RESUMO
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.
Assuntos
Débito Cardíaco , Estudos Cross-Over , Derivados de Hidroxietil Amido , Solução Salina , Animais , Cavalos , Débito Cardíaco/efeitos dos fármacos , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/administração & dosagem , Solução Salina/administração & dosagem , Solução Salina/farmacologia , Masculino , Estudos Prospectivos , Feminino , Monitorização Fisiológica/veterinária , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Hidratação/veterinária , Hidratação/métodos , Termodiluição/veterinária , Termodiluição/métodos , Infusões Intravenosas/veterinária , Infusões Intravenosas/métodosRESUMO
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.
Assuntos
Coagulação Sanguínea , Soluções Cristaloides , Derivados de Hidroxietil Amido , Humanos , Feminino , Masculino , Soluções Cristaloides/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Idoso , Método Duplo-Cego , Pessoa de Meia-Idade , Estudos Prospectivos , Pâncreas/cirurgia , Transfusão de Sangue/estatística & dados numéricos , Perda Sanguínea Cirúrgica/prevenção & controle , Projetos Piloto , Soluções IsotônicasRESUMO
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.
Assuntos
Anafilaxia , Dimetil Sulfóxido , Transplante de Células-Tronco Hematopoéticas , Humanos , Anafilaxia/diagnóstico , Anafilaxia/terapia , Anafilaxia/etiologia , Anafilaxia/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Dimetil Sulfóxido/efeitos adversos , Feminino , Anemia Aplástica/terapia , Anemia Aplástica/imunologia , Anemia Aplástica/diagnóstico , Talassemia beta/terapia , Talassemia beta/imunologia , Talassemia beta/complicações , Talassemia beta/diagnóstico , Crioprotetores/efeitos adversos , Criopreservação , Resultado do Tratamento , Transplante Homólogo , Criança , Derivados de Hidroxietil Amido/efeitos adversos , Pré-EscolarRESUMO
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.
Assuntos
Derivados de Hidroxietil Amido , Hiperuricemia , Luteolina , Nanopartículas , Animais , Nanopartículas/química , Derivados de Hidroxietil Amido/química , Derivados de Hidroxietil Amido/farmacocinética , Derivados de Hidroxietil Amido/administração & dosagem , Derivados de Hidroxietil Amido/farmacologia , Luteolina/farmacocinética , Luteolina/farmacologia , Luteolina/química , Luteolina/administração & dosagem , Camundongos , Células CACO-2 , Hiperuricemia/tratamento farmacológico , Hiperuricemia/sangue , Humanos , Masculino , Tamanho da Partícula , Modelos Animais de Doenças , Solubilidade , Ácido Úrico/sangue , Ácido Úrico/química , Disponibilidade Biológica , Administração Oral , Estabilidade de MedicamentosRESUMO
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.
Assuntos
Estudos Cross-Over , Tempo de Protrombina , Ressuscitação , Lactato de Ringer , Tromboelastografia , Animais , Gatos , Tromboelastografia/veterinária , Tromboelastografia/métodos , Lactato de Ringer/administração & dosagem , Lactato de Ringer/farmacologia , Contagem de Plaquetas/veterinária , Tempo de Protrombina/veterinária , Hematócrito/veterinária , Tempo de Tromboplastina Parcial/veterinária , Ressuscitação/veterinária , Ressuscitação/métodos , Hemorragia/veterinária , Hemorragia/sangue , Doenças do Gato/sangue , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/administração & dosagem , Masculino , Feminino , Gelatina/administração & dosagem , Gelatina/farmacologia , SuccinatosRESUMO
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.
Assuntos
Antioxidantes , Glutationa , Derivados de Hidroxietil Amido , Imunoterapia , Nanomedicina , Espécies Reativas de Oxigênio , Tiorredoxinas , Animais , Tiorredoxinas/metabolismo , Glutationa/metabolismo , Derivados de Hidroxietil Amido/química , Derivados de Hidroxietil Amido/farmacologia , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Imunoterapia/métodos , Nanomedicina/métodos , Linhagem Celular Tumoral , Camundongos , Fotoquimioterapia/métodos , Feminino , Camundongos Endogâmicos BALB C , Humanos , Verde de Indocianina/químicaRESUMO
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.
Assuntos
Portadores de Fármacos , Derivados de Hidroxietil Amido , Verde de Indocianina , Nanopartículas , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Animais , Nanopartículas/química , Camundongos , Portadores de Fármacos/química , Linhagem Celular Tumoral , Derivados de Hidroxietil Amido/química , Derivados de Hidroxietil Amido/farmacologia , Vincristina/farmacologia , Vincristina/química , HumanosRESUMO
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.
