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1.
ScientificWorldJournal ; 2019: 5985207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485198

RESUMO

Acne vulgaris occurs due to the inflammation of sebaceous follicles in the skin. It is triggered by the activity of some bacterial species like Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis. Acquisition of antibiotic resistance by these microorganisms and adverse effects associated with the current treatment regimens necessitate the introduction of novel therapeutic agents for acne vulgaris. Thus, this study was undertaken to develop novel gel formulations from seeds of Nigella sativa L. and to evaluate the antibacterial potential against some acne-causing bacterial species. The antibacterial activity of seed extracts was initially screened against S. aureus and P. acnes by the agar well diffusion method. Thereafter, topical gels were formulated incorporating the ethyl acetate extract of seeds of N. sativa at three different concentrations. These topical formulations were subjected to antimicrobial activity studies while the stability was evaluated over a period of 30 days. All three formulations were capable of inhibiting the growth of S. aureus and P. acnes, with the highest antibacterial activity in the formulation comprising 15% of the seed extract. Interestingly, the antibacterial potency of this formulation against S. aureus surpassed the commercial synthetic product used as the positive control. Moreover, any alteration in color, odor, homogeneity, washability, consistency, and pH was not observed while the antibacterial potency was also retained during the storage period. The potent antibacterial activity in topical gel formulations developed from the ethyl acetate extract of N. sativa signposts their suitability as alternatives to existing antiacne agents in the management of acne vulgaris.


Assuntos
Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Antibacterianos/uso terapêutico , Cosmecêuticos/uso terapêutico , Nigella sativa/química , Acetatos , Administração Tópica , Adolescente , Adulto , Misturas Complexas , Cosmecêuticos/administração & dosagem , Composição de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Testes de Irritação da Pele , Adulto Jovem
2.
Int J Mol Sci ; 20(14)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319552

RESUMO

Acne is an inflammatory skin disorder in puberty with symptoms including papules, folliculitis, and nodules. Propionibacterium acnes (P. acnes) is the main anaerobic bacteria that cause acne. It is known to proliferate within sebum-blocked skin hair follicles. P. acnes activates monocytic cell immune responses to induce the expression of proinflammatory cytokines. Although the anti-inflammatory function of the Laurus nobilis (L. nobilis) extract (LNE) on several immunological disorders have been reported, the effect of LNE in P. acnes-mediated skin inflammation has not yet been explored. In the present study, we examined the ability of the LNE to modulate the P. acnes-induced inflammatory signaling pathway, and evaluated its mechanism. LNE significantly suppressed the expression of P. acnes-mediated proinflammatory cytokines, such as IL-1ß, IL-6, and NLRP3. We also found that LNE inhibited the inflammatory transcription factor NF-κB in response to P. acnes. In addition, eucalyptol, which is the main constituent of LNE, consistently inhibited P. acnes-induced inflammatory signaling pathways. Moreover, LNE significantly ameliorated P. acnes-induced inflammation in a mouse model of acne. We suggest for the first time that LNE hold therapeutic value for the improvement of P. acnes-induced skin inflammation.


Assuntos
Acne Vulgar/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Eucaliptol/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Laurus/química , Extratos Vegetais/farmacologia , Propionibacterium acnes/crescimento & desenvolvimento , Acne Vulgar/metabolismo , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Animais , Anti-Inflamatórios/química , Linhagem Celular , Eucaliptol/química , Infecções por Bactérias Gram-Positivas/metabolismo , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Camundongos , Extratos Vegetais/química
3.
J Dermatol ; 46(9): 787-790, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290561

RESUMO

The skin microbiome plays important roles in the pathogenesis and development of acne. We aimed to investigate the facial skin microbiome of acne and microbiome differences related to different grades of acne. Skin swabs from nine healthy controls and 67 acne patients were collected, and the skin microbiomes were analyzed using 16S rRNA gene sequencing. Compared with healthy controls, acne patients harbored significantly altered skin microbiomes. The skin microbiomes of patients with grade 1-3 acne were similar, but patients with grade 4 acne showed a significantly different skin microbiome compared with grade 1-3 acne, including increased alpha diversity and increased proportions of four Gram-negative bacteria (Faecalibacterium, Klebsiella, Odoribacter and Bacteroides). In conclusion, acne patients harbored an altered skin microbiome, and more significant dysbiosis was found in patients with grade 4 acne (severe acne). Our findings may provide evidence for the pathogenic mechanisms of acne and microbial-based strategies to avoid and treat acne, especially grade 4 acne.


