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1.
Health Educ Res ; 38(4): 320-328, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37002586

RESUMO

Guided by the Icelandic Prevention Model, a community-led coalition in Franklin County, KY, aimed to subsidize costs for participation in supervised organized leisure time programs among its youth via adaptation of the Reykjavik City Leisure Card program, locally known as the 'YES Card' voucher program. This study examined whether the proportion of students participating in supervised out-of-school activities and sports was higher in the YES Card intervention group compared to a similar group of youth who did not receive the voucher across two time points. Two waves of survey data were collected in one intervention middle school and two geographically and demographically similar comparison schools in 2020 (n for intervention = 112, n for comparison = 723) and 2021 (n for intervention = 134, n for comparison = 873). The expected age of students ranged between 12 and 15 years. Analyses were conducted using logistic regression. The YES Card receivers were two-and-a-half times more likely to participate in nonsport organized recreational activities [odds ratio, OR, 2.43 (95% confidence interval, CI, 1.07-5.52)] and almost twice as likely to participate in sports [OR: 1.91 (95%CI: 1.08-3.38)] over the 1-year study period, compared to non-YES Card youth. We conclude that Franklin County in KY in the USA has successfully adapted the Reykjavik City Leisure time voucher program.


Assuntos
Atividades de Lazer , Esportes , Humanos , Adolescente , Criança , Instituições Acadêmicas , Kansas , Modelos Logísticos
2.
J Hosp Infect ; 107: 45-49, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32991941

RESUMO

BACKGROUND: The coronavirus disease 2019 pandemic has greatly increased the frequency of disinfecting surfaces in public places, causing a strain on the ability to obtain disinfectant solutions. An alternative is to use plain alcohols (EtOH and IPA) or sodium hypochlorite (SH). AIM: To determine the efficacy of various concentrations of EtOH, IPA and SH on a human coronavirus (HCoV) dried on to surfaces using short contact times. METHODS: High concentrations of infectious HCoV were dried on to porcelain and ceramic tiles, then treated with various concentrations of the alcohols for contact times of 15 s, 30 s and 1 min. Three concentrations of SH were also tested. Reductions in titres were measured using the tissue culture infectious dose 50 assay. FINDINGS: Concentrations of EtOH and IPA from 62% to 80% were very efficient at inactivating high concentrations of HCoV dried on to tile surfaces, even with a 15-s contact time. Concentrations of 95% dehydrated the virus, allowing infectious virus to survive. The dilutions of SH recommended by the Centers for Disease Control and Prevention (1/10 and 1/50) were efficient at inactivating high concentrations of HCoV dried on to tile surfaces, whereas a 1/100 dilution had substantially lower activity. CONCLUSIONS: Multiple concentrations of EtOH, IPA and SH efficiently inactivated infectious HCoV on hard surfaces, typical of those found in public places. Often no remaining infectious HCoV could be detected.


Assuntos
2-Propanol/farmacologia , Desinfetantes/farmacologia , Etanol/farmacologia , SARS-CoV-2/efeitos dos fármacos , Inativação de Vírus/efeitos dos fármacos , Cerâmica , Porcelana Dentária , Desinfetantes/química , Hipoclorito de Sódio/farmacologia , Propriedades de Superfície
3.
Virology ; 524: 106-113, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30170240

RESUMO

The major capsid protein of HPV, L1, assembles into pentamers that form a T = 7 icosahedral particle, but the location of the co-assembled minor capsid protein, L2, remains controversial. Several researchers have developed useful monoclonal antibodies targeting L2, but most react with linear epitopes toward the N-terminus. As a means to better define the virus capsid and better assess the localization and exposure of L2 epitopes in the context of assembled HPV, we have developed a panel of 30 monoclonal antibodies (mAbs) which target the N-terminus of L2 amino acids 11-200, previously defined as a broadly protective immunogen. Select mAbs were processed with enzymes and anti-L2 Fabs were generated. These new mAb/Fab probes will be beneficial in future studies to unravel the placement of L2 and to help better define the role of L2 in the HPV lifecycle and the nature of the broadly protective epitopes.


