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1.
Glia ; 68(2): 263-279, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490574

RESUMO

Myelination delay and remyelination failure following insults to the central nervous system (CNS) impede axonal conduction and lead to motor, sensory and cognitive impairments. Both myelination and remyelination are often inhibited or delayed due to the failure of oligodendrocyte progenitor cells (OPCs) to mature into myelinating oligodendrocytes (OLs). Digestion products of the glycosaminoglycan hyaluronan (HA) have been implicated in blocking OPC maturation, but how these digestion products are generated is unclear. We tested the possibility that hyaluronidase activity is directly linked to the inhibition of OPC maturation by developing a novel modified flavonoid that functions as a hyaluronidase inhibitor. This compound, called S3, blocks some but not all hyaluronidases and only inhibits matrix metalloproteinase activity at high concentrations. We find that S3 reverses HA-mediated inhibition of OPC maturation in vitro, an effect that can be overcome by excess recombinant hyaluronidase. Furthermore, we find that hyaluronidase inhibition by S3 accelerates OPC maturation in an in vitro model of perinatal white matter injury. Finally, blocking hyaluronidase activity with S3 promotes functional remyelination in mice with lysolecithin-induced demyelinating corpus callosum lesions. All together, these findings support the notion that hyaluronidase activity originating from OPCs in CNS lesions is sufficient to prevent OPC maturation, which delays myelination or blocks remyelination. These data also indicate that modified flavonoids can act as selective inhibitors of hyaluronidase activity and can promote OPC maturation, making them excellent candidates to accelerate myelination or promote remyelination following perinatal and adult CNS insults.


Assuntos
Doenças Desmielinizantes/patologia , Células Precursoras de Oligodendrócitos/citologia , Oligodendroglia/metabolismo , Remielinização/fisiologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Neurogênese/fisiologia , Células-Tronco/metabolismo
2.
Dermatitis ; 15(1): 10-7, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15573643

RESUMO

BACKGROUND: Limited information documents the prevention and treatment benefits of a hand care regimen using moisturizer in a controlled manner for employees in typical manufacturing situations. OBJECTIVE: The objective was to assess the effectiveness of a comprehensive skin care program including skin conditioning lotion in multiple manufacturing environments where employees are at high risk for skin disease. METHODS: A randomized trial test design with multiple measures, including skin bioengineering measurement techniques, visual grading, and self-assessment questionnaires, was used to broadly characterize skin condition. RESULTS: Comparison of the change in the skin condition of workers using the full hand care regimen with moisturizer versus a control group using a regimen without moisturizer demonstrated significant (p < .05) improvements in multiple measures after 1 to 2 weeks. Corneometer readings consistently showed significant improvement for employees using moisturizer, regardless of their work location. CONCLUSION: Improved skin condition resulted from the regular use of an effective skin conditioning hand moisturizer as part of a skin care regimen in work environments in which workers were prone to experiencing occupational irritant contact dermatitis.


Assuntos
Dermatite Ocupacional/tratamento farmacológico , Emolientes/administração & dosagem , Dermatoses da Mão/tratamento farmacológico , Administração Cutânea , Dermatite Ocupacional/patologia , Feminino , Dermatoses da Mão/patologia , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Am J Infect Control ; 31(2): 109-16, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12665745

RESUMO

BACKGROUND: Nosocomial infections are a major problem in health care facilities, resulting in extended durations of care, substantial morbidity and mortality, and excess costs. Since alcohol gel hand sanitizers combine high immediate antimicrobial efficacy with ease of use, this study was carried out to determine the effect of the use of an alcohol gel hand sanitizer by caregivers on infection types and rates in an acute care facility. Patients were educated about the study through a poster on the unit, and teachable patients were given portable bottles of the alcohol hand gel for bedside use, along with an educational brochure explaining how and why to practice good hand hygiene. METHODS: Infection rate and type data were collected in 1 unit of a 498-bed acute care facility for 16 months (February 2000 to May 2001). An alcohol gel hand sanitizer was provided and used by caregivers in the orthopedic surgical unit of the facility during this period. RESULTS: The primary infection types (more than 80%) found were urinary tract (UTI) and surgical site (SSI) infections. Infection types and rates for the unit during the period the alcohol hand sanitizer (intervention) was used were compared with the infection types and rates for the same unit when the alcohol hand sanitizer was not used (baseline); the results demonstrated a 36.1% decrease in infection rates for the 10-month period that the hand sanitizer was used. CONCLUSION: This study indicates that use of an alcohol gel hand sanitizer can decrease infection rates and provide an additional tool for an effective infection control program in acute care facilities.


Assuntos
Infecção Hospitalar/epidemiologia , Desinfecção/métodos , Etanol/farmacologia , Controle de Infecções/métodos , Análise de Variância , Anti-Infecciosos Locais/farmacologia , Custos e Análise de Custo , Infecção Hospitalar/economia , Infecção Hospitalar/prevenção & controle , Feminino , Desinfecção das Mãos/métodos , Desinfecção das Mãos/normas , Pesquisas sobre Atenção à Saúde , Humanos , Incidência , Unidades de Terapia Intensiva , Masculino , Ortopedia/normas , Probabilidade , Fatores de Risco , Sensibilidade e Especificidade
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