Background/Objectives: Antibiotics are commonly used for acne treatment. However, increasing bacterial resistance has prompted interest in natural antimicrobial agents, such as thymol (THY), as alternative therapies. This study investigated the effectiveness of Leciplex cationic nanovesicles encapsulating thymol (LPX-THY) as a promising topical acne management strategy. Methods: Leciplex nanovesicles were assembled using soy phosphatidylcholine (SPC) and cationic surfactants and characterized in terms of particle size, zeta potential, entrapment efficiency, morphology, in vitro release, and ex vivo skin permeation. The optimized formulation was subsequently incorporated into Carbopol/HPMC gel base and evaluated in terms of viscosity, in vitro release, ex vivo skin permeation, in vitro antimicrobial study, and in vivo assessment in a rat model. Results: Optimal THY-LPX nanovesicles made of SPC and Dimethyldidodecylammonium bromide DDAB in a 1:1 molar ratio showed circular outline with particle size, zeta potential, and entrapment efficiency of 187.7 ± 1.78 nm, 36.97 ±0.21 mV, and 60.5 ± 2.3%, respectively. THY-LPX gel demonstrated minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) at a concentration of 156.25 µg·mL[-1] against Staphylococcus aureus, a clear absence of biofilm coating under SEM, and substantial red fluorescence, indicating reduction in viable bacteria under a confocal laser microscope. In vivo study showed enhanced anti-inflammatory effect evidenced by substantial ear skin thickness reduction; 72.7% for THY-LPX gel-treated rats compared to 41.7% and 20% for THY gel and blank LPX gel-treated groups, respectively. Histopathological investigation further confirmed reduced inflammatory response in rats treated with optimized THY-LPX gel. Conclusions: The developed THY-LPX gel serves as a potential topical delivery platform of THY for acne therapy.

Bromoderma is caused by exposure to bromine-containing agents, presenting as exudative plaques, enlarging nodules, necrotic ulcers, and acne-like skin rash. Pseudohyperchloremia, a key finding in some bromoderma patients, is a phenomenon in which the ionic membrane is affected by halogens such as bromine ions (Br[-]) and iodine ions when serum chloride ion (Cl[-]) is measured by the ion-selective membrane electrode (ISE) method. This results in a high value of serum Cl[-] even though the actual level is normal. Here, we report a case of bromoderma that did not show pseudohyperchloremia in a previous hospital. A 43-year-old man came to our hospital with verrucous nodules and erythema on both shins. He had had epilepsy since the age of 3 months and had been treated with potassium bromide. A skin biopsy showed pseudocarcinomatous hyperplasia and dermal infiltration of lymphocytes and neutrophils. His serum Cl[-] level measured in our hospital exceeded the upper threshold. Due to his medication history, clinical and histological appearances, and pseudohyperchloremia, the case was diagnosed with bromoderma. Potassium bromide was discontinued the day after the patient's visit to our hospital. All verrucous nodules disappeared 25 weeks after the first visit. It has been reported that there is no clear correlation between serum levels of Cl[-] and Br[-] and that the degree of pseudohyperchloremia is dependent on the ion exchange membrane used. Therefore, we have to be aware that bromoderma cannot be ruled out even if pseudohyperchloremia is not seen. Clearance of skin rashes after discontinuation of bromine is essential if elevation of serum Br[-] levels is not confirmed. In retrospect, in our case, the serum Cl[-] level was measured by electrochemiluminescence immunoassay in the previous hospital, but was measured by the ISE method in our hospital. It is important to check serum Cl[-] levels and the method of measurement when seeing patients with suspected bromoderma.

Cutibacterium acnes (C. acnes) is the main causative agent of acne vulgaris. The study aims to evaluate the antimicrobial activity of a natural product, Arctostaphylos uva-ursi leaf extract, against C. acnes. Preliminary chemical-physical characterization of the extract was carried out by means of FT-IR, TGA and XPS analyses. Skin permeation kinetics of the extract conveyed by a toning lotion was studied in vitro by Franz diffusion cell, monitoring the permeated arbutin (as the target component of the extract) and the total phenols by HPLC and UV-visible spectrophotometry, respectively. Antimicrobial activity and time-killing assays were performed to evaluate the effects of Arctostaphylos uva-ursi leaf extract against planktonic C. acnes. The influence of different Arctostaphylos uva-ursi leaf extract concentrations on the biofilm biomass inhibition and degradation was evaluated by the crystal violet (CV) method. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test was used to determine the viability of immortalized human keratinocytes (HaCaT) after exposure to Arctostaphylos uva-ursi leaf extract for 24 and 48 h. Levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α were quantified after HaCaT cells cotreatment with Arctostaphylos uva-ursi leaf extract and heat-killed C. acnes. The minimum inhibitory concentration (MIC) which exerted a bacteriostatic action on 90% of planktonic C. acnes (MIC90) was 0.6 mg/mL. Furthermore, MIC and sub-MIC concentrations influenced the biofilm formation phases, recording a percentage of inhibition that exceeded 50 and 40% at 0.6 and 0.3 mg/mL. Arctostaphylos uva-ursi leaf extract disrupted biofilm biomass of 57 and 45% at the same concentrations mentioned above. Active Arctostaphylos uva-ursi leaf extract doses did not affect the viability of HaCaT cells. On the other hand, at 1.25 and 0.6 mg/mL, complete inhibition of the secretion of pro-inflammatory cytokines was recorded. Taken together, these results indicate that Arctostaphylos uva-ursi leaf extract could represent a natural product to counter the virulence of C. acnes, representing a new alternative therapeutic option for the treatment of acne vulgaris.