Assuntos
Acne Vulgar/diagnóstico , Disbiose/diagnóstico , Microbiota/genética , Índice de Gravidade de Doença , Pele/microbiologia , Acne Vulgar/microbiologia , DNA Bacteriano/isolamento & purificação , Disbiose/microbiologia , Feminino , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Masculino , RNA Ribossômico 16S/genética , Adulto Jovem
4.
J Dermatol ; 46(9): 782-786, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254314

RESUMO

Staphylococcus epidermidis is a bacterium known to inhabit the skin. In treatment of acne vulgaris, the cutaneous milieu is exposed to oral or topical antimicrobials. We previously reported that the antimicrobial resistance of Cutibacterium acnes isolated from acne patients is affected by antimicrobial use. The aim of this study was to investigate the relationship between quinolone use and resistance in skin bacteria, particularly S. epidermidis, from acne patients. A total of 92 and 87 S. epidermidis strains isolated from clinic patients and hospital outpatients with acne vulgaris, respectively, were tested. No significant difference was found between the prevalence of methicillin-resistant S. epidermidis (MRSE) strains from clinic patients (37.0%) and hospital outpatients (39.1%). The MRSE strains (20.6%, 14/68 strains) showed a significantly higher ratio of high-level levofloxacin resistance (minimum inhibitory concentrations were 64 to ≥256 µg/mL) compared with methicillin-susceptible S. epidermidis strains (2.7%, 3/111 strains) (P < 0.01). The rate of levofloxacin resistance in C. acnes strains, which were isolated from the same samples of acne patients, showed a strong positive correlation with that in S. epidermidis strains (r = 0.93, P < 0.01). The high-level levofloxacin-resistant strains were frequently found in patients with history of quinolone use compared with those without (P < 0.01). Our data showed for the first time that antimicrobial administration for acne treatment affects the antimicrobial resistance in not only C. acnes but also S. epidermidis. Thus, caution should be exercised in antimicrobial use for acne treatment to prevent increasing antimicrobial resistance in these species.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Quinolonas/administração & dosagem , Staphylococcus epidermidis/fisiologia , Acne Vulgar/microbiologia , Administração Cutânea , Administração Oral , Humanos , Testes de Sensibilidade Microbiana , Propionibacterium acnes/fisiologia , Pele/microbiologia , Staphylococcus epidermidis/isolamento & purificação
5.
Dermatology ; 235(4): 287-294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31112983

RESUMO

BACKGROUND: Cutibacterium acnes has been identified as one of the main triggers of acne. However, increasing knowledge of the human skin microbiome raises questions about the role of other skin commensals, such as Staphylococcus epidermidis, in the physiopathology of this skin disease. SUMMARY: This review provides an overview of current knowledge of the potential role of S. epidermidis in the physiopathology of acne. Recent research indicates that acne might be the result of an unbalanced equilibrium between C. acnes and S. epidermidis,according to dedicated interactions. Current treatments act on C. acnesonly. Other treatment options may be considered, such as probiotics derived from S. epidermidis to restore the naturally balanced microbiota or through targeting the regulation of the host's AMP mediators. Key Messages: Research seems to confirm the beneficial role of S. epidermidis in acne by limiting C. acnes over-colonisation and inflammation.


