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1.
Cancer Med ; 13(14): e7446, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39015047

RESUMO

AIM: The Japanese Interventional oncology group (JIVROSG) showed the efficacy and safety of nonselective transarterial chemoembolization (TACE) with fine cisplatin powder (diamminedichloroplatinum; DDP-H) (65 mg/m2) and porous gelatin particles (DDP-H TACE) without lipiodol for extensive multifocal hepatocellular carcinoma (HCC). However, there are no studies on this method following the JIVROSG study. Therefore, we aimed to evaluate the efficacy of this new DDP-H TACE and its effect on liver function. METHODS: We retrospectively reviewed the medical records of TACE-naïve patients with multifocal HCC (Child-Pugh class A, up-to-seven out, no prior history of systemic therapy) who underwent whole-liver DDP-H TACE between January 2006 and December 2019. RESULTS: Sixty patients were included in this study. The median age of the patients was 71 (range, 35-88) years. The median maximum size of tumors was 26 (range, 8-184) mm; 86.7% of patients met the up-to-11 criteria out. The overall survival duration was 30.3 months. At the time of initial evaluation (median, 45 days), the overall response rate was 65.0%; the disease control rate was 86.7% based on the modified response evaluation criteria in solid tumors guideline. Although nine patients' liver function had deteriorated to Child-Pugh class B at initial evaluation, six of them recovered to Child-Pugh class A. Only three patients (5%) showed permanently impaired liver function. CONCLUSIONS: Whole-liver DDP-H TACE without lipiodol or beads effectively reduced tumors and preserved liver function.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Cisplatino , Gelatina , Neoplasias Hepáticas , Humanos , Quimioembolização Terapêutica/métodos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Gelatina/administração & dosagem , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Pós , Resultado do Tratamento , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Óleo Etiodado/administração & dosagem
2.
Artigo em Inglês | MEDLINE | ID: mdl-38874122

RESUMO

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 , Succinatos
3.
Eur J Nucl Med Mol Imaging ; 51(11): 3191-3201, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38717591

RESUMO

PURPOSE: 68Ga-Trivehexin is an investigational PET radiopharmaceutical (NCT05799274) targeting αvß6-integrin for PET imaging of carcinomas. 177Lu-D0301 is a structurally related therapeutic peptide tetramer. However, it showed considerable kidney uptake in rodents, impeding clinical applicability. We therefore evaluated the impact of different kidney protection strategies on the biodistribution of both agents in normal and tumor-bearing mice. METHODS: Ex-vivo biodistribution of 68Ga-Trivehexin (90 min p.i.) and 177Lu-D0301 (90 min and 24 h p.i.) was determined in healthy C57BL/6N and H2009 (human lung adenocarcinoma) xenografted CB17-SCID mice without and with co-infusion of 100 µL of solutions containing 2.5% arginine + 2.5% lysine (Arg/Lys), 4% succinylated gelatin (gelofusine, gelo), or combinations thereof. Arg/Lys was injected either i.p. 30 min before and after the radiopharmaceutical, or i.v. 2 min before the radiopharmaceutical. Gelo was administered either i.v. 2 min prior activity, or pre-mixed and injected together with the radiopharmaceutical (n = 5 per group). C57BL/6N mice were furthermore imaged by PET (90 min p.i.) and SPECT (24 h p.i.). RESULTS: Kidney uptake of 68Ga-Trivehexin in C57BL/6N mice was reduced by 15% (Arg/Lys i.p.), 25% (Arg/Lys i.v.), and 70% (gelo i.v.), 90 min p.i., relative to control. 177Lu-D0301 kidney uptake was reduced by 2% (Arg/Lys i.p.), 41% (Arg/Lys i.v.), 61% (gelo i.v.) and 66% (gelo + Arg/Lys i.v.) 24 h p.i., compared to control. Combination of Arg/Lys and gelo provided no substantial benefit. Gelo furthermore reduced kidney uptake of 177Lu-D0301 by 76% (90 min p.i.) and 85% (24 h p.i.) in H2009 bearing SCID mice. Since tumor uptake was not (90 min p.i.) or only slightly reduced (15%, 24 h p.i.), the tumor/kidney ratio was improved by factors of 3.3 (90 min p.i.) and 2.6 (24 h p.i.). Reduction of kidney uptake was demonstrated by SPECT, which also showed that the remaining activity was located in the cortex. CONCLUSIONS: The kidney uptake of both investigated radiopharmaceuticals was more efficiently reduced by gelofusine (61-85%) than Arg/Lys (25-41%). Gelofusine appears particularly suitable for reducing renal uptake of αvß6-integrin targeted 177Lu-labeled peptide multimers because its application led to approximately three times higher tumor-to-kidney ratios. Since the incidence of severe adverse events (anaphylaxis) with succinylated gelatin products (reportedly 0.0062-0.038%) is comparable to that of gadolinium-based MRI or iodinated CT contrast agents (0.008% and 0.04%, respectively), clinical use of gelofusine during radioligand therapy appears feasible if similar risk management strategies as for contrast agents are applied.


