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1.
BMJ ; 369: m718, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349978

RESUMO

Head and neck structures govern the vital functions of breathing and swallowing. Additionally, these structures facilitate our sense of self through vocal communication, hearing, facial animation, and physical appearance. Loss of these functions can lead to loss of life or greatly affect quality of life. Regenerative medicine is a rapidly developing field that aims to repair or replace damaged cells, tissues, and organs. Although the field is largely in its nascence, regenerative medicine holds promise for improving on conventional treatments for head and neck disorders or providing therapies where no current standard exists. This review presents milestones in the research of regenerative medicine in head and neck surgery.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Otolaringologia/tendências , Procedimentos Cirúrgicos Reconstrutivos/tendências , Medicina Regenerativa/tendências , Tecidos Suporte , Bioengenharia , Transplante de Células/métodos , Transplante de Células/tendências , Cóclea , Cartilagem da Orelha , Ossos Faciais , Humanos , Laringe , Cartilagens Nasais , Procedimentos Cirúrgicos Reconstrutivos/métodos , Glândulas Salivares , Crânio , Engenharia Tecidual/métodos , Engenharia Tecidual/tendências , Traqueia , Membrana Timpânica
2.
J Appl Oral Sci ; 28: e20190236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32236353

RESUMO

OBJECTIVE: This clinical trial sought to evaluate the clinical effectiveness of concentrated growth factor (CGF) and compare it with connective tissue graft (CTG) with coronally advanced flap (CAF) in the treatment of Miller Class I gingival recessions (GR). METHODOLOGY: This split-mouth study included 74 Miller Class I isolated (24 teeth) or multiple (50 teeth) GRs in 23 jaws of 19 patients. GRs were randomly treated using CGF (test group: 37 teeth; 12 teeth in isolated GRs, 25 teeth in multiple GRs) or CTG with CAF (control group: 37 teeth;12 teeth isolated GRs, 25 teeth in multiple GRs). Clinical variables, plaque index (PI), gingival index (GI), probing depth (PD), recession depth (RD), recession width (RW), clinical attachment level (CAL), keratinized tissue thickness (KTT), keratinized tissue width (KTW), and root coverage (RC) were assessed at the baseline as well as at three and six months post-surgery. Healing index (HI) were obtained in the second and third weeks post-surgery. Postoperative pain was assessed for the first seven days using a horizontal visual analog scale (VAS). RESULTS: No significant change was observed in PI, GI, or PD values in either the intergroup or the intragroup comparisons. A statistically significant decrease was observed in CAL, RD, and RW, and KTT increased in all groups at three and six months compared with the baseline. The control group had greater increases in KTW, KTT, and RC at three and six months. No significant difference was found in CAL or RD at the third and sixth months between the two groups. Healing was found to be similar for both groups in the second and third weeks post-surgery. The VAS values in the control group were higher than in the test group, especially at the second, fourth, fifth, and seventh days postoperatively. CONCLUSIONS: CTG is superior to CGF with CAF for increasing KTT, KTW, and RC. CGF may be preferable due to decreased postoperative pain.


Assuntos
Tecido Conjuntivo/transplante , Retração Gengival/cirurgia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Retalhos Cirúrgicos/transplante , Adulto , Plaquetas , Índice de Placa Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória , Índice Periodontal , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Cicatrização , Adulto Jovem
3.
Acta Cir Bras ; 35(2): e202000204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294688

