RESUMO
The phosphorylation of (+) alpha tocopherol produces adhesive nanostructures that interact with oral biofilms to restrict their growth. The aim of this work was to understand if these adhesive (+) alpha tocopheryl phosphate (α-TP) nanostructures could also control macrophage responses to the presence of oral bacteria. The (+) α-TP planar bilayer fragments (175â¯nm⯱â¯21â¯nm) formed in a Trizma®/ethanol vehicle swelled when exposed to the cell lines (maximum stabilized sizeâ¯=â¯29⯵m). The swelled (+) α-TP aggregates showed selective toxicity towards THP-1 macrophages (LD50â¯=â¯304⯵M) compared to human gingival fibroblasts (HGF-1 cells; LD50â¯>â¯5â¯mM), and they inhibited heat killed bacteria stimulated MCP-1 production in both macrophages (control 57.3⯱â¯18.1â¯pg/mL vs (+) α-TP 6.5⯱â¯3.2â¯pg/mL) and HGF-1 cells (control 673.5⯱â¯133â¯pg/mL vs (+) α-TP - 463.9⯱â¯68.9â¯pg/mL).
Assuntos
Macrófagos/efeitos dos fármacos , Boca/efeitos dos fármacos , Nanoestruturas/administração & dosagem , alfa-Tocoferol/análogos & derivados , Biofilmes/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Quimiocina CCL2/genética , Gengiva/efeitos dos fármacos , Gengiva/crescimento & desenvolvimento , Gengiva/microbiologia , Gengiva/patologia , Fator de Crescimento de Hepatócito/genética , Humanos , Macrófagos/metabolismo , Macrófagos/microbiologia , Monócitos/efeitos dos fármacos , Monócitos/microbiologia , Boca/crescimento & desenvolvimento , Boca/microbiologia , Boca/patologia , Nanoestruturas/química , Fosforilação/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , alfa-Tocoferol/química , alfa-Tocoferol/farmacologiaRESUMO
'Soft' nanomaterials have the potential to produce substantive antibiofilm effects. The aim of this study was to understand the oral antimicrobial activity of soft nanomaterials generated from alpha-tocopherol (α-T) and alpha-tocopherol phosphate (α-TP). (+) α-TP formed planar bilayer islands (175 ± 21 nm, -14.9 ± 3.5 mV) in a Trizma® buffer, whereas (+) α-T formed spherical liposomes (563 ± 1 nm, -10.5 ± 0.2 mV). The (+) α-TP bilayers displayed superior Streptococcus oralis biofilm growth retardation, a more substantive action, generated a superior adsorption to hydroxyapatite and showed an enhanced inhibition of multi-species bacterial saliva biofilm growth (38 ± 7µm vs 58 ± 18 µm, P Ë 0.05) compared to (+) α-T. Atomic force microscopy data indicated that the ability of the 'soft' α-TP nanomaterials to transition into planar bilayer structures upon contact with interfaces facilitated their adhesive properties and substantive antimicrobial effects.
Assuntos
Anti-Infecciosos/administração & dosagem , Biofilmes/efeitos dos fármacos , Bicamadas Lipídicas/química , Saliva/microbiologia , Streptococcus mutans/efeitos dos fármacos , Streptococcus oralis/efeitos dos fármacos , alfa-Tocoferol/análogos & derivados , Adesivos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Biofilmes/crescimento & desenvolvimento , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Microscopia de Força Atômica , Boca/microbiologia , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus oralis/crescimento & desenvolvimento , alfa-Tocoferol/química , alfa-Tocoferol/farmacologiaRESUMO
OBJECTIVES: The purpose of this study was to determine the genotype/allele frequencies of C677T and A1298C polymorphisms of methylenetetrahydrofolate (MTHFR) gene in Jordanian rheumatoid arthritis (RA) patients. In addition, the association between MTHFR gene C677T and A1298C polymorphisms and response to and toxicity of methotrexate (MTX) was evaluated. METHODS: 159 adult rheumatoid arthritis ent Rheumatology Clinic at The Jordan University Hospital, between December, 2011 and April, 2012 were recruited into the study. Genomic DNA was extracted from leukocytes using Wizard Genomic DNA extraction Kit. The DNA extracts were amplified by polymerase chain reaction (PCR), and the PCR products were subjected to restriction enzymes to identify the C677T and A1298C genotypes. Genotype frequencies were identified and their relationship to some measures of MTX response and toxicity were evaluated. RESULTS: The 677 TT genotype frequency was higher in RA patients (15.1%) compared to the healthy control group (5.9%) (odds ratio 3.09, 95% confidence interval (CI) 1.39-6.87, p-value=0.0056). No such differences were seen with the A1298C genotypes. The frequencies of 677T and 1298C variant alleles were 0.346 and 0.296, respectively. None of the change-in-disease-activity measurements in MTX-treated patients has a significant association with the various genotypes. There was no significant association between A1298C genotypes and "any MTX toxicity", but there was an association between C677T polymorphism and "any MTX toxicity" (p=0.037). In addition, there was no association between both SNPs and specific MTX adverse effects. However, some haplotypes or combinations of the C677T and A1298C genotypes were associated with certain MTX side effects. CONCLUSIONS: More data from a larger number of RA patients are needed to evaluate the role of pharmacogenetic studies of MTHFR gene in predicting MTX response and toxicity.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Idoso , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Long-term exposure to solar radiation can lead to skin damage such as photoageing, and photocarcinogenesis. This can be prevented by topically applying α-tocopherol phosphate (α-TP). The major challenge is that a significant amount of α-TP needs to reach viable skin layers for effective photoprotection. This study aims to develop candidate formulations of α-TP (gel-like, solution, lotion, and gel), and investigate formulation characteristics' effect on membrane diffusion and human skin permeation. All the formulations developed in the study had an appealing appearance and no signs of separation. All formulations had low viscosity and high spreadability except the gel. The flux of α-TP through the polyethersulfone membrane was the highest for lotion (6.63⯱â¯0.86â¯mg/cm2/h), followed by control gel-like (6.14⯱â¯1.76â¯mg/cm2/h), solution (4.65⯱â¯0.86â¯mg/cm2/h), and gel (1.02⯱â¯0.22â¯mg/cm2/h). The flux of α-TP through the human skin membrane was numerically higher for lotion compared to the gel-like (328.6 vs.175.2⯵g/cm2/h). The lotion delivered 3-fold and 5-fold higher α-TP in viable skin layers at 3â¯h and 24â¯h, respectively, compared to that of the gel-like. The low skin membrane penetration rate and deposition of α-TP in viable skin layers were observed for the solution and gel. Our study demonstrated that dermal penetration of α-TP was influenced by characteristics of formulation such as formulation type, pH, and viscosity. The α-TP in the lotion scavenged higher DPPH free radicals compared to that of gel-like (almost 73% vs. 46%). The IC50 of α-TP in lotion was significantly lower than that of gel-like (397.2 vs. 626.0⯵g/mL). The preservative challenge test specifications were fulfilled by Geogard 221 and suggested that the combination of benzyl alcohol and Dehydroacetic Acid effectively preserved 2% α-TP lotion. This result confirms the suitability of the α-TP cosmeceutical lotion formulation employed in the present work for effective photoprotection.
Assuntos
Cosmecêuticos , Vitamina E , Humanos , Vitamina E/metabolismo , Absorção Cutânea , Fosfatos/metabolismo , Pele/metabolismo , Emolientes , Administração CutâneaRESUMO
OBJECTIVES: Outbreaks and containment measures implemented to control them can increase stress in affected populations. The impact of the coronavirus disease 2019 (COVID-19) outbreak on perceived stress levels in the Jordanian population is unknown. The aim of the study was to determine the perceived stress level and factors associated with it in the Jordanian population during the COVID-19 outbreak. METHODS: Required data, such as those from the Perceived Stress Scale (PSS-10) and possible predictors of perceived stress, were collected through a Web-based survey. Statistical analysis was conducted through SPSS. RESULTS: The mean (SD) of perceived stress score was 19.8 (6.7). Regression analysis revealed that stress was increased in females, young adults, usually being stressed more than others by a health problem, increased perceived severity of the disease, increased overall worry score, and student's worry regarding their studies/graduation. Perceived stress was decreased if participants' self-rated health status score increased. CONCLUSIONS: In the context of increasing public health preparedness, the results of this study can be used in designing interventions to alleviate stress in susceptible segments of the Jordanian community.
Assuntos
COVID-19 , Ansiedade/epidemiologia , COVID-19/epidemiologia , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Jordânia/epidemiologia , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: The incidence of skin cancer and actinic keratosis has increased worldwide. Measuring the public awareness, attitude, and knowledge about these diseases and the skin protection behaviors are highly important to undertake preventive measures. METHODS: To investigate skin cancer and actinic keratosis-related knowledge, sun protection behaviors, and sunscreen usage among Jordanians, a questionnaire was developed. The questionnaire was provided as a google form to individuals via social media and the data were analyzed using SPSS® 23. RESULTS: A total of 1277 individuals, aged 18-65 years filled the questionnaire. The median melanoma and actinic keratosis knowledge score were 7 (4-9) and 4 (0-9), respectively. The melanoma knowledge was higher among females, those with a medical background, a high level of education, and in the central region, whereas the AK knowledge was higher among those with a medical background. Overall, 75.9% of the participants used sunscreen at least often to prevent sunburn, uneven skin tone, or tanning, 72% were using sunscreen with an SPF of 30 at least. However, 45.3% and 49.2% of sunscreen users did not comply with application, and reapplication times, respectively. Moreover, 58.4% of participants applied less than the recommended amount of sunscreen. CONCLUSION: Our study revealed that public awareness of actinic keratosis is low among Jordanians. Although it was found that a high proportion of Jordanians use sunscreens there are deficits in sunscreen practice indicating an urgent need to design effective interventions to increase awareness of actinic keratosis and correct use of sunscreen via health campaigns or healthcare professions.
Assuntos
Ceratose Actínica , Melanoma , Neoplasias Cutâneas , Queimadura Solar , Feminino , Humanos , Ceratose Actínica/epidemiologia , Ceratose Actínica/prevenção & controle , Ceratose Actínica/complicações , Protetores Solares/uso terapêutico , Jordânia/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Queimadura Solar/epidemiologia , Queimadura Solar/prevenção & controle , Melanoma/tratamento farmacológicoRESUMO
Vitamin E (alpha tocopherol, α-T) is an important skin antioxidant, but its penetration into the viable epidermis, where it acts, is very limited. This study investigated if phosphorylating α-tocopherol (α-TP) to form a provitamin, improved its interactions with skin, its passage into the tissue, and thus its ability to protect the skin from ultraviolet radiation (UVR) damage. At pH 7.4, when the α-TPO4-1 microspecies predominated in solution, dynamic light scattering measurements showed that α-TP formed nanoaggregates with a median hydrodynamic diameter of 9 nm (Critical aggregation constant, CAC, - 4.2 mM). At 9.0 when the α-TPO4-2 microspecies predominated there was no aggregation. The passage of α-TP nanoaggregates through regenerated cellulose membranes was significantly slower than the α-TP monomers (at pH 9) suggesting that aggregation slowed diffusion. However, a lotion formulation containing the nanoaggregates delivered more α-TP into the skin compared to the formulation containing the monomers. In addition, the nanosized α-TP aggregates delivered 8-fold more active into the stratum corneum (SC) (252.2 µg/cm2 vs 29.5 µg/cm2) and 4 fold more active into the epidermis (85.1 µg/cm2 vs 19 µg/cm2, respectively, p < 0.05) compared to α-T. Langmuir subphase injection studies at pH 7.4 (surface pressure 10 mN m-1) showed that the α-TP nanoaggregates more readily fused with the SC compared to the monomers and the membrane compression studies demonstrated that α-TP fluidised the SC lipids. Together the fusion with the SC and its fluidisation were proposed as the causes of the better α-TP penetration into the skin, which enhanced potential of α-TP to protect from UVR-induced skin damage compared to α-T.
Assuntos
Nanoestruturas , alfa-Tocoferol , Epiderme , Pele , Raios Ultravioleta , alfa-Tocoferol/análogos & derivadosRESUMO
OBJECTIVES: The novel 2019 coronavirus outbreak that first appeared in Wuhan has quickly gained global attention, due to its high transmissibility and devastating clinical and economic outcomes. The aim of this study was to assess the possible roles of Jordanian pharmacists in minimizing the stage of community transmission. METHODS: A cross-sectional survey using Google forms targeting Jordanian pharmacists was conducted during March 2020 and distributed electronically by means of social media. Using the survey tool, we measured the pharmacists' knowledge, the educative activities they perform, and their perceptions regarding undertaking traditional and untraditional roles during the COVID-19 outbreak, as specified by the International Pharmaceutical Federation (FIP). Collected data were analyzed using SPSS version-19. RESULTS: Jordanian pharmacists (n = 449) reported performing various educative activities, and in general, they were knowledgeable about various aspects of the COVID-19 disease (median knowledge score: 20 [range, 13-25]), but certain gaps in knowledge were detected that must be addressed. Pharmacists had positive perceptions about both their traditional and untraditional roles specified by the FIP, the median perceptions score was 4 (range, 1-5). CONCLUSIONS: Jordanian pharmacists can be used to reduce community transmission of the outbreak. However, more actions are required to keep pharmacists knowledgeable with recent disease updates to enable them to perform their tasks effectively during times of crisis.