Assuntos
Aminoácidos , Gelatina , Integrinas , Rim , Succinatos , Animais , Camundongos , Aminoácidos/administração & dosagem , Aminoácidos/efeitos adversos , Aminoácidos/farmacocinética , Antígenos de Neoplasias , Transporte Biológico , Linhagem Celular Tumoral , Radioisótopos de Gálio , Gelatina/administração & dosagem , Gelatina/efeitos adversos , Gelatina/farmacocinética , Integrinas/metabolismo , Rim/metabolismo , Rim/diagnóstico por imagem , Lutécio/administração & dosagem , Lutécio/efeitos adversos , Lutécio/farmacocinética , Camundongos Endogâmicos C57BL , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Peptídeos/farmacocinética , Tomografia por Emissão de Pósitrons/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/administração & dosagem , Radioisótopos/efeitos adversos , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Segurança , Succinatos/administração & dosagem , Succinatos/efeitos adversos , Succinatos/farmacocinética , Distribuição Tecidual/efeitos dos fármacos , Ensaios Clínicos Fase I como Assunto
4.
Biomater Sci ; 12(12): 3141-3153, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38687002

RESUMO

Intestine damage is an acute abdominal disease that usually requires emergency sealing. However, traditional surgical suture not only causes secondary damage to the injured tissue, but also results in adhesion with other tissues in the abdominal cavity. To this end, a thermally reversible injectable gelatin-based hydrogel adhesive (GTPC) is constructed by introducing transglutaminase (TGase) and proanthocyanidins (PCs) into a gelatin system. By reducing the catalytic activity of TGase, the density of covalent and hydrogen bond crosslinking in the hydrogel can be regulated to tune the sol-gel transition temperature of gelatin-based hydrogels above the physiological temperature (42 °C) without introducing any synthetic small molecules. The GTPC hydrogel exhibits good tissue adhesion, antioxidant, and antibacterial properties, which can effectively seal damaged intestinal tissues and regulate the microenvironment of the damaged site, promoting tissue repair and regeneration. Intriguingly, temperature-induced hydrogen bond disruption and reformation confer the hydrogel with asymmetric adhesion properties, preventing tissue adhesion when applied in vivo. Animal experiment outcomes reveal that the GTPC hydrogel can seal the damaged intestinal tissue firmly, accelerate tissue healing, and efficiently prevent postoperative adhesion.


Assuntos
Gelatina , Hidrogéis , Intestinos , Temperatura , Animais , Hidrogéis/química , Hidrogéis/administração & dosagem , Hidrogéis/farmacologia , Aderências Teciduais/prevenção & controle , Intestinos/efeitos dos fármacos , Gelatina/química , Gelatina/administração & dosagem , Transglutaminases/metabolismo , Adesivos Teciduais/farmacologia , Adesivos Teciduais/química , Adesivos Teciduais/administração & dosagem , Proantocianidinas/farmacologia , Proantocianidinas/química , Proantocianidinas/administração & dosagem , Cicatrização/efeitos dos fármacos , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Injeções , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/administração & dosagem
5.
J Surg Res ; 298: 316-324, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640617

RESUMO

INTRODUCTION: Intraoperative blood loss and postoperative hemorrhage affect outcomes after liver resection. GATT-Patch is a new flexible, pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with N-hydroxy-succinimide polyoxazoline. We evaluated safety and performance of the GATT-Patch for hemostasis at the liver resection plane. METHODS: Adult patients undergoing elective open liver surgery were recruited in three centers. GATT-Patch was used for minimal to moderate bleeding at the liver resection plane. The primary endpoint was hemostasis of the first-treated bleeding site at 3 min versus a prespecified performance goal of 65.4%. RESULTS: Two trial stages were performed: I (n = 8) for initial safety and II (n = 39) as the primary outcome cohort. GATT-Patch was applied in 47 patients on 63 bleeding sites. Median age was 60.0 (range 25-80) years and 70% were male. Most (66%) surgeries were for colorectal cancer metastases. The primary endpoint was met in 38 out of 39 patients (97.4%; 95% confidence interval: 84.6%-99.9%) versus 65.4% (P < 0.001). Of all the 63 bleeding sites, hemostasis was 82.7% at 30, 93.7% at 60, and 96.8% at 180 s. No reoperations for rebleeding or device-related issues occurred. CONCLUSIONS: When compared to a performance goal derived from state-of-the-art hemostatic agents, GATT-Patch for the treatment of minimal to moderate bleeding during liver surgery successfully and quickly achieved hemostasis with acceptable safety outcomes. (ClinicalTrials.gov Identifier: NCT04819945).


