Antimicrobial activity of enterocins from Enterococcus faecalis SL-5 against Propionibacterium acnes, the causative agent in acne vulgaris, and its therapeutic effect

A lactic acid bacterial strain was isolated from human fecal specimen and identified as Enterococcus faecalis SL-5. The isolated strain showed antimicrobial activity against Gram-positive pathogens assayed, especially the highest activity against Propionibacterium acnes. The antimicrobial substance was purified and verified as a bacteriocin (named ESL5) of E. faecalis SL-5 by activity-staining using P. acnes as an indicator. N-terminal sequence of ESL5 was determined (MGAIAKLVAK) and sequence analysis revealed that it is almost identical to the some of enterocins including L50A/B of E. faecium L50 and MR10A/B of E. faecalis MRR 10-3. From the sequencing data of L50A/B structural genes, the nucleotide sequence showed 100% identity with that of the MR10A/B structural genes, implying that ESL5 is an equivalent of enterocin MR10. Meanwhile, we also tested the therapeutic effect of anti-P. acnes activity in patients with mild to moderate acne because of its pathogenic role to acne vulgaris. For this purpose, a concentrated powder of CBT SL-5 was prepared using cell-free culture supernatant (CFCS) of E. faecalis SL-5 and included in a lotion for application in the patients. The study showed that CBT SL-5 lotion significantly reduced the inflammatory lesions like pustules compared to the placebo lotion. Therefore our results indicate that the anti-P. acnes activity produced by E. faecalis SL-5 has potential role to the treatment of acne as an alternative to topical antibiotics. These authors contributed equally to this work.     

Effect of vaccination therapy for acne,using a staphylococci antigenic complex in combination with clindamycin

A group of 46 patients with acne vulgaris were prescribed clindamycin in combination with a vaccination therapy using a staphylococci antigenic complex (Polystafana; Sevapharma, Czechia). Acne papulopustulosa was diagnosed in 36 patients and acne indurata in 10 patients. The clinical effect of clindamycin and Polystafana was determined on the basis of the regression of the inflammatory manifestation of acne: regression by 0-30% was considered unsuccessful, by 30-80% satisfactory, and above 80% excellent; the immunomodulation effect of the treatment was evaluated in parallel. The clinical effect was excellent in 21 patients with acne papulopustulosa and in 6 with acne indurata; it was accompanied by pronounced immunomodulation effect as both cellular and humoral immunity was also tended to return to normal values. A satisfactory clinical effect was observed in 15 patients with acne papulopustulosa, whose cellular immunity component was also stimulated. Only 4 patients with acne indurata failed to respond successfully. These were the patients who showed a pronounced deficit of the cellular immunity component persisting even after the treatment. The administration of clindamycin in combination with Polystafana vaccination can be recommended as an effective means for the treatment of acne vulgaris.     

Taurine bromamine (TauBr) - its role in immunity and new perspectives for clinical use

This review is an attempt to summarize our knowledge about taurine bromamine (TauBr) properties, its role in innate immunity and its therapeutic potential.TauBr and taurine chloramine (TauCl) are major haloamines generated by eosinophils and neutrophils at a site of inflammation. Both haloamines share anti-inflammatory and anti-oxidant properties. TauBr, similarly to TauCl, decreases the production of proinflammatory mediators. Their anti-inflammatory and anti-oxidant activities are enhanced by their ability to induce the expression of heme oxygenase-1 (HO-1). TauCl is more stable than TauBr. On the other hand, only TauBr was found to be highly membrane-permeable showing stronger microbicidal activity than TauCl.In the light of the anti-inflammatory and antimicrobial properties of TauBr we discuss its therapeutic potential in local treatment of inflammation, especially acne vulgaris, the most common inflammatory skin disorder. TauBr, at non-cytotoxic concentrations, is able to kill Propionibacterium acnes, the skin bacteria involved in pathogenesis of acne vulgaris.As topical antibiotics used in the therapy of acne are associated with the emergence of resistant bacteria, topical TauBr seems to be a good candidate for an alternative therapy.Recently, in a double blind trial, the efficacy of TauBr was compared with the efficacy of clindamycin, one of the most common topical antibiotics used in acne therapy. Comparable reduction of acne lesions was observed in the TauBr and clindamycin groups of patients with mild and moderate inflammatory facial acne vulgaris. We conclude that this pilot study supports our concept that TauBr can be used as a topical agent in the treatment of acne vulgaris, especially in patients who have already developed antibiotic resistance. Further studies are necessary to substantiate the more extended use of TauBr as an anti-inflammatory and anti-oxidant agent in human medicine.     

