lower intraoperative blood loss (700 mL vs 1200 mL) and a lower bleeding rate per kilogram of body weight (13.3 mL/kg vs 20.4 mL/kg). Coagulation parameters favored Group T, with higher TEG maximum amplitude (55.91 mm vs 45.88 mm) and lower activated partial thromboplastin time (38.04 seconds vs 41.49 seconds). Neither group experienced acute renal injury or kidney function deficiency during hospitalization.Conclusion: TXA and ANH in a small dose during liver resection stabilize clotting, reduce blood loss by 6% compared to hydroxyethyl starch 130/0.4, and do not affect renal function. [ABSTRACT FROM AUTHOR]

Fungal infections are caused by opportunistic pathogens that can be life threatening or debilitating. Candida spp. are becoming increasingly resistant to current clinically approved antifungal therapeutics. Candida infections afflict not only immunosuppressed but also immunocompetent individuals. Recurrent vulvovaginal candidiasis (RVVC) is a disease that afflicts 5–9% of women. Occidiofungin is a novel cyclic peptide that has a broad spectrum of antifungal activity with a novel fungicidal mechanism of action. A gel formulation containing occidiofungin (OCF001) is being developed for use to treat vulvovaginal candidiasis. The formulated gel for intravaginal application used hydroxyethyl cellulose as the primary gelling agent and hydroxypropyl β-cyclodextrin as a solubilizing agent for occidiofungin. Franz cells and LC-MS/MS were used to determine the rate of drug substance diffusion in the gel formulation. The formulation was tested in an ex vivo mouse skin efficacy study, and the safety was tested following repeat intravaginal administration in rabbits. In this study, the gel formulation was shown to reduce the drug substance rate of diffusion across a skin memetic membrane. The study showed that the formulation extends exposure time to inhibitory concentrations of occidiofungin over a 24-h period and supports a single daily application for the treatment of RVVC. [ABSTRACT FROM AUTHOR]

Cancer is a genetic disorder and its treatment usually requires a long time and expensive diagnosis. While chemotherapy is the most conventional approach in treating most cancers, patients often suffer from undesired side effects due to various pharmacokinetic aspects. To address this issue, target-oriented drug-delivery systems (DDS) or pulsatile drug-delivery systems (PDDS) have recently been developed as an alternative tool that takes care of the entire pharmacodynamic activities of drug action. Hydroxyethyl starch (HES) has emerged as an effective clinical tool for delivering anticancer agents into target cells. These systems have demonstrated significant potential as anticancer drug carrier conjugates through their innate pharmacokinetic properties with their safety profile. This review focuses primarily on the structural aspect during the use of HES or HES-based polymers as carriers for delivering well-known anticancer drugs. This review also indicates a perspective on the long-term research needed for the sake of improving modern drug-delivery systems based on HES polymers and in the form of nanocarriers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The degree of substitution (DS) of HES describes the average proportion of substituted glucose molecules in a starch molecule. Although no quantitative studies of the in vivo behavior of the DS have been conducted so far, most pharmacokinetic studies to date have measured HES concentrations using the enzymatic method. This method assumes that at any point in time after an infusion, the DS in a serum remains constant and is identical to the DS in the infused solution. In the present study, we examined the changes in the DS of HES 130/0.42 in vivo in an animal model and compared two methods of measuring HES concentrations in plasma (the enzymatic and the o-Toluidine method). Methodology: We randomized 22 pigs into 2 groups. After induction of anesthesia, the pigs received 500 ml or 1000 ml of HES 130/0.42 (Tetraspan®). The DS was measured directly after the infusion, then after 30, 60, 120 and 240 minutes. In determining the DS, the hydroxyethyl starch was extracted from the plasma and hydrolyzed with hydrochloric acid to form non-substituted glucose and hydroxyethyl glucose. Subsequently, the concentration of free unsubstituted glucose was determined enzymatically and the total concentration of all (i.e., substituted and unsubstituted) glucose molecules was determined using the o-Toluidine method. From this, the concentration of the substituted glucose (hydroxyethyl glucose) and the DS could be calculated. In addition, the HES concentration was measured first in vitro and then in vivo at any point after the infusion by both the enzymatic method and the o-Toluidine method. Results: The DS increased significantly directly after the infusion from 0.42 to 0.53 (for 500ml) or to 0.50 (for 1000ml); 4 hours later this had further increased to 0.55 and 0.54, respectively (p <0.0001). The HES concentration in vitro showed no significant difference (p = 0.17) when determined with the enzymatic and the o-Toluidine method. In contrast, the serum concentrations in vivo displayed significant differences (p<0.0001) between the two measurement methods. Immediately after the infusion of 500ml HES, the concentration measured with the o-Toluidine method was 31% higher than the one measured with the enzymatic method; 4 hours later, this discrepancy was still at 25%. For 1000 ml HES, the differences amounted to 16% and 25%, respectively. Conclusion: The DS of HES in vivo increases significantly over time. As a result, an HES concentration measured with the enzymatic method in vivo will be significantly lower than the same concentration determined with the o-Toluidine method. In future pharmacokinetic studies, HES concentrations should be measured using a method that takes into account changes in the DS in vivo. [ABSTRACT FROM AUTHOR]