RESUMO

PURPOSE: To investigate the effect of growth arrest-specific protein 6 (Gas6) on acute liver injury in mice and related mechanisms. METHODS: Thirty C57BL/6 (6-8 weeks old) mice were randomly divided into control, LPS/D-GalN, and LPS/D-GalN+Gas6 groups (10 mice in each group). The LPS/D-GalN group was intraperitoneally administered with LPS (0.25 mg/Kg) and D-GalN (400 mg/Kg) for 5h. The LPS/D-GalN+Gas6 group was intraperitoneally administered with rmGas6 one hour before intraperitoneal application of LPS/D-GalN. All subjects were sacrificed at 5 h for blood and tissue analysis. The expression of protein and mRNA was assessed by western blotting and RT-PCR, respectively. RESULTS: Compared with the control group, AST, ALT, IL-1ß, TNF-α, IL-6 IL-10, MPO activity were increased in the LPS/D-GalN group. However, they were significantly inhibited by Gas6. Gas6 markedly suppressed the expression of apoptosis-related protein induced by LPS/D-GalN. Moreover, Gas6 attenuated the activation of the NF-κB signaling pathway in acute liver injury induced by LPS/D-GalN. CONCLUSIONS: Gas6 alleviates acute liver injury in mice through regulating NF-κB signaling pathways. Gas6 can be a potential therapeutic agent in treating LPS/D-GalN-induced acute liver injury in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Lipopolissacarídeos/efeitos adversos , Fígado/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino , Camundongos
4.
Braz Oral Res ; 34: e034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321052

RESUMO

The aim of this split mouth, double blinded, randomized clinical trial was to evaluate the clinical efficacy of use of Plasma rich in growth factors (PRGF) as an adjunct to scaling and root planing (SRP) in the treatment of periodontal pockets. Twenty six patients (15 males, 11 females) diagnosed with generalized periodontitis with Pocket Depth > 5mm and plaque index score < 1.5, were randomly allocated by using computer generated random sequence, into two groups, one treated with intra-pocket application of PRGF adjunct to SRP and other with SRP alone. The clinical outcomes like pocket depth (PD), relative attachment level (RAL) and sulcus bleeding index (SBI) were assessed at baseline, 3 months and 6 months. Twenty two patients (44 sites) were analyzed at the end of 6 month follow-up, using SPSS 20.0v software. There was a significant statistical difference observed between both the groups favouring SRP +PRGF group in terms of PD (p = 0.007) and RAL (p = 0.021) at the end of 6 month follow-up. Also there was a statistical significant difference (< 0.001) at all time points compared to baseline, for all parameters in intra-group comparison. Moreover, the sites with PD>4mm necessitating further treatment after 6-month follow-up were significantly lesser for SRP+PRGF group. The use of PRGF technology in non-surgical periodontal therapy, by single intra-pocket application in to periodontal pockets as an adjunct to SRP, in chronic periodontitis patients, was found to be effective in reduction of pocket depth and gain in clinical attachment level.


Assuntos
Raspagem Dentária/métodos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Bolsa Periodontal/terapia , Plasma Rico em Plaquetas , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal , Índice Periodontal , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
5.
PLoS One ; 15(1): e0226931, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914125

