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Although the long-term use of topical glucocorticoids (TGC) may induce skin atrophy including striae distensae (SD), patients with atopic dermatitis (AD) appear to have lesser degree of skin atrophy than those with psoriasis (PSO). Periostin, encoded by POSTN, is involved in tissue remodelling processes of chronic AD lesions. This study was designed to investigate the difference in the occurrence of skin atrophy in patients with AD or PSO when treated with TGC and to elucidate the association between skin atrophy and periostin. Big data analysis using Korean Health Claims Database was performed to determine the prevalence of SD in AD and PSO patients. Blood and skin eosinophils count and dermal fibrosis between AD and PSO patients were compared, and immunohistochemistry for periostin and mRNA sequencing in the dermis were performed. Animal experiments using AD and PSO murine model were conducted. Big data analysis revealed that patients with AD have significantly lesser degree of SD than patients with PSO. The ratio of the dermal fibrous tissues and eosinophil counts were significantly higher in AD patients. In AD skin, periostin was more widely distributed in the entire dermis and POSTN mRNAs were significantly upregulated. Dermal thickness and fibrosis were significantly higher in AD mice even after TGC treatment. A significant positive correlation was observed between dermal fibrosis and tissue eosinophil counts. Lesser skin atrophy in AD patients even after long-term TGC application could be resulted from skin fibrosis caused by increased tissue eosinophils and periostin deposition.
Assuntos
Dermatite Atópica , Psoríase , Animais , Atrofia , Dermatite Atópica/patologia , Fibrose , Glucocorticoides/efeitos adversos , Humanos , Camundongos , Psoríase/patologia , Pele/patologiaRESUMO
Inactive cortisone is converted into active cortisol by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11ß-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11ß-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11ß-HSD1 knockout mice (n = 11), 11ß-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11ß-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11ß-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Epiderme/metabolismo , Regulação da Expressão Gênica , Envelhecimento da Pele/fisiologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Adulto , Idoso , Animais , Biomarcadores , Citocinas/sangue , Citocinas/metabolismo , Feminino , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Permeabilidade , Adulto JovemRESUMO
An aerosol electrical mobility spectrum analyzer (AEMSA), developed at Hanyang University, was employed to investigate the particle charge characteristics in the Antarctic and Arctic regions. The particle charge characteristics in these areas were compared with the charging state in Ansan, South Korea, located in the midlatitude, where artificial factors, such as human activity, urbanization, and traffic, might result in a higher total concentration. Furthermore, in Ansan, South Korea, the charged-particle polarity ratio was very stable and was close to 1. However, notably different particle charge characteristics were obtained in the Antarctic and Arctic regions. The imbalance between the numbers of positively and negatively charged particles was evident, resulting in more positive charges on the atmospheric particles. On average, the positively charged particle concentrations in the Antarctic and Arctic areas were 1.4 and 2.8 times higher, respectively, compared with the negatively charged particles. The developed AEMSA system and the findings of this study provide useful information on the characteristics of atmospheric aerosols in the Antarctic and Arctic regions and can be further utilized to study particle formation mechanisms.
Assuntos
Tamanho da Partícula , Aerossóis , Regiões Antárticas , Regiões Árticas , Humanos , República da CoreiaRESUMO
BACKGROUND: Alopecia areata (AA) may be associated with various systemic diseases according to several studies. OBJECTIVE: To identify prevalent and incident diseases in patients with AA and quantify their prevalence and odds and hazard ratios compared with those in controls without AA. METHODS: A systematic review of the studies published before February 28, 2018, was performed by using the MEDLINE, Embase, Web of Science, and Cochrane Library databases. Observational studies on prevalent or incident diseases in patients with AA were included, whereas studies limited to pediatrics or providing only laboratory results or continuous data were excluded. The inverse variance method with a random-effects model was used for meta-analyses. RESULTS: A total of 87 studies were analyzed. Atopic diseases, metabolic syndrome, Helicobacter pylori infection, lupus erythematosus, iron deficiency anemia, thyroid diseases, psychiatric diseases, vitamin D deficiency, and audiologic and ophthalmic abnormalities were more prevalent in patients with AA. Patients with AA had a higher risk of developing autoimmune diseases. LIMITATIONS: Some diseases were investigated by an insufficient number of studies to be meta-analyzed. Meta-analysis of incident diseases was not performed owing to the limited availability of cohort studies. CONCLUSION: AA is associated with various systemic and psychiatric diseases. Physicians are encouraged to evaluate and manage potential comorbid conditions to achieve better outcomes.