Assuntos
Alphapapillomavirus/imunologia , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/imunologia , Proteínas Oncogênicas Virais/imunologia , Infecções por Papillomavirus/virologia , Animais , Anticorpos Monoclonais/imunologia , Reações Cruzadas , Epitopos/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Vírion
4.
HIV Med ; 15(4): 196-202, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24580719

RESUMO

OBJECTIVES: An increasing number of HIV-infected patients are combating HIV infection through the use of antiretroviral drugs, including reverse transcriptase inhibitors. Oral complications associated with these drugs are becoming a mounting cause for concern. In our previous studies, both protease inhibitors and reverse transcriptase inhibitors have been shown to change the proliferation and differentiation state of oral tissues. This study examined the effect of a nonnucleoside and a nucleoside reverse transcriptase inhibitor on the growth and differentiation of gingival epithelium. METHODS: Organotypic (raft) cultures of gingival keratinocytes were treated with a range of efavirenz and tenofovir concentrations. Raft cultures were immunohistochemically analysed to determine the effect of these drugs on the expression of key differentiation and proliferation markers, including cytokeratins and proliferating cell nuclear antigen (PCNA). RESULTS: These drugs dramatically changed the proliferation and differentiation state of gingival tissues when they were present throughout the growth period of the raft tissue as well as when drugs were added to established tissue on day 8. Treatment with the drugs increased the expression of cytokeratin 10 and PCNA and, conversely, decreased expression of cytokeratin 5, involucrin and cytokeratin 6. Gingival tissue exhibited increased proliferation in the suprabasal layers, increased fragility, and an inability to heal itself. CONCLUSIONS: Our results suggest that efavirenz and tenofovir treatments, even when applied in low concentrations for short periods of time, deregulated the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our system could be developed as a potential model for studying the effects of HIV and highly active antiretroviral therapy (HAART) in vitro.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/farmacologia , Benzoxazinas/farmacologia , Gengiva/citologia , Queratinócitos/efeitos dos fármacos , Organofosfonatos/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Adenina/farmacologia , Alcinos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ciclopropanos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Gengiva/efeitos dos fármacos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Queratina-6/metabolismo , Queratinócitos/citologia , Tenofovir
5.
Psychooncology ; 22(10): 2354-63, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23657969

RESUMO

OBJECTIVE: Although chemotherapy-induced cognitive impairment is common among breast cancer patients, evidence for effective interventions addressing cognitive deficits is limited. This randomized controlled trial examined the feasibility and preliminary efficacy of a Tibetan Sound Meditation (TSM) program to improve cognitive function and quality of life in breast cancer patients. METHODS: Forty-seven breast cancer patients (mean age 56.3 years), who were staged I-III at diagnosis, 6-60 months post-chemotherapy, and reported cognitive impairment at study entry were recruited. Participants were randomized to either two weekly TSM sessions for 6 weeks or a wait list control group. Neuropsychological assessments were completed at baseline and 1 month post-treatment. Self-report measures of cognitive function (Functional Assessment of Cancer Therapy (FACT)-Cog), quality of life (SF-36), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sleep disturbance (Pittsburgh Sleep Quality Index), fatigue (Brief Fatigue Inventory), and spirituality (FACT-Sp) were completed at baseline, the end of treatment, and 1 month later. RESULTS: Relative to the control group, women in the TSM group performed better on the verbal memory test (Rey Auditory Verbal Learning Test trial 1) (p = 0.06) and the short-term memory and processing speed task (Digit Symbol) (p = 0.09) and reported improved cognitive function (p = 0.06), cognitive abilities (p = 0.08), mental health (p = 0.04), and spirituality (p = 0.05) at the end of treatment but not 1 month later. CONCLUSIONS: This randomized controlled trial revealed that TSM program appears to be a feasible and acceptable intervention and may be associated with short-term improvements in objective and subjective cognitive function as well as mental health and spirituality in breast cancer patients.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/psicologia , Transtornos Cognitivos/terapia , Meditação/métodos , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/psicologia , Depressão/psicologia , Fadiga/psicologia , Estudos de Viabilidade , Feminino , Humanos , Saúde Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Qualidade de Vida , Espiritualidade , Resultado do Tratamento , Listas de Espera
6.
HIV Med ; 13(5): 276-90, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22276657