Assuntos
Injúria Renal Aguda , Soluções Cristaloides , Derivados de Hidroxietil Amido , Complicações Pós-Operatórias , Pontuação de Propensão , Humanos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/induzido quimicamente , Derivados de Hidroxietil Amido/efeitos adversos , Derivados de Hidroxietil Amido/administração & dosagem , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Soluções Cristaloides/administração & dosagem , Soluções Cristaloides/efeitos adversos , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Incidência , Substitutos do Plasma/efeitos adversos , Substitutos do Plasma/administração & dosagem , Adulto , Terapia de Substituição Renal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/efeitos adversosAssuntos
Injúria Renal Aguda , Derivados de Hidroxietil Amido , Complicações Pós-Operatórias , Pontuação de Propensão , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/etiologia , Derivados de Hidroxietil Amido/efeitos adversos , Derivados de Hidroxietil Amido/administração & dosagem , China/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Substitutos do Plasma/efeitos adversos , Substitutos do Plasma/administração & dosagem , Procedimentos Cirúrgicos Operatórios/efeitos adversosRESUMO
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.
Assuntos
Berberina , Derivados de Hidroxietil Amido , Ácido Linoleico , Nanopartículas , Proteínas Proto-Oncogênicas p21(ras) , Animais , Humanos , Animais Geneticamente Modificados , Antineoplásicos/farmacologia , Antineoplásicos/química , Berberina/farmacologia , Berberina/química , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Células Hep G2 , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/química , Ácido Linoleico/química , Nanopartículas/química , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Peixe-Zebra , Modelos Animais de DoençasRESUMO
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.
Assuntos
Modelos Animais de Doenças , Ressuscitação , Choque Hemorrágico , Animais , Cães , Choque Hemorrágico/terapia , Ressuscitação/métodos , Plasma , Substitutos Sanguíneos , Derivados de Hidroxietil Amido/administração & dosagemRESUMO
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.
Assuntos
Anti-Inflamatórios , Colite Ulcerativa , Curcumina , Microbioma Gastrointestinal , Derivados de Hidroxietil Amido , Microesferas , Estresse Oxidativo , Curcumina/farmacologia , Curcumina/química , Animais , Colite Ulcerativa/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Derivados de Hidroxietil Amido/química , Derivados de Hidroxietil Amido/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Colo/microbiologia , Inflamação/tratamento farmacológico , Modelos Animais de Doenças , Portadores de Fármacos/química , MasculinoRESUMO
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.
Assuntos
Derivados de Hidroxietil Amido , Micelas , Ácido Oleanólico , Oxirredução , Derivados de Hidroxietil Amido/química , Ácido Oleanólico/química , Polímeros/química , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Humanos , Hemólise/efeitos dos fármacos , Técnicas de Química Sintética , Animais , Tamanho da PartículaRESUMO
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.
Assuntos
Sobrevivência Celular , Criopreservação , Crioprotetores , Dimetil Sulfóxido , Células Endoteliais da Veia Umbilical Humana , Criopreservação/métodos , Humanos , Animais , Sobrevivência Celular/efeitos dos fármacos , Crioprotetores/farmacologia , Suínos , Dimetil Sulfóxido/farmacologia , Sulfatos de Condroitina/farmacologia , Células Endoteliais/citologia , Derivados de Hidroxietil Amido/farmacologia , Células Cultivadas , Endotélio Corneano/citologia , Endotélio Corneano/lesõesRESUMO
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.
Assuntos
Anestésicos , Transplante de Rim , Humanos , Transplante de Rim/métodos , Anestésicos/uso terapêutico , Inquéritos e Questionários , Derivados de Hidroxietil Amido , Complicações Pós-Operatórias , Assistência PerioperatóriaRESUMO
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.
Assuntos
Objetivos , Traumatismo por Reperfusão , Humanos , Animais , Suínos , Soluções Cristaloides , Microcirculação , Hidratação/métodos , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/uso terapêutico , Isquemia/terapia , Coloides/uso terapêutico , Reperfusão , Soluções Isotônicas/farmacologia , Soluções Isotônicas/uso terapêuticoRESUMO
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.
Assuntos
Vasos Coronários , Tomografia de Coerência Óptica , Humanos , Vasos Coronários/diagnóstico por imagem , Derivados de Hidroxietil Amido/efeitos adversos , Estudos de Viabilidade , CoraçãoRESUMO
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.