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1.
J Appl Oral Sci ; 27: e20180693, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596370

RESUMO

OBJECTIVES: To compare the sealing ability and biocompatibility of Biodentine with mineral trioxide aggregate (MTA) when used as root-end filling materials. METHODOLOGY: The Cell Counting Kit-8 (CCK-8) assay was used to compare the cytotoxicity of MTA and Biodentine. Twenty-one extracted teeth with a single canal were immersed in an acidic silver nitrate solution after root-end filling. Then, the volume and depth of silver nitrate that infiltrated the apical portion of the teeth were analyzed using micro-computed tomography (micro-CT). Seventy-two roots from 3 female beagle dogs were randomly distributed into 3 groups and apical surgery was performed. After six months, the volume of the bone defect surrounding these roots was analyzed using micro-CT. RESULTS: Based on the results of the CCK-8 assay, MTA and Biodentine did not show statistically significant differences in cytotoxicity (P>0.05). The volume and the depth of the infiltrated nitrate solution were greater in the MTA group than in the Biodentine group (P<0.05). The volume of the bone defect was larger in the MTA group than in the Biodentine group. However, the difference was not significant (P>0.05). The volumes of the bone defects in the MTA and Biodentine groups were smaller than the group without any filling materials (P<0.05). CONCLUSIONS: MTA and Biodentine exhibited comparable cellular biocompatibility. Biodentine showed a superior sealing ability to MTA in root-end filling. Both Biodentine and MTA promoted periradicular bone healing in beagle dog periradicular surgery models.


Assuntos
Compostos de Alumínio/farmacologia , Compostos de Cálcio/farmacologia , Óxidos/farmacologia , Tecido Periapical/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Materiais Restauradores do Canal Radicular/farmacologia , Tratamento do Canal Radicular/métodos , Silicatos/farmacologia , Cicatrização/efeitos dos fármacos , Adolescente , Animais , Regeneração Óssea/efeitos dos fármacos , Contagem de Células , Células Cultivadas , Cães , Combinação de Medicamentos , Humanos , Masculino , Teste de Materiais , Osteogênese/efeitos dos fármacos , Tecido Periapical/citologia , Tecido Periapical/diagnóstico por imagem , Ligamento Periodontal/diagnóstico por imagem , Reprodutibilidade dos Testes , Fatores de Tempo , Raiz Dentária/diagnóstico por imagem , Raiz Dentária/efeitos dos fármacos , Raiz Dentária/cirurgia , Resultado do Tratamento , Microtomografia por Raio-X , Adulto Jovem
2.
Niger J Clin Pract ; 22(10): 1328-1334, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31607720

RESUMO

Objective: The aim of the this study was to evaluate the effect of honey on the healing of tooth extraction wounds in children 4‒9 years of age. Subjects and Methods: In the present randomized clinical trial, 51 patients, 4‒9 years of age were selected randomly. All the subjects required extraction of one deciduous molar tooth. The subjects were randomly assigned to two groups. In group 1, after extraction of the tooth, the dentist used a cotton swab applicator to place a layer of honey on a piece of gauze moistened with normal saline solution (NSS) and placed it on the socket. In group 2, honey was not used; rather, NSS was applied. On days 3 and 7 after tooth extraction, the wound sizes were measured. Results: In both groups, the wound sizes decreased significantly on the third day compared with baseline and on the seventh day compared with the third day (P < 0.05). On the third and seventh days after tooth extraction, wound sizes in the honey group were significantly lower than those in the NSS group (P < 0.05). Conclusion: Honey resulted in a decrease in wound sizes and faster healing after extraction of teeth in children. Therefore, use of honey can be recommended after minor surgeries in the oral cavity.


