Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Int Wound J ; 16(4): 1000-1008, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31063243

RESUMO

The use of sacral dressings for pressure ulcer prevention is growing rapidly. In addition to their passive biomechanical role in pressure and shear reduction, in the near future, prophylactic dressings may also provide active tissue protection by releasing preventive agents or drugs into skin and deeper tissues. We investigated delivery of sodium pyruvate (NaPy) from an active dressing to potentially protect the sacral skin and underlying tissues in addition. We used four finite element model variants describing different skin roughness levels to determine time profiles of NaPy diffusion from the dressing into the skin layers. The NaPy concentrations for the different modelled cases stabilised after 1 to 6.5 hours from the time of application of the dressings, at 1% to 3% of the NaPy concentration in the dressing reservoir, which is considered potent. We conclude that prophylactic sacral dressings have the potential to deliver NaPy into skin and subdermally, to potentially increase soft tissue tolerance to sustained bodyweight-caused cell and tissue deformations. The time durations to achieve the steady-state potent NaPy dermal concentrations are clinically feasible, for example, for preparation of patients for surgery or for use in intensive care units.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bandagens , Úlcera por Pressão/tratamento farmacológico , Úlcera por Pressão/prevenção & controle , Piruvatos/uso terapêutico , Dobras Cutâneas , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Região Sacrococcígea
2.
J Tissue Viability ; 27(1): 23-31, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28446371

RESUMO

A pressure injury (PrI) compromises quality of life and can be life-threatening. The fundamental cause of PrIs is sustained deformations in weight-bearing soft tissues, e.g., during prolonged sitting on inadequate surfaces such as a toilet seat. In nursing homes and geriatric facilities, patients need assistance using the restroom, and patients being left on the toilet for tens-of-minutes is a real-world scenario, unfortunately. Nevertheless, there are no published studies regarding sustained tissue loads during toilet sitting and their effects on tissue physiology. Here, the biomechanical and microcirculatory responses of the buttock tissues to toilet sitting were investigated using finite element modeling and cutaneous hemodynamic measurements, to explore the potential etiology of PrIs occurring on the toilet. We found that prolonged sitting on toilet seats involves a potential risk for PrI development, the extent of which is affected by the seat design. Additionally, we found that specialized toilet seat cushions are able to reduce this risk, by lowering instantaneous tissue exposures to internal stresses (by up to 88%) and maintaining reduced interface pressures. Furthermore, hemodynamic variables were altered during the toilet sitting; in particular, tcPO2 was decreased by 49% ± 7% (44 ± 2[mmHg] to 22 ± 4[mmHg]) during sitting. The current study confirms that investing in expensive PrI prevention (PIP) products is likely to be ineffective for an immobilized patient who is left to sit on a bare toilet seat for long times. This argument highlights the need for a holistic-care approach, employing PIP devices that span across the entire environment where bodyweight forces apply to tissues.


Assuntos
Postura/fisiologia , Úlcera por Pressão/prevenção & controle , Banheiros/normas , Adulto , Fenômenos Biomecânicos/fisiologia , Nádegas/irrigação sanguínea , Nádegas/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pressão/efeitos adversos
3.
J Wound Ostomy Continence Nurs ; 45(5): 432-437, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30086102

RESUMO

PURPOSE: The sacrum is the most common location of pressure injuries (PIs) in bedridden patients. The purpose of this study was to measure the effect of specific pressure preventive devices on sacral skeletal muscle, subcutaneous fat, and skin tissue deformations. SUBJECTS AND SETTING: The sample comprised 3 healthy adults residing in a community setting in Tel Aviv, Israel. DESIGN: Descriptive, comparative design. METHODS: Tissue thickness changes of 3 healthy adults were measured using magnetic resonance imaging (MRI) in weight-bearing sacral skin, subcutaneous fat, and muscle. Changes in tissue thickness were compared under the following conditions: (1) lying supine on a rigid surface (unpadded MRI table), (2) lying on a standard foam mattress, (3) lying on a mattress after application of a prophylactic multilayer dressing, and (4) lying on a standard foam mattress with a prophylactic multilayer dressing and a positioning system. One-way analysis of variance and post hoc Tukey-Kramer multiple pairwise comparisons were used to compare outcomes. RESULTS: The mattress, the prophylactic multilayer dressing, and the turning and positioning device when applied together resulted in significantly lower deformation levels of each of the soft tissue layers (ie, skin, subcutaneous fat, and muscle separately) as well as of the total soft tissue bulk, with respect to the rigid MRI table (P < .05). CONCLUSION: Study findings suggest that a combination of preventive interventions may reduce the risk of developing a sacral PI.