The main objective of this study was to develop, characterize and evaluate the potential use of dapsone-loaded nanostructured lipid carriers (NLCs) as a topical treatment for acne. Differently charged NLC formulations were successfully prepared using an emulsification/sonication method. The particle sizes ranged from 106.2 ± 5.6 nm to 151.3 ± 7.4 nm, and the NLCs possessed the predicted surface charges, depending on the emulsifier used (Tween 80, Transcutol P, or cetyltrimethylammonium bromide). The entrapment efficiencies ranged from 76.5 ± 3.8% to 91.1 ± 3.9%. Selected formulations were assessed for possible interactions, in vitro release, ex vivo skin permeation, pharmacological efficacy and safety compared with a hydroalcoholic solution. Dapsone was embedded in the lipid matrix of NLCs and behaved as controlled release system with a good occlusive effect. Dapsone-loaded cationic NLC formulation enhanced the skin permeation of dapsone, increase the amount of dapsone retained in the skin in controlled manner, and improved the anti-rosacea activity. Based on these encouraging results, cationic NLC represents a promising carrier for the safe topical delivery of dapsone.

The antibacterial activity of gold nanorod (GNR) suspensions of different surface functionalities was investigated against standard strains of Staphylococcus aureus and Propionibacterium acnes, taking into consideration two commonly "overlooked" factors: the colloidal stability of GNR suspensions upon mixing with bacterial growth media and the possible contribution of "impurities/molecules" in GNR suspensions to the observed antibacterial activity. The results demonstrated that cationic polyallylamine hydrochloride (PAH)-GNR were severely aggregated when exposed to bacterial growth media compared to other GNR suspensions. In addition, the free cetyltrimethylammonium bromide (CTAB) present in GNR suspensions is most likely the origin of the observed antibacterial activity. However, the antibacterial activity of GNR themselves could not be excluded. Probing these two critical control studies prevents misinterpretations and artifacts of the antibacterial activity of nanoparticles. Unfortunately, these practices are usually ignored in the published studies and may explain the significant conflicting results. In addition, this study indicates that GNR could be a promising candidate for the treatment of skin follicular diseases such as acne vulgaris.

Acneiform eruptions are dermatoses that resemble true acne. They are almost always drug induced (Indian J Dermatol Venereol Leprol 2009;75:255). Unlike true acne, acneiform eruptions have sudden onset, widespread involvement, occur in unusual locations, occur beyond typical acne age, consist of monomorphous lesions, and clear after the offending drug has been discontinued. The most common culprits are corticosteroids, iodides, bromides, anticonvulsants, Isoniazid (Acta Derm Venereol Suppl (Stockh) 1975;74:119), and immunosuppressants. We present a case of immunosuppressant-induced acneiform eruption of the breast in a 36-year-old female renal transplant recipient. To our knowledge, this is the first description of this condition appearing in the breast. Both the mammographic and ultrasound features will be described.

Honokiol and magnolol, two major phenolic constituents of Magnolia sp., have been known to exhibit antibacterial activities. However, until now, their antibacterial activity against Propionibacterium sp. has not been reported. To this end, the antibacterial activities of honokiol and magnolol were detected using the disk diffusion method and a two-fold serial dilution assay. Honokiol and magnolol showed strong antibacterial activities against both Propionibacterium acnes and Propionibacterium granulosum, which are acne-causing bacteria. The minimum inhibitory concentrations (MIC) of honokiol and magnolol was 3-4 microg/ml (11.3-15 microM) and 9 microg/ml (33.8 microM), respectively. In addition, the killing curve analysis showed that magnolol and honokiol killed P. acnes rapidly, with 10(5) organisms/ml eliminated within 10 min of treatment with either 45 microg (169.2 microM) of magnolol or 20 microg (75.2 microM) of honokiol per ml. The cytotoxic effect of honokiol and magnolol was determined by a colorimetric (3-(4,5-dimetyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay using two animal cell lines, human normal fibroblasts and HaCaT. In this experiment, magnolol exhibited lower cytotoxic effects than honokiol at the same concentration, but they showed similar cytotoxicity when triclosan was employed as an acne-mitigating agent. In addition, they reduced secretion of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) induced by P. acnes in THP-1 cells indicating the anti-inflammatory effects of them. When applied topically, neither phenolic compound induced any adverse reactions in a human skin primary irritation test. Therefore, based on these results, we suggest the possibility that magnolol and honokiol may be considered as attractive acne-mitigating candidates for topical application.