Assuntos
Perda Sanguínea Cirúrgica , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Perda Sanguínea Cirúrgica/prevenção & controle , Hemostasia Cirúrgica/métodos , Hemostasia Cirúrgica/instrumentação , Hemostáticos/administração & dosagem , Hemostáticos/uso terapêutico , Hemostáticos/efeitos adversos , Resultado do Tratamento , Gelatina/efeitos adversos , Gelatina/administração & dosagem , Estudos Prospectivos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário
6.
BMC Pulm Med ; 24(1): 203, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658883

RESUMO

BACKGROUND: Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. METHODS: A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500-750 µm microspheres, and group B patients were treated with 700-900 µm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. RESULTS: Median follow-up was 30.2 months (range, 20.3-56.5 months). The final analysis included a total of 112 patients (49-77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500-750 µm Embosphere microspheres, and group B (N = 44), which received 700-900 µm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12-2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10-2.72; P = 0.028) were independent risk factors for recurrent bleeding. CONCLUSIONS: For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500-750 µm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700-900 µm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700-900 µm) Embosphere microspheres is associated with the reduced cost of an embolic agent.


Assuntos
Resinas Acrílicas , Artérias Brônquicas , Bronquiectasia , Embolização Terapêutica , Hemoptise , Microesferas , Humanos , Hemoptise/terapia , Hemoptise/etiologia , Estudos Retrospectivos , Masculino , Feminino , Embolização Terapêutica/métodos , Pessoa de Meia-Idade , Idoso , Bronquiectasia/complicações , Bronquiectasia/terapia , Gelatina/administração & dosagem , Gelatina/uso terapêutico , Resultado do Tratamento , Tamanho da Partícula
7.
J Vet Pharmacol Ther ; 47(4): 266-273, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38519447

RESUMO

Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60-90) to release BIPS™ compared to gelatin capsules (15 min, range 15-30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.


Assuntos
Cápsulas , Preparações de Ação Retardada , Gelatina , Animais , Cães , Gelatina/administração & dosagem , Gelatina/química , Masculino , Feminino
8.
Biomed Pharmacother ; 151: 113165, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35609370

RESUMO

OBJECTIVE: To investigate the efficacy of a paeoniflorin-sodium alginate (SA)-gelatin skin scaffold for treating diabetic wound in a rat model. METHODS: Bioinks were prepared using various percentages of paeoniflorin in the total weight of a solution containing SA and gelatin. Skin scaffolds containing 0%, 1%, 3%, 5%, and 10% paeoniflorin were printed using 3D bioprinting technology, and scaffold microstructure was observed with scanning electron microscopy. Skin scaffolds were then used in rats with diabetic wounds. H&E staining, Masson staining, and immunohistochemical staining for IL-1ß and CD31 were performed on days 7 and 14. RESULTS: All skin scaffolds had a mesh-like structure with uniform pore distribution. Wounds healed well in each group, with the 1% and 3% groups demonstrating the most complete healing. H&E staining showed that skin accessory organs had appeared in each group. On day 7, collagen deposition in the 3% group was higher than in the other groups (P<0.05), and IL-1ß infiltration was lower in the 10% group than in the 3% group (P = 0.002). On day 14, IL-1ß infiltration was not significantly different between the 10% and 3% groups (P = 0.078). The CD31 level was higher in the 3% group than in the other groups on days 7 and 14 (P<0.05). CONCLUSION: A 3% paeoniflorin-SA-gelatin skin scaffold promoted the healing of diabetic wounds in rats. This scaffold promoted collagen deposition and microvascular regeneration and demonstrated anti-inflammatory properties, suggesting that this scaffold type could be used to treat diabetic wounds.