Assuntos
Bandagens/normas , Posicionamento do Paciente/métodos , Região Sacrococcígea/fisiologia , Adulto , Análise de Variância , Bandagens/estatística & dados numéricos , Feminino , Humanos , Israel , Imageamento por Ressonância Magnética/métodos , Masculino , Posicionamento do Paciente/instrumentação , Pressão , Úlcera por Pressão/prevenção & controle , Região Sacrococcígea/fisiopatologia
4.
Int Wound J ; 15(3): 402-416, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29250903

RESUMO

Scientific evidence regarding microclimate and its effects on the risk of pressure ulcers (PU) remains sparse. It is known that elevated skin temperatures and moisture may affect metabolic demand as well as the mechanical behaviour of the tissue. In this study, we incorporated these microclimate factors into a novel, 3-dimensional multi-physics coupled model of the human buttocks, which simultaneously determines the biothermal and biomechanical behaviours of the buttocks in supine lying on different support surfaces. We compared 3 simulated thermally controlled mattresses with 2 reference foam mattresses. A tissue damage score was numerically calculated in a relevant volume of the model, and the cooling effect of each 1°C decrease of tissue temperature was deduced. Damage scores of tissues were substantially lower for the non-foam mattresses compared with the foams. The percentage tissue volume at risk within the volume of interest was found to grow exponentially as the average tissue temperature increased. The resultant average sacral skin temperature was concluded to be a good predictor for an increased risk of PU/injuries. Each 1°C increase contributes approximately 14 times as much to the risk with respect to an increase of 1 mmHg of pressure. These findings highlight the advantages of using thermally controlled support surfaces as well as the need to further assess the potential damage that may be caused by uncontrolled microclimate conditions on inadequate support surfaces in at-risk patients.


Assuntos
Pessoas Acamadas , Microclima , Úlcera por Pressão/prevenção & controle , Adulto , Leitos , Nádegas , Feminino , Humanos , Posicionamento do Paciente , Modelagem Computacional Específica para o Paciente , Sacro , Temperatura Cutânea , Decúbito Dorsal
5.
Int Wound J ; 15(6): 866-874, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29797409

RESUMO

Sustained pressure, shear forces, and friction, as well as elevated humidity/moisture, are decisive physical factors in the development of pressure injuries (PIs). To date, further research is needed in order to understand the influence of humidity and moisture on the coefficient of friction (COF) of skin against different types of medical textiles. The aim of this work was to investigate the effects of moisture caused by sweat, urine, or saline on the resulting COF of skin against different textiles used in the medical setting in the context of PI prevention. For that purpose, we performed physical measurements of static COFs of porcine skin followed by finite element (FE) computational modelling in order to illustrate the effect of increased COF at the skin on the resulting strains and stresses deep within the soft tissues of the buttocks. The COF of dry skin obtained for the 3 textiles varied between 0.59 (adult diaper) and 0.91 (polyurethane dressing). In addition, the COF increased with the added moisture in all of the tested cases. The results of the FE simulations further showed that increased COF results in elevated strain energy density and shear strain values in the skin and deeper tissues and, hence, in an increased risk for PI development. We conclude that moisture may accelerate PI formation by increasing the COF between the skin and the medical textile, regardless of the type of the liquid that is present. Hence, reduction of the wetness/moisture between the skin and fabrics in patients at a high risk of developing PIs is a key measure in PI prevention.


