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1.
Cochrane Database Syst Rev ; 3: CD000475, 2020 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-32199406

RESUMO

BACKGROUND: Pelvic adhesions can form secondary to inflammation, endometriosis, or surgical trauma. Strategies to reduce pelvic adhesion formation include placing barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene, and fibrin or collagen sheets between pelvic structures. OBJECTIVES: To evaluate the effects of barrier agents used during pelvic surgery on rates of pain, live birth, and postoperative adhesions in women of reproductive age. SEARCH METHODS: We searched the following databases in August 2019: the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, and trial registries. We searched reference lists of relevant papers, conference proceedings, and grey literature sources. We contacted pharmaceutical companies for information and handsearched relevant journals and conference abstracts. SELECTION CRITERIA: Randomised controlled trials (RCTs) on the use of barrier agents compared with other barrier agents, placebo, or no treatment for prevention of adhesions in women undergoing gynaecological surgery. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for eligibility and risk of bias and extracted data. We calculated odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) using a fixed-effect model. We assessed the overall quality of the evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods. MAIN RESULTS: We included 19 RCTs (1316 women). Seven RCTs randomised women; the remainder randomised pelvic organs. Laparoscopy (eight RCTs) and laparotomy (11 RCTs) were the primary surgical techniques. Indications for surgery included myomectomy (seven RCTs), ovarian surgery (five RCTs), pelvic adhesions (five RCTs), endometriosis (one RCT), and mixed gynaecological surgery (one RCT). The sole indication for surgery in three of the RCTs was infertility. Thirteen RCTs reported commercial funding; the rest did not state their source of funding. No studies reported our primary outcomes of pelvic pain and live birth rate. Oxidised regenerated cellulose versus no treatment at laparoscopy or laparotomy (13 RCTs) At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose at laparoscopy reduced the incidence of de novo adhesions (OR 0.50, 95% CI 0.30 to 0.83, 3 RCTs, 360 participants; I² = 75%; very low-quality evidence) or of re-formed adhesions (OR 0.17, 95% CI 0.07 to 0.41, 3 RCTs, 100 participants; I² = 36%; very low-quality evidence). At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose affected the incidence of de novo adhesions after laparotomy (OR 0.72, 95% CI 0.42 to 1.25, 1 RCT, 271 participants; very low-quality evidence). However, the incidence of re-formed adhesions may have been reduced in the intervention group (OR 0.38, 95% CI 0.27 to 0.55, 6 RCTs, 554 participants; I² = 41%; low-quality evidence). No studies reported results on pelvic pain, live birth rate, adhesion score, or clinical pregnancy rate. Expanded polytetrafluoroethylene versus oxidised regenerated cellulose at gynaecological surgery (two RCTs) We are uncertain whether expanded polytetrafluoroethylene reduced the incidence of de novo adhesions at second-look laparoscopy (OR 0.93, 95% CI 0.26 to 3.41, 38 participants; very low-quality evidence). We are also uncertain whether expanded polytetrafluoroethylene resulted in a lower adhesion score (out of 11) (MD -3.79, 95% CI -5.12 to -2.46, 62 participants; very low-quality evidence) or a lower risk of re-formed adhesions (OR 0.13, 95% CI 0.02 to 0.80, 23 participants; very low-quality evidence) when compared with oxidised regenerated cellulose. No studies reported results regarding pelvic pain, live birth rate, or clinical pregnancy rate. Collagen membrane with polyethylene glycol and glycerol versus no treatment at gynaecological surgery (one RCT) Evidence suggests that collagen membrane with polyethylene glycol and glycerol may reduce the incidence of adhesions at second-look laparoscopy (OR 0.04, 95% CI 0.00 to 0.77, 47 participants; low-quality evidence). We are uncertain whether collagen membrane with polyethylene glycol and glycerol improved clinical pregnancy rate (OR 5.69, 95% CI 1.38 to 23.48, 39 participants; very low-quality evidence). One study reported adhesion scores but reported them as median scores rather than mean scores (median score 0.8 in the treatment group vs median score 1.2 in the control group) and therefore could not be included in the meta-analysis. The reported P value was 0.230, and no evidence suggests a difference between treatment and control groups. No studies reported results regarding pelvic pain or live birth rate. In total, 15 of the 19 RCTs included in this review reported adverse events. No events directly attributed to adhesion agents were reported. AUTHORS' CONCLUSIONS: We found no evidence on the effects of barrier agents used during pelvic surgery on pelvic pain or live birth rate in women of reproductive age because no trial reported these outcomes. It is difficult to draw credible conclusions due to lack of evidence and the low quality of included studies. Given this caveat, low-quality evidence suggests that collagen membrane with polyethylene glycol plus glycerol may be more effective than no treatment in reducing the incidence of adhesion formation following pelvic surgery. Low-quality evidence also shows that oxidised regenerated cellulose may reduce the incidence of re-formation of adhesions when compared with no treatment at laparotomy. It is not possible to draw conclusions on the relative effectiveness of these interventions due to lack of evidence. No adverse events directly attributed to the adhesion agents were reported. The quality of the evidence ranged from very low to moderate. Common limitations were imprecision and poor reporting of study methods. Most studies were commercially funded, and publication bias could not be ruled out.