Assuntos
Alginatos , Complicações do Diabetes , Gelatina , Glucosídeos , Pele , Alicerces Teciduais , Alginatos/administração & dosagem , Alginatos/uso terapêutico , Animais , Colágeno/metabolismo , Complicações do Diabetes/complicações , Complicações do Diabetes/terapia , Diabetes Mellitus , Modelos Animais de Doenças , Gelatina/administração & dosagem , Gelatina/uso terapêutico , Glucosídeos/administração & dosagem , Glucosídeos/uso terapêutico , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Monoterpenos/administração & dosagem , Monoterpenos/uso terapêutico , Impressão Tridimensional , Ratos , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Pele/lesões , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
9.
J Healthc Eng ; 2022: 1424021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126897

RESUMO

Prostatic hyperplasia can cause dysuria, such as frequent urination, urgency of urination, increased nocturia, poor urination, and other symptoms, which seriously affect the quality of life of old men. We aim to compare and analyze the safety and clinical effect of embolization of the target blood vessels of ruptured prostatic hyperplasia with gelatin sponge particles and embosphere microspheres. Methods. The transcatheter MRI was performed in 422 patients. Among them, 198 patients were treated with gelfoam particles and 224 patients were treated with embosphere microspheres. The clinical effect and adverse reactions were observed and analyzed by biochemical and imaging examination. Four hundred and twenty two cases were hemostasis. In the gelatin sponge group, 34 patients had recurrent bleeding 24-36 hours after embolization, 122 patients had different degrees of elevation of prostatic hyperplasia transaminase (31 cases increased to more than 1000 U/L), 198 patients had different degrees of elevation of bilirubin; in the microsphere group, there was no significant difference in prostatic hyperplasia function indexes between the two groups. Conclusion. Compared with the gelfoam embolic agent, the embosphere embolic microsphere has a good efficacy and safety in the treatment of prostatic hyperplasia rupture and hemorrhage, with a light adverse reaction, a low probability of recanalization, and little damage to the postoperative prostatic hyperplasia function, which is conducive to the benign recovery of perioperative patients and is worthy of clinical application.


Assuntos
Embolização Terapêutica , Gelatina , Hiperplasia Prostática , Resinas Acrílicas , Artérias , Gelatina/administração & dosagem , Humanos , Masculino , Microesferas , Próstata/irrigação sanguínea , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/terapia , Qualidade de Vida , Resultado do Tratamento
10.
J Vasc Interv Radiol ; 33(2): 169-176.e1, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34715322

RESUMO

PURPOSE: To evaluate the safety and efficacy of a newly developed technique of balloon-occluded alternate infusions of cisplatin and gelatin particles in transarterial chemoembolization in hepatocellular carcinoma (HCC) and to evaluate the liver damage following the procedure. MATERIALS AND METHODS: Forty-three patients with HCC from 4 medical centers were enrolled in this multicenter prospective study. Of these, 41 patients were observed for 6 months following balloon-occluded alternate infusion transarterial chemoembolization. The primary endpoint was the safety of the procedure, and the secondary endpoint was the objective response rate (ORR) of the HCCs at 2 months following treatment. RESULTS: Three patients experienced adverse events, including 1 patient with facial swelling and skin rash, dissection of the celiac artery, and bland portal vein thrombus. No major adverse events were identified. Two (5.3%) patients regressed from a Child-Pugh classification of A to B. The balloon-occluded alternate infusion transarterial chemoembolization treatment achieved a 22.0% complete response (CR) rate and a 73.2% ORR (95% confidence interval [CI], 57.9%-84.4%). In a retrospective analysis of 23 patients with HCCs above the up-to-7 criteria, the CR rate and ORR of the balloon-occluded alternate infusion transarterial chemoembolization were 21.7% and 82.6% (95% CI, 62.3%-93.6%), respectively. CONCLUSIONS: Balloon-occluded alternate infusion transarterial chemoembolization is safe and effective for achieving a high ORR while preserving liver function.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Cisplatino/administração & dosagem , Gelatina/administração & dosagem , Humanos , Neoplasias Hepáticas/terapia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
11.
ACS Appl Mater Interfaces ; 14(1): 236-244, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34935360