Assuntos
Curativos Biológicos , Fricção , Umidade/efeitos adversos , Úlcera por Pressão/prevenção & controle , Suor , Têxteis/efeitos adversos , Urina , Animais , Humanos , Modelos Animais , Cicatrização/fisiologia
6.
Neurourol Urodyn ; 36(6): 1645-1650, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27862230

RESUMO

AIMS: Prostate cancer is the most frequently diagnosed male cancer and urinary incontinence represents a major consequence following surgery. Penile compression clamps (PCCs) which externally occlude the urethra may be used to manage the incontinence. Despite potential complication of PCCs, such as deformation-inflicted tissue damage, to date, there are no reported biomechanical criteria for design of PCCs, in terms of quantitative parameters for evaluating the safety-versus-efficacy of existing or future designs. METHODS: We developed a set of computational three-dimensional models of the penis, to which compression was applied using five generic PCC designs. The internal mechanical states of the soft tissues of the penis were then analysed using finite element simulations. RESULTS: Stresses in skin, fat, and tunica albuginea regularly exceeded 10 kPa (75 mmHg). Cuff-type and knurl-type PCCs pose the highest potential risks to tissue health with elevated tissue stresses around the entire penile perimeter (cuff) or urethral stress concentrations (knurl). The soft and contoured PCCs produced the lowest values of these mechanical parameters. CONCLUSIONS: The present study identified design characteristics, including envelopment, adaptability, and durability which provide the safest mechanical conditions in the penis and thus minimize the risk of tissue damage while still managing incontinence. Such data should help to design a safer clamp.


Assuntos
Pênis/fisiopatologia , Pressão , Uretra/fisiopatologia , Incontinência Urinária/terapia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Humanos , Masculino , Modelos Teóricos , Neoplasias da Próstata/cirurgia , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia
7.
J Tissue Viability ; 26(1): 57-68, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26927980

RESUMO

Pressure ulcers (PUs) in the pediatric population are inherently different from those in adults, in their risk factors and etiology, with more than 50% of the cases related to contact with medical equipment at the care setting. The aims of this study were to: (i) Determine the mechanical loads in the scalp of a newborn lying supine, near a wedged encephalogram electrode or wire, which is deforming the scalp at the occiput. (ii) Evaluate the effect of a doughnut-shaped headrest on the mechanical state of tissues at the same site. We used finite element computational modeling to simulate a realistic three-dimensional head of a newborn interacting with the above devices. We examined effective (von Mises) stresses, shear stresses and strain energy density (SED) in the fat and skin tissues at the occipital region. The interfering wire resulted in the worse mechanical conditions in the soft tissues, compared to the lodged electrode and use of a doughnut-shaped headrest, with 345% and 50% increase in effective stresses in skin and fat tissues, respectively. Considering that elevated and localized tissue deformations, stresses and SED indicate a risk for PUs, our simulations suggest that misplaced medical devices, and using a doughnut-shaped headrest, impose an actual risk for developing device-related PUs. We conclude that guidelines for pediatric clinical care should recommend routine inspection of the medical device placement to prevent harmful contact conditions with the patient. Furthermore, improved design of medical equipment for pediatric settings is needed in order to protect these fragile young patients from PUs.


Assuntos
Equipamentos e Provisões/efeitos adversos , Úlcera por Pressão/prevenção & controle , Dermatoses do Couro Cabeludo/prevenção & controle , Estresse Mecânico , Sobrevivência de Tecidos , Fenômenos Biomecânicos , Eletrodos/efeitos adversos , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Modelos Anatômicos , Úlcera por Pressão/etiologia , Dermatoses do Couro Cabeludo/etiologia , Decúbito Dorsal
8.
Int Wound J ; 14(6): 1370-1377, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28960851