Assuntos
Celulose Oxidada/uso terapêutico , Infertilidade Feminina/cirurgia , Politetrafluoretileno/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Colo do Útero/cirurgia , Colágeno/administração & dosagem , Feminino , Fibrina/administração & dosagem , Glicerol/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Incidência , Laparoscopia/efeitos adversos , Laparotomia/efeitos adversos , Membranas Artificiais , Dor Pós-Operatória/prevenção & controle , Pelve/cirurgia , Polietilenoglicóis/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Cirurgia de Second-Look , Aderências Teciduais/epidemiologia , Aderências Teciduais/prevenção & controle , Viscossuplementos/administração & dosagem
2.
Clin Orthop Relat Res ; 478(3): 653-664, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31842142

RESUMO

BACKGROUND: Augmentation of soft-tissue repairs with an autologous fibrin clot has been used clinically for nearly four decades; however, fibrin clots tend to produce an abundance of scar tissue, which is known to inhibit soft-tissue regeneration. Mesenchymal stem cells (MSCs) embedded in fibrin clots before repair could reduce scar tissue deposition and facilitate soft-tissue regeneration. To our knowledge, no published studies have directly evaluated the viability or bioactivity of MSCs in fresh human fibrin clots over time. The purpose of this study was to evaluate the viability and bioactivity of human MSCs inside human fibrin clots over time in nutritive and non-nutritive culture media. QUESTIONS/PURPOSES: We hypothesized that human MSCs would (1) be captured inside fibrin clots and retain their proliferative capacity, (2) remain viable for at least 7 days in the fibrin clots, (3) maintain their proliferative capacity for at least 7 days in the fibrin clots without evidence of active apoptosis, and (4) display similar viability and proliferative capacity when cultured in a non-nutritive medium over the same time periods. METHODS: Twelve patients (mean age 33.7 years; range 4-72 years) who underwent elective knee surgery were approached between February 2016 and October 2017; all patients agreed to participate and were enrolled. MSCs isolated from human skeletal muscle and banked after prior studies were used for this analysis. On the day of surgery and after expansion of the MSC population, 3-mL aliquots of phosphate-buffered saline containing approximately 600,000 labeled with anti-green fluorescent protein (GFP) antibodies were transported to the operating room, mixed in 30 mL of venous blood from each enrolled patient, and stirred at 95 rpm for 10 minutes to create MSC-embedded fibrin clots. The fibrin clots were transported to the laboratory with their residual blood for analysis. Eleven samples were analyzed after exclusion of one sample because of a processing error. MSC capture was qualitatively demonstrated by enzymatically digesting half of each clot specimen, thus releasing GFP-positive MSCs into culture. The released MSCs were allowed to culture for 7 days. Manual counting of GFP-positive MSCs was performed at 2, 3, 4, and 7 days using an inverted microscope at 100 x magnification to document the change in the number of GFP-positive MSCs over time. The intact remaining half of each clot specimen was immediately placed in proliferation media and allowed to culture for 7 days. On Days 1, 2, 3, 4, and 7, a small portion of the clot was excised, flash-frozen, cryosectioned (8-µm thickness), and immunostained with antibodies specific to GFP, Ki67 (indicative of active proliferation), and cleaved caspase-3 ([CC3]; indicative of active apoptosis). Using an inverted microscope, we obtained MSC cell counts manually at time zero and after 1, 2, 3, 4, and 7 days of culture. Intact fresh clot specimens were immediately divided in half; one half was placed in nutritive (proliferation media) and the other was placed in non-nutritive (saline) media for 1, 2, 3, 4, and 7 days. At each timepoint, specimens were processed in an identical manner as described above, and a portion of each clot specimen was excised, immediately flash-frozen with liquid nitrogen, cryosectioned (8-µm thickness), and visualized at 200 x using an inverted microscope. The numbers of stain-positive MSCs per field of view, per culture condition, per timepoint, and per antibody stain type were counted manually for a quantitative analysis. Raw data were statistically compared using t-tests, and time-based correlations were assessed using Pearson's correlation coefficients. Two-tailed p values of less than 0.05 (assuming unequal variance) were considered statistically significant. RESULTS: Green fluorescence, indicative of viable GFP-positive MSCs, was absent in all residual blood samples after 48 hours of culturing; GFP-positive MSCs were visualized after enzymatic digestion of clot matrices. The number of GFP-positive MSCs per field of view increased between the 2-day and 7-day timepoints (mean 5.4 ± 1.5; 95% confidence interval, 4.7-6.1 versus mean 17.0 ± 13.6; 95% CI, 10.4-23.5, respectively; p = 0.029). Viable GFP-positive MSCs were present in each clot cryosection at each timepoint up to 7 days of culturing (mean 6.2 ± 4.3; 95% CI, 5.8-6.6). There were no differences in MSC counts between any of the timepoints. There was no visible evidence of GFP +/CC3 + double-positive MSCs. Combining all timepoints, there were 0.34 ± 0.70 (95% CI, 0.25-0.43) GFP+/Ki67+ double-positive MSCs per field of view. The mitotic indices at time zero and Day 7 were 7.5% ± 13.4% (95% CI, 3.0%-12.0%) and 7.2% ± 14.3% (95% CI, 3.3%-12,1%), respectively (p = 0.923). There was no visible evidence of GFP +/CC3 + double-positive MSCs (active apoptosis) at any timepoint. For active proliferation in saline-cultured fibrin clots, we found averages of 0.1 ± 0.3 (95% CI, 0.0-0.2) and 0.4 ± 0.9 (95% CI, 0.0-0.8) GFP/Ki67 double-positive MSCs at time zero and Day 7, respectively (p = 0.499). The mitotic indices in saline culture at time zero and Day 7 were 2.9% ± 8.4% (95% CI, 0.0%-5.8%) and 9.1% ± 20.7% (95% CI, 1.2%-17.0%; p = 0.144). There was no visible evidence of GFP +/CC3 + double-positive MSCs (active apoptosis) at any timepoint in either culturing condition. CONCLUSION: These preliminary in vitro results show that human MSCs mixed in unclotted fresh human venous blood were nearly completely captured in fibrin clots and that seeded MSCs were capable of maintaining their viability, proliferation capacity, and osteogenic differentiation capacity in the fibrin clot for up to 7 days, independent of external sources of nutrition. CLINICAL RELEVANCE: Fresh human fibrin clots have been used clinically for more than 30 years to improve soft-tissue healing, albeit with scar tissue. Our results demonstrate that allogenic human MSCs, which reduce soft-tissue scarring, can be captured and remain active inside human fibrin clots, even in the absence a nutritive culture medium.