RESUMO

Gelatin is one of the most versatile biopolymers in various biomedical applications. A gelatin derivative gelatin-catechol (Gel-C) was developed in this study to further optimize its chemical and physical properties such as thermal reversibility and injectability. We found that Gel-C remains in a solution state at room temperature, and the temperature-dependent gelation capability of gelatin is well preserved in Gel-C. Its gel-forming temperature decreased to about 10 °C (about 30 °C for gelatin), and a series of gelatin derivatives with different gel-forming temperatures (10-30 °C) were formed by mixing gelatin and Gel-C in different ratios. Additionally, irreversible Gel-C hydrogels could be made without the addition of external stimuli by combining the physical cross-linking of gelatin and the chemical cross-linking of catechol. At the same time, properties of Gel-C hydrogels such as thermal reversibility and injectability could be manipulated by controlling the temperature and pH of the precursor solution. By simulating the formation of an irreversible Gel-C hydrogel in vivo, an in situ gelling system was fabricated by lowering the local temperature of the hydrogel with cold shock, thus realizing targeted and localized molecular delivery with prolonged retention time. This simple system integrated with the temperature responsiveness of gelatin and chemical cross-linking of catechol groups thus provides a promising platform to fabricate an in situ gelling system for drug delivery.


Assuntos
Catecóis/química , Preparações de Ação Retardada/química , Gelatina/química , Hidrogéis/química , Animais , Catecóis/administração & dosagem , Catecóis/síntese química , Catecóis/toxicidade , Linhagem Celular , Temperatura Baixa , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/toxicidade , Liberação Controlada de Fármacos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Gelatina/administração & dosagem , Gelatina/síntese química , Gelatina/toxicidade , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Hidrogéis/toxicidade , Concentração de Íons de Hidrogênio , Injeções Subcutâneas , Masculino , Camundongos Nus , Transição de Fase/efeitos dos fármacos , Soroalbumina Bovina/química , Temperatura de Transição
12.
Sci Rep ; 11(1): 23617, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34880372

RESUMO

Optimal fluid therapy significantly affects the maintenance of proper tissue perfusion and, consequently, kidney function. An adverse effect of colloids on kidney function is related to the incidence of postoperative kidney failure. The study aimed to assess the effect of a 3% gelatin solution on kidney function based on the urinary kidney injury molecule-1 (uKIM-1) level. This study used a parallel design and enrolled 64 adult patients with a mean age of 52.5 ± 13.1 years, all of whom underwent a thyroidectomy procedure under general anesthesia. Patients were randomly assigned to three comparison groups, each receiving a different dose of 3% gelatin solution during the thyroidectomy procedure. The patients from study groups A (n = 21) and B (n = 21) received a 3% gelatin solution at a dose of 30 ml/kg and 15 ml/kg body weight, respectively, during the first hour of the procedure. The patients from the control group C (n = 22) received an isotonic multi-electrolyte solution. Serum creatinine levels were determined, and urine samples were collected to determine levels of uKIM-1 before, 2 h, and 24 h after surgery. The patients' demographic data, type and volume of fluid and hemodynamic status during the surgery were collected from relevant anesthesia protocols and were included in the study data. There were no statistically significant changes between groups in hemodynamic parameters such as systolic and diastolic blood pressure, heart rate, and oxygen saturation values. A statistically significant increase in uKIM-1 level was noted in patients receiving the 3% gelatin solution regardless of the dose. A statistically significant difference in uKIM-1 level was observed between groups A, B, and C measured 24 h after surgery, with the highest uKIM-1 level in group A. Measurement of uKIM-1 level could be an early and sensitive biomarker of kidney injury. Kidney toxicity of a 3% gelatin solution, evaluated based on the level of uKIM-1 in urine, correlates with transfused fluid volume. This study was retrospectively registered in the ISRCTN clinical trials registry (ISRCTN73266049, 08/04/2021: https://www.isrctn.com/ISRCTN73266049 ).


Assuntos
Gelatina/administração & dosagem , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Tireoidectomia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções , Urinálise
13.
Plast Reconstr Surg ; 148(5): 742e-752e, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34705777