Assuntos
Apiterapia/métodos , Mel , Extração Dentária , Alvéolo Dental , Cicatrização/efeitos dos fármacos , Administração Tópica , Bandagens , Criança , Pré-Escolar , Assistência Odontológica , Feminino , Humanos , Masculino , Cloreto de Sódio/uso terapêutico , Alvéolo Dental/efeitos dos fármacos , Alvéolo Dental/patologia , Resultado do Tratamento
3.
Braz J Med Biol Res ; 52(9): e8290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482998

RESUMO

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Ácido Ascórbico/administração & dosagem , Colágeno/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Animais , Colágeno/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Tenotomia , Cicatrização/efeitos dos fármacos
4.
Soft Matter ; 15(38): 7686-7694, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31498364

RESUMO

We report a simple and facile self-assembly approach to fabricate polyelectrolyte complex (PEC) hydrogel films with positively charged chitosan (CS) and negatively charged heparin sodium (HS) by combining hydrogen bonding and electrostatic interactions. The CS/HS hydrogel films exhibited excellent tensile strength and toughness, good self-recovery ability, superior water absorbency, and pH-dependent surface charge characteristics. The gelation mechanism was investigated by zeta potential measurements. The CS/HS hydrogel films exhibited high antibacterial efficacy against E. coli at selected pHs or when coordinated with various metal ions and a significant effect on accelerating wound healing. The self-assembly approach presented in this work may serve as a generic strategy for the fabrication of novel multi-functional PEC hydrogels for broad biomedical applications.


Assuntos
Antibacterianos/química , Quitosana/química , Heparina/química , Polieletrólitos/química , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Cátions , Escherichia coli/efeitos dos fármacos , Humanos , Hidrogéis , Concentração de Íons de Hidrogênio , Membranas Artificiais , Metais/química , Pele , Propriedades de Superfície , Resistência à Tração , Água
5.
Int J Nanomedicine ; 14: 5449-5475, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409998

RESUMO

Purpose: We created and evaluated an enhanced topical delivery system featuring a combination of highly skin-permeable growth factors (GFs), quercetin (QCN), and oxygen; these synergistically accelerated re-epithelialization and granulation tissue formation of/in diabetic wounds by increasing the levels of GFs and antioxidants, and the oxygen partial pressure, at the wound site. Methods: To enhance the therapeutic effects of exogenous administration of GFs for the treatment of diabetic wounds, we prepared highly skin-permeable GF complexes comprised of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF), genetically attached, via the N-termini, to a low-molecular-weight protamine (LMWP) to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. Furthermore, quercetin (QCN)- and oxygen-carrying 1-bromoperfluorooctane (PFOB)-loaded nanoemulsions (QCN-NE and OXY-PFOB-NE) were developed to improve the topical delivery of QCN and oxygen, respectively. After confirming the enhanced penetration of LMWP-GFs, QCN-NE, and oxygen delivered from OXY-PFOB-NE across human epidermis, we evaluated the effects of combining LMWP-GFs, QCN-NE, and OXY-PFOB-NE on proliferation of keratinocytes and fibroblasts, and the chronic wound closure rate of a diabetic mouse model. Results: The optimal ratios of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, LMWP-bFGF, QCN-NE, and OXY-PFOB-NE were 1, 1, 0.02, 0.02, 0.2, and 60, respectively. Moreover, a Carbopol hydrogel containing LMWP-GFs, QCN-NE, and OXY-PFOB-NE (LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL) significantly improved scratch-wound recovery of keratinocytes and fibroblasts in vitro compared to that afforded by hydrogels containing each component alone. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL significantly accelerated wound-healing in a diabetic mouse model, decreasing wound size by 54 and 35% compared to the vehicle and LMWP-GFs, respectively. Conclusion: LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL synergistically accelerated the healing of chronic wounds, exerting both rapid and prolonged effects.


Assuntos
Diabetes Mellitus/patologia , Hidrogéis/química , Fator de Crescimento Insulin-Like I/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Oxigênio/metabolismo , Quercetina/farmacologia , Absorção Cutânea , Cicatrização/efeitos dos fármacos , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno/biossíntese , Modelos Animais de Doenças , Emulsões/química , Fator de Crescimento Epidérmico/farmacologia , Epiderme/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Peso Molecular , Nanopartículas/química , Nanopartículas/ultraestrutura , Octanos/química , Fator de Crescimento Derivado de Plaquetas/farmacologia , Protaminas/química , Absorção Cutânea/efeitos dos fármacos
6.
Chem Pharm Bull (Tokyo) ; 67(8): 849-854, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366834