Assuntos
Acne Vulgar/microbiologia , Infecções por Bactérias Gram-Positivas/fisiopatologia , Fenômenos Microbiológicos , Propionibacteriaceae/patogenicidade , Pele/microbiologia , Staphylococcus epidermidis/fisiologia , Acne Vulgar/etiologia , Acne Vulgar/fisiopatologia , Acne Vulgar/terapia , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/microbiologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Interações Microbianas/fisiologia , Microbiota/fisiologia , Propionibacteriaceae/isolamento & purificação , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/fisiopatologia , Staphylococcus epidermidis/isolamento & purificação
6.
J Drugs Dermatol ; 18(5): 412-418, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31141847

RESUMO

Cortexolone 17α-propionate (clascoterone) is a novel topical androgen antagonist that is being analyzed for its ability to treat acne. The pathogenesis of acne is attributed to multiple factors, including altered sebum production, inflammatory processes, dysregulation of the hormone microenvironment, and the proliferation of the skin commensal bacteria, Propionibacterium acnes (P. acnes). Androgens induce the proliferation and differentiation of sebocytes, (cells that comprise the sebaceous gland), help regulate the synthesis of the lipids that are incorporated into sebum and stimulate the production of cytokines that are found in inflammatory acne lesions. Several studies have established that clascoterone is a potent antiandrogen that is well tolerated and has selective topical activity. Its potency as an acne therapeutic is currently being analyzed in a large phase 3 clinical trial. The study described herein elucidates for the first time the mechanism of action of clascoterone. Clascoterone was found to bind the androgen receptor (AR) with high affinity in vitro, inhibit AR-regulated transcription in a reporter cell line, and antagonize androgen-regulated lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. In particular, when compared to another AR antagonist, spironolactone, clascoterone was significantly better at inhibiting inflammatory cytokine synthesis from sebocytes. Therefore, clascoterone may be an excellent candidate to be the first topical antiandrogen to treat acne. J Drugs Dermatol. 2019;18(5):412-418.


Assuntos
Acne Vulgar/tratamento farmacológico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Cortodoxona/análogos & derivados , Propionatos/uso terapêutico , Glândulas Sebáceas/efeitos dos fármacos , Acne Vulgar/microbiologia , Antagonistas de Receptores de Andrógenos/farmacologia , Linhagem Celular/efeitos dos fármacos , Cortodoxona/farmacologia , Cortodoxona/uso terapêutico , Citocinas/metabolismo , Humanos , Lipogênese/efeitos dos fármacos , Propionatos/farmacologia , Propionibacterium acnes , Receptores Androgênicos/metabolismo , Glândulas Sebáceas/citologia , Glândulas Sebáceas/metabolismo
8.
Immunity ; 50(4): 1069-1083.e8, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30926233

RESUMO

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAM+CD59+Ly-6D+ cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.


Assuntos
Acne Vulgar/imunologia , Células Dendríticas/classificação , Infecções por Bactérias Gram-Positivas/imunologia , Infiltração de Neutrófilos/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Acne Vulgar/microbiologia , Animais , Apresentação do Antígeno , Quimiotaxia de Leucócito/imunologia , Células Dendríticas/imunologia , Orelha Externa , Regulação da Expressão Gênica , Ontologia Genética , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Injeções Intradérmicas , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Propionibacterium acnes , RNA Mensageiro/biossíntese , Análise de Célula Única , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
9.
J Drugs Dermatol ; 18(3): 240-244, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30909327

RESUMO

Oral antibiotics are well established treatments for acne vulgaris but are associated with undesirable side effects. Topical antibiotics offer an improved safety profile but have led to an alarming rise in worldwide P. acnes resistance. Fortunately, a new class of topical minocycline products has been developed for the treatment of acne and rosacea that decreases the risk for antibiotic resistance while maintaining safety and efficacy. Recent clinical studies have demonstrated that a hydrophilic minocycline gel (BPX-01) and a lipophilic minocycline foam (FMX101) both reduced acne lesion counts with negligible systemic absorption. Head-to-head studies have yet to be completed, but the hydrophilic gel studies reported greater treatment efficacy than the lipophilic foam studies. J Drugs Dermatol. 2019;18(3):240-244.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/farmacologia , Minociclina/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Administração Cutânea , Antibacterianos/uso terapêutico , Ensaios Clínicos como Assunto , Farmacorresistência Bacteriana , Humanos , Minociclina/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento
11.
JAMA Dermatol ; 155(4): 425-434, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30758497