RESUMO

OBJECTIVES: Oral complications associated with HIV infection and with the antiretroviral drugs used to treat it are of increasing concern in HIV-infected patients. Protease inhibitors have been shown to change the proliferation and differentiation state of oral tissues but the effect of nucleoside reverse transcriptase inhibitors is currently unknown. This study examined the effect of zidovudine on the growth and differentiation of the gingival epithelium. METHODS: Gingival keratinocyte organotypic (raft) cultures were established. The raft cultures were treated with a range of zidovudine concentrations. Haematoxylin and eosin staining was performed to examine the effect of zidovudine on gingival epithelium growth and stratification. Raft cultures were immunohistochemically analysed to determine the effect of this drug on the expression of key differentiation and proliferation markers, including cytokeratins and proliferating cell nuclear antigen (PCNA). RESULTS: Zidovudine dramatically changed the proliferation and differentiation state of gingival tissues both when it was present throughout the growth period of the tissue and when it was added to established tissue at day 8. Zidovudine treatment increased the expression of cytokeratin 10, PCNA and cyclin A. Conversely, cytokeratin 5, involucrin and cytokeratin 6 expression was decreased. The tissue exhibited characteristics of increased proliferation in the suprabasal layers as well as an increased fragility and an inability to heal itself. CONCLUSIONS: Zidovudine treatment, even when applied at low concentrations for short periods of time, deregulated the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our system could potentially be developed as a model for studying the effects of HIV and highly active antiretroviral therapy in vitro.


Assuntos
Fármacos Anti-HIV/farmacologia , Gengiva/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Zidovudina/farmacologia , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Gengiva/citologia , Gengiva/metabolismo , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo
7.
J Neurooncol ; 107(1): 165-74, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21964738

RESUMO

Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients. An open-label, randomized, pilot trial examined both the general and differential efficacy of 4 weeks of methylphenidate (MPH) and modafinil (MOD) in 24 brain tumor patients. Participants completed cognitive tests and self-report measures of fatigue, sleep disturbance, mood and quality of life at baseline and after 4 weeks.Following stimulant treatment, there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention. Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy. Inconsistent, differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD. There was also evidence of a general beneficial effect on patient-reported measures of fatigue, mood, and quality of life, with no statistically significant differences between treatment arms in these measures over time. The results from this small pilot study should be interpreted with caution, but appear to warrant additional research, in larger study samples, targeting fatigue, processing speed and executive function, and exploring different doses of stimulants. Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Neoplasias Encefálicas/complicações , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Glioma/complicações , Metilfenidato/uso terapêutico , Adulto , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Seguimentos , Glioma/patologia , Glioma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila , Gradação de Tumores , Projetos Piloto , Prognóstico
8.
Crit Rev Oncol Hematol ; 81(2): 123-35, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21435899