RESUMO

The sacral region is the most common site for pressure injuries (PIs) associated with lying in bed, and such sacral PIs often commence as deep tissue injuries (DTIs) that later present as open wounds. In complex patients, diabetes is common. Because, among other factors, diabetes affects connective tissue stiffness properties, making these tissues less able to dissipate mechanical loads through physiological deformations, diabetes is an additional biomechanical risk factor for PIs and DTIs. A preventive measure with established successful clinical outcomes is the use of sacral prophylactic dressings. The objective of this study has been to expand our previous work regarding the modes of action and biomechanical efficacy of prophylactic dressings in protecting the soft tissues adjacent to the sacrum by specifically examining the role of a directional stiffness preference (anisotropy) of the dressing while further accounting for diabetic tissue conditions. Multiple three-dimensional anatomically detailed finite element (FE) model variants representing diabetic tissue conditions were used, and tissue loading state data were compared with healthy tissue simulations. We specifically compared soft tissue exposures to elevated internal shear stresses and strain energy densities (SED) near the sacrum during supine weight bearing on a standard (foam) hospital mattress without a dressing, with a prophylactic dressing lacking directional stiffness preferences and with an anisotropic dressing. Our results have clearly shown that an anisotropic dressing design reduces the peak tissue stresses and exposure to sustained tissue deformations in both healthy and diabetic cases. The present study provides additional important insights regarding the optimal structural and material design of prophylactic dressings, which in turn, informs clinicians and decision makers regarding beneficial features.


Assuntos
Bandagens , Tecido Conjuntivo/fisiopatologia , Úlcera por Pressão/prevenção & controle , Região Sacrococcígea/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Complicações do Diabetes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Ann Neurol ; 78(1): 88-103, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25893674

RESUMO

OBJECTIVE: Alzheimer's disease (AD)-associated dementia is due to tissue damage caused by amyloid ß (Aß) deposition within the brain and by accompanying neuroinflammation. The nicotinamide adenine dinucleotide (NAD) glycohydrolase CD38, which is expressed by neurons, astrocytes, and microglial cells, regulates inflammatory and repair processes in the brain and other tissues by degrading NAD and repressing the activity of other NAD-consuming enzymes and by producing NAD-derived metabolites that regulate calcium signaling and migration of inflammatory cells. Given the role of CD38 in neuroinflammation and repair, we examined the effect of CD38 deletion on AD pathology. METHODS: We crossed APPswePS1ΔE9 (APP.PS) mice with Cd38(-) (/) (-) mice to generate AD-prone CD38-deficient animals (APP.PS.Cd38(-) (/) (-) ) and examined AD-related phenotypes in both groups. RESULTS: APP.PS.Cd38(-) (/) (-) mice exhibited significant reductions in Aß plaque load and soluble Aß levels compared to APP.PS mice, and this correlated with improved spatial learning. Although CD38 deficiency resulted in decreased microglia/macrophage (MM) accumulation, the transcription profile of the Cd38(-) (/) (-) and Cd38(+/) (+) MM was similar, suggesting that the decreased Aß burden in APP.PS.Cd38(-) (/) (-) mice was not due to alterations in MM activation/function. Instead, APP.PS.Cd38(-) (/) (-) neuronal cultures secreted less Aß and this reduction was mimicked when APP.PS neuronal cultures were treated with inhibitors that blocked CD38 enzyme activity or the signaling pathways controlled by CD38-derived metabolites. Furthermore, ß- and γ-secretase activity was decreased in APP.PS.Cd38(-) (/) (-) mice, which correlated with decreased Aß production. INTERPRETATION: CD38 regulates AD pathology in the APP.PS model of AD, suggesting that CD38 may be a novel target for AD treatment.


Assuntos
ADP-Ribosil Ciclase 1/genética , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Comportamento Animal , Encéfalo/patologia , Glicoproteínas de Membrana/genética , Placa Amiloide/patologia , RNA Mensageiro/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/metabolismo , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Microglia/metabolismo , Placa Amiloide/metabolismo , Aprendizagem Espacial , Transcriptoma
10.
Int J Cancer ; 136(6): 1422-33, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25053177