Purpose: To reassess the results of former meta-analyses focusing on the relationship between novel HES preparations (130/0.4 and 130/0.42) and acute kidney injury. Previous meta-analyses are based on studies referring to partially or fully unpublished data or data from abstracts only. Methods: The studies included in the former meta-analyses were scrutinized by the authors independently. We completed a critical analysis of the literature, including the strengths, weaknesses and modifiers of the studies when assessing products, formulations and outcomes. Results: Both the published large studies and meta-analyses show significant bias in the context of the deleterious effect of 6% 130/0.4–0.42 HES. Without (1) detailed hemodynamic data, (2) the exclusion of other nephrotoxic events and (3) a properly performed evaluation of the dose–effect relationship, the AKI-inducing property of 6% HES 130/0.4 or 0.42 should not be considered as evidence. The administration of HES is safe and effective if the recommended dose is respected. Conclusions: Our review suggests that there is questionable evidence for the deteriorating renal effect of these products. Further well-designed, randomized and controlled trials are needed. Additionally, conclusions formulated for resource-rich environments should not be extended to more resource-scarce environments without proper qualifiers provided. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plasma expanders are colloidal solutions that expand the circulating blood volume more than isotonic crystalloids and are among the most commonly used fluids in critical care and perioperative medicine worldwide. We begin our review of these agents by introducing the modified Starling model, which incorporates the fundamental physiologic role of the endothelial glycocalyx in transcapillary fluid movement. Next, we individually discuss each fluid, starting with their relevant pharmacological properties before delving into the trials on their clinical use. Human trial data on gelatins and dextrans are scarce, making their routine use difficult to justify outside resource-poor settings. Trials on the use of hydroxyethyl starch in critical care imply increased risk of kidney injury, coagulopathy and, possibly, mortality; whether these harms apply to the surgical setting remains an area of debate and ongoing study, but there is no compelling evidence to support the routine use of hydroxyethyl starch in the operating room. Multiple trials suggest that albumin is a safe, albeit more expensive, alternative to crystalloid use in the intensive care unit, with secondary analyses suggesting harm in traumatic brain injury and benefit in septic shock. Finally, more data are required to better define the role of albumin in perioperative medicine. [ABSTRACT FROM AUTHOR]

In this study, amphoteric hydroxyethyl starch/p([2(acryloyloxy)ethyl]trimethylammonium chloride-co-itaconic acid (HES/p(AETAC-co-IA) hydrogels containing both cationic and anionic groups in their structure were synthesized by the redox polymerization method. The synthesized hydrogels were modified with gold nanoparticles, and nanocomposite hydrogels were obtained. The characterizations of the nanocomposite HES/p(AETAC-co-IA)@Au hydrogels prepared for biomedical applications were carried out by SEM, TEM, FT-IR, TGA, and XRD techniques and swelling tests in simulated biological environments. Hydrogels designed as drug carrier cargo materials were loaded with sodium diclofenac (NaDcF) and ibuprofen drugs, and their release properties were studied. The release mechanisms and release kinetics of the two drugs were studied. The release kinetics determined for the drug NaDcF is consistent with the Higuchi model, while the release kinetics determined for ibuprofen is consistent with the first-order model. In addition, the antibacterial and antifungal properties of the hydrogels were tested. It was found that the HES/p(AETAC-co-IA)@Au hydrogel was effective against gram-positive Staphylococcus aureus, gram-negative Pseudomonas aeruginosa, and the fungal species Candida albicans. [ABSTRACT FROM AUTHOR]