RESUMO

Health-related quality of life (HRQOL) and other patient-reported outcomes (PROs) might be crucial in comparing effectiveness of treatments as they could provide invaluable information to better inform clinical decision-making. This is particularly true in the era of targeted therapies (TT). A systematic review was undertaken on all studies with CML patients published from 1980 to 2010 and including a PRO evaluation. Out of 619 articles scrutinized, 15 met eligibility criteria and no study was published before 1995. Six dealt mainly with interferon-based therapies, 7 with bone marrow transplantation and only 2 evaluated PROs in the context of TT. No disease-specific, validated PRO instrument for these patients was found. The main evidence being that Imatinib provides clear advantage in terms of HRQOL over interferon-based treatments. There is lack of data concerning PROs in patients treated with current TT. Documenting HRQOL and side effects of CML treatments, from the patients' perspective is needed to evaluate overall treatment effectiveness and net clinical benefit of newer therapeutic strategies.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Terapia de Alvo Molecular , Qualidade de Vida , Transplante de Medula Óssea , Humanos , Fatores de Tempo , Resultado do Tratamento
9.
HIV Med ; 12(3): 145-56, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20722750

RESUMO

OBJECTIVE: This study was designed to evaluate the effects of the HIV protease inhibitor lopinavir/ritonavir on gingival epithelium growth, integrity and differentiation. METHODS: Organotypic (raft) cultures of gingival keratinocytes were established and treated with a range of lopinavir/ritonavir concentrations. To examine the effect of lopinavir/ritonavir on gingival epithelium growth and stratification, haematoxylin and eosin staining was performed. To investigate the effect of this drug on tissue integrity, transmission electron microscopy (TEM) was performed on untreated and drug-treated tissues. Further, immunohistochemical analysis of raft cultures was performed to assess the effect of lopinavir/ritonavir on the expression of key differentiation and proliferation markers including cytokeratins, proliferating cell nuclear antigen (PCNA) and cyclin A. RESULTS: Lopinavir/ritonavir treatments drastically inhibited the growth of gingival epithelium when the drug was present throughout the growth period of the tissue. When the drug was added on day 8 of tissue growth, lopinavir/ritonavir treatments compromised tissue integrity over time and altered the proliferation and differentiation of gingival keratinocytes. Expression of cytokeratins 5, 14, 10 and 6, PCNA and cyclin A was induced, and their expression patterns were also altered over time in treated rafts. CONCLUSIONS: The findings of our studies suggest that lopinavir/ritonavir treatments compromised tissue integrity over time and deregulated the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our study provides a model of potential utility in studying the effects of antiretroviral drugs in vitro.


Assuntos
Gengiva/efeitos dos fármacos , Inibidores da Protease de HIV/farmacologia , Queratinócitos/efeitos dos fármacos , Pirimidinonas/farmacologia , Ritonavir/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Células Epiteliais/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Gengiva/citologia , Humanos , Lopinavir , Microscopia Eletrônica de Transmissão
10.
Br J Cancer ; 101(4): 615-20, 2009 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-19672263

RESUMO

BACKGROUND: Because of the poor outcomes for patients with recurrent glioblastoma multiforme (GBM), and some laboratory and clinical evidence of efficacy using interferon in GBM, we assessed the toxicity and efficacy of temozolomide (TMZ) combined with either short-acting (IFN) or long-acting (pegylated) interferon alpha2b (PEG) in two single-arm phase II studies, and compared the results to 6-month progression-free survival (PFS-6) data from historical controls. METHODS: Two single-arm phase II studies were carried out in adults with GBM. Patients were treated with the standard regimen of TMZ (150-200 mg m(-2) per day x 5 days every month) combined with either 4 million units per m(2) subcutaneously (SQ) three times weekly of IFN or 0.5 microg kg(-1) SQ weekly of PEG. Physical exams and imaging evaluations were carried out every 8 weeks. RESULTS: On the IFN study, 34 adults (74% men) were enrolled, and 29 adults (55% men) on the PEG study; median Karnofsky performance status was 80 and 90 for the IFN and PEG studies, respectively. Grade 3 or 4 toxicities were common, leucopoenia and thrombocytopoenia occurring in 35-38% and 18-21% of patients, respectively. Grade 3 or 4 fatigue occurred in 18% of patients on both studies. Lymphopoenia was infrequent. PFS-6 was 31% for 29 evaluable patients in the IFN study and 38% for 26 evaluable patients in the PEG study. CONCLUSION: In recurrent GBM patients, both studies of standard dose TMZ with either IFN or PEG showed improved efficacy when compared to historical controls, or reports using TMZ alone. Even though the TMZ+PEG study met criteria for further study, the results of both of these studies must be considered in light of the standard of care (TMZ plus radiotherapy) for newly diagnosed GBM, which has evolved since the inception of these studies. Despite the results of the current studies being eclipsed by the new GBM standard of care, these results can still inform the development of newer approaches for GBM, either in an earlier, upfront setting, or by extrapolation of the results and consideration of the use of PEG or IFN in conjunction with other antiglioma strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Idoso , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Interferon Tipo I/administração & dosagem , Interferon Tipo I/efeitos adversos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes , Temozolomida , Resultado do Tratamento , Adulto Jovem
11.
J Dent Res ; 88(4): 307-17, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19407149