Therapeutic Agents in Acne Vulgaris: I. Tetracycline

A total of 120 consecutive patients with pustular and cystic acne vulgaris were selected for study. Patients were assigned a placebo and a tetracycline medication in a random method. Of the 53 patients who were given tetracycline, 45 showed some response, which was fair in 19 and excellent in 26. Of the 55 patients who received placebo, 24 showed no response while 31 showed some improvement. No side effects were reported. The difference in response between the two groups is statistically significant. It is concluded that administration of 250 mg. tetracycline four times daily, even for periods as short as two weeks, enhances the likelihood of improvement of cystic or pustular acne vulgaris.     

Association of TNF-α polymorphisms (−857, −863 and −1031), TNF-α serum level and lipid profile with acne vulgaris

BackgroundAcne is an inflammatory condition principally affected by genetic and dietary factors. Investigation into functional polymorphisms of TNF-α gene and their association with acne vulgaris will be helpful in exploring genetic influence on skin immune mediated inflammatory events. In the present study, we analyzed association of TNF-α gene polymorphisms, its expression levels and lipid profiles in a large cohort of acne patients and controls.MethodsWe used PCR-RFLP to study association of TNF-α polymorphisms at −857C/T, −863C/A and −1031 T/C sites with acne vulgaris. Lipid profiles were measured using enzymatic end-point method. The serum levels of TNF-α and apolipoprotein a were measured using ELISA. NIH, LDlink was used to investigate patterns of linkage disequilibrium across south Asian reference genome (Punjabi from Lahore Pakistan).ResultsWe found that TNF-α −863 polymorphism is strongly associated with acne in overall population as well as in gender and severity based groups of acne patients. Polymorphisms at −863 and −1031 position were in linkage disequilibrium. Importantly, TNF-α serum level was significantly increased in acne patients with severe disease symptoms. Furthermore, levels of total cholesterol (TC) and triglycerides (TG) were significantly increased, whereas high density lipoprotein cholesterol (HDL-C) level was significantly decreased in acne patients. The levels of apolipoprotein a varied widely in studied populations and no significant difference was found in the analyzed groups.ConclusionIn conclusion, we found that TNF-α expression increases in acne patients affected by TNF-α polymorphisms, and that the lipid profile is specifically disrupted in acne patients.     

Role of Tissue Liver X-Receptors Level in Skin Diseases

Liver X receptors (LXRs) among many nuclear receptors expressed within the skin. It has been widely recognized in the regulation of genes involved in immunity, inflammation and lipid biosynthesis. LXRs genes are involved in regulation of keratinocytes, melanocytes as well as sebocytes and they might have an important role in pathogenesis of skin disorders such as psoriasis, vitiligo and acne vulgaris. The aim of this study was to detect if there is a difference in the expression of LXRs in psoriatic, vitiligo and acne vulgaris. This study included 60 patients; 20 psoriatic patients, 20 vitiligo patients, 20 acne patients and 20 controls with matched age and sex. The level of LXR α and β were measured in the lesional skin and in the control skin by PCR technique from plaque-type psoriasis, perilesional vitiligo and inflammatory acne as well as from controls. The mean values of LXR α and β in the lesional skin of psoriatic patients were significantly higher than that in the controls (P < 0.001). While, the mean values of LXR α and β in the perilesional vitiligo and acne patients were significantly lower than the controls (P < 0.001). LXR was significantly inversely correlated to the severity of psoriasis while there were insignificant correlation with acne and vitiligo. In conclusion, changes in the level of LXR α and β expression could be a consequence of certain downstream genes in some skin disorders.     