It has been documented that hemodynamic disturbances occur in hypovolemic patients. Therefore, the early management of hypovolemia is essential to achieve optimal outcomes. Blood gas, which changes rapidly during hemodynamic instability, can be used as a diagnostic approach for monitoring emergency patients. The objective of the current study was to evaluate the results of resuscitation with hydroxyethyl starch (HES) or lactated Ringer's solution (LR) on venous and arterial blood gas. In addition, the difference between venous and arterial blood gas parameters is investigated to assess the possibility of using venous blood gas analysis as a successor for arterial blood gas analysis in the resuscitation of hypovolemic dogs. Venous and arterial pH, PO2, PCO2, HCO3-, and base excess were analyzed at the end of each study stage as follow: 1) Establishment of anesthesia, 2) Blood collection to an arterial mean pressure of 40-50 mm Hg, 3) Maintaining dogs in a hypovolemic state, 4) Resuscitation with LR (group A) or HES (group B) in four steps, and 5) One hour after the final resuscitation step. Hypovolemia decreased the studied parameters, except venous PCO2, which showed a significant increase (p < 0.05). Fluid resuscitation returned the studied parameters to the control values as venous PCO2 in group A and HCO3- in group B showed a significant change in comparison with the control values (p < 0.05). We found that venous pH, HCO3-, and PCO2 can be used as less invasive and safer alternatives to similar arterial parameters to monitor the fluid resuscitation of hypovolemic dogs.

Background: Two‐dimensional shear wave elastography (2D‐SWE) provides information on hepatic elastic modulus as shear wave velocity (SWV). Hypothesis/Objectives: 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. Animals: Six healthy beagles. Methods: 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. Results: 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. Conclusions and Clinical Importance: 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

A novel type of temperature-pH dual-responsive amphiphilic hydrogel, PD(hydroxyethyl starch(HES)-propynyl glycidylether(PGE)-2-dimethylamino ethanethiol (DMAET)-triethoxyvinylsilane (TEVS)) was synthesized and characterized. HES, a hydrophilic polysaccharide, underwent etherification of hydroxyl groups in its glucose units with PGE and then click reaction between carbon–carbon triple bonds in PGE and thiol groups in DMAET thereby possessing a hydrophilic-hydrophobic structure to be used for the preparation of PD, a temperature-pH dual-responsive material, with pH-responsive tertiary amine groups. Next, it further became a dual-responsive hydrogel through the formation of its internal network by TEVS. The hydrogel exhibited its maximum hydroswelling ratio of 2000 and a good transference between its shrinking and swelling. Moreover, during the test experiments to use it as a drug carrier for oral delivery, a doxorubicin (DOX) release was ≤ 15% in acidic conditions in the stomach (pH < 2.0) and ≤ 94% in basic conditions in the small intestine, ensuring that it exhibits relatively good protective and release properties of drugs. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) play an important role in facilitating the progression of triple-negative breast cancer (TNBC) by deteriorating the tumor mechanical microenvironment (TMME). Herein, we designed a CAFs-targeting nanomedicine by conjugating doxorubicin (DOX)-loaded hydroxyethyl starch-IR780 nanoparticles (NPs) with Cys-Arg-Glu-Lys-Ala (CREKA) peptide, which had a special affinity for fibronectin overexpressed on CAFs. After systemic administration, the NPs efficiently targeted CAFs and generated hyperthermia upon light irradiation, decreasing CAFs through the combination of chemo- and photothermal-therapies. Thus, a series of changes in TMME were achieved by reducing CAFs, which further disrupted the niche of cancer stem cells (CSCs) to affect their survival. As a result, the tumor growth was significantly inhibited in 4T1 tumors. The strategy of TMME modulation and CSCs elimination through targeting and depleting CAFs provides a novel therapeutic treatment for desmoplastic solid tumors. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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). Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the most prevalent malignancies in the urinary system, including non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). Radical cystectomy combined with systemic chemotherapy remains the standard treatment for MIBC. However, serious undesired side effects and drug resistance of chemotherapy have hampered its wide application. Here, we facilely fabricated a pH-responsive RGD- and MoS2-conjugated hydroxyethyl starch-doxorubicin (HES-DOX-RGD/MoS2). The prodrug could self-assemble into nanoscopic micelle with a radius of ~ 56 nm in the aqueous environment and was stable in the physiological environment. The targeted HES-DOX-RGD/MoS2 showed a significant in vitro antiproliferative capability toward bladder cancer cells through the chemotherapy combined with photothermal therapy. Hence, we had reasons to believe that targeted HES-DOX-RGD/MoS2 had great potential to treat bladder cancer in the future. [ABSTRACT FROM AUTHOR]