RESUMO

Glioma, the most common cancer of the central nervous system, has very poor prognosis and no effective treatment. It has been shown that activated microglia/macrophages in the glioma tumor microenvironment support progression. Hence, inhibition of the supporting effect of these cells may constitute a useful therapeutic approach. Recently, using a syngeneic mouse glioma progression model, we showed that the ectoenzyme CD38 regulated microglia activation and, in addition, that the loss of CD38 from the tumor microenvironment attenuated glioma progression and prolonged the life span of the tumor-bearing mice. These studies, which employed wild-type (WT) and Cd38(-/-) C57BL/6J mice, suggest that inhibition of CD38 in glioma microenvironment may be used as a new therapeutic approach to treat glioma. Our study tested this hypothesis. Initially, we found that the natural anthranoid, 4,5-dihydroxyanthraquinone-2-carboxylic acid (rhein), and its highly water-soluble tri-potassium salt form (K-rhein) are inhibitors of CD38 enzymatic (nicotinamide adenine dinucleotide glycohydrolase) activity (IC50 = 1.24 and 0.84 µM, respectively, for recombinant mouse CD38). Treatment of WT, but not Cd38(-/-) microglia with rhein and K-rhein inhibited microglia activation features known to be regulated by CD38 (lipopolysaccharide/IFN-γ-induced activation, induced cell death and NO production). Furthermore, nasal administration of K-rhein into WT, but not Cd38(-/-) C57BL/6J, mice intracranially injected with GL261 cells substantially and significantly inhibited glioma progression. Hence, these results serve as a proof of concept, demonstrating that targeting CD38 at the tumor microenvironment by small-molecule inhibitors of CD38, for example, K-rhein, may serve as a useful therapeutic approach to treat glioma.


Assuntos
ADP-Ribosil Ciclase 1/antagonistas & inibidores , Antraquinonas/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Citocinas , Progressão da Doença , Glioma/patologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Ubiquitinas
11.
Adv Skin Wound Care ; 28(7): 303-16, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26080017

RESUMO

OBJECTIVE: To determine changes in internal soft-tissue loads in the buttocks of individuals with a spinal cord injury (SCI), who undergo pathoanatomical changes during the first months and years following the occurrence of the SCI, while sitting on a contoured foam cushion (CFC) that has been fitted close to the time of the injury but has not been replaced in subsequent years. DESIGN: Internal tissue loads in variant buttocks anatomies on a CFC were analyzed by means of finite element computer simulations. The pathoanatomical changes that are characteristic to SCI and were simulated here are: increase in fat tissue mass, intramuscular fat infiltration, muscle atrophy, and combinations of these conditions. SETTING: Computational biomechanical modeling. MAIN RESULTS: Simulating the aforementioned pathoanatomical changes consistently resulted in greater mechanical strain and stress magnitudes and more inhomogeneity in the loading state of muscle and fat tissues, with a more profound effect in fat. The simulations further indicated a clear trend of exacerbation in tissue exposure to loads as the pathoanatomical changes progress chronologically and the CFC is not replaced. CONCLUSIONS: A CFC that has been fitted at a time close to the SCI, but has not been replaced in subsequent years, substantially loses its efficacy in protecting patients from developing pressure ulcers and deep tissue injury in particular.


Assuntos
Simulação por Computador , Úlcera por Pressão/prevenção & controle , Traumatismos da Medula Espinal/complicações , Estresse Mecânico , Fenômenos Biomecânicos , Peso Corporal , Nádegas , Desenho de Equipamento , Humanos , Modelos Biológicos , Úlcera por Pressão/etiologia , Equipamentos de Proteção , Fatores de Tempo
12.
J Tissue Viability ; 24(1): 1-11, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25639600

RESUMO

The heels are the most common site for facility-acquired pressure ulcers (PUs), and are also the most susceptible location for deep tissue injuries. The use of multilayer prophylactic dressings to prevent heel PUs is a relatively new prevention concept, generally aimed at minimizing the risk for heel ulcers (HUs) through mechanical cushioning and reduction of friction at the dressing-support interface. We used 9 finite element model variants of the posterior heel in order to evaluate the biomechanical performance of a multilayer dressing in prevention of HUs during supine lying. We compared volumetric exposures of the loaded soft tissues to effective and maximal shear strains, as well as peak stresses in the Achilles tendon, without any dressing and with a single-layer or a multilayer dressing (Mepilex(®) Border Heel-type), on supports with different stiffnesses. The use of the multilayer dressing consistently and considerably reduced soft tissue exposures to elevated strains at the posterior heel, on all of the tested support surfaces and when loaded with either pure compression or combined compression and shear. The aforementioned multilayer design showed (i) clear benefit over a single-layer dressing in terms of dissipating tissue strains, by promoting internal shear in the dressing which diverts loads from tissues; (ii) a protective effect that was consistent on supports with different stiffnesses. Recent randomized controlled trials confirmed the efficacy of the simulated multilayer dressing, and so, taken together with this modeling work, the use of a prophylactic multilayer dressing indicates a great promise in taking this route for prevention.