RESUMO

Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the etiologic agents of most cervical cancers and are associated with a growing percentage of oropharyngeal cancers. The HPV capsid is non-enveloped, having a T=7 icosahedral symmetry formed via the interaction among 72 pentamers of the major capsid protein, L1. The minor capsid protein L2 associates with L1 pentamers, although it is not known if each L1 pentamer contains a single L2 protein. The HPV life cycle strictly adheres to the host cell differentiation program, and as such, native HPV virions are only produced in vivo or in organotypic "raft" culture. Research producing synthetic papillomavirus particles--such as virus-like particles (VLPs), papillomavirus-based gene transfer vectors, known as pseudovirions (PsV), and papillomavirus genome-containing quasivirions (QV)--has bypassed the need for stratifying and differentiating host tissue in viral assembly and has allowed for the rapid analysis of HPV infectivity pathways, transmission, immunogenicity, and viral structure.


Assuntos
Alphapapillomavirus/fisiologia , Proteínas Virais/síntese química , Vírion/fisiologia , Montagem de Vírus/fisiologia , Replicação Viral/fisiologia , Humanos , Proteínas Virais/classificação , Proteínas Virais/metabolismo
12.
Curr Protoc Nucleic Acid Chem ; Appendix: 3D, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18819080

RESUMO

TLC is used extensively in nucleic acid chemistry to monitor the progress of chemical reactions, to assay fractions collected from a larger chromatographic separation (e.g., column chromatography), and to determine optimal conditions prior to column chromatography. This unit describes methods for spotting test compounds onto a TLC plate, developing the plate in a suitable solvent system, visualizing the results, and calculating the retention factor (R(f)). Candidate compounds can be co-spotted for identification without relying on R(f) values.


Assuntos
Cromatografia em Camada Fina/métodos , Ácidos Nucleicos/isolamento & purificação , Adsorção , Cromatografia em Camada Fina/instrumentação , Corantes , Solventes
13.
Neuroscience ; 148(1): 230-7, 2007 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-17640819

RESUMO

While activation of alpha7 nicotinic receptors protects neurons from a variety of apoptotic insults in vitro, little is known about this neuroprotective action in vivo, especially under amyloidogenic conditions that mimic Alzheimer's disease. We therefore investigated the effects of 4OH-GTS-21, a selective partial agonist for these receptors, on septohippocampal cholinergic and GABAergic neuron survival following fimbria fornix (FFX) lesions in three strains of mice: C57BL/6J wild type mice; human presenilin-1 mutant M146L (PS1) transgenic mice; and mice expressing both mutant PS1 and Swedish mutant K670N/M671L amyloid precursor protein (APP). Initial studies to demonstrated that 4OH-GTS-21 is likely brain permeant based on its ability to improve passive avoidance and Morris water task behaviors in nucleus basalis-lesioned rats. In FFX-lesioned mice, twice per day i.p. injections of 1 mg/kg of 4OH-GTS-21 for 2 weeks promoted the survival and prevented the atrophy of septal cholinergic neurons. Septal parvalbumin-staining GABAergic neurons were not protected by this treatment, although they also express alpha7 nicotinic receptors, suggesting an indirect, nerve growth factor (NGF)-mediated mechanism. No protection of cholinergic neurons was observed in similarly treated PS1 or APP/PS1 transgenic mice. 4OH-GTS-21 treatment actually reduced cholinergic neuronal size in APP/PS1 mice. Hippocampal amyloid deposition was not affected by FFX lesions or treatment with this alpha7 nicotinic receptor agonist in APP/PS1 mice under these conditions. These results indicate that brain alpha7 nicotinic receptors are potential targets for protecting at-risk brain neurons in Alzheimer's disease, perhaps via their effects on NGF receptors; however, this protection may be sensitive under some conditions to environmental factors such as inhibitory amyloid-peptides.