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. Hydroxyethyl starch (HES) is leveraged to stabilize copper-diethyldithiocarbamate (CuET) nanocrystals and obtain CuET@HES nanoparticles, which conspicuously suppress cancer stem cells (CSCs) not only in vitro but also in numerous tumor models in vivo. Furthermore, CuET@HES nanoparticles effectively inhibit CSCs in fresh tumor tissues surgically excised from hepatocellular carcinoma patients. [Display omitted] • HES stabilizes CuET nanocrystals via copper=oxygen coordination interactions, producing CuET@HES nanoparticles. • CuET@HES nanoparticles promote CuET colloidal stability and ROS production. • CuET@HES nanoparticles suppress CSCs in numerous tumor models and fresh tumor tissues from HCC patients. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs), enabled to self-renew, differentiate, and initiate the bulk tumor, are recognized as the culprit of treatment resistance, metastasis, and recurrence. Simultaneously eradicating CSCs and bulk cancer cells is crucial for successful cancer therapy. Herein, we reported that doxorubicin (Dox) and erastin co -loaded hydroxyethyl starch-polycaprolactone nanoparticles (DEPH NPs) eliminated CSCs and cancer cells by regulating redox status. We found that an excellently synergistic effect existed when Dox and erastin were co-delivered by DEPH NPs. Specifically, erastin could deplete intracellular glutathione (GSH), thereby inhibiting the efflux of intracellular Dox and boosting Dox-induced reactive oxygen species (ROS) to amplify redox imbalance and oxidative stress. The high ROS levels restrained CSCs self-renewal via downregulating Hedgehog pathways, promoted CSCs differentiation, and rendered differentiated cancer cells vulnerable to apoptosis. As such, DEPH NPs significantly eliminated not only cancer cells but more importantly CSCs, contributing to suppressed tumor growth, tumor-initiating capacity, and metastasis, in various tumor models of triple negative breast cancer. This study demonstrates that the combination of Dox and erastin is potent in elimination of both cancer cells and CSCs, and that DEPH NPs represent a promising treatment against CSCs-rich solid tumors. DEPH nanoparticles eliminate cancer stem cells (CSCs) by destroying the redox equilibrium to suppress CSCs self-renewal pathway, promote differentiation and induce apoptosis. [Display omitted] • DEPH NPs simultaneously and precisely release erastin and Dox for synergistic effect. • Erastin enhances Dox tumor accumulation and aggrandizes Dox-induced oxidative stress. • DEPH NPs potently suppress both CSCs and cancer cells by regulating redox balance. • This study provides novel insights on combination therapy and anti-CSCs therapy. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine the effect of fresh frozen plasma (FFP) for priming of cardiopulmonary bypass (CPB) circuit on rotational thromboelastometry (ROTEM) and transfusion in pediatric cardiac surgery. Methods: Eighty patients younger than seven years old, were divided into case (FFP) (n = 40) and control (n = 40) groups. In the case group,10-20 mL/kg fresh frozen plasm was used for priming the CPB. The control group received 10-20 mL/kg of hydroxyethyl starch. ROTEM was done before surgical incision and after separation from CPB. The amount of transfusion (platelet and FFP) in the operating room and 24 hours after surgery were recorded. Results: Statistically significant difference was found between the case and control group in terms of changes in the Rotem parameters. The amount of transfusion of platelets in the operating room was significantly higher in the control group than in the case group. Conclusion: It seems that adding FFP to the prime solution is more effective in young patients and infants due to the higher susceptibility of the infant coagulation system to coagulation and hemorrhagic disorders in comparison with other patients. [ABSTRACT FROM AUTHOR]

Curcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), disulfide bond (QHES-SS-CUR), and carbon-carbon bond (QHES-CC-CUR) were implemented, respectively. The effect of above three linkers on the self-assembly behavior of QHES-curcumin prodrugs was evaluated. QHES-2S-CUR and QHES-SS-CUR could facilely self-assemble into spherical micelles in water, while QHES-CC-CUR was lack of conformational stability. In vitro drug release profiles of prodrug micelles were further investigated. Concretely, QHES-2S-CUR presented ROS-sensitive drug release, with 73.57 ± 4.22% of curcumin released under the addition of H2O2 over 24 h. The release of curcumin from QHES-SS-CUR lasted for 54 h due to the slower oxidization of disulfide bonds, and QHES-CC-CUR was insensitive to ROS. In addition, QHES-2S-CUR prodrug micelles demonstrated superior cytotoxicity to murine colonic adenocarcinoma (CT-26) cells compared to QHES-SS-CUR and QHES-CC-CUR, which were internalized by CT-26 cells with high efficiency. These results reveal the potential of QHES-2S-CUR prodrug micelles as tumor microenvironment-responsive anticarcinogen.