Assuntos
Bandagens , Úlcera do Pé/prevenção & controle , Calcanhar , Fenômenos Biomecânicos , Humanos
13.
J Tissue Viability ; 23(1): 13-23, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24405723

RESUMO

A sitting-acquired pressure ulcer (PU) is a common injury in wheelchair-bound patients. Preventative measures for the post spinal cord injury (SCI) population include prescription of a supportive thick cushion on the wheelchair, in order to better distribute loads between the buttocks and support surface (which are quantifiable using interface pressure measurements), and potentially, to minimize internal soft tissue loads (which are typically unknown). Information about the biomechanical efficacy of commercially-available structured cushion designs such as air-cell-based (ACB) cushions, gel, and honeycomb-like cushions is sparse. Considering the importance of such evaluations to patient safety and quality of life, we studied the biomechanical performances of an ACB cushion in comparison to standard, flat foam cushions with different stiffness properties. Using a set of finite element (FE) model variants, we determined the mechanical stresses in muscle, fat, and skin tissues under the ischial tuberosities during sitting. Tissue stress analyses were conducted in a reference SCI anatomy, incorporating pathoanatomical and pathophysiological changes associated with chronic SCI, including bone shape adaptation, muscle atrophy, and spasms. We found up to 57% greater immersion and 4 orders-of-magnitude lower muscle, fat, and skin tissue stresses for the ACB cushion. We also found the ACB cushion provides better protection against the aforementioned bone shape adaptation, muscle atrophy, and spasms. Hence, theoretically, the use of a suitable ACB cushion should provide longer safe sitting times for SCI patients with respect to standard foam cushions.


Assuntos
Úlcera por Pressão/prevenção & controle , Equipamentos de Proteção , Estresse Fisiológico , Fenômenos Biomecânicos , Nádegas , Desenho de Equipamento , Análise de Elementos Finitos , Humanos
14.
Sci Rep ; 12(1): 22131, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550142

RESUMO

Fibroblast growth factor-2 (FGF2) has multiple roles in cutaneous wound healing but its natural low stability prevents the development of its use in skin repair therapies. Here we show that FGF2 binds the outer surface of dermal fibroblast (DF)-derived extracellular vesicles (EVs) and this association protects FGF2 from fast degradation. EVs isolated from DF cultured in the presence of FGF2 harbor FGF2 on their surface and FGF2 can bind purified EVs in absence of cells. Remarkably, FGF2 binding to EVs is restricted to a specific subpopulation of EVs, which do not express CD63 and CD81 markers. Treatment of DF with FGF2-EVs activated ERK and STAT signaling pathways and increased cell proliferation and migration. Local injection of FGF2-EVs improved wound healing in mice. We further demonstrated that binding to EVs protects FGF2 from both thermal and proteolytic degradation, thus maintaining FGF2 function. This suggests that EVs protect soluble factors from degradation and increase their stability and half-life. These results reveal a novel aspect of EV function and suggest EVs as a potential tool for delivering FGF2 in skin healing therapies.