RESUMO

BACKGROUND: Apolipoprotein-AI (apo-AI) is the major apolipoprotein found in high density lipoprotein particles (HDLs). We previously demonstrated that apo-AI injected directly into high-fat diet fed mice improved insulin sensitivity associated with decreased hepatic inflammation. While our data provides compelling proof of concept, apoA-I mimetic peptides are more clinically feasible. The aim of this study was to test whether apo-AI mimetic peptide (D-4F and L-5F) treatment will emulate the effects of full-length apo-AI to improve insulin sensitivity. METHODS: Male C57BL/6 mice were fed a high-fat diet for 16 weeks before receiving D4F mimetic peptide administered via drinking water or L5F mimetic peptide administered by intraperitoneal injection bi-weekly for a total of five weeks. Glucose tolerance and insulin tolerance tests were conducted to assess the effects of the peptides on insulin resistance. Effects of the peptides on inflammation, gluconeogenic enzymes and lipid synthesis were assessed by real-time PCR of key markers involved in the respective pathways. RESULTS: Treatment with apo-AI mimetic peptides D-4F and L-5F showed: (i) improved blood glucose clearance (D-4F 1.40-fold AUC decrease compared to HFD, P<0.05; L-4F 1.17-fold AUC decrease compared to HFD, ns) in the glucose tolerance test; (ii) improved insulin tolerance (D-4F 1.63-fold AUC decrease compared to HFD, P<0.05; L-5F 1.39-fold AUC compared to HFD, P<0.05) in the insulin tolerance test. The metabolic test results were associated with (i) decreased hepatic inflammation of SAA1, IL-1ß IFN-γ and TNFα (2.61-5.97-fold decrease compared to HFD, P<0.05) for both mimetics; (ii) suppression of hepatic mRNA expression of gluconeogenesis-associated genes (PEPCK and G6Pase; 1.66-3.01-fold decrease compared to HFD, P<0.001) for both mimetics; (iii) lipogenic-associated genes, (SREBP1c and ChREBP; 2.15-3.31-fold decrease compared to HFD, P<0.001) for both mimetics and; (iv) reduced hepatic macrophage infiltration (F4/80 and CD68; 1.77-2.15-fold compared to HFD, P<0.001) for both mimetics. CONCLUSION: Apo-AI mimetic peptides treatment led to improved glucose homeostasis. This effect is associated with reduced expression of inflammatory markers in the liver and reduced infiltration of macrophages, suggesting an overall suppression of hepatic inflammation. We also showed altered expression of genes associated with gluconeogenesis and lipid synthesis, suggesting that glucose and lipid synthesis is suppressed. These findings suggest that apoA-I mimetic peptides could be a new therapeutic option to reduce hepatic inflammation that contributes to the development of overnutrition-induced insulin resistance.


Assuntos
Apolipoproteína A-I/uso terapêutico , Inflamação/tratamento farmacológico , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Fígado/efeitos dos fármacos , Animais , Glicemia/análise , Inflamação/patologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL
6.
Int. j. morphol ; 37(4): 1564-1571, Dec. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1040170

RESUMO

Las glándulas salivales humanas pueden ser gravemente lesionadas por la radioterapia utilizada contra neoplasias de cabeza y cuello, produciendo hiposialia y xerostomía, las cuales afectan la salud oral y sistémica, mermando la calidad de vida de la persona. Los tratamientos convencionales actuales están diseñados para disminuir los síntomas, sin actuar sobre los cambios fisiopatológicos que se dan a nivel glandular. Esta revisión intenta analizar aquellas terapias preventivas y/o curativas que están desarrollándose en el campo biomolecular y que tienen un futuro prometedor por sus características innovadoras: terapia génica, terapia con células madre y terapia con factores de crecimiento. Se evidencia un aporte adicional de la nanotecnología, la cual está mejorando las vías de aplicación de los tratamientos.


Human salivary glands can be seriously injured by the radiotherapy used against head and neck neoplasms, producing hyposialia and xerostomy, which affect oral and systemic health, diminishing the person's quality of life. Current conventional treatments are designed to reduce symptoms, without acting on the pathophysiological changes that occur at the glandular level. This review attempts to analyze those preventive and /or curative therapies that are developing in the biomolecular field and that have a promising future due to their innovative features: Gene therapy, stem cell therapy and growth factor therapy. An additional contribution of nanotechnology is evident, which is improving the routes of treatment application.


Assuntos
Humanos , Radioterapia/efeitos adversos , Doenças das Glândulas Salivares/prevenção & controle , Células-Tronco/fisiologia , Terapia Genética/métodos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Lesões por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Doenças das Glândulas Salivares/terapia , Glândulas Salivares/efeitos da radiação , Xerostomia/prevenção & controle , Nanotecnologia
7.
Artigo em Russo | MEDLINE | ID: mdl-31626220