Assuntos
Alopecia em Áreas/diagnóstico , Alopecia em Áreas/epidemiologia , Comorbidade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologia , Doenças do Tecido Conjuntivo/patologia , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Humanos , Masculino , Neoplasias/epidemiologia , Neoplasias/patologia , Prevalência , Prognóstico , República da Coreia/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/epidemiologiaRESUMO
BACKGROUND: Contact immunotherapy with diphenylcyclopropenone (DPCP) is presently considered the treatment of choice for extensive alopecia areata. However, a major concern with contact immunotherapy is that it causes various adverse effects (AEs) that contribute to discontinuation of treatment. OBJECTIVE: We investigated whether a modified DPCP treatment protocol can promote hair regrowth with fewer AEs. METHODS: All patients were sensitized with 0.1% DPCP and began treatment with 0.01% DPCP. Thereafter, the DPCP concentration was slowly increased according to the treatment response and AEs. This was a retrospective review of DPCP treatment with modified protocols in 159 patients with alopecia areata. RESULTS: Of the 159 patients, 46 (28.9%) showed a complete response and 59 (37.1%) showed a partial response. No patients had AEs after sensitization. During the treatment, only 3 patients (1.9%) showed severe AEs, and 55 showed moderate AEs; however, all were well controlled with antihistamines alone or antihistamines and medium-potency topical steroids. There was no association between treatment response and AEs. LIMITATIONS: Sample size, subject composition, and the retrospective study design represent potential limitations. CONCLUSION: A modified DPCP treatment protocol with subclinical sensitization could induce a favorable therapeutic response and result in fewer AEs.
Assuntos
Alopecia em Áreas/terapia , Ciclopropanos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Imunoterapia/métodos , Adolescente , Adulto , Idoso , Ciclopropanos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Feminino , Cabelo/crescimento & desenvolvimento , Humanos , Imunoterapia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemAssuntos
Alopecia em Áreas/terapia , Ciclopropanos/administração & dosagem , Imunoterapia/métodos , Cooperação do Paciente/estatística & dados numéricos , Autocuidado/métodos , Administração Cutânea , Alopecia em Áreas/imunologia , Seguimentos , Humanos , Perda de Seguimento , Estudos RetrospectivosRESUMO
The indole nucleus is an important element of many natural and synthetic molecules with significant biological activity. This review covers some of the relevant and recent achievements in the biological, chemical and pharmacological activity of important indole derivatives in the areas of drug discovery and analysis.
Assuntos
Indóis/química , Descoberta de Drogas , Indóis/síntese química , Indóis/farmacologia , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/químicaRESUMO
Whether having a tattoo increases the risk of transfusion-transmitted diseases (TTDs) is controversial. Although a few studies have suggested a strong association between having tattoos and TTDs, other studies have not shown the significance of the association. In addition, previous studies mainly focused only on hepatitis C viral infections. The objective of our study was to identify the prevalence and risk of TTDs in people with tattoos as compared with the non-tattooed population. A systematic review of the studies published before January 22, 2021, was performed using the Pubmed, Embase, and Web of Science databases. Observational studies on hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and syphilis infections in people with and without tattoos were included. Studies that reported disease status without serological confirmation were excluded. A total of 121 studies were quantitatively analyzed. HCV (odds ratio [OR], 2.37; 95% confidence interval [CI], 2.04-2.76), HBV (OR, 1.55; 95% CI, 1.31-1.83), and HIV infections (OR, 3.55; 95% CI, 2.34-5.39) were more prevalent in the tattooed population. In subgroup analyses, the prevalence of HCV infection was significantly elevated in the general population, hospital patient, blood donor, intravenous (IV) drug user, and prisoner groups. IV drug users and prisoners showed high prevalence rates of HBV infection. The prevalence of HIV infection was significantly increased in the general population and prisoner groups. Having a tattoo is associated with an increased prevalence of TTDs. Our approach clarifies in-depth and supports a guideline for TTD screening in the tattooed population.
