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1.
PLoS One ; 19(7): e0303165, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38991044

RESUMEN

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.


Asunto(s)
Coagulación Sanguínea , Soluciones Cristaloides , Derivados de Hidroxietil Almidón , Humanos , Femenino , Masculino , Soluciones Cristaloides/administración & dosificación , Coagulación Sanguínea/efectos de los fármacos , Anciano , Método Doble Ciego , Persona de Mediana Edad , Estudios Prospectivos , Páncreas/cirugía , Transfusión Sanguínea/estadística & datos numéricos , Pérdida de Sangre Quirúrgica/prevención & control , Proyectos Piloto , Soluciones Isotónicas
2.
Exp Clin Transplant ; 22(6): 475-478, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39072521

RESUMEN

Hematopoietic stem cell transplantation is a curative treatment for many malignant and nonmalignant diseases in children and adults. It is performed with peripheral blood stem cells, bone marrow, and umbilical cord blood. Anaphylaxis may occur during hematopoietic stem cell transplantation, similar to that shown with blood transfusions. In children, although a few cases of anaphylaxis have been reported with cord blood transplantation, no cases of anaphylaxis have been reported with other hematopoietic stem cell transplantations. In this case report, we present the cases of 2 children, one diagnosed with thalassemia major and the other with aplastic anemia, both of whom developed anaphylaxis associated with bone marrow transplantation products cryopreserved with dimethyl sulfoxide and hydroxyethyl starch. Hematopoietic stem cell transplantation-induced anaphylaxis could be associated with cryoprotective agents, especially dimethyl sulfoxide, and alloantigens. In both anaphy-lactic reactions, dimethyl sulfoxide was thought to be the trigger, but it could not be excluded that it was related to stem cell components, plasma, or hydroxyethyl starch.


Asunto(s)
Anafilaxia , Dimetilsulfóxido , Trasplante de Células Madre Hematopoyéticas , Humanos , Anafilaxia/diagnóstico , Anafilaxia/terapia , Anafilaxia/etiología , Anafilaxia/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Dimetilsulfóxido/efectos adversos , Femenino , Anemia Aplásica/terapia , Anemia Aplásica/inmunología , Anemia Aplásica/diagnóstico , Talasemia beta/terapia , Talasemia beta/inmunología , Talasemia beta/complicaciones , Talasemia beta/diagnóstico , Crioprotectores/efectos adversos , Criopreservación , Resultado del Tratamiento , Trasplante Homólogo , Niño , Derivados de Hidroxietil Almidón/efectos adversos , Preescolar
3.
Artículo en Inglés | MEDLINE | ID: mdl-38874122

RESUMEN

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.


Asunto(s)
Estudios Cruzados , Tiempo de Protrombina , Resucitación , Lactato de Ringer , Tromboelastografía , Animales , Gatos , Tromboelastografía/veterinaria , Tromboelastografía/métodos , Lactato de Ringer/administración & dosificación , Lactato de Ringer/farmacología , Recuento de Plaquetas/veterinaria , Tiempo de Protrombina/veterinaria , Hematócrito/veterinaria , Tiempo de Tromboplastina Parcial/veterinaria , Resucitación/veterinaria , Resucitación/métodos , Hemorragia/veterinaria , Hemorragia/sangre , Enfermedades de los Gatos/sangre , Derivados de Hidroxietil Almidón/farmacología , Derivados de Hidroxietil Almidón/administración & dosificación , Masculino , Femenino , Gelatina/administración & dosificación , Gelatina/farmacología , Succinatos
4.
Biomaterials ; 311: 122673, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38897030

RESUMEN

The adaptive antioxidant systems of tumor cells, predominantly glutathione (GSH) and thioredoxin (TRX) networks, severely impair photodynamic therapy (PDT) potency and anti-tumor immune responses. Here, a multistage redox homeostasis nanodisruptor (Phy@HES-IR), integrated by hydroxyethyl starch (HES)-new indocyanine green (IR820) conjugates with physcion (Phy), an inhibitor of the pentose phosphate pathway (PPP), is rationally designed to achieve PDT primed cancer immunotherapy. In this nanodisruptor, Phy effectively depletes intracellular GSH of tumor cells by inhibiting 6-phosphogluconate dehydrogenase (6PGD) activity. Concurrently, it is observed for the first time that the modified IR820-NH2 molecule not only exerts PDT action but also interferes with TRX antioxidant pathway by inhibiting thioredoxin oxidase (TRXR) activity. The simultaneous weakening of two major antioxidant pathways of tumor cells is favorable to maximize the PDT efficacy induced by HES-IR conjugates. By virtue of the excellent protecting ability of the plasma expander HES, Phy@HES-IR can remain stable in the blood circulation and efficiently enrich in the tumor region. Consequently, PDT and metabolic modulation synergistically induced immunogenic cell death, which not only suppressed primary tumors but also stimulated potent anti-tumor immunity to inhibit the growth of distant tumors in 4T1 tumor-bearing mice.