Assuntos
Vesículas Extracelulares , Fator 2 de Crescimento de Fibroblastos , Animais , Camundongos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Cicatrização , Vesículas Extracelulares/metabolismo , Proliferação de Células , Fibroblastos/metabolismo
15.
Glia ; 59(3): 397-412, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21264947

RESUMO

Apoptosis is a controlled cell-death process mediated inter alia by proteins of the Bcl-2 family. Some proteins previously shown to promote the apoptotic process were found to have nonapoptotic functions as well. Microglia, the resident immune cells of the central nervous system, respond to brain derangements by becoming activated to contend with the brain damage. Activated microglia can also undergo activation-induced cell death. Previous studies have addressed the role of core apoptotic proteins in the death process, but whether these proteins also play a role or not in the activation process is not been reported. Here we explore the effect of the BH3-only protein Bid on the immunological features of microglia and macrophages. Our results showed that Bid regulates both the phagocytotic activities and the inflammatory profiles of these cells. Deficiency of Bid attenuated the phagocytotic activity of primary microglia and peritoneal macrophages. It also changed the expression profile of distinct inflammation-related genes in lipopolysaccharide-activated microglia and peritoneal macrophages in vitro and in an in vivo sepsis-like paradigm. Notably, similar changes followed downregulation of Bid in the N9 microglial cell line. Cell death could not be detected in any of the systems examined. Our findings demonstrate that Bid can regulate the immunological profiles of activated microglial and macrophages, via a novel nonapoptotic activity. In view of the critical role of these cells in various pathologies, including acute and chronic brain insults, our findings suggest that impairments in Bid expression may contribute to these pathologies also via a nonapoptotic activity.


Assuntos
Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/fisiologia , Macrófagos/imunologia , Microglia/imunologia , Degeneração Neural/imunologia , Animais , Apoptose/imunologia , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/antagonistas & inibidores , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/genética , Linhagem Celular , Células Cultivadas , Feminino , Células HEK293 , Humanos , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/fisiologia , Lipopolissacarídeos/toxicidade , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/patologia , Degeneração Neural/genética , Degeneração Neural/patologia , Fagocitose/imunologia , Transdução de Sinais/imunologia
16.
Ann Fam Med ; 9(6): 549-51, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22084267

RESUMO

The cornerstone of family medicine is the belief in both the continuity and availability of care. These beliefs are challenged when a doctor leaves his or her clinic because of personal reasons. In the example described in this article, the involvement of colleagues in a Balint group led a doctor to a flash insight into her conflicting feelings related to leaving her clinic. The group process helped her to prepare and deal with her own feelings and needs, as well as those of her patients and staff. Balint groups are a secure place to explore and gain insight into the emotional aspects of attachment and separation of physicians from their patients.


Assuntos
Ansiedade de Separação/psicologia , Processos Grupais , Relações Médico-Paciente , Médicos de Família/psicologia , Continuidade da Assistência ao Paciente , Emoções , Feminino , Humanos , Masculino , Apego ao Objeto
17.
Methods Mol Biol ; 2154: 63-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32314208

RESUMO

Extracellular vesicles (EVs) secreted by all cells are key players in information transfer within a tissue or organism. With their highly cell-specific protein and RNA content, EVs can propagate cellular signals and modulate distant cells' behavior. Dermal fibroblasts are supportive cells for all skin cells and the roles of their EVs start to come to light only recently. In this chapter, we describe a protocol to isolate small EVs from primary human fibroblast culture using classical differential centrifugation methodology.


Assuntos
Fracionamento Celular/métodos , Micropartículas Derivadas de Células/metabolismo , Vesículas Extracelulares/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Pele/citologia , Exossomos/metabolismo , Humanos , Ultracentrifugação
18.
Biomech Model Mechanobiol ; 19(6): 2049-2059, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32236747