Assuntos
Amiloide/metabolismo , Anabasina/análogos & derivados , Fibras Colinérgicas/efeitos dos fármacos , Degeneração Neural/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Receptores Nicotínicos/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Amiloide/genética , Anabasina/farmacologia , Animais , Axotomia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Fibras Colinérgicas/metabolismo , Modelos Animais de Doenças , Feminino , Fórnice/efeitos dos fármacos , Fórnice/metabolismo , Fórnice/fisiopatologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Degeneração Neural/genética , Degeneração Neural/metabolismo , Agonistas Nicotínicos/farmacologia , Receptores de Fator de Crescimento Neural/efeitos dos fármacos , Receptores de Fator de Crescimento Neural/metabolismo , Receptores Nicotínicos/metabolismo , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo , Núcleos Septais/fisiopatologia , Receptor Nicotínico de Acetilcolina alfa7 , Ácido gama-Aminobutírico/metabolismo
14.
Atherosclerosis ; 192(2): 253-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16945375

RESUMO

Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent cardiovascular disease, yet its widespread use is limited by the prostaglandin D2 (PGD2) mediated niacin flush. Previous research suggests that nicotinic acid-induced PGD2 secretion is mediated by the skin, but the exact cell type remains unclear. We hypothesized that macrophages are a source of nicotinic acid-induced PGD2 secretion and performed a series of experiments to confirm this. Nicotinic acid (0.1-3 mM) induced PGD2 secretion in cultured human macrophages, but not monocytes or endothelial cells. The PGD2 secretion was dependent on the concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but not nicotinamide, also induced PGD2 secretion. Pre-incubation of the cells with aspirin (100 microM) entirely prevented the nicotinic acid effects on PGD2 secretion. The PGD2 secreting effects of nicotinic acid were additive to the effects of the calcium ionophore A23187 (6 microM), but were independent of extra cellular calcium. These findings, combined with recent in vivo work, provide evidence that macrophages play a significant role in mediating the niacin flush and may lead to better strategies to eliminate this limiting side effect.


Assuntos
Rubor/induzido quimicamente , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Niacina/efeitos adversos , Niacina/farmacologia , Prostaglandina D2/metabolismo , Aspirina/farmacologia , Calcimicina/farmacologia , Cálcio/fisiologia , Humanos , Modelos Biológicos , Niacina/antagonistas & inibidores , Ácidos Nicotínicos/farmacologia , Células Tumorais Cultivadas
15.
Virology ; 347(1): 28-35, 2006 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-16460777

RESUMO

The study of the human papillomavirus (HPV) life cycle was hampered for more than 50 years by the lack of a conventional cell culture system for propagating HPV. Considerable progress has been made in the production of several HPV types using either organotypic rafts or human epithelial xenografts in immunocompromised mice. In this study, we demonstrated episomal maintenance of HPV-11 DNA in N-Tert cells. HPV-11 episomal DNA containing cell populations grown in raft culture showed induction of the productive viral life cycle. HPV-11 DNA amplification and viral capsid antigen synthesis were detected in differentiated layers of epithelia. The viruses generated were able to infect keratinocytes in vitro, which indicate that viruses generated were infectious. The demonstration of the productive HPV-11 life cycle in raft culture from cloned HPV-11 DNA will facilitate genetic analyses of viral gene functions that was not possible using the human xenograft athymic mouse model.