Asunto(s)
Antioxidantes , Glutatión , Derivados de Hidroxietil Almidón , Inmunoterapia , Nanomedicina , Especies Reactivas de Oxígeno , Tiorredoxinas , Animales , Tiorredoxinas/metabolismo , Glutatión/metabolismo , Derivados de Hidroxietil Almidón/química , Derivados de Hidroxietil Almidón/farmacología , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Inmunoterapia/métodos , Nanomedicina/métodos , Línea Celular Tumoral , Ratones , Fotoquimioterapia/métodos , Femenino , Ratones Endogámicos BALB C , Humanos , Verde de Indocianina/química
5.
Int J Nanomedicine ; 19: 5139-5156, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859954

RESUMEN

Introduction: 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.


Asunto(s)
Derivados de Hidroxietil Almidón , Hiperuricemia , Luteolina , Nanopartículas , Animales , Nanopartículas/química , Derivados de Hidroxietil Almidón/química , Derivados de Hidroxietil Almidón/farmacocinética , Derivados de Hidroxietil Almidón/administración & dosificación , Derivados de Hidroxietil Almidón/farmacología , Luteolina/farmacocinética , Luteolina/farmacología , Luteolina/química , Luteolina/administración & dosificación , Ratones , Células CACO-2 , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/sangre , Humanos , Masculino , Tamaño de la Partícula , Modelos Animales de Enfermedad , Solubilidad , Ácido Úrico/sangre , Ácido Úrico/química , Disponibilidad Biológica , Administración Oral , Estabilidad de Medicamentos
6.
J Trauma Acute Care Surg ; 97(2S Suppl 1): S105-S112, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38706102

RESUMEN

BACKGROUND: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available. METHODS: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product. RESULTS: At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01). CONCLUSION: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.


Asunto(s)
Modelos Animales de Enfermedad , Resucitación , Choque Hemorrágico , Animales , Perros , Choque Hemorrágico/terapia , Resucitación/métodos , Plasma , Sustitutos Sanguíneos , Derivados de Hidroxietil Almidón/administración & dosificación
7.
Int J Biol Macromol ; 271(Pt 1): 132616, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38795885

RESUMEN

Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy.


Asunto(s)
Portadores de Fármacos , Derivados de Hidroxietil Almidón , Verde de Indocianina , Nanopartículas , Verde de Indocianina/química , Verde de Indocianina/farmacología , Animales , Nanopartículas/química , Ratones , Portadores de Fármacos/química , Línea Celular Tumoral , Derivados de Hidroxietil Almidón/química , Derivados de Hidroxietil Almidón/farmacología , Vincristina/farmacología , Vincristina/química , Humanos
8.
Biomed Pharmacother ; 176: 116798, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38795642

RESUMEN

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.


Asunto(s)
Berberina , Derivados de Hidroxietil Almidón , Ácido Linoleico , Nanopartículas , Proteínas Proto-Oncogénicas p21(ras) , Animales , Humanos , Animales Modificados Genéticamente , Antineoplásicos/farmacología , Antineoplásicos/química , Berberina/farmacología , Berberina/química , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Liberación de Fármacos , Células Hep G2 , Derivados de Hidroxietil Almidón/farmacología , Derivados de Hidroxietil Almidón/química , Ácido Linoleico/química , Nanopartículas/química , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Pez Cebra , Modelos Animales de Enfermedad
9.
J Clin Anesth ; 96: 111493, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38723416

RESUMEN

STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.


Asunto(s)
Lesión Renal Aguda , Soluciones Cristaloides , Derivados de Hidroxietil Almidón , Complicaciones Posoperatorias , Puntaje de Propensión , Humanos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/inducido químicamente , Derivados de Hidroxietil Almidón/efectos adversos , Derivados de Hidroxietil Almidón/administración & dosificación , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , China/epidemiología , Soluciones Cristaloides/administración & dosificación , Soluciones Cristaloides/efectos adversos , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Incidencia , Sustitutos del Plasma/efectos adversos , Sustitutos del Plasma/administración & dosificación , Adulto , Terapia de Reemplazo Renal/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/efectos adversos
12.
Int J Biol Macromol ; 266(Pt 1): 131211, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552688

RESUMEN

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


Asunto(s)
Derivados de Hidroxietil Almidón , Micelas , Ácido Oleanólico , Oxidación-Reducción , Derivados de Hidroxietil Almidón/química , Ácido Oleanólico/química , Polímeros/química , Liberación de Fármacos , Portadores de Fármacos/química , Humanos , Hemólisis/efectos de los fármacos , Técnicas de Química Sintética , Animales , Tamaño de la Partícula
13.
Int J Biol Macromol ; 266(Pt 1): 131107, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38527677