RESUMO

BACKGROUND: A novel biocompatible sealant composed of Alaska pollock-derived gelatin (ApGltn) has recently shown good burst strength and biocompatibility in a porcine aorta. The purpose of this study was to investigate the bonding strength and biocompatibility of the ApGltn sealant in transected digital nerves of fresh frozen cadavers and in the sciatic nerves of a rat model. METHODS: Eighty human digital nerves of fresh frozen cadavers were transected for biomechanical traction testing. They were treated with four surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; and (4) fibrin sealant. Forty-three sciatic nerves of male Wistar rats were used for functional and histopathologic evaluation. They were treated with six surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; (4) fibrin sealant; (5) resection with a 5-mm gap (10 rats per group); and (6) sham operation (three rats). Macroscopic confirmation, muscle weight measurement, and histopathologic findings including G-ratio were examined 8 weeks after the procedure. RESULTS: The maximum failure load of the ApGltn sealant was significantly higher than that of a fibrin sealant (0.22 ± 0.05 N versus 0.06 ± 0.04 N). The maximum failure load of the ApGltn sealant was significantly lower that of suture plus ApGltn sealant (1.37 N) and suture (1.27 N). Functional evaluation and histologic examination showed that sciatic nerves repaired with ApGltn sealant showed similar nerve recovery compared to repair with the suture and fibrin sealant. CONCLUSION: The ApGltn sealant showed higher bonding strength and equal effect of nerve regeneration when compared with the fibrin sealant.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Proteínas de Peixes/administração & dosagem , Gelatina/administração & dosagem , Adesivos Teciduais/administração & dosagem , Idoso de 80 Anos ou mais , Animais , Materiais Biocompatíveis/química , Cadáver , Feminino , Adesivo Tecidual de Fibrina/administração & dosagem , Adesivo Tecidual de Fibrina/química , Traumatismos dos Dedos/cirurgia , Dedos/inervação , Proteínas de Peixes/química , Gelatina/química , Humanos , Masculino , Teste de Materiais , Modelos Animais , Ratos , Ratos Wistar , Nervo Isquiático/lesões , Nervo Isquiático/cirurgia , Adesivos Teciduais/química
14.
J Mater Sci Mater Med ; 32(10): 127, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591193

RESUMO

Topical hemostatic agents have become essential tools to aid in preventing excessive bleeding in surgical or emergency settings and to mitigate the associated risks of serious complications. In the present study, we compared the hemostatic efficacy of SURGIFLO® Hemostatic Matrix Kit with Thrombin (Surgiflo-flowable gelatin matrix plus human thrombin) to HEMOBLAST™ Bellows Hemostatic Agent (Hemoblast-a combination product consisting of collagen, chondroitin sulfate, and human thrombin). Surgiflo and Hemoblast were randomly tested in experimentally induced bleeding lesions on the spleens of four pigs. Primary endpoints included hemostatic efficacy measured by absolute time to hemostasis (TTH) within 5 min. Secondary endpoints included the number of product applications and the percent of product needed from each device to achieve hemostasis. Surgiflo demonstrated significantly higher hemostatic efficacy and lower TTH (p < 0.01) than Hemoblast. Surgiflo-treated lesion sites achieved hemostasis in 77.4% of cases following a single product application vs. 3.3% of Hemoblast-treated sites. On average, Surgiflo-treated sites required 63% less product applications than Hemoblast-treated sites (1.26 ± 0.0.51 vs. 3.37 ± 1.16). Surgiflo provided more effective and faster hemostasis than Hemoblast. Since both products contain thrombin to activate endogenous fibrinogen and accelerate clot formation, the superior hemostatic efficacy of Surgiflo in the porcine spleen punch biopsy model seems to be due to Surgiflo's property as a malleable barrier able to adjust to defect topography and to provide an environment for platelets to adhere and aggregate. Surgiflo combines a flowable gelatin matrix and a delivery system well-suited for precise application to bleeding sites where other methods of hemostasis may be impractical or ineffective.


Assuntos
Hemorragia/terapia , Técnicas Hemostáticas , Hemostáticos/administração & dosagem , Baço/efeitos dos fármacos , Administração Tópica , Animais , Biópsia/efeitos adversos , Biópsia/veterinária , Modelos Animais de Doenças , Feminino , Gelatina/administração & dosagem , Gelatina/farmacologia , Hemostasia Cirúrgica/métodos , Hemostáticos/farmacologia , Índice de Gravidade de Doença , Baço/patologia , Suínos , Trombina/administração & dosagem , Trombina/farmacologia , Resultado do Tratamento
15.
CNS Neurosci Ther ; 27(7): 857-861, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34050606

RESUMO

Microvascular Decompression for Hemifacial Spasm Involving the Vertebral Artery (VA): A Modified Effective Technique Using a Gelatin Sponge with a FuAiLe Medical Adhesive. (a)The VA pushes the anterior inferior cerebellar artery (AICA) which compressed the root exit zone (REZ) of the facial nerve. (b) The VA was adhered to the petrous dura, and the AICA was decompressed from the REZ by a Teflon pad.