RESUMO

Regenerative therapy with keratinocyte growth factor (KGF) is a novel therapeutic approach for treatment of chronic wounds. However, KGF cannot be used directly to the wound site due to its physicochemical instability. In previous study, sacran, a natural megamolecular polysaccharide, showed potential properties as a biomaterial for hydrogel film in wound healing. In this study, we fabricated sacran hydrogel film containing KGF (Sac/KGF-HF) and evaluated the effects of Sac/KGF-HF on fibroblasts migration and re-epithelialization process. We successfully prepared a homogenous and -amorphous Sac/KGF-HF by a casting method. In addition, Sac/KGF-HF had a high swelling ratio and flexibility. Sac/KGF-HF promoted a migration process of NIH3T3 cells and improved wound healing ability in mice with a percentage of wound closure reaching 90.4% at 9 d. Interestingly, the addition of KGF in Sac-HF considerably increased the number of epithelial cells compared to control, which is important in the re-epithelialization process. It could be concluded that KGF in Sac-HF has the potential for promoting Sac-HF abilities in wound healing process.


Assuntos
Fator 7 de Crescimento de Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Metilgalactosídeos/farmacologia , Polissacarídeos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fator 7 de Crescimento de Fibroblastos/química , Metilgalactosídeos/química , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Polissacarídeos/química
7.
Khirurgiia (Mosk) ; (8): 91-94, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31464282

RESUMO

A successful administration of NPWT-therapy combined with Reamberin infusion for gastroenterostomy failure after stomach resection is reported in the article. It was noted that antioxidant/antihypoxic drug Reamberin combined with NPWT-therapy has a positive metabolic effect and results more active and rapid healing of the wounds. The absence of adverse effects of the drug allows us to recommend its inclusion into complex treatment of patients with this pathology.


Assuntos
Antioxidantes/uso terapêutico , Gastrectomia/métodos , Gastroenterostomia/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Meglumina/análogos & derivados , Tratamento de Ferimentos com Pressão Negativa , Estômago/cirurgia , Succinatos/uso terapêutico , Gastrectomia/efeitos adversos , Humanos , Meglumina/uso terapêutico , Cicatrização/efeitos dos fármacos
8.
Int J Nanomedicine ; 14: 5051-5060, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371946

RESUMO

Background: Chronic cutaneous wounds represent a major issue in medical care and are often prone to infections. Purpose: The aim of this study was the design of a clay mineral-drug nanocomposite based on montmorillonite and norfloxacin (NF, antimicrobial drug) as a powder for cutaneous application, to enhance wound healing in infected skin lesions. Methods: The nanocomposite has been prepared by means of an intercalation solution procedure. Adsorption isotherm, solid-state characterization of the nanocomposite, drug loading capacity and its release have been performed. Moreover, cytocompatibility, in vitro fibroblast proliferation and antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus were assessed. Results: The clay drug adsorption isotherm demonstrates that the mechanism of NF intercalation into montmorillonite galleries is the adsorption as one single process, due to the charge-charge interaction between protonated NF and negatively charged montmorillonite edges in the interlayer space. Nanocomposite is biocompatible and it is characterized by antimicrobial activity greater than the free drug: this is due to its nanostructure and controlled drug release properties. Conclusion: Considering the results obtained, NF-montmorillonite nanocomposite seems a promising tool to treat infected skin lesions or skin wounds prone to infection, as chronic ulcers (diabetic foot, venous leg ulcers) and burns.