Assuntos
Infecções por HIV , HIV-1 , Hepacivirus , Vírus da Hepatite B , Hepatite B , Hepatite C , Tatuagem , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Hepatite B/epidemiologia , Hepatite B/transmissão , Hepatite C/epidemiologia , Hepatite C/transmissão , Humanos , PrevalênciaRESUMO
BACKGROUND: Fractional picosecond lasers is effective for the treatment of wrinkles or acne scars. OBJECTIVE: To investigate the safety and efficacy of treatment with a fractional 1,064-nm picosecond laser with a diffractive optic element for facial wrinkles and acne scars. METHODS: This prospective open-labeled trial comprised 22 subjects with facial wrinkles or acne scars. Subjects received three laser treatments with a fractional 1,064-nm picosecond laser at 3-week intervals. The efficacy and safety were evaluated at every visit and 2 months after the final treatment (14 weeks from the first treatment session). Global photographic assessments were performed by three blinded dermatologists and the subjects. Skin profilometry was performed using three-dimensional digital photographs; viscoelasticity was measured. RESULTS: The overall mean global improvement scores assessed by the dermatologists at weeks 3, 6, and 14, were 1.8±1.46, 2.5±1.88, and 3.5±1.84, respectively, and those assessed by the subjects were 2.7±2.08, 4.1±2.24, and 5.0±2.52, respectively. Skin profilometry showed significant improvements in the skin wrinkles, texture, depressions, and pores. The gross elasticity and skin firmness significantly improved by 10.96% and 9.04%, respectively. The major adverse reactions were erythema, pruritus, and petechiae, which disappeared within 2~3 days. CONCLUSION: The fractional 1,064-nm picosecond laser is an effective and safe therapeutic modality for skin rejuvenation.
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We compared the effects of aerobic exercise, resistance exercise, and combined aerobic and resistance exercise on total, regional subcutaneous adipose tissue (SAT) and visceral AT (VAT), skeletal muscle (SM), and biomarkers of cardiovascular disease in adolescents. Adolescents with overweight/obesity (N = 118; body mass index ≥ 85th percentile; age, 12-17 years) were randomized to 1 of the following groups for 6 months (3 days/week, 180 min/week): aerobic exercise (n = 38), resistance exercise (n = 40), or combined aerobic and resistance exercise (n = 40). After accounting for age, sex, and baseline value, there was a greater (P < 0.05) reduction in body weight in the aerobic exercise group compared with the resistance exercise group and the combined groups. There were reductions (P < 0.05) in total and regional SAT within the aerobic exercise group only, and the reductions in lower-body SAT were greater (P = 0.02) than the combined group. All groups had reductions (P < 0.01) in VAT, with no group differences. There were significant increases in total and regional SM mass in the resistance exercise and combined group, and not in the aerobic exercise group. Although all exercise modalities are effective in reducing VAT, aerobic exercise is superior at reducing total and regional SAT, but inferior for increasing SM in adolescents with obesity. Despite reductions in VAT, carotid-femoral pulse wave velocity and carotid intima-media thickness did not improve with either exercise. Clinicaltrials.gov identifier: NCT01938950. Novelty Regular exercise (180 min/week) is associated with reductions in visceral fat independent of exercise modality. Resistance exercise alone and combined resistance and aerobic exercise are similarly effective in increasing SM mass.
Assuntos
Composição Corporal , Exercício Físico , Fatores de Risco de Doenças Cardíacas , Sobrepeso/fisiopatologia , Obesidade Infantil/fisiopatologia , Adiposidade , Adolescente , Criança , Dieta Saudável , Feminino , Humanos , Gordura Intra-Abdominal , Masculino , Músculo Esquelético , Treinamento Resistido , Gordura SubcutâneaRESUMO
Glucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic-pituitary-adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), including the skin. The inactive GC cortisone is converted by 11ß-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11ß-HSD1 in inflammation is unclear. We assessed whether 11ß-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11ß-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11ß-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11ß-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11ß-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11ß-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Dermatite Atópica/metabolismo , Oxazolona/efeitos adversos , Regulação para Cima , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Animais , Estudos de Casos e Controles , Linhagem Celular , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Modelos Animais de Doenças , Epiderme/metabolismo , Epiderme/patologia , Feminino , Técnicas de Inativação de Genes , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Camundongos , Timo/metabolismoRESUMO
Importance: Diverse assessment tools and classification have been used for alopecia areata; however, their prognostic values are limited. Objective: To identify the topographic phenotypes of alopecia areata using cluster analysis and to establish a prediction model and grading system for stratifying prognoses. Design, Setting, and Participants: A retrospective cohort study of 321 patients with alopecia areata who visited a single tertiary referral center between October 2012 and February 2017 and underwent 4-view photographic assessment. Exposures: Clinical photographs were reviewed to evaluate hair loss using the Severity of Alopecia Tool 2. Topographic phenotypes of alopecia areata were identified using hierarchical clustering with Ward's method. Differences in clinical characteristics and prognosis were compared across the clusters. The model was evaluated for its performance, accuracy, and interobserver reliability by comparison to conventional methods. Main Outcomes and Measures: Topographic phenotypes of alopecia areata and their major (60%-89%) and complete regrowth probabilities (90%-100%) within 12 months. Results: A total of 321 patients were clustered into 5 subgroups. Grade 1 (n = 200; major regrowth, 93.4%; complete regrowth, 65.2%) indicated limited hair loss, whereas grades 2A (n = 66; major regrowth, 87.8%; complete regrowth, 64.2%) and 2B (n = 20; major regrowth, 73.3%; complete regrowth, 45.5%) exhibited greater hair loss than grade 1. The temporal area was predominantly involved in grade 2B, but not in grade 2A, despite being comparable in total extent of hair loss. Grade 3 (n = 20; major regrowth, 45.5%; complete regrowth, 25.5%) included diffuse or extensive alopecia areata, and grade 4 (n = 15; major regrowth, 28.2%; complete regrowth, 16.7%) corresponded to alopecia (sub)totalis. No significant differences in prognosis (hazard ratio [HR] for major regrowth, 0.79; 95% CI, 0.56-1.12) were found between grades 2A and 1, whereas grades 2B (HR, 0.41; 95% CI, 0.21-0.81), 3 (HR, 0.24; 95% CI, 0.12-0.50), and 4 (HR, 0.16; 95% CI, 0.06-0.39) had significantly poorer response. Among multiple models, the cluster solution had the greatest prognostic performance and accuracy. The tree model of the cluster solution was converted into the Topography-based Alopecia Areata Severity Tool (TOAST), which revealed an excellent interobserver reliability among 4 dermatologists (median quadratic-weighted κ, 0.89). Conclusions and Relevance: Temporal area involvement should be independently measured for better prognostic stratification. The TOAST is an effective tool for describing the topographical characteristics and prognosis of hair loss and may enable clinicians to establish better treatment plans.
Assuntos
Alopecia em Áreas/patologia , Cabelo/crescimento & desenvolvimento , Modelos Teóricos , Adulto , Alopecia em Áreas/classificação , Análise por Conglomerados , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
Background@#Contact immunotherapy with diphenylcyclopropenone is one of the first-line treatments for extensive alopecia areata, despite its adverse effects (AEs). @*Objective@#This study aimed to investigate whether a modified contact immunotherapy treatment protocol can safely promote hair regrowth in children. @*Methods@#Children with alopecia areata who were treated with modified contact immunotherapy with diphenylcyclopropenone were retrospectively reviewed. All patients were sensitized with 0.1% diphenylcyclopropenone and began treatment at subsequent increasing concentrations. The efficacy, AEs, and demographic factors were evaluated. @*Results@#A total of 32 patients, aged 9 to 17 years (mean age, 14.6 years), were included in the study. The mean disease duration was 26.8 months. Ten (31.3%) and 11 patients (34.4%) showed complete and partial responses, respectively. No AEs were observed after the sensitization. During treatment, 13 patients (40.6%) did not experience any AEs. Sixteen patients (50.0%) showed mild to moderate pruritus, and only three patients (9.4%) had severe pruritus. However, all AEs were well controlled. @*Conclusion@#A modified diphenylcyclopropenone treatment protocol with subclinical sensitization could induce a favorable therapeutic response and fewer AEs in children.
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Background@#Fractional picosecond lasers is effective for the treatment of wrinkles or acne scars. @*Objective@#To investigate the safety and efficacy of treatment with a fractional 1,064-nm picosecond laser with a diffractive optic element for facial wrinkles and acne scars. @*Methods@#This prospective open-labeled trial comprised 22 subjects with facial wrinkles or acne scars. Subjects received three laser treatments with a fractional 1,064-nm picosecond laser at 3-week intervals. The efficacy and safety were evaluated at every visit and 2 months after the final treatment (14 weeks from the first treatment session). Global photographic assessments were performed by three blinded dermatologists and the subjects. Skin profilometry was performed using three-dimensional digital photographs; viscoelasticity was measured. @*Results@#The overall mean global improvement scores assessed by the dermatologists at weeks 3, 6, and 14, were 1.8±1.46, 2.5±1.88, and 3.5±1.84, respectively, and those assessed by the subjects were 2.7±2.08, 4.1±2.24, and 5.0±2.52, respectively. Skin profilometry showed significant improvements in the skin wrinkles, texture, depressions, and pores. The gross elasticity and skin firmness significantly improved by 10.96% and 9.04%, respectively. The major adverse reactions were erythema, pruritus, and petechiae, which disappeared within 2∼3 days. @*Conclusion@#The fractional 1,064-nm picosecond laser is an effective and safe therapeutic modality for skin rejuvenation.
RESUMO
Background@#Fractional picosecond lasers is effective for the treatment of wrinkles or acne scars. @*Objective@#To investigate the safety and efficacy of treatment with a fractional 1,064-nm picosecond laser with a diffractive optic element for facial wrinkles and acne scars. @*Methods@#This prospective open-labeled trial comprised 22 subjects with facial wrinkles or acne scars. Subjects received three laser treatments with a fractional 1,064-nm picosecond laser at 3-week intervals. The efficacy and safety were evaluated at every visit and 2 months after the final treatment (14 weeks from the first treatment session). Global photographic assessments were performed by three blinded dermatologists and the subjects. Skin profilometry was performed using three-dimensional digital photographs; viscoelasticity was measured. @*Results@#The overall mean global improvement scores assessed by the dermatologists at weeks 3, 6, and 14, were 1.8±1.46, 2.5±1.88, and 3.5±1.84, respectively, and those assessed by the subjects were 2.7±2.08, 4.1±2.24, and 5.0±2.52, respectively. Skin profilometry showed significant improvements in the skin wrinkles, texture, depressions, and pores. The gross elasticity and skin firmness significantly improved by 10.96% and 9.04%, respectively. The major adverse reactions were erythema, pruritus, and petechiae, which disappeared within 2∼3 days. @*Conclusion@#The fractional 1,064-nm picosecond laser is an effective and safe therapeutic modality for skin rejuvenation.
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Background@#Increasing numbers of individuals are getting tattoos in recent times; however, the possible adverse effects of tattoos performed by non-medical practitioners are often overlooked. Limited information is available regarding the actual numbers of individuals getting tattoos and the perception regarding tattoos in the general population. @*Objective@#We investigated the prevalence of tattoos and public perception of tattoos. @*Methods@#Between August and September 2019, we performed a questionnaire survey that included 1,000 individuals aged ≥20 years. @*Results@#Among the 1,000 participants in this survey, 370 (37%) had received a tattoo; the number of participants with cosmetic tattoos (68.4%) was nearly 2-fold higher than the number of participants with body tattoos (31.6%). The most common motivation for getting a tattoo was “for beauty” (44.9%), followed by “convenience of make-up” (34.1%), and “recommendation from friends or others” (14.6%). In the tattoo-related satisfaction category, information regarding injected dye-induced adverse effects, facility hygiene, and pre-allergy testing were commonly rated as unsatisfactory by respondents. Only 322 (32.2%) participants were aware that semi-permanent tattoos could not be erased. Furthermore, 780 (78.0%) participants had a negative impression regarding body tattoos, and 844 (84.4%) participants preferred to get tattoos at specialized medical institutions based on the national regulations to minimize possible tattoo-induced adverse effects. @*Conclusion@#This study confirmed that a relatively large number of individuals had received tattoos but had a negative impression regarding this procedure. Educational and institutional management for public safety are necessary owing to a lack of awareness regarding tattoos and tattoo-related safety.
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In this study, we show the selective and efficient anti-cancer effects of plasma (at a low dose) when cell metabolic modifiers are also included. 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor, was used with effective doses of non-thermal plasma, synergistically attenuating cell metabolic viability and inducing caspase-dependent and independent cell death. The combination treatment decreased the intracellular ATP and lactate production in various types of blood cancer cells in vitro. Taken together, our findings suggest that 2-DG enhances the efficacy and selectivity of plasma and induces the synergistic inhibition of cancer cell growth by targeting glycolysis and apoptosis. Specifically, this treatment strategy demonstrated an enhanced growth inhibitory effect of plasma in the presence of a metabolic modifier that was selective against cancer cells, not non-malignant cells. This is the first study to report the advantage of combining plasma with 2-DG to eradicate blood cancer cells. Finally, we conclude that 2-DG with non-thermal plasma may be used as a combination treatment against blood cancer cells.
Assuntos
Apoptose/efeitos dos fármacos , Desoxiglucose/farmacologia , Glicólise/efeitos dos fármacos , Gases em Plasma/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Caspases/genética , Caspases/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Camundongos , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células U937RESUMO
In this study, we assessed the role of different reactive oxygen species (ROS) generated by soft jet plasma and chemical-induced ROS systems with regard to cell death in T98G, A549, HEK293 and MRC5 cell lines. For a comparison with plasma, we generated superoxide anion (O2(-)), hydroxyl radical (HO·), and hydrogen peroxide (H2O2) with chemicals inside an in vitro cell culture. Our data revealed that plasma decreased the viability and intracellular ATP values of cells and increased the apoptotic population via a caspase activation mechanism. Plasma altered the mitochondrial membrane potential and eventually up-regulated the mRNA expression levels of BAX, BAK1 and H2AX gene but simultaneously down-regulated the levels of Bcl-2 in solid tumor cells. Moreover, a western blot analysis confirmed that plasma also altered phosphorylated ERK1/2/MAPK protein levels. At the same time, using ROS scavengers with plasma, we observed that scavengers of HO· (mannitol) and H2O2 (catalase and sodium pyruvate) attenuated the activity of plasma on cells to a large extent. In contrast, radicals generated by specific chemical systems enhanced cell death drastically in cancer as well as normal cell lines in a dose-dependent fashion but not specific with regard to the cell type as compared to plasma.
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Gases em Plasma/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Trifosfato de Adenosina/metabolismo , Apoptose , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica , Células HEK293 , Histonas/genética , Histonas/metabolismo , Humanos , Potencial da Membrana Mitocondrial , Oxirredução , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Nitrogênio/farmacologia , Regulação para Cima , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoAssuntos
Alopecia/tratamento farmacológico , Visita a Consultório Médico/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Fotografação , Inibidores de 5-alfa Redutase/uso terapêutico , Corticosteroides/uso terapêutico , Alopecia em Áreas/tratamento farmacológico , Ciclopropanos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermoscopia , Feminino , Humanos , Masculino , Minoxidil/uso terapêutico , Probabilidade , Estudos RetrospectivosRESUMO
Single-particle characterization of summertime Arctic aerosols is useful to understand the impact of air pollutants on the polar atmosphere. In the present study, a quantitative single particle analytical technique, low-Z particle electron probe X-ray microanalysis, was used to characterize 8100 individual particles overall in 16 sets of aerosol samples collected at Ny-Alesund, Svalbard, Norway on 25-31 July, 2007. Based on their X-ray spectral and secondary electron image data of individual particles, 13 particle types were identified, in which particles of marine origin were the most abundant, followed by carbonaceous and mineral dust particles. A number of aged (reacted) sea salt (and mixture) particles produced by the atmospheric reaction of genuine sea-salts, especially with NO(x) or HNO(3), were significantly encountered in almost all the aerosol samples. They greatly outnumbered genuine sea salt particles, implying that the summertime Arctic atmosphere, generally regarded as a clean background environment, is disturbed by anthropogenic air pollutants. The main sources of airborne NO(x) (or HNO(3)) are probably ship emissions around the Arctic Ocean, industry emission from northern Europe and northwestern Siberia, and renoxification of NO(3)(-) within or on the melting snow/ice surface.