Assuntos
Adesivos/administração & dosagem , Esponja de Gelatina Absorvível/administração & dosagem , Gelatina/administração & dosagem , Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Artéria Vertebral/cirurgia , Adulto , Idoso , Feminino , Espasmo Hemifacial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
16.
Biomed Pharmacother ; 140: 111747, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34044276

RESUMO

Management of non-healing and slow to heal diabetic wounds is a major concern in healthcare across the world. Numerous techniques have been investigated to solve the issue of delayed wound healing, though, mostly unable to promote complete healing of diabetic wounds due to the lack of proper cell proliferation, poor cell-cell communication, and higher chances of wound infections. These challenges can be minimized by using hydrogel based wound healing patches loaded with bioactive agents. Gelatin methacrylate (GelMA) has been proven to be a highly cell friendly, cell adhesive, and inexpensive biopolymer for various tissue engineering and wound healing applications. In this study, S-Nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was incorporated in a highly porous GelMA hydrogel patch to improve cell proliferation, facilitate rapid cell migration, and enhance diabetic wound healing. We adopted a visible light crosslinking method to fabricate this highly porous biodegradable but relatively stable patch. Developed patches were characterized for morphology, NO release, cell proliferation and migration, and diabetic wound healing in a rat model. The obtained results indicate that SNAP loaded visible light crosslinked GelMA hydrogel patches can be highly effective in promoting diabetic wound healing.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Gelatina/administração & dosagem , Hidrogéis/administração & dosagem , Metacrilatos/administração & dosagem , Doadores de Óxido Nítrico/administração & dosagem , S-Nitroso-N-Acetilpenicilamina/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Gelatina/química , Hidrogéis/química , Luz , Metacrilatos/química , Óxido Nítrico/química , Doadores de Óxido Nítrico/química , Ratos Sprague-Dawley , S-Nitroso-N-Acetilpenicilamina/química
17.
Cell Biol Int ; 45(8): 1624-1632, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33818836

RESUMO

Metallic materials are commonly used for load-bearing implants and as internal fixation devices. It is customary to use austenitic stainless steel, especially surgical grade type 316L SS as temporary and Ti alloys as permanent implants. However, long-term, poor bonding with bone, corrosion, and release of metal ions, such as chromium and nickel occur. These ions are powerful allergens and carcinogens and their uncontrolled leaching may be avoided by surface coatings. Therefore, bioactive glasses (BGs) became a vital biomedical material, which can form a biologically active phase of hydroxycarbonate apatite on their surface when in contact with physiological fluids. To reduce the high coefficient of friction and the brittle nature of BGs, polymers are normally incorporated to avoid the high-temperature sintering/densification of ceramic-only coatings. For medical application, electrophoretic deposition (EPD) is now used for polymer (organic) and ceramic (inorganic) components at room temperature due to its simplicity, control of coating thickness and uniformity, low cost of equipment, ability to coat substrates of intricate shape and to supply thick films in composite form, high purity of deposits as well as no phase transformation during coating. Although extensive research has been conducted on polymer/inorganic composite coatings, only some studies have reported multifunctional properties, such as biological antibacterial activity, enhanced cell adhesion, controlled drug release ability, and mechanical properties. This review will focus on biodegradable coatings, including zien, chitosan, gelatin, cellulose loaded with antibacterial drugs/metallic ions/natural herbs on biostable substrates (PEEK/PMMA/PCL/PLLA layers), which have the potential of multifunctional coating for metallic implants.


Assuntos
Antibacterianos/química , Materiais Biocompatíveis/química , Implantes de Medicamento/química , Teste de Materiais/métodos , Metais/química , Ligas/administração & dosagem , Ligas/química , Ligas/metabolismo , Animais , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/metabolismo , Quitosana/administração & dosagem , Quitosana/química , Quitosana/metabolismo , Implantes de Medicamento/administração & dosagem , Implantes de Medicamento/metabolismo , Gelatina/administração & dosagem , Gelatina/química , Gelatina/metabolismo , Humanos , Metais/administração & dosagem , Metais/metabolismo
18.
Theranostics ; 11(8): 3948-3960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664872