Assuntos
Bentonita/química , Nanocompostos/química , Norfloxacino/farmacologia , Norfloxacino/uso terapêutico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Adsorção , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Disponibilidade Biológica , Liberação Controlada de Fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Nanocompostos/ultraestrutura , Pseudomonas aeruginosa/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Temperatura Ambiente , Infecção dos Ferimentos/microbiologia , Difração de Raios X
9.
Life Sci ; 233: 116728, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31386877

RESUMO

Impaired wound healing is a serious concern of uncontrolled hyperglycemia that can lead to gangrene, and even death. There is an urgent need to look for better alternative therapy because of the undesirable side effects of currently available synthetic drugs in the market. Syringic acid (SA) is a natural phenolic compound abundantly available in edible fruits and plants. In this study, wound healing activities of 2.5% and 5.0% SA were evaluated in type 2 diabetic rats using incisional wound model. SA-treated diabetic wounds showed faster rate of wound closure and epithelization with enhanced contents of hydroxyproline and protein compared to diabetic wounds. SA effectively prevents alterations in blood glucose levels, serum insulin and dyslipidemia in diabetic wound rats. The SA-treated diabetic wounds after 14 days of treatment demonstrated inhibition of pro-inflammatory response (NF-κB p65, TNF-α, IL-1ß, IL-8 and IL-2) with improvement in anti-inflammatory response (IL-10), inhibited the elevated oxidative stress and decreased the concentrations of matrix metalloproteinases (MMP-2, -8 and -9) and increased the concentrations of TIMP-1 & TIMP- 2. Furthermore, the diabetic wounds were presented with an increase in expression of CD 31 and 68, growth factors (TGF-ß1, collagen-I and α-SMA and VEGF) with significant improvement in collagen deposition, re-epithelialization and complete skin structure as revealed by histological analysis after treatment of diabetic wounds with SA for 14 days. Hence, the results of this study designate that SA significantly improves wound healing in diabetic rats and could be used as a potential therapy for treatment of diabetic wounds.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ácido Gálico/análogos & derivados , Regulação da Expressão Gênica/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Ácido Gálico/farmacologia , Insulina/sangue , Lipídeos/análise , Masculino , Ratos , Ratos Wistar
10.
J Photochem Photobiol B ; 197: 111539, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31301638

RESUMO

Treatment of burn injury is clinically challenging one, therefore several steps and noteworthy approaches have been taken to improve wound mechanisms. Citrus pectin plays a stabilizing agent to synthesis of ZnO nanoparticles (ZnO NPs). The present study is focused on ZnO loaded collagen/chitosan nanofibrous were synthesized by electrospinning method using ZnO NPs. The chemical structure, phase purity and morphological observation were investigated under spectroscopic and mircoscopic techniques and demonstrated their suitable properties as a wound healing material. In addition, that prepared nanoparticles loaded biopolymeric fibrous nanomaterial showed suitable antibacterial activity against S. aureus and E. coli bacterial pathogens and also in vitro studies was confirmed the enhanced proliferation, cell viability and biocompatibility. In vitro evaluations have been exhibited acceptable cell proliferation is observed throughout the ZnO loaded Coll/CS nanofibrous within 3 days, which was comparable to the control material. In vivo wound healing ability was monitored on the rat wound experimental model. From the in vivo observations, revealed that the loaded of ZnO NPs with Coll/CS nanofibrous can effectively quicken wound healing mechanism, expressed in the initial stage healing process. These results suggest that ZnO loaded collagen/chitosan nanofibrous is a potential candidate for wound healing applications with enhanced biological properties.


Assuntos
Queimaduras/patologia , Quitosana/química , Colágeno/química , Nanopartículas Metálicas/química , Nanofibras/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/prevenção & controle , Queimaduras/veterinária , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Nanofibras/uso terapêutico , Nanofibras/toxicidade , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Óxido de Zinco/química
11.
J Photochem Photobiol B ; 197: 111556, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326842