RESUMO

Importance: Given the widespread use of systemic antibiotics for treatment of moderate to severe acne, it is important to understand the associations of such antibiotic use with changes not only in Cutibacterium acnes (formerly Propionibacterium acnes) but also in the complete bacterial community of the skin. Objective: To examine the composition, diversity, and resilience of skin microbiota associated with systemic antibiotic perturbation in individuals with acne. Design, Setting, and Participants: This longitudinal cohort study conducted at an academic referral center in Maryland from February 11 to September 23, 2014, included 4 female participants who had received a recent diagnosis of acne vulgaris, showed comedonal and inflammatory acne on the face, were at least 18 years old, and had no recent use of systemic or topical treatments for acne, including antibiotics and retinoids. Data analysis was performed between July 5, 2017, and November 7, 2018. Interventions: Participants were prescribed oral minocycline, 100 mg, twice daily for 4 weeks. Skin areas on the forehead, cheek, and chin were sampled for 16S ribosomal RNA gene sequencing at baseline, 4 weeks after starting minocycline treatment, and then 1 week and 8 weeks after discontinuation of treatment. Main Outcomes and Measures: Skin microbiota examined with respect to relative abundance of bacterial taxa, α diversity (represents within-sample microbial diversity), and ß diversity (represents between-sample microbial diversity). Acne status evaluated with photography and lesion count. Results: Of the 4 patients included in this study, 2 were 25 years old, 1 was 29 years old, and 1 was 35 years old; 2 were white women, 1 was an African American woman, and 1 was an Asian woman. Across all 4 patients, antibiotic treatment was associated with a 1.4-fold reduction in the level of C acnes (difference, -10.3%; 95% CI, -19.9% to -0.7%; P = .04) with recovery following cessation of treatment. Distinct patterns of change were identified in multiple bacterial genera, including a transient 5.6-fold increase in the relative abundance of Pseudomonas species (difference, 2.2%; 95% CI, 0.9%-3.4%; P < .001) immediately following antibiotic treatment, as well as a persistent 1.7-fold increase in the relative abundance of Streptococcus species (difference, 5.4%; 95% CI, 0.3%-10.6%; P = .04) and a 4.7-fold decrease in the relative abundance of Lactobacillus species (difference, -0.8%; 95% CI, -1.4% to -0.2%; P = .02) 8 weeks following antibiotic treatment withdrawal. In general, antibiotic administration was associated with an initial decrease from baseline of bacterial diversity followed by recovery. Principal coordinates analysis results showed moderate clustering of samples by patient (analysis of similarity, R = 0.424; P = .001) and significant clustering of samples by time in one participant (analysis of similarity, R = 0.733; P = .001). Conclusions and Relevance: In this study, systemic antibiotic treatment of acne was associated with changes in the composition and diversity of skin microbiota, with variable rates of recovery across individual patients and parallel changes in specific bacterial populations. Understanding the association between systemic antibiotic use and skin microbiota may help clinicians decrease the likelihood of skin comorbidities related to microbial dysbiosis.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/administração & dosagem , Minociclina/administração & dosagem , Pele/patologia , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Administração Oral , Adulto , Bactérias/isolamento & purificação , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Microbiota , Projetos Piloto , Propionibacterium acnes/isolamento & purificação , Pele/microbiologia , Resultado do Tratamento
12.
J Dermatol ; 46(5): 431-435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30811070