Anti-inflammatory activity of cationic peptides: application to the treatment of acne vulgaris

Cationic antimicrobial peptides exhibit potent antimicrobial activity against clinically relevant microorganisms including Propionibacterium acnes. Recent studies showed that, in addition to the antimicrobial activity, these peptides can exhibit an anti-inflammatory effect. These properties make cationic peptides attractive drug candidates for the treatment of acne vulgaris, a disease with both bacterial and inflammatory components. This review focuses on the anti-inflammatory activity of cationic antimicrobial peptides and its application for the treatment of acne vulgaris. The anti-inflammatory activity of cationic peptides in acne vulgaris can be explained by their ability to both bind proinflammatory bacterial factors (e.g. lipoteichoic acid), sequestering them from the site of inflammation, and to inhibit the secretion of proinflammatory cytokines (e.g. tumor necrosis factor-alpha, IL-1) by host cells. These anti-inflammatory effects combined with potent antimicrobial activity may translate into a novel therapeutic option for acne vulgaris.     

Oxidative stress in patients with acne vulgaris

Acne vulgaris is one of the common dermatological diseases and its pathogenesis is multifactorial. In this study, we aim to determine the effects of oxidative stress in acne vulgaris. Forty-three consecutive acne patients and 46 controls were enrolled. The parameters of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood of cases were measured spectrophotometrically. The values compared with control group, the relation between the severity and distribution of acne, and the correlation of each enzyme level were researched. CAT and G6PD levels in patients were found to be statistically decreased, and SOD and MDA levels were found to be statistically increased (P < .001). However, any statistical difference and correlation could not be found between the severity and distribution of lesions and the mean levels of enzymes. In addition, we found that each enzyme is correlated with one another. Our findings show that oxidative stress exists in the acne patients. It will be useful to apply at least one antioxidant featured drug along with the combined acne treatment.     

复方壳聚糖消痤乳膏的制备和临床观察

目的制备复方壳聚糖乳膏并用于寻常痤疮的临床观察。方法研制以壳聚糖和苦杏仁酸等为主药的复方消痤乳膏。结果３４例寻常痤疮患者用上述消痤乳膏治疗３周总有效率为９４．１２％。结论消痤乳膏可作为治疗寻常痤疮的一种安全、稳定、有效的制剂。     

Association of TNF-α polymorphisms (−857, −863 and −1031), TNF-α serum level and lipid profile with acne vulgaris

BackgroundAcne is an inflammatory condition principally affected by genetic and dietary factors. Investigation into functional polymorphisms of TNF-α gene and their association with acne vulgaris will be helpful in exploring genetic influence on skin immune mediated inflammatory events. In the present study, we analyzed association of TNF-α gene polymorphisms, its expression levels and lipid profiles in a large cohort of acne patients and controls.MethodsWe used PCR-RFLP to study association of TNF-α polymorphisms at −857C/T, −863C/A and −1031 T/C sites with acne vulgaris. Lipid profiles were measured using enzymatic end-point method. The serum levels of TNF-α and apolipoprotein a were measured using ELISA. NIH, LDlink was used to investigate patterns of linkage disequilibrium across south Asian reference genome (Punjabi from Lahore Pakistan).ResultsWe found that TNF-α −863 polymorphism is strongly associated with acne in overall population as well as in gender and severity based groups of acne patients. Polymorphisms at −863 and −1031 position were in linkage disequilibrium. Importantly, TNF-α serum level was significantly increased in acne patients with severe disease symptoms. Furthermore, levels of total cholesterol (TC) and triglycerides (TG) were significantly increased, whereas high density lipoprotein cholesterol (HDL-C) level was significantly decreased in acne patients. The levels of apolipoprotein a varied widely in studied populations and no significant difference was found in the analyzed groups.ConclusionIn conclusion, we found that TNF-α expression increases in acne patients affected by TNF-α polymorphisms, and that the lipid profile is specifically disrupted in acne patients.     

Therapeutic Agents in Acne Vulgaris: Part II. D-Alpha Amino Benzyl Penicillin,Erythromycin and Sulfadimethoxine

A total of 379 patients with pustular and cystic acne vulgaris were selected for study in three groups. Each group was assigned one of the following medications: benzyl penicillin, erythromycin, sulfadimethoxine, or placebo; these were to be compared with tetracycline, a medication whose effectiveness was previously demonstrated in this type of acne. The study revealed a larger number of favourable responses to tetracycline and erythromycin than to sulfadimethoxine. Sulfadimethoxine, however, produced a greater number of favourable responses than did the benzyl penicillin or the placebo; the last-named had equivalent results.     