RESUMO

Facile green synthesis of copper nanoparticles from different biological procedures has been indicated, but among all, biosynthesis of copper nanoparticles from medicinal plants is considered as the most suitable method. The use of medicinal plant material increases the therapeutical effects of copper nanoparticles. The aim of this study was green synthesis of copper nanoparticles from aqueous extract of Falcaria vulgaris leaf (CuNPs) and assessment of their cytotoxicity, antioxidant, antifungal, antibacterial, and cutaneous wound healing properties. These nanoparticles were characterized by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), transmission electron microscopy (TEM), and field emission scanning electron microscopy (FE-SEM) analysis. The synthesized CuNPs had great cell viability dose-dependently (Investigating the effect of the CuNPs on human umbilical vein endothelial cell (HUVEC) line) and indicated this method was nontoxic. Also, 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was done to assess the antioxidant activities, which indicated similar antioxidant potentials for CuNPs and butylated hydroxytoluene. In part of cutaneous wound healing property of CuNPs, after creating the cutaneous wound, the rats were randomly divided into six groups: treatment with 0.2% CuNPs ointment, treatment with 0.2% CuSO4 ointment, treatment with 0.2% F. vulgaris ointment, treatment with 3% tetracycline ointment, treatment with Eucerin basal ointment, and untreated control. These groups were treated for 10 days. Treatment with CuNPs ointment remarkably increased (p ≤ .01) the wound contracture, vessel, hexosamine, hydroxyl proline, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate and substantially reduced (p ≤ .01) the wound area, total cells, neutrophil, and lymphocyte compared to other groups. In antibacterial and antifungal parts of this research, the concentration of CuNPs with minimum dilution and no turbidity was considered minimum inhibitory concentration (MIC). To determine minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC), 60 µL MIC and three preceding chambers were cultured on Sabouraud Dextrose Agar and Muller Hinton Agar, respectively. The minimum concentration with no fungal and bacterial growth were considered MFC and MBC, respectively. CuNPs inhibited the growth of all fungi at 2-4 mg/mL concentrations and removed them at 4-8 mg/mL concentrations (p ≤ .01). In case of antibacterial effects of CuNPs, they inhibited the growth of all bacteria at 2-8 mg/mL concentrations and removed them at 4-16 mg/mL concentrations (p ≤ .01). The results of XRD, FT-IR, UV, TEM, and FE-SEM confirm that the aqueous extract of F. vulgaris leaf can be used to yield copper nanoparticles with notable amount of antioxidant, antifungal, antibacterial, and cutaneous wound healing potentials without any cytotoxicity. Further clinical trials are necessary for confirmation these therapeutical effects of CuNPs in human.


Assuntos
Apiaceae/química , Cobre/química , Nanopartículas Metálicas/química , Extratos Vegetais/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antioxidantes/química , Apiaceae/metabolismo , Candida/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Nanopartículas Metálicas/toxicidade , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Folhas de Planta/metabolismo , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Cicatrização/efeitos dos fármacos
12.
Medicine (Baltimore) ; 98(27): e16288, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277160

RESUMO

RATIONALE: Enterocutaneous fistula (ECF) has long been difficult to treat in clinical settings. The current approaches, including surgery, antibiotics, and nutritional support, cannot achieve satisfactory outcomes. PATIENT CONCERNS: A 54-year-old man presented with intermittent discharge of purulent material from the fistula of an umbilical incision post colon surgery. His symptoms did not improve after receipt of antibiotic and surgical treatment. DIAGNOSIS: The patient's symptoms, radiographic findings, and pathological examination led to a diagnosis of ECF. INTERVENTIONS: Sterilized Bletilla striata was injected into the fistula once every 3 days for a total of 6 doses. OUTCOMES: The ECF completely healed, and the patient was symptom-free after 1 month. LESSONS: The patient's pronounced improvement and the merit of this easy-to-perform low-cost method suggest that Bletilla striata may be used by surgeons for the treatment of chronic abdominal wall fistulas.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Fístula Intestinal/terapia , Polissacarídeos/farmacologia , Cicatrização/efeitos dos fármacos , Humanos , Fístula Intestinal/diagnóstico , Masculino , Pessoa de Meia-Idade
13.
Medicine (Baltimore) ; 98(30): e16570, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348286