RESUMO

Cutaneous disorders remain a major problem in HIV-infected patients, even under antiretroviral therapy (ART). Patients at any stage of HIV/AIDS may suffer from skin lesions. Acnes and psoriasis are both common chronic and inflammatory skin diseases, and the treatment becomes more challenging and complex when combined with HIV infection. Whether the incidence and severity of acne and psoriasis are related to HIV infection is still controversial. Here, we report a rare case of an AIDS patient who developed severe acne along with psoriasis. The patient had initially received multiple systemic and topical antipsoriatic and anti-acne treatments which failed. Ultimately, he achieved dramatic clinical improvement after initiation of ART for main treatment. An 8-year follow up demonstrated that the patient has been free of symptoms of both psoriasis and acne till now.


Assuntos
Acne Vulgar/tratamento farmacológico , Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Psoríase/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Acne Vulgar/diagnóstico , Acne Vulgar/imunologia , Acne Vulgar/microbiologia , Adulto , Fármacos Dermatológicos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Psoríase/diagnóstico , Psoríase/imunologia , Psoríase/microbiologia , Índice de Gravidade de Doença , Pele/patologia , Infecções Cutâneas Estafilocócicas/diagnóstico , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/microbiologia , Resultado do Tratamento , Carga Viral
13.
BMJ Open ; 9(2): e022938, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782869

RESUMO

OBJECTIVE: Antibiotics have been routinely used for several decades against Propionibacterium acnes (P. acnes), but antibiotic resistance of P. acnes is becoming a global problem. Only one related Chinese study is available. The aim of this study was to assess the antibiotic susceptibility of P. acnes obtained from patients with acne in Southwest China. DESIGN: This was a prospective cross-sectional study. Cutaneous samples were obtained from acne lesions on the face of 375 patients. Samples were cultured in anaerobic medium to identify the presence of P. acnes. Susceptibility tests of isolated P. acnes were performed for tetracycline, doxycycline, clindamycin, erythromycin, azithromycin and clarithromycin using the Epsilometer test. RESULTS: P. acnes was isolated from 227 patients; 224 isolates (98.7%) were susceptible to doxycycline and 220 (96.9%) were susceptible to tetracycline, followed by clindamycin and clarithromycin in 101 (44.5%) and 102 (44.93%) isolates, respectively. Susceptibility of P. acnes was detected for erythromycin in 96 (42.3%) patients, followed by azithromycin in 94 (41.4%). Subjects who received antibiotics (topical and oral) had higher frequencies of antibiotic-resistant P. acnes as well as increased antibiotic minimum inhibitory concentrations compared with patients without antibiotic treatment. CONCLUSIONS: P. acnes was highly sensitive to cyclines (doxycycline and tetracycline). P. acnes showed higher resistance rates to macrolides-lincosamides-streptogramins antibiotics (such as erythromycin, azithromycin, clarithromycin and clindamycin). The irrational use of antibiotics for acne treatment is probably a problem in China and elsewhere. These results suggest that dermatologists should be more prudent in prescribing antibiotics for acne.


Assuntos
Acne Vulgar/microbiologia , Antibacterianos/farmacologia , Hospitais Públicos , Propionibacterium acnes/efeitos dos fármacos , Adolescente , Adulto , Criança , China , Estudos Transversais , Resistência Microbiana a Medicamentos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Propionibacterium acnes/isolamento & purificação , Estudos Prospectivos , Adulto Jovem
14.
J Dermatol ; 46(4): 308-313, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803018

RESUMO

Antimicrobial agents have been used for eradication of Cutibacterium (formerly Propionibacterium) acnes that is an exacerbation factor of the skin disease acne vulgaris. However, the use of antibiotics is associated with an increased risk of promoting the emergence of resistant bacteria and leading to skin dysbiosis. Traditional Japanese Kampo medicines, such as Keigairengyoto, are used to treat acne. However, there is incomplete understanding regarding their functional mechanism in treatment of acne. In this study, we examined the antimicrobial and anti-lipase activity of the Kampo medicines used empirically for acne treatment. Three oral medicines, Keigairengyoto, Seijoboufuto and Jumihaidokuto, were found to inhibit the growth of C. acnes and decrease the lipase activity. Especially, Keigairengyoto caused remarkable decrease of bacterial lipase activity. Furthermore, topical medicines such as Shiunko and Chuoko significantly decreased the lipase activity in a dose-dependent manner, without inhibiting C. acnes growth. The topical medicines were found to inhibit the expression of gehA, which codes for extracellular lipase. Our results indicate that Shiunko and Chuoko have potential as effective acne therapeutic agents, especially because they do not promote the emergence of antimicrobial-resistant bacteria and skin dysbiosis.


Assuntos
Acne Vulgar/tratamento farmacológico , Anti-Infecciosos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Propionibacterium acnes/efeitos dos fármacos , Acne Vulgar/microbiologia , Administração Tópica , Anti-Infecciosos/uso terapêutico , Proteínas de Bactérias/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Lipase/metabolismo , Medicina Kampo/métodos , Testes de Sensibilidade Microbiana , Propionibacterium acnes/isolamento & purificação , Propionibacterium acnes/metabolismo
15.
Molecules ; 24(2)2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30634461

RESUMO

Acne is associated with hyperkeratosis, elevated levels of skin sebum and growth of Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). Furthermore, P. acnes promotes inflammation by inducing IL-6 production and oxidative stress. The aim of this study was to assess the antioxidant, anti-inflammatory and antibacterial potential of a hop-CO2-extract with 50% humulone and lupulone. The susceptibility of P. acnes and S. aureus to the hop extract was tested by using the broth microdilution technique. The minimal inhibitory concentrations (MIC) for P. acnes and S. aureus were 3.1 and 9.4 µg/mL, respectively. In addition, the hop extract showed an antioxidative effect with a half maximal inhibitory concentration (IC50) of 29.43 µg/mL as well as additional anti-inflammatory effects by reducing the IL-6 expression (IC50: 0.8 µg/mL). In addition, a gel formulation with 0.3% hop extract (w/w) had antibacterial activity against P. acnes and S. aureus (inhibition zone value: 5.5 mm and 3 mm, respectively) which was significantly superior to the placebo gel. The positive control (a gel with the antibiotic clindamycin) showed an inhibition zone of 9 mm. Due to its antioxidant, anti-inflammatory and antibacterial effects hop extract might be a treatment option for acne-prone skin.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Humulus/química , Extratos Vegetais/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/metabolismo , Acne Vulgar/microbiologia , Antibacterianos/química , Antioxidantes/química , Células Cultivadas , Humanos , Interleucina-6/metabolismo , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/microbiologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/metabolismo
16.
Am J Clin Dermatol ; 20(3): 335-344, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30632097

RESUMO

Acne vulgaris is a chronic skin disorder involving hair follicles and sebaceous glands. Multiple factors contribute to the disease, including skin microbes. The skin microbiome in the follicle is composed of a diverse group of microorganisms. Among them, Propionibacterium acnes and Malassezia spp. have been linked to acne development through their influence on sebum secretion, comedone formation, and inflammatory response. Antibiotics targeting P. acnes have been the mainstay in acne treatment for the past four decades. Among them, macrolides, clindamycin, and tetracyclines are the most widely prescribed. As antibiotic resistance becomes an increasing concern in clinical practice, understanding the skin microbiome associated with acne and the effects of antibiotic use on the skin commensals is highly relevant and critical to clinicians. In this review, we summarize recent studies of the composition and dynamics of the skin microbiome in acne and the effects of antibiotic treatment on skin microbes.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Acne Vulgar/imunologia , Acne Vulgar/microbiologia , Antibacterianos/uso terapêutico , Folículo Piloso/imunologia , Folículo Piloso/microbiologia , Humanos , Malassezia/isolamento & purificação , Malassezia/fisiologia , Microbiota/imunologia , Propionibacterium acnes/isolamento & purificação , Propionibacterium acnes/fisiologia , Glândulas Sebáceas/imunologia , Glândulas Sebáceas/microbiologia , Simbiose/efeitos dos fármacos , Resultado do Tratamento
17.
Pediatr Dermatol ; 36(2): 200-206, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30656737

RESUMO

BACKGROUND/OBJECTIVES: The pathogenesis of preadolescent acne has not been well studied, and it is uncertain if Cutibacterium acnes is a predominant organism in the microbiome in this age group. The aim of this study was to analyze the microbiome of preadolescent females and to assess whether benzoyl peroxide impacts the microbiome. METHODS: The study enrolled girls, aged 7-12 years, with evidence of at least six acne lesions who had not been previously treated. Participants' skin surface of forehead, cheeks, nose, chin, left retroauricular crease, and extruded contents of a comedonal lesion were sampled at baseline. Participants used benzoyl peroxide 4% wash for 6-8 weeks and returned for skin surface sampling and extraction collection. Microbiome analysis was performed using 16S ribosomal RNA gene amplicon sequencing on all swab and lesional extraction samples. RESULTS: Fifty-one participants were enrolled with a median IGA score of 2 (mild). Changes in microbiome diversity were associated with increasing age and number of acne lesions (P = 0.001). C. acnes had higher abundances on forehead and nose, as opposed to cheeks and chin (P = 0.009). Bacterial diversity (alpha diversity) of the skin microbiome was comparable between preadolescent at baseline and after treatment with benzoyl peroxide. CONCLUSION: This is the first large assessment characterizing female acne microbiome in early and late preadolescence. Results show that preadolescent acne can vary in its microbial profile, reflecting surrounding changes associated with the onset of puberty. Although benzoyl peroxide use was associated with decreased acne counts, its effect on microbial diversity was not demonstrated in our study.


Assuntos
Acne Vulgar/microbiologia , Antibacterianos/uso terapêutico , Peróxido de Benzoíla/uso terapêutico , Microbiota/efeitos dos fármacos , Pele/patologia , Acne Vulgar/tratamento farmacológico , Criança , Feminino , Humanos , Estudos Prospectivos , RNA Ribossômico 16S , Pele/microbiologia
18.
Inflammation ; 42(1): 35-44, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30120655

RESUMO

Propionibacterium acnes (P. acnes) has been implicated in the progression of acne inflammation. Because current acne medications have various side effects, it is necessary to explore alternative medications possessing anti-inflammatory activity against P. acnes. We investigated the inhibitory effects of polyphyllin I (PPI) on P. acnes-induced inflammation in vitro. In this study, we examined the effects of PPI on the production of inflammatory cytokines in HaCaT keratinocytes treated with heat-killed P. acnes. These treated HaCaT keratinocytes showed increased expression of Toll-like receptor 2 (TLR2) and production of inflammatory cytokines. PPI significantly suppressed the secretion of inflammatory cytokines, including interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α, and the expression of TLR2 in P. acnes-treated cells. Moreover, we studied the influence of PPI on the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in P. acnes-treated keratinocytes. PPI diminished the activation of NF-κB. Phosphorylated p38 levels were markedly increased after treatment with heat-killed P. acnes but were decreased after treatment with PPI, while the effect of PPI on ERK phosphorylation was not significant. Heat-killed P. acnes and PPI did not have any effect on JNK phosphorylation. Furthermore, we confirmed that NF-κB p65 inhibitor (BAY11-7082), p38 MAPK inhibitor (SB203580), and PPI blocked the expression of IL-8 in heat-killed P. acnes-treated cells. These results demonstrated that PPI has potential for development as a treatment for acne inflammation.