RESUMO

AIM: To evaluate the efficacy and safety of cortexin in the complex of rehabilitation measures for verticalization in patients with ischemic stroke in the acute period. MATERIAL AND METHODS: The study included 90 patients with hemispheric ischemic stroke. Patients of the first group (n=30) received cortexin in a dose of 20 mg per day intramuscularly for 10 days, along with basic therapy during early verticalization. Patients of the second group (n=30) received basic therapy during early verticalization and patients of the third group (n=30) received only basic therapy without verticalization. To assess the severity of condition, NIHSS, modified Rankin scale, the Barthel index, the Rivermead mobility index, MMSE, MOCA were used. To study cardiovascular function in patients, the segmental part of the autonomic nervous system was studied: a test with isometric load, a Valsalva test, a test based on the change in heart rate with slow deep breathing. All studies were conducted before and 10-14 days after treatment. RESULTS AND CONCLUSION: The most complete regression of neurological deficits and manifestations of cardiac autonomic neuropathy during the acute period of ischemic stroke was observed in the group of patients treated with cortexin (20 mg per day for 10 days), along with basic therapy and early verticalization, compared to the groups, which received basic therapy with early verticalization or basic therapy without verticalization.


Assuntos
Isquemia Encefálica , Peptídeos e Proteínas de Sinalização Intercelular , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Peptídeos , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
8.
Cancer Radiother ; 23(5): 449-465, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400956

RESUMO

Nowadays, ionizing radiations have numerous applications, especially in medicine for diagnosis and therapy. Pharmacological radioprotection aims at increasing detoxification of free radicals. Radiomitigation aims at improving survival and proliferation of damaged cells. Both strategies are essential research area, as non-contained radiation can lead to harmful effects. Some advances allowing the comprehension of normal tissue injury mechanisms, and the discovery of related predictive biomarkers, have led to developing several highly promising radioprotector or radiomitigator drugs. Next to these drugs, a growing interest does exist for biotherapy in this field, including gene therapy and cell therapy through mesenchymal stem cells. In this review article, we provide an overview of the management of radiation damages to healthy tissues via gene or cell therapy in the context of radiotherapy. The early management aims at preventing the occurrence of these damages before exposure or just after exposure. The late management offers promises in the reversion of constituted late damages following irradiation.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Genética/métodos , Lesões por Radiação/prevenção & controle , Proteção Radiológica/métodos , Amifostina/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Ensaios Clínicos como Assunto , Fracionamento da Dose de Radiação , Edição de Genes , Vetores Genéticos/uso terapêutico , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Camundongos , Oxirredutases/genética , Oxirredutases/uso terapêutico , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/terapia , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo
9.
J Stroke Cerebrovasc Dis ; 28(10): 104299, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31371141

RESUMO

Cognitive dysfunction is the most common nonphysical impairment in the stroke survivors. This impairment has a negative impact on patients' quality of life affects their daily living activities. Both pharmacological and nonpharmacological interventions are employed to improve cognitive impairment. Recently, nonpharmacological interventions have attracted great attention. Cognitive rehabilitation is considered as a therapeutic strategy to improve and maintain cognitive skills in patients with stroke. Enriched environment (EE), as a cognitive rehabilitation strategy, has been shown to facilitate physical, cognitive, as well as social abilities. Moreover, EE has been shown to increase endogenous growth factors. Growth factors have pivotal role in neurogenesis, synaptogenesis, as well as brain remodeling through neuron development, differentiation, and survival. In addition, administration of exogenous growth factors prevents cognitive dysfunction. Here, we review preclinical and clinical evidence of cognitive rehabilitation and role of growth factors in treating poststroke cognitive impairment.


Assuntos
Isquemia Encefálica/reabilitação , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Terapia Cognitivo-Comportamental , Disfunção Cognitiva/reabilitação , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/psicologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Resultado do Tratamento
10.
Oral Maxillofac Surg Clin North Am ; 31(3): 473-487, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31133506

RESUMO

Traditional reconstruction of major alveolar ridge deficiency has required autogenous cortical cancellous particulate bone grafts, often augmented with particulate allogeneic components. Now there is a new concept to consider, that of orthoalveolar form. This paradigm shift involves components of the tissue engineering triad of inductive growth factors combined with a matrix and stem cells, together with osteotomies or devices designed for space maintenance. Reported here is early experience with computer technology used to redesign deficient alveolar ridges deriving ideal alveolar-shaped bone-forms made from powdered titanium, sintered by laser at high temperature using rapid prototype technology.