RESUMEN

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


Asunto(s)
Antiinflamatorios , Colitis Ulcerosa , Curcumina , Microbioma Gastrointestinal , Derivados de Hidroxietil Almidón , Microesferas , Estrés Oxidativo , Curcumina/farmacología , Curcumina/química , Animales , Colitis Ulcerosa/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones , Derivados de Hidroxietil Almidón/química , Derivados de Hidroxietil Almidón/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Colon/microbiología , Inflamación/tratamiento farmacológico , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Masculino
14.
Cryobiology ; 115: 104857, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38350589

RESUMEN

The cryopreservation of endothelial cell monolayers is an important step that bridges the cryopreservation of cells in suspension to that of tissues. Previous studies have identified clear distinctions in freezing mechanisms between cells in suspension and in monolayers, as well as developed novel protocols for monolayer cryopreservation. Recently, our group has shown that human umbilical vein endothelial cell (HUVEC) and porcine corneal endothelial cell (PCEC) monolayers grown on Rinzl plastic substrate can be cryopreserved in 5% dimethyl sulfoxide, 6% hydroxyethyl starch, and 2% chondroitin sulfate, following a slow-cooling protocol (-1 °C/min) with rapid plunge into liquid nitrogen from -40 °C. However, membrane integrity assessments were done immediately post thaw, which may result in an overestimation of cell viability due to possible delayed injury responses. Here, we show that for the optimal protocol condition of plunge at the -40 °C interrupt temperature, HUVEC and PCEC monolayers exhibited no significant immediate post-thaw injuries nor delayed injury responses during the 24-h post-thaw overnight culture period. HUVEC monolayers experienced no significant impact to their natural growth rate during the post-thaw culture, while PCEC monolayers experienced significantly higher growth than the unfrozen controls. The difference in the low-temperature responses between HUVEC and PCEC monolayers was further shown under high temperature plunge conditions. At these suboptimal plunge temperatures, HUVEC monolayers exhibited moderate immediate membrane injury but a pronounced delayed injury response during the 24-h post-thaw culture, while PCEC monolayers showed significant immediate membrane injury but no additional delayed injury response during the same period. Therefore, we provide further validation of our group's previously designed endothelial monolayer cryopreservation protocol for HUVEC and PCEC monolayers, and we identify several cell-type-specific responses to the freezing process.


Asunto(s)
Supervivencia Celular , Criopreservación , Crioprotectores , Dimetilsulfóxido , Células Endoteliales de la Vena Umbilical Humana , Criopreservación/métodos , Humanos , Animales , Supervivencia Celular/efectos de los fármacos , Crioprotectores/farmacología , Porcinos , Dimetilsulfóxido/farmacología , Sulfatos de Condroitina/farmacología , Células Endoteliales/citología , Derivados de Hidroxietil Almidón/farmacología , Células Cultivadas , Endotelio Corneal/citología , Endotelio Corneal/lesiones
15.
PLoS One ; 19(2): e0298051, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38354172

RESUMEN

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.


Asunto(s)
Anestésicos , Trasplante de Riñón , Humanos , Trasplante de Riñón/métodos , Anestésicos/uso terapéutico , Encuestas y Cuestionarios , Derivados de Hidroxietil Almidón , Complicaciones Posoperatorias , Atención Perioperativa
16.
Microvasc Res ; 152: 104630, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38048876

RESUMEN

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


Asunto(s)
Objetivos , Daño por Reperfusión , Humanos , Animales , Porcinos , Soluciones Cristaloides , Microcirculación , Fluidoterapia/métodos , Derivados de Hidroxietil Almidón/farmacología , Derivados de Hidroxietil Almidón/uso terapéutico , Isquemia/terapia , Coloides/uso terapéutico , Reperfusión , Soluciones Isotónicas/farmacología , Soluciones Isotónicas/uso terapéutico
17.
Sci Rep ; 13(1): 13818, 2023 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-37620359

RESUMEN

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.


Asunto(s)
Vasos Coronarios , Tomografía de Coherencia Óptica , Humanos , Vasos Coronarios/diagnóstico por imagen , Derivados de Hidroxietil Almidón/efectos adversos , Estudios de Factibilidad , Corazón
19.
Int J Biol Macromol ; 247: 125629, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37399874

RESUMEN

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


Asunto(s)
Amilosa , Almidón , Almidón/química , Amilosa/química , Pisum sativum , Derivados de Hidroxietil Almidón
20.
Pancreas ; 52(1): e1-e6, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37378895

RESUMEN

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


Asunto(s)
Pancreatitis , Animales , Pancreatitis/patología , Enfermedad Aguda , Derivados de Hidroxietil Almidón , Fluidoterapia/métodos , Oxígeno , Hemoglobinas/uso terapéutico
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