Novel 3,4-dihydro-naphthalene-2-carboxylic acids were synthesized and evaluated for 5alpha reductase inhibitory activity. This enzyme exists in two isoforms and is a pharmacological target for the treatment of benign prostatic hyperplasia, male pattern baldness and acne. In the present study non-steroidal compounds capable of mimicking the transition state of the steroidal substrates were prepared. The synthetic strategy for the preparation of compounds 1-6 consisted of triflation followed by subsequent Heck-type carboxylation or methoxy carbonylation for 6-phenyl-3,4-dihydronaphthalen-2(1H)-one 1c. A Negishi-type coupling reaction between 6-(trifluoro-methanesulfonyloxy)-3,4-dihydro-naphthalene-2-carboxylic acid methyl ester 7b and various aryl bromides led, after further transformations, to 6-substituted 3,4-dihydro-naphthalene-2-carboxylic acids 7-15. In a similar way the corresponding naphthalene-2-carboxylic acids 16 and 17 were obtained. The DU 145 cell line and prostate homogenates served as enzyme sources for the human type 1 and type 2 isozymes, whereas ventral prostate was employed to evaluate rat isozyme inhibitory potency. The most active inhibitors identified in this study were 6-[4-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (3) (IC50 = 0.09 microM, rat type 1), 6-[3-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (13) (IC50 = 0.75 microM, human type 2; IC50 = 0.81 microM, human type 1) and 6-[4-(N,N-diisopropylamino-carbonyl)phenyl]naphthalene-2-carboxylic acid (16) (IC50 = 0.2 microM, human type 2). The latter compound was shown to deactivate the enzyme in an uncompetitive manner (Ki = 90 nM; Km, Testosterone = 0.8-1.0 microM) similar to the steroidal inhibitor Epristeride. Select inhibitors (13 and 16) were tested in vivo using testosterone propionate-treated, juvenile, orchiectomized SD-rats. None of the compounds was active at a dose of 25 mg/kg. This result might in part be ascribed to the relatively poor in vitro rat isozyme inhibitory potency.

A set of new water-soluble organic peroxides has been synthesized and evaluated for in vitro antibacterial activity as part of an effort to develop new antibacterial agents for the treatment of acne vulgaris. The water solubility of these new dialkyl peroxides and peroxyesters was achieved by incorporating either a quaternary ammonium group or a polyethylene glycol moiety. These peroxides are effective against both gram-positive and gram-negative bacteria and have a prolonged activity compared to that of benzoyl peroxide and other peroxide-type antiseptic agents. Among them 4-[[(tert-butylperoxy)carbonyl]benzyl]triethylammonium chloride and [10-(tert-butylperoxy)decyl]trimethylammonium bromide have the broadest antimicrobial spectrums. We have shown that the oxidizing properties of the dioxy group of these compounds are responsible for their antibacterial activities.

Thirty-six children with epilepsy resistant to conventional treatment were treated with bromides in addition to the current therapy. Six out of 19 cases with prevailingly or exclusively generalized tonic-clonic seizures became seizure-free and in 9 cases a reduction in seizure frequency of more than 50% was achieved. Freedom from seizures could not be obtained in 13 cases, who had frequent minor seizures in addition to generalized tonic-clonic seizures. In some, minor seizures were even activated. Tonic and focal seizures showed no response. Side effects were observed in one-third of the cases (acne, loss of appetite, loss of weight, fatigue) but in no case they did become intolerable. Fifty to 80 mg potassium bromide per kg body weight seems to be an effective daily dose range. There is a preferential indication of bromides for patients suffering from early onset epilepsy with generalized tonic-clonic seizures and/or alternating hemi-grand mal, for whom other treatment is ineffective. This disorder is characterized by a high familial incidence of epileptic seizures, onset between 6 months and 3 years of age, normal development until the onset of seizures, generalized tonic-clonic seizures and often alternating hemi-grand mal, seizure precipitation by fever, and occasional combination with or transition to myoclonic-astatic and/or myoclonic seizures. EEG is often normal or shows slight slowing in the initial phase; later it shows theta rhythms and generalized spikes and waves. Especially, if the onset is during the first year of life, the course of the epilepsy is often unfavourable.

A definition and classification of acneiform dermatoses is presented to distinguish these diseases from true acne. True acne is a follicular eruption which begins with a comedo, sometimes evolving into various inflammatory lesions. Members of true acne are acne vulgaris with its varieties, acne venenata, and comedonal acne due to physical agencies. Acneiform reactions begin with an inflammatory lesion, usually a papule or pustule. Comedones are uncommon and may follow pustules. Acneiform eruptions are almost always drug-induced, the commonest agents being corticosteroids and ACTH, iodides, bromides, anti-convulsive drugs, and INH. Topical treatment with VAA is indicated in every variety of true acne; VAA is helpful in acneiform dermatoses with secondary comedo formation, as for instance in steroid acne. Very satisfying results can be achieve with this regimen.