Assuntos
Aloenxertos/irrigação sanguínea , Processo Alveolar/cirurgia , Aumento do Rebordo Alveolar/métodos , Proteína Morfogenética Óssea 2/uso terapêutico , Transplante Ósseo/métodos , Titânio , Implantação Dentária Endo-Óssea , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Procedimentos Cirúrgicos Reconstrutivos/métodos , Cirurgia Assistida por Computador
11.
Radiat Res ; 192(1): 92-97, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063041

RESUMO

In response to concerns over possible radiological or nuclear incidents, the Radiation and Nuclear Countermeasures Program within the National Institute of Allergy and Infectious Diseases (NIAID) was tasked by the U.S. Department of Health and Human Services to support development of medical countermeasures (MCM) to treat the acute and delayed injuries that can result from radiation exposure. To date, the only three drugs approved by the U.S. Food and Drug Administration for treatment of acute radiation syndrome are growth factors targeting granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages. Although these are currently stockpiled for deployment in response to a mass casualty scenario, these growth factors will likely be administered in a scarce-resources environment and availability may be limited. Therefore, there is growing interest in understanding the role that these growth factors play in mitigating radiation damage, to optimize their use and maximize the number of people who can be treated. For these reasons, the NIAID and the Radiation Injury Treatment Network organized a workshop to explore the use of growth factors and other cytokines as MCMs in the treatment of radiation-induced injuries. Subject matter experts from government, industry and academia gathered at this workshop to discuss the concept of operations, triage and treatment, administration to diverse civilian populations, growth factors under development for radiation indications, and how the practice of medicine can inform other potential approaches.


Assuntos
Citocinas/farmacologia , Emergências , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Saúde Pública , Lesões por Radiação/tratamento farmacológico , Citocinas/uso terapêutico , Descoberta de Drogas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
12.
Int J Mol Sci ; 20(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052503

RESUMO

Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases, of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Spectacular advances in regenerative medicine have arrived, giving new hope to patients that can benefit from new tissue engineering therapies based on the supportive action of 3D biomaterials together with the synergic action of osteo-inductive molecules and recruited stem cells that can be driven to the process of bone regeneration. However, few studies have focused on the application of tissue engineering to the regeneration of the cleft/lip and only a few have reported significant advances to offer real clinical solutions. This review provides an updated and deep analysis of the studies that have reported on the use of advanced biomaterials and cell therapies for the regeneration of cleft lip and palate regeneration.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Fenda Labial/terapia , Fissura Palatina/terapia , Medicina Regenerativa/métodos , Animais , Fenda Labial/epidemiologia , Fenda Labial/patologia , Fenda Labial/fisiopatologia , Fissura Palatina/epidemiologia , Fissura Palatina/patologia , Fissura Palatina/fisiopatologia , Ácido Fólico/análogos & derivados , Ácido Fólico/uso terapêutico , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Osteogênese/efeitos dos fármacos , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos
13.
Radiat Res ; 192(1): 99-120, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31081742

RESUMO

Due to the threat of a radiological or nuclear incident that could impact citizens, the U.S. Department of Health and Human Services tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early- to mid-stage medical countermeasure (MCM) development to treat radiation-induced injuries. Given that the body's natural response to radiation exposure includes production of growth factors and cytokines, and that the only drugs approved by the U.S. Food and Drug Administration to treat acute radiation syndrome are growth factors targeting either the granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages, there is interest in understanding the role that these factors play in responding to and/or ameliorating radiation damage. Furthermore, in an environment where resources are scarce, such as what might be expected during a radiation public health emergency, availability of growth factor or other treatments may be limited. For these reasons, the NIAID partnered with the Radiation Injury Treatment Network (RITN), whose membership includes medical centers with expertise in the management of bone marrow failure, to explore the use of growth factors and other cytokines as MCMs to mitigate/treat radiation injuries. A workshop was convened that included government, industry and academic subject matter experts, with presentations covering the anticipated concept of operations during a mass casualty incident including triage and treatment, growth factors under development for a radiation indication, and how the practice of medicine can inform other potential approaches, as well as considerations for administration of these products to diverse civilian populations. This report reviews the information presented, and provides an overview of the discussions from a guided breakout session.