Assuntos
Acne Vulgar/patologia , Diosgenina/análogos & derivados , Inflamação/prevenção & controle , Propionibacterium acnes , Acne Vulgar/microbiologia , Linhagem Celular , Citocinas/biossíntese , Citocinas/efeitos dos fármacos , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Humanos , Inflamação/microbiologia , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-30397052

RESUMO

Sarecycline is the first narrow-spectrum tetracycline-class antibiotic being developed for acne treatment. In addition to exhibiting activity against important skin/soft tissue pathogens, sarecycline exhibits targeted antibacterial activity against clinical isolates of Cutibacterium acnes In the current study, sarecycline was 16- to 32-fold less active than broad-spectrum tetracyclines-such as minocycline and doxycycline-against aerobic Gram-negative bacilli associated with the normal human intestinal microbiome. Also, reduced activity against Escherichia coli was observed in vivo in a murine septicemia model, with the 50% protective doses, or the doses required to achieve 50% survival, being >40 mg/kg of body weight and 5.72 mg/kg for sarecycline and doxycycline, respectively. Sarecycline was also 4- to 8-fold less active than doxycycline against representative anaerobic bacteria that also comprise the normal human intestinal microbiome. Additionally, C. acnes strains displayed a low propensity for the development of resistance to sarecycline, with spontaneous mutation frequencies being 10-10 at 4 to 8 times the MIC, similar to those for minocycline and vancomycin. When tested against Gram-positive pathogens with defined tetracycline resistance mechanisms, sarecycline was more active than tetracycline against tet(K) and tet(M) strains, with MICs ranging from 0.125 to 1.0 µl/ml and 8 µl/ml, respectively, compared with MICs of 16 to 64 µl/ml and 64 µl/ml for tetracycline, respectively. However, sarecycline activity against the tet(K) and tet(M) strains was decreased compared to that against the wild type, which demonstrated MICs ranging from 0.06 to 0.25 µl/ml, though the decrease in the activity of sarecycline against the tet(K) and tet(M) strains was not as pronounced as that of tetracycline. These findings support sarecycline as a narrow-spectrum tetracycline-class antibiotic that is effective for the treatment of acne, and further investigation into the potential reduced effects on the gut microbiome compared with those of other agents is warranted.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/farmacologia , Propionibacteriaceae/efeitos dos fármacos , Propionibacterium acnes/efeitos dos fármacos , Tetraciclinas/farmacologia , Acne Vulgar/microbiologia , Animais , Proteínas de Bactérias/genética , Doxiciclina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , Proteínas de Membrana/genética , Camundongos , Testes de Sensibilidade Microbiana , Propionibacteriaceae/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/isolamento & purificação , Tetraciclina/farmacologia
20.
J Med Microbiol ; 68(1): 26-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30431414

RESUMO

Cutibacterium acnes (C. acnes) can become an exacerbating factor in acne vulgaris. Clindamycin has been most frequently used for the treatment of inflammatory acne vulgaris. We studied clindamycin susceptibility and resistance determinants of C. acnes isolated from acne patients in Japan. The isolation rate of clindamycin-resistant C. acnes had significantly increased from 20.3 % in 2009-2010 to 44.1 % in 2016-2017. Strains carrying erm(X), which confers high-level resistance to clindamycin, had significantly increased from 1.4 to 11.8 %. Sequence analysis of the resistance determinant showed that erm(X) was coded on transposon Tn5432. A transconjugation experiment showed that erm(X) can be transferred between C. acnes strains with high frequency and the transconjugants harboured transposon Tn5432 encoding erm(X). Our data show the transconjugation of erm(X) in C. acnes and strongly suggest that the transmission of erm(X) between C. acnes contributes to the increase and spread of clindamycin-resistant C. acnes strains in acne patients.


Assuntos
Acne Vulgar/microbiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Clindamicina/farmacologia , Farmacorresistência Bacteriana , Propionibacterium acnes/efeitos dos fármacos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/epidemiologia , Conjugação Genética , Humanos , Japão , Testes de Sensibilidade Microbiana , Prevalência , Propionibacterium acnes/genética
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