RESUMO

Background: Pacemaker implantation is currently used in patients with symptomatic bradycardia. Since a pacemaker is a lifetime therapeutic device, its energy consumption contributes to battery exhaustion, along with its voltage stimulation resulting in local fibrosis and greater resistance, which are all detrimental to patients. The possible resolution for those clinical issues is an injection of a conductive hydrogel, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), to reduce the myocardial threshold voltage for pacemaker stimulation. Methods: PAMB-G is synthesized by covalently linking PAMB to gelatin, and its conductivity is measured using two-point resistivity. Rat hearts are injected with gelatin or PAMB-G, and pacing threshold is evaluated using electrocardiogram and cardiac optical mapping. Results: PAMB-G conductivity is 13 times greater than in gelatin. The ex vivo model shows that PAMB-G significantly enhances cardiac tissue stimulation. Injection of PAMB-G into the stimulating electrode location at the myocardium has a 4 times greater reduction of pacing threshold voltage, compared with electrode-only or gelatin-injected tissues. Multi-electrode array mapping reveals that the cardiac conduction velocity of PAMB-G group is significantly faster than the non- or gelatin-injection groups. PAMB-G also reduces pacing threshold voltage in an adenosine-induced atrial-ventricular block rat model. Conclusion: PAMB-G hydrogel reduces cardiac pacing threshold voltage, which is able to enhance pacemaker efficacy.


Assuntos
Estimulação Cardíaca Artificial/métodos , Marca-Passo Artificial , Animais , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/terapia , Materiais Biocompatíveis/administração & dosagem , Modelos Animais de Doenças , Condutividade Elétrica , Estimulação Elétrica/métodos , Eletrocardiografia , Eletrodos Implantados , Gelatina/administração & dosagem , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Éteres de Hidroxibenzoatos/administração & dosagem , Éteres de Hidroxibenzoatos/síntese química , Éteres de Hidroxibenzoatos/química , Técnicas In Vitro , Injeções , Teste de Materiais , Medicina de Precisão , Ratos , Ratos Sprague-Dawley
19.
J Vasc Interv Radiol ; 32(6): 819-825, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33640516

RESUMO

PURPOSE: To evaluate the safety and efficacy of superior rectal artery embolization (SRAE) with different-sized tris-acryl gelatin microspheres in symptomatic hemorrhoidal disease (HD). MATERIALS AND METHODS: Forty-two patients (male, 30; female, 12; median age, 45 years) with symptomatic HD (2 grade I, 8 grade II, 17 grade III, and 15 grade IV) were divided into 3 experimental arms (500-700 µm, 700-900 µm, and 900-1,200 µm groups; each had 14 patients) in a prospective randomized style to perform SRAE. Follow-up was performed by rectoscopy, clinical examination, and questionnaires. The primary outcome measure was the clinical success rate at 12 months. Secondary outcome measures were technical success rate, recurrence rate, procedure-related mortality, procedure-related complications, and any outcome changes between particle sizes. RESULTS: No procedure-related deaths or major morbidities were observed. There was a 54% minor complication rate (n = 23/42) in the treated zone: 45% sustained small superficial ulcerations (n = 19/42), 7% small rectosigmoid junction ulcerations (n = 3/42), and 2% small fibrotic scar tissue (n = 1/42). The clinical success rate was 93%. Of the groups, the best French bleeding score decrease was obtained in the 900-1,200 µm group. There were improvements in the quality of life score and visual analogue scale score after the SRAE procedure, although not in the Goligher score. No recurrent disease was observed. CONCLUSIONS: SRAE with tris-acryl gelatin microspheres for symptomatic HD is a safe and efficient treatment, with results favoring the use of larger microspheres.


Assuntos
Resinas Acrílicas/administração & dosagem , Artérias , Embolização Terapêutica , Hemorragia Gastrointestinal/terapia , Gelatina/administração & dosagem , Hemorroidas/terapia , Reto/irrigação sanguínea , Resinas Acrílicas/efeitos adversos , Adolescente , Adulto , Idoso , Embolização Terapêutica/efeitos adversos , Feminino , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Gelatina/efeitos adversos , Hemorroidas/complicações , Hemorroidas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Estudos Prospectivos , Qualidade de Vida , Recidiva , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Turquia , Adulto Jovem
20.
J Vasc Interv Radiol ; 32(6): 853-860, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33636309

RESUMO

PURPOSE: To evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver. MATERIAL AND METHODS: From October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35-78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1-9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient. RESULTS: The overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4-14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3-9.5). No grade 3-5 adverse events were detected in either group. CONCLUSIONS: HAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.


Assuntos
Resinas Acrílicas/administração & dosagem , Embolização Terapêutica , Gelatina/administração & dosagem , Artéria Hepática , Neoplasias Hepáticas/terapia , Neoplasias Ovarianas/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Resinas Acrílicas/efeitos adversos , Adulto , Idoso , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Gelatina/efeitos adversos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Cidade de Nova Iorque , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Tamanho da Partícula , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo
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