Assuntos
Citocinas/farmacologia , Emergências , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Saúde Pública , Lesões por Radiação/tratamento farmacológico , Animais , Citocinas/uso terapêutico , Descoberta de Drogas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
14.
Adv Skin Wound Care ; 32(5): 234-237, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31008759

RESUMO

BACKGROUND: Pilonidal sinus is one of the most complicated chronic wounds common in younger adults. This disabling condition affects the natal clefts of the buttocks and often requires surgery. OBJECTIVE: To investigate the effect of autologous platelet-rich plasma and fibrin glue (PRP-FG) on pain reduction and the healing process of pilonidal sinus after excisional surgery with primary closure. METHODS: This randomized clinical trial study included 40 patients with pilonidal sinus admitted to a surgical ward. Patients were randomly divided into two groups: the control group, who underwent wide excision of the sinus with primary closure, and the case group, who had wide excision of the sinus with primary closure along with injection of autologous PRP-FG into the wound. For 6 months, patients were followed up for their severity of pain, wound healing process, the time it took them to get back to normal activities, infection, and other complications. RESULTS: In the first and second week after surgery, the severity of pain in the case group was reduced significantly in comparison with the control group. Healing time decreased but not significantly. There was no significant difference in infection and recurrence between the two groups. CONCLUSIONS: The addition of PRP-FG has the potential to reduce pain significantly in primary closure of pilonidal sinus.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Seio Pilonidal/cirurgia , Plasma Rico em Plaquetas/fisiologia , Atividades Cotidianas , Adulto , Citocinas/uso terapêutico , Feminino , Seguimentos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino , Qualidade de Vida , Fatores de Tempo , Cicatrização/fisiologia , Adulto Jovem
15.
Clin Calcium ; 29(3): 349-355, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30814381

RESUMO

Multiple myeloma(MM)develops and expands almost exclusively in the bone marrow, and generates devastating bone destruction. A variety of cytokines are overproduced in MM to stimulate RANKL-mediated osteoclastogenesis while suppressing osteoblastic differentiation from bone marrow stromal cells, leading to extensive bone destruction with rapid loss of bone. Soluble Wnt inhibitors elaborated from MM cells and/or their surrounding cells in bone lesions play an important role. Novel therapeutic neutralizing antibodies against DKK-1 or sclerotin are expected as bone anabolic agents;however, their effects on MM tumor progression through activation of the Wnt/ß-catenin pathway remain to be carefully clarified.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Via de Sinalização Wnt , Proteínas Morfogenéticas Ósseas/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Marcadores Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/fisiopatologia
16.
Pancreatology ; 19(3): 401-408, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30833212

RESUMO

OBJECTIVE: Chemerin, an adipokine, works as the chemoattractant for the immune cells. The role of chemerin in the inflammatory reaction is controversial. Chemerin has been shown to aggravate the inflammatory response, but other studies demonstrated its anti-inflammatory influence. This study assessed the effects of chemerin on acute pancreatitis (AP) in vivo and in vitro. METHODS: For in vivo experiments male Wistar rats were used. For in vitro study rat pancreatic AR42J cells were employed. Chemerin (1, 5 or 10 µg/kg) was given to the rats prior to the induction of AP by subcutaneous caerulein infusion (25 µg/kg). For in vitro studies cells were subjected to caerulein (10 nM) with or without chemerin (100 nM). Serum amylase activity was measured by enzymatic method, serum TNFα concentration - by ELISA kit. Western-blot was used to examine cellular proteins. RESULTS: AP was confirmed by histological examination. Chemerin given to AP rats decreased histological manifestations of AP, reduced serum amylase activity and TNFα concentration. In AR42J cells subjected to caerulein with addition of chemerin signal for TNFα was reduced comparing to the cultures treated with caerulein alone. Analysis of the dynamics of nuclear translocation for p50, p65 and Bcl-3 points out to NF-κB attenuation as a mechanism of observed anti-inflammatory action of chemerin. CONCLUSION: Chemerin significantly alleviated severity of AP in the rat, this is possibly due to the inhibition of pro-inflammatory signaling in the pancreatic cells.


Assuntos
Quimiocinas/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , NF-kappa B/metabolismo , Pancreatite/induzido quimicamente , Animais , Linhagem Celular , Ceruletídeo/toxicidade , Quimiocinas/administração & dosagem , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Masculino , Pâncreas/citologia , Pancreatite/tratamento farmacológico , Ratos , Ratos Wistar
17.
Blood ; 133(10): 1096-1107, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30670446

RESUMO

The heterogeneous nature of myelodysplastic syndromes (MDS) demands a complex and personalized variety of therapeutic approaches. Among them, allogeneic hematopoietic stem cell transplantation remains the only potentially curative option and is accessible to only a small number of fit patients. For the majority of patients with MDS, treatment strategies are nonintensive and risk-adapted (by the revised version of the International Prognostic Scoring System), ranging from iron chelation and growth factors to lenalidomide and hypomethylating agents. These approaches are noncurative and aimed instead at improving cytopenias and quality of life and delaying disease progression. These limitations underpin the need for more translational research-based clinical trials in well-defined subgroups of patients with MDS. Indeed, much progress has been made over the past decade in understanding the complex molecular mechanisms underlying MDS. Unfortunately, this has not yet translated into approval of novel treatment options. There is a particularly urgent medical need in patients failing current first-line therapies, such as with erythropoiesis-stimulating or hypomethylating agents. Nevertheless, actual developments are expected to pave the way for exciting novel therapeutic opportunities. This review provides an overview of the current therapeutic landscape in MDS focusing on recent advances in clinical and translational research.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Progressão da Doença , Eritropoese , Hematologia/métodos , Hematologia/normas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Quelantes de Ferro/uso terapêutico , Lenalidomida/uso terapêutico , Metilação , Prognóstico , Risco , Índice de Gravidade de Doença , Pesquisa Médica Translacional , Transplante Homólogo
18.
Balkan Med J ; 36(1): 43-48, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30238923

RESUMO

Background: Chemerin is a novel chemoattractant adipokine expressed in cardiovascular system, and its receptor has been detected in the epicardial adipose tissue. Aims: To determine the effects of chemerin on the cardiac parameters and gene expressions in the isolated perfused rat heart. Study Design: Animal experiment. Methods: The hearts were retrogradely perfused with Langendorff technique to measure the cardiac parameters. The experimental groups were acutely treated with 10, 100, and 1000 nM doses of chemerin. Another group was given 10 µM L-nitric oxide synthase inhibitor for 5 min before 1000 nM chemerin administration. The real-time polymerase chain reaction was performed for detecting the expression of target genes. Results: All doses of chemerin significantly decreased the left ventricular developed pressure (max 35.33 Δ%, p<0.001), and +dP/dtmax (max 31.3 Δ%, p<0.001), which are the indexes of cardiac contractile force. In addition, 1000 nM chemerin reduced the coronary flow (max 31 Δ%, p<0.001). N(W)-nitro-L-arginine methyl ester antagonized the negative inotropic effect of chemerin on contractility. Chemerin induced a 2.16-fold increase in endothelial nitric oxide synthase mRNA and increased the cyclic guanosine monophosphate levels (p<0.001) but decreased the PI3Kγ gene expression (1.8-fold, p<0.001). Furthermore, all doses of chemerin decreased the CaV1.2 gene expression (1.69-fold, p<0.001). Conclusion: Acute chemerin treatment induces a negative inotropic action with the involvement of nitric oxide pathway, CaV1.2, and PI3Kγ on isolated rat heart.