Metabolomics and Trace Element Analysis of Camel Tear by GC-MS and ICP-MS

Acne vulgaris is a very common skin disorder affecting human beings. There is a paucity of report on the role of heavy metals—lead (Pb) and cadmium (Cd)—globally, and trace metals—zinc (Zn) and copper (Cd)—particularly in Nigeria in the development/severity of acne vulgaris. This study is aimed to determine the blood levels of some heavy metals—cadmium and lead—and trace metals—zinc and copper—in acne vulgaris sufferers in a Nigerian population. Venous blood samples were collected from a total number of 90 non-obese female subjects consisting of 30 mild, 30 moderate and 30 severe acne vulgaris sufferers for blood Cd, Pb, Cu and Zn determination. They were age-matched with 60 females without acne vulgaris who served as the control subjects. Acne sufferers had significantly higher blood Cd and Pb (P = 0.0143 and P = 0.0001 respectively) and non-significantly different blood levels of Cu and Zn (P = 0.910 and P = 0.2140 respectively) compared to controls. There were significant progressive increases in blood levels of Cd and Pb (P = 0.0330 and P = 0.0001 respectively) and non-significant differences in the mean blood level of Cu and Zn (P = 0.1821 and P = 0.2728 respectively) from mild to moderate and severe acne vulgaris sufferers. Increases in blood Cd and Pb may play critical roles in the pathogenesis/severity of acne vulgaris, while Cu and Zn seem to play less significant roles in the development of this disorder in this environment.     

Treatment of Acne Vulgaris with Tetracyline Hydrochloride: a Double-blind Trial with 51 Patients

Fifty-one patients with acne vulgaris were included in a double-blind trial to assess the therapeutic effect of 250 mg. tetracycline hydrochloride twice daily for three months. The results, assessed clinically and photographically, showed that tetracycline hydrochloride had a statistically significant beneficial effect. Hence, since it is cheap and rarely has side-effects in healthy young adults, its use is suggested, as well as local therapy, in the more severe forms of acne.     

中药面膜联合红蓝光治疗寻常痤疮疗效观察

目的：观察中药面膜联合红蓝光治疗仪治疗寻常痤疮临床疗效及安全性。方法：66例寻常痤疮患者按就诊先后顺序随机分为3组：对照组、面膜组、联合组,治疗4周后进行疗效评估,治疗结束后4周随访复发情况。结果：联合组及面膜组疗效高于对照组（P〈0.05）。结论：中药面膜联合红蓝光治疗仪治疗寻常痤疮疗效好,不良反应少,优于单用疗法,痤疮后期维持治疗同样值得重视。     

ACNE VULGARIS—Evaluation of a Medicated Cleansing Pad

Using the technique of simultaneous, symmetrical paired comparisons, a medicated cleansing pad that can be easily used at work or at school as an adjunctive in the treatment of acne vulgaris was evaluated.The experimental pads were significantly beneficial in reducing skin oiliness and in clinical improvement of the acne. Response to standard acne therapy was faster when the pads were used adjunctively, although the significant results seen initially tended to even out as therapy continued.Use of the medicated pads produced no untoward side effects and were well accepted by patients.     

Inhibition of Propionibacterium acnes lipase activity by the antifungal agent ketoconazole

The common skin disease acne vulgaris is caused by Propionibacterium acnes. A lipase secreted by this microorganism metabolizes sebum and the resulting metabolites evoke inflammation in human skin. The antifungal drug ketoconazole inhibits P. acnes lipase activity. We previously showed that the drug also inhibits the growth of P. acnes. Thus, ketoconazole may serve as an alternative treatment for acne vulgaris, which is important because the number of antibiotic‐resistant P. acnes strains has been increasing.     

Cyproterone acetate treatment of females with hyperandrogenism

Five females with idiopathic hirsutism, ten with adrenogenital syndrome, four with acne vulgaris, and three with Stein-Leventhal syndrome were treated for nine months with large or small doses of cyproterone acetate (100 or 2 mg daily, respectively) in combination with oestrogen. The drug had a good effect on the acne vulgaris and moderated the hirsutism. In the various patient groups the serum testosterone level was decreased to between 58.6% (+/- 28.7% S.E.) and 10.8% (+/- 8.2% S.E.) of the basal value. No essential difference in effectiveness was observed between the large and small doses. Based on study of the side-effects, it is recommended that laboratory liver tests are used for control.     

Physicochemical Properties and Anti-Propionibacterium acnes Activity of Film-Forming Solutions Containing Alpha-Mangostin-Rich Extract

The objective of this study was to study the effect of formulation compositions on physicochemical properties and anti-Propionibacterium acnes activity of film-forming solutions containing alpha-mangostin-rich extract (AM). Film-forming solution bases and film-forming solutions containing AM were prepared by using Eudragit RL PO or Klucel LF or combinations of them as film-forming polymers. Rheological properties, pH values of the solutions, and mechanical properties of the dry films were investigated. An optimized formulation was selected and evaluated for the film surface, in vitro AM release, an anti-P. acnes activity, and potential for being a skin irritant. It was found that mechanical properties of the dry films were affected by total polymer contents, ratios of Klucel LF/Eudragit RL PO, AM, and contents of triethyl citrate. The film-forming solutions containing AM had pH values around 7.0. Their flow curves exhibited Newtonian flow behaviors. The optimized formulation provided films possessing smooth and nonporous surfaces. These films showed greater anti-P. acnes activity than their base films without toxicity to skin fibroblasts. Furthermore, AM released from the film matrix obeyed Higuchi's equation. In conclusion, the film-forming solutions containing AM had potential for treatment of acne vulgaris caused by P. acnes. However, further in vivo study is necessary to determine their efficacy and safety for using in patients suffering from acne vulgaris.     

Vaccination targeting a surface sialidase of P. acnes: implication for new treatment of acne vulgaris

Background

Acne vulgaris afflicts more than fifty million people in the United State and the severity of this disorder is associated with the immune response to Propionibacterium acnes (P. acnes). Systemic therapies for acne target P. acnes using antibiotics, or target the follicle with retinoids such as isotretinoin. The latter systemic treatment is highly effective but also carries a risk of side effects including immune imbalance, hyperlipidemia, and teratogenicity. Despite substantial research into potential new therapies for this common disease, vaccines against acne vulgaris are not yet available.

Methods and Findings

Here we create an acne vaccine targeting a cell wall-anchored sialidase of P. acnes. The importance of sialidase to disease pathogenesis is shown by treatment of a human sebocyte cell line with recombinant sialidase that increased susceptibility to P. acnes cytotoxicity and adhesion. Mice immunized with sialidase elicit a detectable antibody; the anti-sialidase serum effectively neutralized the cytotoxicity of P. acnes in vitro and P. acnes-induced interleukin-8 (IL-8) production in human sebocytes. Furthermore, the sialidase-immunized mice provided protective immunity against P. acnes in vivo as this treatment blocked an increase in ear thickness and release of pro-inflammatory macrophage inflammatory protein (MIP-2) cytokine.

Conclusions

Results indicated that acne vaccines open novel therapeutic avenues for acne vulgaris and other P. acnes-associated diseases.     

Effect of oral contraceptives on sebum excretion rate.

Oral contraceptives containing a high dose of oestrogen reduce the sebum excretion rate (SER) and improve acne vulgaris, but more progestogenic preparations may exacerbate acne. The effect on the SER of several oral contraceptives with varying progestogenic potencies was studied in 81 women. The predominantly progestogenic pills (Eugynon 30, Gynovlar) produced no significant change in SER, whereas the rate in women taking a more oestrogenic pill (Minovlar) was significantly reduced compared with the rate in controls. Progestogens therefore do not exacerbate acne by inducing seborrhoea, but in the doses we studied they nullified the inhibitory effect of oestrogens on the sebaceous glands. Acne-prone women who require an oral contraceptive should be given a predominantly oestrogenic preparation.