Assuntos
Papillomavirus Humano 11/crescimento & desenvolvimento , Cultura de Vírus/métodos , Animais , Sequência de Bases , Técnicas de Cultura de Células/métodos , Linhagem Celular , Técnicas de Cocultura , DNA Viral/genética , Células Epiteliais/virologia , Papillomavirus Humano 11/genética , Humanos , Camundongos , Plasmídeos/genética
16.
Int J Cosmet Sci ; 28(1): 9-20, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18492197

RESUMO

The cellular morphology of the stratum corneum was studied in vivo using a novel imaging technique that uses confocal fluorescence microscopy in combination with topical application of a fluorescent contrast agent. Images obtained with this method show a strong variation in skin surface cellular morphology among healthy subjects. The results of several clinical studies suggest that cellular morphology is affected by the efficiency of the process of desquamation. As such, cellular morphology shows strong potential to serve as an indicator of skin health that yields mechanistic insight into the origins of skin ailments, such as xerosis, and the effectiveness of their treatments.

17.
J Biomed Opt ; 10(3): 031107, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16229632

RESUMO

A near infrared (NIR) multispectral imaging method for measuring skin hydration has been applied in a clinical study for estimating skin hydration effects of skin moisturizers and cleansers. The method has been compared to the commercially available, standard electrical methods for evaluating changes in skin hydration based on conductance and capacitance measurements. All of the instrumental methods have been compared to the visual assessment of skin dryness. It has been shown that the NIR imaging method is capable of detecting changes in skin hydration induced by skin moisturizers and cleansers. A large positive hydration change upon treatment by a moisturizing cream was easily detected by all three instrumental methods and by the expert visual assessment of dryness. The imaging technique is rapid, noncontact and noninvasive, and has the additional important advantage of showing the degree of hydration as a function of location, for rapid assessment of change in hydration. There was a clear difference between the instrumental methods when the induced changes were not as great as that from the moisturizing cream. The imaging technique showed more sensitive discrimination between treatments and control, and strong correlation to visual appearance of dryness. (c) 2005 Society of Photo-Optical Instrumentation Engineers.


Assuntos
Água Corporal/química , Cosméticos/administração & dosagem , Interpretação de Imagem Assistida por Computador/métodos , Pele/química , Pele/citologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Administração Tópica , Água Corporal/efeitos dos fármacos , Estudos de Viabilidade , Feminino , Humanos , Variações Dependentes do Observador , Pletismografia de Impedância/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Perda Insensível de Água/efeitos dos fármacos , Perda Insensível de Água/fisiologia
18.
Curr Opin Cardiol ; 20(4): 307-12, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15956828