Assuntos
Débito Cardíaco/efeitos dos fármacos , Quimiocinas/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Contração Miocárdica/efeitos dos fármacos , Animais , Arginina/efeitos adversos , Arginina/análogos & derivados , Arginina/farmacologia , Arginina/uso terapêutico , Débito Cardíaco/fisiologia , Quimiocinas/uso terapêutico , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Coração/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Contração Miocárdica/fisiologia , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Ratos/genética , Ratos Sprague-Dawley/genética , Estatísticas não Paramétricas
19.
Artif Organs ; 43(4): 413-423, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30311249

RESUMO

Fabrication of nanofibrous biomaterials composed of natural and synthetic materials that incorporated with antibiotic and growth factors with controlled release manner is an attractive topic in wound healing. The purpose of this study was to prepare optimal composite of materials as biomimetic nanofibrous mats for application in wound healing. The mat was prepared of polycaprolactone (PCL) in the bottom, chitosan/poly ethylene oxide (Cs/PEO) in the middle, and PCL/collagen (PCL/Coll) in the top layer. A panel of standard characterization tests of nanofibrous mat was performed and its compatibilities in strength and integration were confirmed. Middle layer was loaded with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and silver sulfadiazine (SSD) was incorporated in the bottom layer as an anti-infection factor. Then, on the dorsum of rats, a 400-mm2 wound was created and surrounded by a silicone ring to control the usual tissue contractions. Nanofibrous mats with or without growth factors were applied as wound dressings and at day 14, the healing process was evaluated. At day 14, the treated group by designed mat showed faster epithelialization and angiogenesis. Silicone ring in the test group was desirable in wound closure compared to the control group. Reformation of skin tissue was manifested in a shorter time. This composite nanofibrous mat could be introduced as a dynamic and effective candidate for wound dressing.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Bandagens , Quitosana/química , Colágeno/química , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Poliésteres/química , Sulfadiazina de Prata/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Anti-Infecciosos Locais/uso terapêutico , Materiais Biocompatíveis/química , Fator de Crescimento Epidérmico/administração & dosagem , Fator de Crescimento Epidérmico/uso terapêutico , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino , Nanofibras/química , Nanofibras/ultraestrutura , Ratos , Ratos Sprague-Dawley , Sulfadiazina de Prata/uso terapêutico
20.
Int Wound J ; 16(1): 275-285, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30460739

RESUMO

Fat grafting is becoming a common procedure in regenerative medicine because of its high content of growth factors and adipose derived stem cells (ADSCs) and the ease of harvest, safety, and low cost. The high concentration of ADSCs found in fat has the potential to differentiate into a wide range of wound-healing cells including fibroblasts and keratinocytes as well as demonstrating proangiogenic qualities. This suggests that fat could play an important role in wound healing. However retention rates of fat grafts are highly variable due in part to inconsistent vascularisation of the transplanted fat. Furthermore, conditions such as diabetes, which have a high prevalence of chronic wounds, reduce the potency and regenerative potential of ADSCs. Platelet-rich plasma (PRP) is an autologous blood product rich in growth factors, cell adhesion molecules, and cytokines. It has been hypothesised that PRP may have a positive effect on the survival and retention of fat grafts because of improved proliferation and differentiations of ADSCs, reduced inflammation, and improved vascularisation. There is also increasing interest in a possible synergistic effect that PRP may have on the healing potential of fat, although the evidence for this is very limited. In this review, we evaluate the evidence in both in vitro and animal studies on the mechanistic relationship between fat and PRP and how this translates to a benefit in wound healing. We also discuss future directions for both research and clinical practice on how to enhance the regenerative potential of the combination of PRP and fat.


Assuntos
Tecido Adiposo/transplante , Proliferação de Células/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Plasma Rico em Plaquetas/fisiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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