Assuntos
Coagulação Sanguínea/fisiologia , Fibrina/administração & dosagem , Células-Tronco Mesenquimais/citologia , Adolescente , Adulto , Idoso , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese/fisiologia , Cicatrização/fisiologia , Adulto Jovem
3.
Toxicol Appl Pharmacol ; 385: 114811, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31705944

RESUMO

In vivo local antitumor activity of fibrin gels (FBGs) loaded with the poly-cyclodextrin oCD-NH2/Dox, compared to free Dox, was evaluated in two mouse orthotopic neuroblastoma (NB) models, after positioning of the releasing devices in the visceral space. FBGs were prepared at the fibrinogen (FG) concentrations of 22 and 40 mg/ml clotted in the presence of 0.81 mM/mg FG Ca2+ and 1.32 U/mg FG thrombin. Our results indicate that FBGs loaded with oCD-NH2/Dox and applied as neoadjuvant loco-regional treatment, show an antitumor activity significantly greater than that displayed by the same FBGs loaded with identical dose of Dox or after free Dox administered intra venous (iv). In particular, FBGs prepared at 40 mg/ml showed a slightly lower antitumor activity, although after their positioning we observed a significant initial reduction of tumor burden lasting for several days after gel implantation. FBGs at 22 mg/ml loaded with oCD-NH2/Dox and applied after tumor removal (adjuvant treatment model) showed a significantly better antitumor activity than the iv administration of free Dox, with 90% tumor regrowth reduction compared to untreated controls. In all cases the weight loss post-treatment was limited after gel application, although in the adjuvant treatment the loss of body weight lasted longer than in the other treatment modality. In accordance with our recent published data on the low local toxic effects of FBGs, the present findings also underline an increase of the therapeutic index of Dox when locally administered through FBGs loaded with the oCD-NH2/Dox complex.


Assuntos
Celulose/química , Ciclodextrinas/química , Doxorrubicina/administração & dosagem , Fibrina/administração & dosagem , Neuroblastoma/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Fibrina/farmacologia , Fibrina/toxicidade , Géis , Humanos , Camundongos , Terapia Neoadjuvante , Neuroblastoma/patologia
4.
Cienc. tecnol. salud ; 6(2): 149-157, jul dic 2019.
Artigo em Espanhol | LILACS | ID: biblio-1095877

RESUMO

La recesión gingival (RG) es un problema de salud bucodental frecuente que aumenta con la edad, predispone a hipersensibilidad dentaria, caries radicular, inflamación gingival y efectos antiestéticos. El objetivo de este ensayo clínico aleatorizado fue evaluar comparativamente el efecto clínico del recubrimiento radicular utilizando la técnica estenopéica Pinhole con colágeno y la técnica estenopéica Pinhole modificada al incorporarle plasma rico en fibrina (PRF). Veintiséis participantes sistémicamente sanos, con diagnóstico de RG grado I de Miller, fueron reclutados y seguidos por 6 meses después de la cirugía. Los parámetros clínicos registrados fueron nivel de inserción clínica (NIC), RG y banda de encía queratinizada. Los participantes fueron asignados aleatoriamente a un grupo en quienes se utilizó PRF con 14 participantes, tratando 36 piezas dentales, y otro grupo en quienes se utilizó membrana de colágeno con 12 participantes, tratando 35 piezas dentales. Los resultados muestran un logro de ganancia en el NIC en ambos grupos, (M = 45.24 %, DE = 17.37 %) en el grupo PRF y (M = 47.37 %, DE = 15.67 %) en el grupo colágeno, diferencia que no fue significativa (p = .59). En ambos grupos existió un aumento significativo en la banda de encía queratinizada (p < .01). El uso de PRF como material de relleno al realizar la técnica estenopéica genera resultados similares al ser comparado con la técnica convencional que utiliza colágeno. Al presentar un menor costo el PRF aumenta las posibilidades que más personas tengan acceso al tratamiento.


Gingival recession (GR) is a frequent oral health disease that increases with age and may increase risk of dental hypersensitivity, root decay, gingival inflammation and aesthetic problems. The aim of this randomized clinical trial was to compare clinical parameters of dental root coverage using Pinhole technique with collagen and modi¬fied Pinhole technique using platelet-rich fibrin (PRF). Twenty-six participants, systemically healthy, with Miller class I GR diagnosis, were recruited and measured at baseline and after 6 months follow-up. Clinical parameters measured included clinical attachment level (ICL), GR and keratinized gingival width (KGW). All participants were randomly assigned to a group using PRF, with 14 participants and 36 teeth treated, and other group using collagen, with 12 participants and 35 teeth treated. Both PRF group and collagen group gained ICL, (M = 45.24 %, SD = 17.37 %) in PRF group and (M = 47.37 %, SD = 15.67 %) in collagen group, with no statistically significant difference (p = .59). Both groups gained KGW (p < .01). Use of PRF as filled material by using Pinhole technique resulted in similar clinical improvements compare to collagen as filled material. Considering that PRF is cheaper than collagen, it increases chances that people can have access to treatment.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Tratamento do Canal Radicular/métodos , Fibrina/administração & dosagem , Procedimentos Cirúrgicos Bucais/métodos , Retração Gengival/cirurgia , Colágeno
5.
Biomed Res Int ; 2019: 9148183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531371

RESUMO

Periodontal bone regeneration relies on coupled and cooperative bone formation and resorption. Accordingly a novel strategy on concurrent use of platelet-rich fibrin (PRF) (anabolic agent) and 1% alendronate (ALN) (anticatabolic agent) was proposed recently in regenerative periodontal treatment. It was supposed to enhance bone formation and reduce bone resorption simultaneously. However, there is a lack of evidence-based studies to answer whether this concurrent application was superior to single application until now. Besides, concerns on ALN lead to some reservation on this synergistic way. ALN may impair new bone formation and necrotize jaws. Thus, in order to compare the clinical efficacy between PRF plus 1%ALN and PRF alone on periodontal bone regeneration, we performed present systematic review and meta-analysis. Because it is the prerequisite for measuring the combined efficacy of PRF plus 1%ALN, firstly we evaluated the effectiveness of 1%ALN. Our data indicated that adjunctive 1%ALN was effective in promoting periodontal bone repair. Further, PRF plus 1%ALN showed a greater capacity for periodontal regeneration than PRF alone with statistical significance. The findings of this study revealed the promising prospects on synergistic application of bone anabolic agents (PRF) and antiresorption medications (1%ALN) in regenerative periodontal treatment.


Assuntos
Alendronato/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Fibrina/administração & dosagem , Fibrina Rica em Plaquetas/metabolismo , Regeneração Tecidual Guiada Periodontal , Humanos , Osteogênese/efeitos dos fármacos
6.
Oral Maxillofac Surg Clin North Am ; 31(4): 579-591, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31445759

RESUMO

For several decades, the multidisciplinary field of tissue engineering has striven to improve conventional methods of dental, oral, and craniofacial rehabilitation for millions of people annually. Several bone tissue engineering strategies are now readily available in the clinic. Enrichment of autologous products, growth factors, and combination approaches are discussed as ways to enhance the surgeon's traditional armamentarium. Lastly, cutting-edge research such as customized 3-dimensional printed bone scaffolds, tissue engineering strategies for volumetric muscle loss, and temporomandibular joint disc and condyle engineering are briefly discussed as future applications.


Assuntos
Regeneração Óssea/fisiologia , Transplante Ósseo/métodos , Fibrina/metabolismo , Regeneração Tecidual Guiada Periodontal/métodos , Plasma Rico em Plaquetas/fisiologia , Cirurgia Bucal/métodos , Engenharia Tecidual , Fibrina/administração & dosagem , Humanos
7.
J Control Release ; 294: 247-258, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30572032

RESUMO

To date no disease-modifying drugs for osteoarthritis (OA) are available, with treatment limited to the use of pain killers and prosthetic replacement. The ADAMTS (A Disintegrin and Metallo Proteinase with Thrombospondin Motifs) enzyme family is thought to be instrumental in the loss of proteoglycans during cartilage degeneration in OA, and their inhibition was shown to reverse osteoarthritic cartilage degeneration. Locked Nucleic Acid (LNA)-modified antisense oligonucleotides (gapmers) released from biomaterial scaffolds for specific and prolonged ADAMTS inhibition in co-delivered and resident chondrocytes, is an attractive therapeutic strategy. Here, a gapmer sequence identified from a gapmer screen showed 90% ADAMTS5 silencing in a monolayer culture of human OA chondrocytes. Incorporation of the gapmer in a fibrin-hyaluronic acid hydrogel exhibited a sustained release profile up to 14 days. Gapmers loaded in hydrogels were able to transfect both co-embedded chondrocytes and chondrocytes in a neighboring gapmer-free hydrogel, as demonstrated by flow cytometry and confocal microscopy. Efficient knockdown of ADAMTS5 was shown up to 14 days in both cell populations, i.e. the gapmer-loaded and gapmer-free hydrogel. This work demonstrates the use applicability of a hydrogel as a platform for combined local delivery of chondrocytes and an ADAMTS-targeting gapmer for catabolic gene modulation in OA.


Assuntos
Proteína ADAMTS5/antagonistas & inibidores , Condrócitos , Fibrina/administração & dosagem , Hidrogéis/administração & dosagem , Oligonucleotídeos Antissenso/administração & dosagem , Osteoartrite/genética , Proteína ADAMTS5/genética , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Ácido Hialurônico/administração & dosagem
8.
Keio J Med ; 68(3): 45-53, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30504650

RESUMO

Previous reports have suggested that direct oral anticoagulants exert a prothrombolytic effect against intracardiac thrombi. We hypothesized that these anticoagulants may also help recanalize occluded intracranial arteries via prothrombolytic effects. In this study, we evaluated the effects of rivaroxaban, a direct oral anticoagulant, on fibrin emboli within the cerebrocortical microvessels in a mouse model of embolic stroke. Fibrin emboli prepared ex vivo were injected into the common carotid artery of male C57BL/6 mice, and embolization in the microvessels on the brain surface was observed through a cranial window. Oral administration of rivaroxaban was initiated a week before injection of the emboli. The number and sizes of the emboli were measured at two time points: immediately after and 3 h after the embolus injection in the rivaroxaban-treated mice (n =6) and untreated mice (n =7). The rates of recanalization and change in the embolus size were analyzed between the two groups. Complete recanalization was observed only in the rivaroxaban group (three mice in the rivaroxaban group compared with none in the control group). A significantly higher rate of reduction of the embolus size was observed in the rivaroxaban group than in the control group (P=0.0216). No significant differences between the two groups were observed in the serum levels of the following coagulation markers: thrombin-antithrombin III complexes, D-dimers, or plasmin-α2-plasmin inhibitor complex. Our findings indicate that rivaroxaban may promote reduction in the size of stagnated fibrin emboli in cerebrocortical microvessels in cases of embolic stroke.


Assuntos
Anticoagulantes/farmacologia , Córtex Cerebral/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Embolia/tratamento farmacológico , Fibrina/antagonistas & inibidores , Rivaroxabana/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Administração Oral , Animais , Antitrombina III , Biomarcadores/sangue , Coagulação Sanguínea/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Embolia/sangue , Embolia/induzido quimicamente , Fibrina/administração & dosagem , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinolisina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microvasos/efeitos dos fármacos , Peptídeo Hidrolases/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/induzido quimicamente , alfa 2-Antiplasmina/metabolismo
9.
Int J Pharm ; 552(1-2): 319-327, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30308269

RESUMO

Colorectal cancer (CRC) exhibited high incidence rate worldwide and the advanced CRC had a poor prognosis. Thereupon, seeking efficient treatment for CRC is critical. Apatinib is a novel vascular epithelial growth factor receptor (VEGFR) inhibitor with inspiring therapeutic effect in some malignant cancers. In our study, doxorubicin was mixed in fibrin gel and apatinib was encapsulated with self-synthesized liposome. The results showed liposomal apatinib (Lipo-Apatinib) could enhance the intracellular uptake of doxorubicin in vitro. Moreover, compared with doxorubicin loaded fibrin gel (DOX-FG) alone, the combination of DOX-FG and Lipo-Apatinib significantly improved the anti-tumor effect in mice CRC subcutaneous model and abdominal metastasis model Drug combination successfully inhibited tumor angiogenesis and tumor proliferation, and also promoted tumor apoptosis. Our data suggested that combined therapy of DOX-FG and Lipo-Apatinib would be a promising treatment approach for CRC.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/administração & dosagem , Fibrina/administração & dosagem , Piridinas/administração & dosagem , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Doxorrubicina/química , Combinação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Fibrina/química , Géis , Lipossomos , Camundongos Endogâmicos BALB C , Piridinas/química , Resultado do Tratamento
10.
Pharmacol Rep ; 70(4): 760-765, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29936363

RESUMO

BACKGROUND: Local delivery of anticancer drugs represents a desirable type of treatment. Nevertheless, characteristics such as availability, biocompatibility, ease of operation, and efficacy sometimes represent difficult to overcome hurdles. Fibrin gels (FBGs) may be attractive biomaterials for local treatment when loaded with different chemotherapeutics or with polymer-anticancer-drug conjugates and nanoparticles. These components, linked together, might represent candidates to counteract local recurrences or reduce the volume of inoperable tumors. In the present study we analyzed the features of in vitro release of different formulations of doxorubicin (DOXO) from FBGs, and in vivo FBGs degradation. METHODS: In vitro DOXO release from FBGs was studied as a function of thrombin and Ca2+ ion concentrations. DOXO was loaded in FBGs either alone or pre-incorporated in nanoparticles characterized by different physical features. The FBGs in vivo degradation was analyzed after sc or ip positioning. RESULTS: Our results suggest that each of the factors involved in the FBGs preparation may have different effects on drug release. In particular, the fibrinogen (FG) concentration and, above all, the DOXO formulation were found to have the greatest impact. Not surprisingly, we have also found a longer permanence in vivo of FBGs prepared at the highest thrombin, Ca2+ ion, and FG concentrations. CONCLUSIONS: The aim of this work was to study the effect of several conditions for preparing drug delivery systems based on FBGs loaded with different clinical or experimental formulations of DOXO. Our data identify some of these modalities that will be tested in vivo to evaluate their antitumor activity.


Assuntos
Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos/efeitos dos fármacos , Fibrina/química , Animais , Cálcio/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/análise , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Implantes de Medicamento/administração & dosagem , Implantes de Medicamento/farmacocinética , Feminino , Fibrina/administração & dosagem , Géis/química , Humanos , Injeções Subcutâneas , Camundongos , Nanopartículas/química , Trombina/farmacologia , Fatores de Tempo , Ensaio Tumoral de Célula-Tronco
11.
Sports Med Arthrosc Rev ; 26(2): 42-47, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29722762

RESUMO

Arthroscopic rotator cuff repair is a commonly performed repair. Technical developments provide surgeons the tools to create biomechanically robust repairs. How can the biological response mirror the strong and stable surgery? Platelet-rich plasma (PRP) is a supraphysiological platelet concentration which may positively augment rotator cuff healing. Not all PRPs are the same. High leukocyte levels and thrombin activation may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors and may actually inhibit some parts of the healing response. Clear differences exist between liquid PRP (products released within hours after activation) and solid fibrin PRP which slowly releases factors over days. The heterogenicity data and grouping liquid and solid PRP together make systematic reviews confusing. Solid PRP fibrin constructs are often associated with increased tendon healing. PRP fibrin matrix offers the greatest promise for improving clinical success after rotator cuff tendon repair.


Assuntos
Artroscopia , Plasma Rico em Plaquetas , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/terapia , Fibrina/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Cicatrização
12.
Stem Cells Transl Med ; 7(4): 360-372, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29457376

RESUMO

Harvesting of autografts results in donor site morbidities and is limited in scenarios such as large total body surface area burns. In these instances, coverage is increased by meshing grafts at the expense of delayed biologic closure. Moreover, graft meshing increases the likelihood of contraction and hypertrophic scarring, limits range of motion, and worsens cosmesis. Many tissue engineering technologies have touted the promise of adipose-derived stem cells (ASCs) for burn wounds. The primary objective of the current study was to determine feasibility and efficacy of in situ ASC delivery via PEGylated fibrin (FPEG) hydrogels as adjuncts to meshed split thickness skin grafts in a porcine model. Deep partial thickness burns were created on the dorsum of anesthetized Yorkshire pigs, and subsequently debrided on post-burn day 4. After debridement, wounds were treated with: split thickness skin grafts (STSG); meshed STSG (mSTSG); and mSTSG + FPEG with increasing doses of ASCs. We show that FPEG hydrogels can be delivered in situ to prevent the contraction seen after meshing of STSG. Moreover, ASCs delivered in FPEG dose-dependently increase blood vessel size which significantly correlates with CD31 protein levels. The current study reports a dual-action adjunct therapy to autografting administered in situ, wherein FPEG acts as both scaffolding to prevent contraction, and as a delivery vehicle for ASCs to accelerate angiogenesis. This strategy may be used to incorporate other biologics for generating tissue engineered products aimed at improving wound healing and minimizing donor sites or scarring. Stem Cells Translational Medicine 2018;7:360-372.


Assuntos
Adipócitos/citologia , Autoenxertos/citologia , Queimaduras/terapia , Fibrina/administração & dosagem , Hidrogéis/administração & dosagem , Polietilenoglicóis/química , Células-Tronco/citologia , Animais , Materiais Biocompatíveis/química , Cicatriz/terapia , Desbridamento/métodos , Feminino , Pele/citologia , Transplante de Pele/métodos , Suínos , Transplante Autólogo/métodos , Cicatrização/fisiologia
14.
Biomed Res Int ; 2017: 7320953, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29082254

RESUMO

Surgical techniques in dental and maxillofacial surgery request fast bone tissue regeneration, so there is a significant need to improve therapy for bone regeneration. Several studies have recently underlined the importance of nucleotides and nucleosides to increase cell proliferation and activity; in particular, the ability of polydeoxyribonucleotide (PDRN) to induce growth and activity of human osteoblasts was demonstrated. Sodium-DNA is the deoxyribonucleic acid (DNA) extracted from the gonadic tissue of male sturgeon and then purified, depolymerized, and neutralized with sodium hydroxide. To date, there are no evidences about the use of Sodium-DNA for bone tissue regeneration. Consequently, our question is about the efficacy of Sodium-DNA in bone healing. For testing the role of Sodium-DNA in bone healing we used a rat calvarial defect model. Sodium-DNA at different concentrations used alone or in association with Fibrin and/or Bio-Oss was used for healing treatments and the bone healing process was evaluated by histomorphometric and immunohistochemical analyses. Our results suggested a positive effect of Sodium-DNA in bone regeneration, providing a useful protocol and a model for the future clinical evaluation of its osteogenic properties.


Assuntos
Regeneração Óssea/efeitos dos fármacos , DNA/administração & dosagem , Polidesoxirribonucleotídeos/administração & dosagem , Crânio/efeitos dos fármacos , Sódio/administração & dosagem , Animais , Osso e Ossos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA/química , Fibrina/administração & dosagem , Fibrina/química , Humanos , Minerais/administração & dosagem , Minerais/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Polidesoxirribonucleotídeos/química , Ratos , Crânio/crescimento & desenvolvimento , Sódio/química
15.
Trials ; 18(1): 469, 2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-29017535

RESUMO

BACKGROUND: Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. METHODS: People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. DISCUSSION: Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.


Assuntos
Plaquetas , Pé Diabético/terapia , Fibrina/administração & dosagem , Leucócitos , Cicatrização , Curativos Biológicos/efeitos adversos , Protocolos Clínicos , Pé Diabético/diagnóstico , Pé Diabético/fisiopatologia , Europa (Continente) , Fibrina/efeitos adversos , Humanos , Reepitelização , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento
16.
Spine Deform ; 5(5): 310-313, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28882348

RESUMO

BACKGROUND: Decorticated bone is a significant source of blood loss in scoliosis surgery. Current hemostatic methods include packed gauze (GS), physical barriers such as bone wax, and xenograft collagen-based materials. We assessed the safety and efficacy of a novel fibrin dressing (dextran-thrombin-fibrinogen [DTF]) compared to GS. This dressing comprises lyophilized thrombin and fibrinogen embedded in an elastic electrospun nanofiber dextran matrix. PURPOSE: The study tests the hypothesis that DTF is more efficacious than GS in control of bleeding from cancellous bone. STUDY DESIGN: A preclinical Good Laboratory Practices (GLP) study. METHODS: We enrolled 10 goats that were followed for 28 ± 1 days. Each animal was randomly assigned to the test or control group. Both test and control animals had 4 cancellous bone injuries. Test animal injuries were treated with DTF, whereas standard GS was used to control bleeding in the control animals. Bleeding at the bone injury site was characterized as either none, oozing, flowing, or pulsatile and was assessed at 4 and 8 minutes after dressing application. Goats were survived 28 ± 1 days and then necropsied. RESULTS: Application of the fibrin dressing to bleeding cancellous bone, both posterior spinal lamina, and iliac crest graft sites, resulted in control of bleeding within 4 minutes at all injury sites. Eighty percent of control injury sites continued to bleed after 8 minutes and required application of bone wax to control bleeding. There were no differences in prothrombin time, partial thromboplastin time, or fibrinogen levels between test and control animals at 1 or 28 days. We observed no adverse histologic reactions at 28 days. CONCLUSION: The fibrin dressing is an efficacious and safe method of controlling blood loss from cancellous bone in a spine surgery model.


Assuntos
Bandagens , Osso Esponjoso/cirurgia , Fibrina/administração & dosagem , Hemostasia Cirúrgica/métodos , Hemostáticos/administração & dosagem , Animais , Osso Esponjoso/lesões , Dextranos/administração & dosagem , Fibrinogênio/administração & dosagem , Cabras , Modelos Animais , Distribuição Aleatória , Trombina/administração & dosagem , Resultado do Tratamento
17.
Microsc Res Tech ; 80(11): 1167-1173, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28742256

RESUMO

The focus of this double-blind randomized study was on evaluating the effect of an aqueous extract of Mastruz (Chenopodium ambrosioides L.) on the bone repair process in vivo. In total, 36 male Wistar rats were randomly selected for this study, and divided into 3 groups (n = 12): Group HS (Hemostatic Sponge), Group SM (Hemostatic Sponge with Mastruz) and Group BC (Blood Clot). In each animal, bone defects measuring 2 mm in diameter were performed in both tibias for placement of the substances. After 3 and 10 days, the animals were sacrificed, and the tissues were analyzed under an optical microscope relative to the following events: inflammatory infiltrate; necrosis; young fibroblasts; osteoclastic and osteoblastic activity; endosteal and periosteal bone formation; and bone repair. The results were assessed by using Kruskal-Wallis and Mann-Whitney tests (p < .05). Inflammatory infiltrate demonstrated difference between Groups SM and BC in the time interval of 3 days (p = .004); an event related to the presence of the fibrin sponge and liquid of the extract, which induced a foreign body initial reaction. The presence of young fibroblasts (p = .003), osteoclastic (p = .003), and osteoblastic (p = .020) activity was statistically significant between Groups HS and BC in the time interval of 10 days; performance was related to the presence of the sponge within bone. As regards injured bone tissue repair, Group SM demonstrated a higher level of regenerative capacity (p = 0.004), due to a larger quantities of endosteal and periosteal bone formation, demonstrated in Group SM. The aqueous extract of mastruz stimulated bone neoformation, presenting wound closure with bone tissue at the end of 10 days.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Chenopodium ambrosioides/química , Fitoterapia , Extratos Vegetais/administração & dosagem , Animais , Osso e Ossos/imunologia , Osso e Ossos/patologia , Método Duplo-Cego , Fibrina/administração & dosagem , Inflamação , Masculino , Necrose , Osteogênese/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Wistar , Cicatrização/efeitos dos fármacos
18.
Pain Physician ; 20(5): E653-E660, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28727710

RESUMO

BACKGROUND: Symptomatic Tarlov cysts are a common cause of chronic pain. Many methods have been reported to treat this disease, with variable results. Most previous reports concerning the treatment methods of symptomatic Tarlov cysts were either sporadic case reports or series of limited cases. OBJECTIVE: This study aimed to further optimize the management for patients with symptomatic Tarlov cysts (TCs) by analyzing the results of 82 patients who were treated with different strategies. STUDY DESIGN: Three different strategies were applied to 82 patients with symptomatic TCs and their clinical effects were evaluated in 13 months to 12 years follow-up. SETTING: A pain management practice, a medical center, major metropolitan city, China. METHODS: From June 2003 to August 2015, a total number of 82 patients with symptomatic TCs were treated with 3 different methods (microsurgical cyst fenestration and imbrication, C-arm fluoroscopy guided percutaneous fibrin gel injection, and conservative management) in the first affiliated hospital of Chongqing Medical University. The pain severity was assessed according to visual analog scale (VAS), and imaging changes were evaluated by magnetic resonance imaging (MRI). Patient improvements in pain and neurologic function were evaluated during a follow-up the period of 13 months to 12 years. RESULTS: All the patients who underwent microsurgical cyst fenestration and imbrication had either complete (7 patients, 50%) or substantial (7 patients, 50%) resolution of their preoperative symptoms and neurological deficits. However, 3 patients (21%) had cerebrospinal fluid (CSF) leakage and 3 patients (21%) suffered from recurrent symptoms. In C-arm fluoroscopy guided percutaneous fibrin gel injection group, 34 patients (61%) had complete resolution and 22 patients had (39%) substantial resolution, and no CSF leakage or recurrence occurred. Only 3 patients (25%) got substantial resolution in the conservative management group, but 9 patients (75%) had aggravation. LIMITATIONS: An observational study with a relatively small sample size. CONCLUSIONS: C-arm fluoroscopy guided percutaneous fibrin gel injection therapy could be recommend as a better consideration for symptomatic TCs. KEY WORDS: Tarlov cysts, C-arm fluoroscopy guided, fibrin gel, microsurgical cyst fenestration, conservative management.


Assuntos
Dor nas Costas/terapia , Fibrina/administração & dosagem , Microcirurgia/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Cistos de Tarlov/terapia , Adulto , Idoso , Dor nas Costas/tratamento farmacológico , Dor nas Costas/etiologia , Dor nas Costas/cirurgia , China , Feminino , Seguimentos , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cistos de Tarlov/complicações , Cistos de Tarlov/tratamento farmacológico , Cistos de Tarlov/cirurgia , Adulto Jovem
19.
J Orthop Surg Res ; 12(1): 73, 2017 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-28499451

RESUMO

BACKGROUND: Growth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration (IVD) induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with poly(lactic-co-glycolic acid)/fibrin gel (PLGA) plugs. METHODS: New Zealand white rabbits (n = 24) received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter; 4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and (d) uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG) content. Nerve ingrowth into the discs was assessed by immunostaining with the nerve marker protein gene product 9.5. RESULTS: Injured discs showed a progressive disc space narrowing with significant disc degeneration and proteoglycan loss, as confirmed by imaging results, molecular and compositional analysis, and histological examinations. In 16G punctured discs, nerve ingrowth was observed on the surface of scar tissue. In annular defects, nerve fibers were found to be distributed along small fissures within the fibrocartilaginous-like tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve fibers were observed growing deeper into the inner AF along the open annular track.  In addition, innervations scores showed significantly higher than those of punctured discs and empty defects. A limited vascular proliferation was found in the injured sites and regenerated tissues. CONCLUSIONS: Nerve ingrowth was significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible explanations include (i) annular fissures along the defect and early loss of proteoglycan may facilitate the ingrowth process and (ii) biodegradable PLGA/fibrin gel may promote adverse growth of nerves and blood vessels into deeper parts of injured disc. The rabbit annular defect model of disc degeneration appears suitable to investigate the effects of nerve ingrowth in relation to pain generation.


Assuntos
Modelos Animais de Doenças , Fibrina/administração & dosagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Ácido Láctico/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Tecidos Suporte , Animais , Géis , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Distribuição Aleatória , Resultado do Tratamento
20.
J Foot Ankle Surg ; 56(3): 581-585, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28476390

RESUMO

The relationship between surgical technique and ankle biomechanical properties after surgery for acute rupture of the Achilles tendon (ATR) has not yet been fully investigated. Platelet-rich fibrin (PRF) matrices seem to play a central role in the complex processes of tendon healing. Our aim was to analyze the biomechanical characteristics, stiffness, and mechanical work of the ankle during walking in patients who had undergone surgery after ATR with and without PRF augmentation. We performed a retrospective review of all consecutive patients who had been treated with surgical repair after ATR. Of the 20 male subjects enrolled, 9 (45%) had undergone conventional open repair of the Achilles tendon using the Krackow technique (no-PRF) and 11 (55%) had undergone surgery with PRF augmentation. An additional 8 healthy subjects were included as a control group. A gait analysis evaluation was performed at 6 months after surgery. The percentage of the stance time of the operated leg, double-support time of the healthy leg, and net work of the ankle during the gait cycle showed statistically significant differences between the no-PRF and the healthy group (p < .005). No differences were found between the PRF and healthy groups. Treatment with suture and PRF augmentation could result in significant functional improvements in term of efficiency of motion.


Assuntos
Tendão do Calcâneo/cirurgia , Plaquetas/metabolismo , Fibrina/administração & dosagem , Técnicas de Sutura , Tendão do Calcâneo/lesões , Adulto , Fenômenos Biomecânicos/fisiologia , Estudos de Casos e Controles , Fibrina/metabolismo , Marcha/fisiologia , Humanos , Masculino , Amplitude de Movimento Articular/fisiologia , Estudos Retrospectivos , Ruptura/cirurgia , Caminhada/fisiologia
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