RESUMO

PURPOSE OF REVIEW: With the limited effects of low-density lipoprotein-based lipid intervention, more attention is being paid to drugs that augment or mimic high-density lipoprotein's beneficial effects. A thorough understanding of the anti-atherogenic effects of high-density lipoprotein, and the mechanisms of existing or emerging high-density lipoprotein-based therapies, is essential for rational strategy for the prevention of cardiovascular disease. RECENT FINDINGS: High-density lipoprotein mediates its beneficial effects through reverse cholesterol transport and direct anti-inflammatory effects of apolipoprotein AI and other component parts. Currently available drugs increase high-density lipoprotein-C through increasing apoAI synthesis (statins, fibrates) and decreasing apolipoprotein AI catabolism (niacin). Cholesteryl ester transfer protein inhibitors dramatically raise high-density lipoprotein-C, but clinical data are still required to verify their cardioprotective effects. Novel therapies such as apolipoprotein AImilano, apolipoprotein AI mimetic peptide, and exogenous phospholipids show tremendous promise as treatments for atherosclerosis. SUMMARY: High-density lipoprotein and its defining functional protein apoAI prevent atherosclerosis through reverse cholesterol transport and other direct effects. Research has led to the development of novel therapies that increase high-density lipoprotein-C or that mimic direct anti-atherogenic effects of apolipoprotein AI. As these emerging therapies find a place in clinical medicine, we can anticipate preventing a much higher degree of cardiovascular events.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipoproteínas HDL/uso terapêutico , Amidas , Animais , Apolipoproteína A-I/uso terapêutico , Aterosclerose/prevenção & controle , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Proteínas de Transferência de Ésteres de Colesterol , Ácido Clofíbrico/uso terapêutico , Ésteres , Glicoproteínas/antagonistas & inibidores , Glicoproteínas/metabolismo , Humanos , Hipolipemiantes/uso terapêutico , Compostos de Sulfidrila/uso terapêutico , Tiazolidinedionas/uso terapêutico
19.
Curr Opin Lipidol ; 15(6): 659-65, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15529025

RESUMO

PURPOSE OF REVIEW: Well designed, randomized, placebo-controlled studies show that niacin prevents cardiovascular disease and death. Unfortunately, early studies and anecdotal evidence have limited its use by promoting the opinion that niacin is intolerable and contraindicated in diabetes. As evidence mounts that treating multiple lipid risk factors decreases cardiovascular risk, the use of niacin in the treatment of atherosclerosis is experiencing somewhat of a renaissance. RECENT FINDINGS: Emerging clinical evidence shows that niacin is both safe and effective in diabetes. Niacin beneficially alters lipoprotein subclass distribution and when used in combination with statins, has additional effects on lipoproteins. Niacin selectively and directly inhibits hepatic diacylglycerol acyltransferase 2, but not diacylglycerol acyltransferase 1, thus inhibiting hepatic triglyceride synthesis and very low density lipoprotein secretion. The recent discovery and characterization of a membrane-bound nicotinic acid receptor (HM74) explains niacin's acute inhibition of adipocyte lipolysis, but the role of HM74 in lowering triglycerides is unclear. Niacin possesses antioxidant, antiinflammatory, and other beneficial effects on atherosclerosis unrelated to lipid lowering. Finally, niacin appears to activate nuclear transcription factors such peroxisome proliferator activator receptor gamma, possibly via prostaglandin metabolism. SUMMARY: New data indicate that niacin alters lipoprotein metabolism in novel ways, and mediates other beneficial nonlipid changes that may be atheroprotective. This information forms the rationale for the use of niacin in combination with agents possessing complementary mechanisms of action (e.g. statins) for cardiovascular risk reduction beyond that observed with monotherapy. Further research into the specific mechanisms of niacin may identify additional targets for future drug development.


Assuntos
Arteriosclerose/tratamento farmacológico , Niacina/uso terapêutico , Anti-Inflamatórios/farmacologia , Arteriosclerose/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Humanos , Lovastatina/farmacologia , Niacina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Endocrinol Metab Clin North Am ; 33(3): 557-75, vii, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15262297

RESUMO

Nicotinic acid effectively treats each of the common lipid abnormalities found in the metabolic syndrome, and much progress has recently been made in understanding its mechanisms of action. Early concern that nicotinic acid can precipitate or worsen diabetes has been eased with recent trials, which demonstrated its safety and effectiveness in insulin-resistant states. Furthermore, nicotinic acid prevents cardiovascular disease and death in persons with a high prevalence of risk factors for the metabolic syndrome. When used by an experienced physician and taken by a motivated patient, nicotinic acid can be safe and effective in treating the dyslipidemia of the metabolic syndrome.


Assuntos
Hipolipemiantes/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Niacina/uso terapêutico , Humanos
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