RESUMO

BACKGROUND: Perioperative bleeding during total knee arthroplasty (TKA) is an ongoing problem for surgeons. Intravenous or topical application of tranexamic acid (TXA) can effectively stop bleeding, but there is still no uniform standard for the best method of administration and dose. METHODS: From October 2016 to September 2018, 218 patients with unilateral primary knee osteoarthritis requiring knee replacement were enrolled and randomly divided into four groups. Group 1 (n = 55) received intra-articular injection (IAI) of TXA and peri-articular injection (PAI) of placebo, group 2 (n = 55) received IAI of placebo and PAI of TXA, group 3 (n = 51) received IAI of TXA and PAI of TXA, and group 4 (n = 57) received double placebo (IAI of placebo and PAI of placebo). The demographic characteristics, surgical indices, hematological indices, wound healing history, and thromboembolic events were investigated. RESULTS: Eight patients were lost to follow-up and 210 patients were included in the analysis. The median TBLs in patients who received IAI of TXA and PAI of placebo and those who received IAI of placebo and PAI of TXA were 470.81 ml and 481.54 ml, respectively. These TBL levels were significantly higher compared to those in patients who received IAI of TXA and PAI of TXA (359.18 ml, P ≤ .001), but significantly lower compared to those in patients who received the double placebo (522.71 ml, P ≤ .001). Compared to other groups, more patients in the double placebo group needed a blood transfusion (P = .013). In the short-term, the double placebo group had higher VAS pain scores and less ROM after surgery (P = .011 and P = .001, respectively). In the long-term (6-month follow-up), there were no significant differences in ROM, VAS, DVT, PE, or wound-related complications. CONCLUSION: The combined use of IAI and PAI of TXA can significantly reduce the TBL and the need for blood transfusion without delaying wound healing or increasing the risk of DVT and PE. In the short-term after surgery, this combined method reduces the pain VAS scores and improves the ROM; however, there are no long-term effects on VAS and ROM.


Assuntos
Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/uso terapêutico , Fatores Etários , Idoso , Antifibrinolíticos/administração & dosagem , Transfusão de Sangue/estatística & dados numéricos , Índice de Massa Corporal , Relação Dose-Resposta a Droga , Método Duplo-Cego , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Fatores Sexuais , Fatores Socioeconômicos , Tromboembolia/epidemiologia , Cicatrização/efeitos dos fármacos
14.
Gastroenterology ; 157(4): 1019-1031.e7, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279870

RESUMO

BACKGROUND & AIMS: Although ustekinumab is an effective therapy for moderate to severe Crohn's disease (CD), its effects on the microscopic manifestations of CD are unknown. METHODS: We evaluated the effects of ustekinumab on histologic CD activity in an analysis of data from 251 participants in phase 3 induction and maintenance studies. Two endoscopic biopsy samples were collected at weeks 0, 8, and 44 from the ileum, splenic flexure, and rectum (18 biopsy samples from each patient). Histologic activity was assessed based on global histology activity scores (GHASs). RESULTS: At week 8, the mean GHAS was significantly reduced after ustekinumab induction treatment (from 10.4 ± 7.0 to 7.1 ± 5.9; P < .001) but not in patients who received placebo (from 9.2 ± 6.4 to 7.8 ± 6.2). At week 44 in the randomized maintenance therapy population, the mean GHAS remained reduced from week 8 in patients who received subcutaneous ustekinumab (90 mg every 8 weeks; from 7.4 ± 7.7 to 6.1 ± 4.7) but not every 12 weeks (from 5.3 ± 3.9 to 8.7 ± 4.1) or placebo (from 9.2 ± 3.8 to 10.9 ± 7.1). In the pooled (randomized and nonrandomized) maintenance therapy population, histologic improvement continued in patients given ustekinumab every 8 weeks (from 7.1 ± 6.2 to 5.2 ± 4.2; P < .0001) but not in those given ustekinumab every 12 weeks (from 6.1 ± 5.7 to 7.2 ± 5.1) or placebo (from 8.2 ± 4.2 to 8.9 ± 6.8). A significantly greater proportion of patients achieved histologic response (≥50% decrease in GHAS from baseline) at week 44 if they received ustekinumab every 8 weeks (50% in the randomized maintenance population and 54% in the pooled maintenance population) compared with every 12 weeks (17% and 39% in the randomized and pooled populations, respectively) or placebo (0% and 22% in the randomized and pooled populations, respectively) (P = .0137 for every 8 weeks vs placebo and P = .3529 for every 12 weeks vs placebo in the randomized population; P = .0168 for every 8 weeks vs placebo and P = .3069 for every 12 weeks vs placebo in the pooled population). Regional and overall mean GHASs correlated with the simple endoscopic score for CD (r = .6255, P < .0001). Multivariate analysis found an association between histologic improvement and endoscopic or histologic burden at baseline. CONCLUSIONS: In an analysis of data from participants in phase 3 induction and maintenance trials, we found histologic improvement in a greater proportion of patients given ustekinumab vs placebo. The largest improvements occurred in patients who received ustekinumab maintenance therapy every 8 weeks. ClinicalTrials.gov nos. NCT01369329, NCT01369342, and NCT01369355.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Ustekinumab/administração & dosagem , Cicatrização/efeitos dos fármacos , Adulto , Anti-Inflamatórios/efeitos adversos , Biópsia , Doença de Crohn/patologia , Esquema de Medicação , Endoscopia Gastrointestinal , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Quimioterapia de Indução , Mucosa Intestinal/patologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Ustekinumab/efeitos adversos
15.
Gastroenterology ; 157(4): 1007-1018.e7, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279871

RESUMO

BACKGROUND & AIMS: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy. METHODS: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less). RESULTS: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naïve to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations. CONCLUSIONS: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD. ClinicalTrials.gov no: NCT02425111.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Endoscopia Gastrointestinal , Fármacos Gastrointestinais/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Imagem por Ressonância Magnética , Cicatrização/efeitos dos fármacos , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biópsia , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Eur J Med Chem ; 179: 246-256, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31255925

RESUMO

Ruthenium complexes have attracted a surge of interest as anticancer drug candidates because of their low toxicity, diversity in mode-of-actions and non-cross drug resistance with conventional platinum-based agents. Despite remarkable advances, only a limited number of ruthenium complexes have been demonstrated to kill cancer cells and suppress metastasis simultaneously. Here, two organometallic tetranuclear Ru(II) arene complexes (Ru-1 and Ru-2) have been synthesized and evaluated for their in vitro activity against a panel of human cancer cell lines, including a cisplatin-resistant human lung cancer A549 cell line. A superior cytotoxic activity of the ruthenium complexes compared to cisplatin across distinct cell lines was observed. Further examination of the mechanism indicated that anticancer activity was accomplished by inducing apoptosis in cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Importantly, choosing Ru-1 as a target compound, a significantly enhanced safety profile relative to cisplatin in animals was validated, suggesting that these complexes can be used as promising candidates for cancer therapy and deserve further investigation.


Assuntos
Antineoplásicos/farmacologia , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Células RAW 264.7 , Rutênio/química , Relação Estrutura-Atividade , Cicatrização/efeitos dos fármacos
17.
Eur J Med Chem ; 179: 667-679, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279299

RESUMO

Ovarian cancer is associated with a high percentage of recurrence of tumors and resistance to chemotherapy. Cancer stem cells (CSCs) are responsible for cancer progression, tumor recurrence, metastasis, and chemoresistance. Thus, developing CSC-targeting therapy is an urgent need in cancer research and clinical application. In an attempt to achieve potent and selective anti-CSC agents, a series of celastrol derivatives with cinnamamide chains were synthesized and evaluated for their anti-ovarian cancer activities. Most of the compounds exhibited stronger antiproliferative activity than celastrol, and celastrol derivative 7g with a 3,4,5-trimethoxycinnamamide side chain was found to be the most potent antiproliferative agent against ovarian cancer cells with an IC50 value of 0.6 µM. Additionally, compound 7g significantly inhibited the colony formation ability and reduced the number of tumor spheres. Furthermore, compound 7g decreased the percentage of CD44+, CD133+ and ALDH+ cells. Thus, compound 7g is a promising anti-CSC agent and could serve as a candidate for the development of new anti-ovarian cancer drugs.


Assuntos
Antineoplásicos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Triterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Estrutura Molecular , Neoplasias Ovarianas/patologia , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/química , Cicatrização/efeitos dos fármacos
18.
Eur J Med Chem ; 179: 805-827, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295714

RESUMO

A novel series of benzylidene-succinimide derivatives were synthesized, characterized and evaluated for their cytotoxicities against HCT116, and SW480 cancer cells and NCM460 normal human cells. Their antiangiogenic capabilities were evaluated using a chick chorioallantoic membrane (CAM) assay. The compound, XCF-37b, was selected as the most potent antiangiogenic inhibitor with noncytotoxicity to evaluate the pharmacological effects on human umbilical vein endothelial cells (HUVECs) and cancer cells in vivo and in vitro. The results showed that XCF-37b inhibited HT29-cell colon tumor growth in vivo, without showing cytotoxicity against the five other cancer cell lines in vitro. Experiments confirmed that XCF-37b had obvious antiangiogenic activity by HUVEC migration and invasion and rat aortic ring angiogenesis ex vivo. Mechanism studies showed that XCF-37b inhibited the AKT/mTOR and VEGFR2 signaling pathways, as evidenced by decreased expressions of phosphor-AKT (p-AKT), p-mTOR, p-VEGFR2 (Tyr175), p-Src (Tyr416), p-FAK (Tyr925), and p-Erk1/2 (Thr202/Tyr204). Moreover, XCF-37b significantly decreased the protein expressions of matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1α (HIF-1α). XCF-37b generally regulated angiogenic inhibition through several regulatory pathways, without significantly interfering with colorectal cancer cell growth.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Compostos de Benzilideno/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Succinimidas/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Benzilideno/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Galinhas , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neovascularização Patológica/patologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Succinimidas/química , Cicatrização/efeitos dos fármacos
19.
Eur J Med Chem ; 179: 470-482, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271959

RESUMO

A series of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides was designed and synthesized as new tropomyosin receptor kinases (Trks) inhibitors by utilizing a structure-guided optimization strategy. One of the most potent compounds 9o suppressed TrkA/B/C with IC50 values of 2.65, 10.47 and 2.95 nM, respectively. The compound dose-dependently inhibited brain-derived neurotrophic factor (BDNF)-mediated TrkB activation and suppressed migration and invasion of SH-SY5Y-TrkB neuroblastoma cells expressing high level of TrkB. Inhibitor 9o also inhibited the proliferation of SH-SY5Y-TrkB cells with an IC50 value of 58 nM, which was comparable to that of an US FDA recently approved drug LOXO-101. Compound 9o may serve as a new lead compound for further anti-cancer drug discovery.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Desenho de Drogas , Imidazóis/farmacologia , Glicoproteínas de Membrana/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/farmacologia , Receptor trkB/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Benzamidas/síntese química , Benzamidas/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Imidazóis/síntese química , Imidazóis/química , Glicoproteínas de Membrana/metabolismo , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazinas/síntese química , Pirazinas/química , Receptor trkB/metabolismo , Relação Estrutura-Atividade , Cicatrização/efeitos dos fármacos
20.
J Nanobiotechnology ; 17(1): 82, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291960

RESUMO

Skin damages are defined as one of most common lesions people suffer from, some of wounds are notoriously difficult to eradicate such as chronic wounds and deep burns. Existing wound therapies have been proved to be inadequate and far from satisfactory. The cutting-edge nanotechnology offers an unprecedented opportunity to revolutionize and invent new therapies or boost the effectiveness of current medical treatments. In particular, the nano-drug delivery systems anchor bioactive molecules to applied area, sustain the drug release and explicitly enhance the therapeutic efficacies of drugs, thus making a fine figure in field relevant to skin regeneration. This review summarized and discussed the current nano-drug delivery systems holding pivotal potential for wound healing and skin regeneration, with a special emphasis on liposomes, polymeric nanoparticles, inorganic nanoparticles, lipid nanoparticles, nanofibrous structures and nanohydrogel.


Assuntos
Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Fenômenos Fisiológicos da Pele , Cicatrização/efeitos dos fármacos , Animais , Liberação Controlada de Fármacos , Humanos , Hidrogéis/química , Lipídeos/química , Lipossomos/química , Polímeros/química , Regeneração
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