RESUMO

The altered biomechanical function of the knee following partial meniscectomy results in ongoing articular cartilage overload, which may lead to progressive osteoarthritis (OA). An artificial medial meniscus implant (NUsurface® Meniscus Implant, Active Implants LLC., Memphis, TN, USA) was developed to mimic the native meniscus and may provide an effective long-term solution for OA patients, alleviate pain, and restore joint function. The goal of the current study was to investigate the potential effect of an artificial medial meniscus implant on the function of the lateral compartment of the knee and on the potential alterations in load distribution between the two compartments under static axial loading, using advanced piezo-resistive sensors. We used an integrated in situ/in vivo experimental approach combining contact pressure measurements of cadaveric knees with MRI joint space measurements of 72 mild OA patients. We employed this integrated approach to evaluate the mechanical consequences in both the medial (treated) and lateral knee compartments of two levels of meniscectomy and implantation of an artificial meniscus implant. Partial and subtotal meniscectomies of the medial meniscus resulted in statistically significant decrease in contact areas (p = 0.008 and p < 0.0001, respectively) and increased contact pressures in the medial compartment; however, implantation of the artificial meniscus implant restored the average contact pressure to 93 ± 14% of its pre-meniscectomy, intact value. Additionally, we found that neither the two different grades of medial meniscectomies, nor implantation of the artificial medial meniscus implant affected the lateral compartment of the knee. The MRI data from the patient cohort facilitated the integration of real-life clinical results together with the laboratory measurements from our cadaveric study, as these two approaches complement each other. We conclude that the use of the artificial medial meniscus implant may re-establish normal load distribution across the articulating surfaces of the medial compartment and not increase loading across the lateral knee compartment.


Assuntos
Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Adulto , Fenômenos Biomecânicos , Cadáver , Cartilagem Articular/cirurgia , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Masculino , Meniscectomia/métodos , Meniscos Tibiais/fisiopatologia , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Pressão , Próteses e Implantes , Desenho de Prótese , Amplitude de Movimento Articular , Estresse Mecânico , Tíbia/fisiopatologia , Suporte de Carga
19.
J Homosex ; 66(11): 1513-1534, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30142289

RESUMO

The Parental Acceptance and Rejection of Sexual Orientation Scale was administered to 256 self-identified lesbian, gay, bisexual, or queer adults who had been out of the closet to their parents for at least 1 year. Principal component analysis revealed a clear two-component solution: parental acceptance and parental rejection. Findings showed that perceived maternal sexual orientation-specific acceptance was higher, and perceived maternal sexual orientation-specific rejection was lower, for gay/bisexual sons compared to their lesbian/bisexual daughters. Results of regression analyses suggest that both perceived sexual orientation specific acceptance and rejection predicted adult children's psychological symptoms after accounting for perceived global parental acceptance and rejection and the child's gender. The scale's utility for research and practice are noted.


Assuntos
Filhos Adultos/psicologia , Relações Pais-Filho , Pais/psicologia , Comportamento Sexual , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Psicológicos , Percepção Social , Adulto Jovem
20.
Ostomy Wound Manage ; 64(7): 18-26, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30059336

RESUMO

The sacral area is the most common site for pressure injuries (PIs) associated with prolonged supine bedrest. In previous studies, an anisotropic multilayer prophylactic dressing was found to reduce the incidence of PIs and redistribute pressure. The purpose of the current study was to further investigate relationships between design features and biomechanical efficacy of sacral prophylactic dressings. Using computer modeling, the anisotropic multilayer dressing and a hypothetical dressing with different mechanical properties were tested under dry and 3 levels of moist/wet conditions. Sixteen (16) finite element model variants representing the buttocks were developed. The model variants utilized slices of the weight-bearing buttocks of a 28-year-old healthy woman for segmentation of the pelvic bones and soft tissues. Effective stresses and maximal shear stresses in a volume of interest of soft tissues surrounding the sacrum were calculated from the simulations, and a protective endurance (PE) index was further calculated. Resistance to deformations along the direction of the spine when wet was determined by rating simulation outcomes (volumetric exposures to effective stress) for the different dressing conditions. Based on this analysis, the anisotropic multilayer prophylactic dressing exhibited superior PE (80%), which was approximately 4 times that of the hypothetical dressing (22%). This study provides additional important insights regarding the optimal design of prophylactic dressings, especially when exposed to moisture. A next step in research would be to optimize the extent of the anisotropy, particularly the property ratio of stiffnesses (elastic moduli).


Assuntos
Bandagens/normas , Simulação por Computador , Umidade/efeitos adversos , Úlcera por Pressão/prevenção & controle , Adulto , Bandagens/efeitos adversos , Nádegas/lesões , Nádegas/fisiopatologia , Desenho de Equipamento/normas , Feminino , Humanos , Umidade/prevenção & controle , Distribuição de Poisson , Úlcera por Pressão/enfermagem , Estresse Mecânico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA