Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge

ABSTRACT In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge.

In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

The immunomodulatory potential of phage therapy to treat acne: a review on bacterial lysis and immunomodulation.

Background: Characterized by an inflammatory pathogenesis, acne is the most common skin disorder worldwide. Altered sebum production, abnormal proliferation of keratinocytes, and microbiota dysbiosis represented by disbalance in Cutibacterium acnes population structure, have a synergic effect on inflammation of acne-compromised skin. Although the role of C. acnes as a single factor in acne development is still under debate, it is known that skin and skin-resident immune cells recognize this bacterium and produce inflammatory markers as a result. Control of the inflammatory response is frequently the target for acne treatment, using diverse chemical or physical agents including antibiotics. However, some of these treatments have side effects that compromise patient adherence and drug safety and in the case of antibiotics, it has been reported C. acnes resistance to these molecules. Phage therapy is an alternative to treat antibiotic-resistant bacterial strains and have been recently proposed as an immunomodulatory therapy. Here, we explore this perspective about phage therapy for acne, considering the potential immunomodulatory role of phages. Methodology: Literature review was performed using four different databases (Europe PubMed Central-ePMC, Google Scholar, PubMed, and ScienceDirect). Articles were ordered and selected according to their year of publication, number of citations, and quartile of the publishing journal. Results: The use of lytic bacteriophages to control bacterial infections has proven its promising results, and anti-inflammatory effects have been found for some bacteriophages and phage therapy. These effects can be related to bacterial elimination or direct interaction with immune cells that result in the regulation of pro-inflammatory cytokines. Studies on C. acnes bacteriophages have investigated their lytic activity, genomic structure, and stability on different matrices. However, studies exploring the potential of immunomodulation of these bacteriophages are still scarce. Conclusions: C. acnes bacteriophages, as well as other phages, may have direct immunomodulatory effects that are yet to be fully elucidated. To our knowledge, to the date that this review was written, there are only two studies that investigate anti-inflammatory properties for C. acnes bacteriophages. In those studies, it has been evidenced reduction of pro-inflammatory response to C. acnes inoculation in mice after bacteriophage application. Nevertheless, these studies were conducted in mice, and the interaction with the immune response was not described. Phage therapy to treat acne can be a suitable therapeutic alternative to C. acnes control, which in turn can aid to restore the skin's balance of microbiota. By controlling C. acnes colonization, C. acnes bacteriophages can reduce inflammatory reactions triggered by this bacterium.

Evaluation of tea tree oil physicochemical features and its antimicrobial activity against Cutibacterium acnes (Propionibacterium acnes) ATCC 6919 / [Evaluación de las características fisicoquímicas y de la actividad antimicrobiana del aceite del árbol de té contra Cutibacterium acnes (Propionibacterium acnes) ATCC 6919].

Introduction: Tea tree oil is an essential oil recognized for its antimicrobial properties. Objective: To evaluate the composition, features, and antimicrobial effect at 2% v/v, and its minimal inhibitory concentration (MIC) against Cutibacterium acnes (Propionibacterium acnes). Materials and methods: Three different batches of tea tree oil were evaluated. We characterized its chemotype by gas chromatography and its 2% v/v antimicrobial activity against C. acnes by agar diffusion assay (guide M11-A8 CLSI). Results: The three batches of oil had the chemotypes required by the ISO 4730 standard, which indicates that it is a high-quality product. Additionally, they had 30% to 40% of terpinen-4-ol, a compound that favors its antimicrobial activity. Antimicrobial activity against C. acnes for all batches had a concentration-dependent effect with microbial growth inhibitory activity in all assays at 2% v/v. The MIC obtained against C. acnes for all batches was 0.25% v/v. The antimicrobial activity of tea tree oil against this microorganism has been previously reported with a MIC between 0.05% and 1.25% v/v, a range that covers the one obtained in this study. Conclusion: These results show the high quality of the oil and its capacity as an antibacterial agent against C. acnes. New studies should be conducted to confirm its activity and that of its components in isolates of the microorganism from patients with acne vulgaris.

Introducción. El aceite del árbol de té es un aceite esencial reconocido por sus propiedades antimicrobianas. Objetivos. Evaluar la composición, características y efecto antimicrobiano del aceite al 2 % del árbol de té y su concentración inhibitoria mínima (CIM) contra Cutibacterium acnes (Propionibacterium acnes). Materiales y métodos. Se evaluó el quimiotipo en tres lotes diferentes de este aceite mediante cromatografía de gases, así como su actividad antimicrobiana en concentración al 2 % v/v y la CIM contra C. acnes mediante ensayo de difusión en agar (guía M11-A8 CLSI). Resultados. Los lotes evaluados presentaron los quimiotipos ajustados a la norma ISO 4730, lo que indicó la alta calidad del producto. Los lotes contenían de 30 a 40 % de terpinen-4-ol, compuesto que favorece la actividad antimicrobiana, la cual presentó en todos los lotes un efecto dependiente de la concentración contra C. acnes, con una inhibición del crecimiento microbiano en concentración al 2 % v/v en todas las pruebas. La concentración inhibitoria mínima fue de 0,25 % v/v. La actividad antimicrobiana del aceite del árbol de té contra este microorganismo ya ha sido reportada con una concentración inhibitoria mínima entre 0,05 y 1,25 % v/v, rango que cobija la obtenida en este estudio. Conclusiones. Los resultados evidenciaron la gran calidad de este producto y su capacidad como agente antibacteriano contra C. acnes. Se deben hacer estudios con otros aislamientos del microorganismo provenientes de pacientes con acné vulgar para confirmar su actividad general y la de cada uno de sus componentes.

Evaluación de las características fisicoquímicas y de la actividad antimicrobiana del aceite del árbol de té contra Cutibacterium acnes (Propionibacterium acnes) ATCC 6919 / Evaluation of tea tree oil physicochemical features and its antimicrobial activity against Cutibacterium acnes (Propionibacterium acnes) ATCC 6919

Resumen: Introducción. El aceite del árbol de té es un aceite esencial reconocido por sus propiedades antimicrobianas. Objetivos. Evaluar la composición, características y efecto antimicrobiano del aceite al 2 % del árbol de té y su concentración inhibitoria mínima (CIM) contra Cutibacterium acnes (Propionibacterium acnes). Materiales y métodos. Se evaluó el quimiotipo en tres lotes diferentes de este aceite mediante cromatografía de gases, así como su actividad antimicrobiana en concentración al 2 % v/v y la CIM contra C. acnes mediante ensayo de difusión en agar (guía M11-A8 CLSI). Resultados. Los lotes evaluados presentaron los quimiotipos ajustados a la norma ISO 4730, lo que indicó la alta calidad del producto. Los lotes contenían de 30 a 40 % de terpinen-4-ol, compuesto que favorece la actividad antimicrobiana, la cual presentó en todos los lotes un efecto dependiente de la concentración contra C. acnes, con una inhibición del crecimiento microbiano en concentración al 2 % v/v en todas las pruebas. La concentración inhibitoria mínima fue de 0,25 % v/v. La actividad antimicrobiana del aceite del árbol de té contra este microorganismo ya ha sido reportada con una concentración inhibitoria mínima entre 0,05 y 1,25 % v/v, rango que cobija la obtenida en este estudio. Conclusiones. Los resultados evidenciaron la gran calidad de este producto y su capacidad como agente antibacteriano contra C. acnes. Se deben hacer estudios con otros aislamientos del microorganismo provenientes de pacientes con acné vulgar para confirmar su actividad general y la de cada uno de sus componentes.

Abstract: Introduction: Tea tree oil is an essential oil recognized for its antimicrobial properties. Objective: To evaluate the composition, features, and antimicrobial effect at 2% v/v, and its minimal inhibitory concentration (MIC) against Cutibacterium acnes (Propionibacterium acnes). Materials and methods: Three different batches of tea tree oil were evaluated. We characterized its chemotype by gas chromatography and its 2% v/v antimicrobial activity against C. acnes by agar diffusion assay (guide M11-A8 CLSI). Results: The three batches of oil had the chemotypes required by the ISO 4730 standard, which indicates that it is a high-quality product. Additionally, they had 30% to 40% of terpinen-4-ol, a compound that favors its antimicrobial activity. Antimicrobial activity against C. acnes for all batches had a concentration-dependent effect with microbial growth inhibitory activity in all assays at 2% v/v. The MIC obtained against C. acnes for all batches was 0.25% v/v. The antimicrobial activity of tea tree oil against this microorganism has been previously reported with a MIC between 0.05% and 1.25% v/v, a range that covers the one obtained in this study. Conclusion: These results show the high quality of the oil and its capacity as an antibacterial agent against C. acnes. New studies should be conducted to confirm its activity and that of its components in isolates of the microorganism from patients with acne vulgaris.

Protective Cellular Immune Response Induction for Cutaneous Leishmaniasis by a New Immunochemotherapy Schedule.

The palladacycle complex DPPE 1.2 was previously shown to inhibit Leishmania (Leishmania) amazonensis infection in vitro and in vivo. The present study aimed to evaluate the effect of DPPE 1.2 associated with a recombinant cysteine proteinase, rLdccys1, and the adjuvant Propionibacterium acnes on L. (L.) amazonensis infection in two mouse strains, BALB/c, and C57BL/6. Treatment with this association potentiated the leishmanicidal effect of DPPE 1.2 resulting in a reduction of parasite load in both strains of mice which was higher compared to that found in groups treated with either DPPE 1.2 alone or associated with P. acnes or rLdccys1. The reduction of parasite load in both mice strains was followed by immunomodulation mediated by an increase of memory CD4+ and CD8+ T lymphocytes, IFN-γ levels and reduction of active TGF-ß in treated animals. No infection relapse was observed 1 month after the end of treatment in mice which received DPPE 1.2 associated with rLdccys1 or rLdccys1 plus P. acnes in comparison to that exhibited by animals treated with DPPE 1.2 alone. Evaluation of serum levels of AST, ALT, urea, and creatinine showed no alterations among treated groups, indicating that this treatment schedule did not induce hepato or nephrotoxicity. These data indicate the potential use of this association as a therapeutic alternative for cutaneous leishmaniasis caused by L. (L) amazonensis.

A Therapeutic Oral Vaccine Candidate against Propionibacterium acnes: Preparation and Immunological Evaluation of Nanoparticles Encapsulated Sialidase-CAMP Fusion Protein

Abstract Acne Vulgaris is a common skin disease caused by Propionibacterium acnes, an anaerobic microbiota of human skin that plays a vital role in the pathology of acne. The aim of this study was to prepare nanoparticles containing an acne recombinant protein and determine its ability as an oral acne vaccine in mice. The recombinant Sialidase-CAMP gene was expressed and purified in a prokaryotic host. The chitosan nanoparticles containing the recombinant protein were prepared, encapsulated, and administered by both oral and subcutaneous routes to Balb/c mice. Sera IgA and IgG and stool IgA titers were measured by ELISA, and the immunized mice were challenged against P. acnes. A 65 kDa recombinant protein was confirmed by SDS-PAGE and western blot. The size and zeta potential of nanoparticles were 80 nm and +18 mV, respectively. After oral immunization, the serum IgG and IgA titers were 1:3200 and 1:16, respectively, and the stool IgA titer was 1:8. In the subcutaneous route, the serum IgG titer was 1:51200. Immunized mice showed no inflammation in the ear of challenged mice. It is the first study that examines a chitosan-nanoparticulated acne fusion protein as an applicable acne vaccine candidate with appropriate immunogenicity potential. Further studies are required to validate the clinical usefulness of this vaccine candidate.

Evidências do efeito da terapia fotodinâmica sobre a Propionibacterium acnes / Evidence of the effect of photodynamic therapy on Propionibacterium acnes

Introdução: A Propionibacterium acnes é uma bactéria causadora da acne. Devido aos efeitos colaterais ou à falta de resposta ao tratamento da acne, foi proposta a terapia fotodinâmica como um tratamento alternativo para a acne. Objetivo: O objetivo foi evidenciar a ação fotodinâmica do LED vermelho 660 nm e do fotossensibilizador azul de metileno sobre Propionibacterium acnes in vitro. Métodos: Os ensaios foram constituídos por quatro grupos: 1. controle (sem aplicação de luz e sem fotossensibilizador); 2. com aplicação de luz; 3. com fotossensibilizador e sem aplicação de luz; 4. com fotossensibilizador e com aplicação de luz. Os ensaios foram submetidos a aplicação de luz por 4 ciclos de 5 minutos com intervalos de 3 minutos. Resultados: Houve redução estatisticamente significante (p<0,05) nas médias dos grupos 1, 2 e 4, ainda que o grupo 3 não tenha apresentado significância estatística, mas houve redução detectada nas médias. Conclusão: A ação fotodinâmica é eficiente para a destruição do material biológico por irradiação a 660nm atribuída ao processo de fotossensibilização pela presença do fotossensibilizador.(AU)

Introduction: Propionibacterium acnes is a bacterium that causes acne. Due to the side effects or the lack of response to acne treatment, photodynamic therapy was proposed as an alternative treatment for acne. Objective: To demonstrate the photodynamic action of the 660 nm red LED and the methylene blue photosensitizer on Propionibacterium acnes in vitro. Methods: Four groups were studied: 1. control (without light application and without photosensitizer); 2. with light application; 3. with photosensitizer and without light application; 4. with photosensitizer and light application. The assays were subjected to light application for 4 cycles of 5 minutes at 3 minute intervals. Results: There was a statistically significant reduction (p <0.05) in the means of groups 1, 2 and 4, although group 3 did not present statistical significance, but there was a reduction detected in the means. Conclusion: The photodynamic action is efficient for the destruction of the biological material by irradiation at 660nm attributed to the process of photosensitization by the presence of the photosensitizer.(AU)

Propionibacterium acnes Enhances the Immunogenicity of HIVBr18 Human Immunodeficiency Virus-1 Vaccine.

Immunization of BALB/c mice with HIVBr18, a DNA vaccine containing 18 CD4+ T cell epitopes from human immunodeficiency virus (HIV), induced specific CD4+ and CD8+ T cell responses in a broad, polyfunctional and persistent manner. With the aim of increasing the immunogenicity of this vaccine, the effect of Propionibacterium acnes as an adjuvant was evaluated. The adjuvant effects of this bacterium have been extensively demonstrated in both experimental and clinical settings. Herein, administration of two doses of HIVBr18, in the presence of P. acnes, increased the proliferation of HIV-1-specific CD4+ and CD8+ T lymphocytes, the polyfunctional profile of CD4+ T cells, the production of IFN-γ, and the number of recognized vaccine-encoded peptides. One of the bacterial components responsible for most of the adjuvant effects observed was a soluble polysaccharide extracted from the P. acnes cell wall. Furthermore, within 10 weeks after immunization, the proliferation of specific T cells and production of IFN-γ were maintained when the whole bacterium was administered, demonstrating a greater effect on the longevity of the immune response by P. acnes. Even with fewer immunization doses, P. acnes was found to be a potent adjuvant capable of potentiating the effects of the HIVBr18 vaccine. Therefore, P. acnes may be a potential adjuvant to aid this vaccine in inducing immunity or for therapeutic use.

Assessment of Chitosan-Based Hydrogel and Photodynamic Inactivation against Propionibacterium acnes.

Chitosan (CH) is a biopolymer that exhibits a number of interesting properties such as anti-inflammatory and antibacterial activity and is also a promising platform for the incorporation of photosensitizing agents. This study aimed to evaluate the efficacy of antimicrobial activity of chitosan hydrogel formulation alone and in combination with the methylene blue (MB) associated with antimicrobial photodynamic therapy (aPDT) against planktonic and biofilm phase of Propionibacterium acnes. Suspensions were sensitized with 12.5, 25.0, 37.5, 50.0 µg/mL of MB for 10 min and biofilms to 75, 100 and 150 µg/mL for 30 min then exposed to red light (660 nm) at 90 J/cm² and 150 J/cm² respectively. After treatments, survival fractions were calculated by counting the number of colony-forming units. The lethal effect of aPDT associated with CH hydrogel in planktonic phase was achieved with 12.5 µg/mL MB and 1.9 log10 biofilm reduction using 75 µg/mL MB. Rheological studies showed that formulations exhibited pseudoplastic non-Newtonian behavior without thixotropy. Bioadhesion test evidenced that the formulations are highly adhesive to skin and the incorporation of MB did not influence the bioadhesive force of the formulations.

Improvement of Mesenchymal Stem Cell Immunomodulatory Properties by Heat-Killed Propionibacterium acnes via TLR2.

Mesenchymal stem cells (MSCs) are an essential tool for regenerative medicine, which aims to develop new technologies to improve their effects to obtain useful transplantation results. MSC immunomodulatory role has been just demonstrated; however, how they react when they are stimulated by an adjuvant is poorly understood. Our group showed the adjuvant effect of killed Propionibacterium acnes (P. acnes) on hematopoietic stem cells. As these cells share the same MSCs bone marrow (BM) site and interact with each other, here we evaluated the P. acnes and its soluble polysaccharide (PS) effect on MSCs and their immunomodulatory role in a murine model of traumatic brain injury (TBI). The bacteria increased the absolute number of MSCs, including MSC subpopulations, and maintained MSC plasticity. P. acnes and PS enhanced MSC proliferation and improved their immunomodulatory effect. P. acnes-MSC and PS-MSC transplantation increased anti-inflammatory cytokine expression and diminished pro-inflammatory cytokine expression after injury. This effect seemed to be mediated via TLR2 since P. acnes-KOTLR2-MSC transplantation decreased TGF-ß and IL-10 expression. Increasing in neural stem cells and neuroblasts after PS-MSC transplantation was also observed. The adjuvant effect of P. acnes is an alternative means of expanding MSCs and important to identify their subpopulations to know better their role under exogenous stimuli including inflammation resolution in an experimental model.

Susceptibility of Enterococcus faecalis and Propionibacterium acnes to antimicrobial photodynamic therapy.

Bacterial resistance to available antibiotics nowadays is a global threat leading researchers around the world to study new treatment modalities for infections. Antimicrobial photodynamic therapy (aPDT) has been considered an effective and promising therapeutic alternative in this scenario. Briefly, this therapy is based on the activation of a non-toxic photosensitizing agent, known as photosensitizer (PS), by light at a specific wavelength generating cytotoxic singlet oxygen and free radicals. Virtually all studies related to aPDT involve a huge screening to identify ideal PS concentration and light dose combinations, a laborious and time-consuming process that is hardly disclosed in the literature. Herein, we describe an antimicrobial Photodynamic Therapy (aPDT) study against Enterococcus faecalis and Propionibacterium acnes employing methylene blue, chlorin-e6 or curcumin as PS. Similarities and discrepancies between the two bacterial species were pointed out in an attempt to speed up and facilitate futures studies against those clinical relevant strains. Susceptibility tests were performed by the broth microdilution method. Our results demonstrate that aPDT mediated by the three above-mentioned PS was effective in eliminating both gram-positive bacteria, although P. acnes showed remarkably higher susceptibility to aPDT when compared to E. faecalis. PS uptake assays revealed that P. acnes is 80 times more efficient than E. faecalis in internalizing all three PS molecules. Our results evidence that the cell wall structure is not a limiting feature when predicting bacterial susceptibility to aPDT treatment.

Subclinical Propionibacterium acnes infection estimation in the intervertebral disc (SPInE-ID): protocol for a prospective cohort.

INTRODUCTION: Low back pain and vertebral endplate abnormalities are common conditions within the population. Subclinical infection caused by indolent pathogens can potentially lead to these findings, with differentiation between them notably challenging from a clinical perspective. Progressive infection of the intervertebral disc has been extensively associated with increasing low back pain, with Propionibacterium acnes specifically implicated with in relation to sciatica. The main purpose of this study is to identify if the presence of an infective pathogen within the intervertebral disc is primary or is a result of intraoperative contamination, and whether this correlates to low back pain. METHODS AND ANALYSIS: An open prospective cohort study will be performed. Subjects included within the study will be between the ages of 18 and 65 years and have a diagnosis of lumbar disc herniation requiring open decompression surgery. Excised herniated disc fragments, muscle and ligamentum flavum samples will be collected during surgery and sent to microbiology for tissue culture and pathogen identification. Score questionnaires for pain, functionality and quality of life will be given preoperatively and at 1, 3, 6 and 12 months postoperatively. A MRI will be performed 12 months after surgery for analysis of Modic changes and baseline comparison. The primary endpoint is the rate of disc infection in patients with symptomatic degenerative disc disease. The secondary endpoints will be performance scores, Modic incidence and volume. ETHICS AND DISSEMINATION: This study was approved by our Institutional Review Board and was only initiated after it (CAAE 65102617.2.0000.0071). Patients agreeing to participate will sign an informed consent form before entering the study. Results will be published in a peer reviewed medical journal irrespective of study findings. If shown to be the case, this would have profound effects on the way physicians treat chronic low back pain, even impacting health costs. TRIALS REGISTRATION NUMBER: NCT0315876; Pre-results.

Lâmpada de Wood na dermatologia: aplicações na prática diária / Wood's lamp in dermatology: applications in the daily practice

A prática clínica do dermatologista baseia-se na análise das lesões cutâneas. Essa análise é feita essencialmente pela observação clínica, e atualmente complementada com exames como a dermatoscopia e a microscopia confocal. Apesar de seu baixo custo, a lâmpada de Wood tem sido cada vez menos utilizada como método diagnóstico auxiliar. Apresentamos diversos casos de utilização da lâmpada de Wood sendo de grande auxílio ao dermatologista. Esperamos assim incentivar o uso desse aparelho na prática diária.

The dermatologist's clinical practice is based on the analysis of cutaneous lesions that is carried out mainly by clinical observation, and currently supplemented with tests such as dermoscopy and confocal microscopy. Despite its low cost, the Wood's lamp has been decreasingly used as an auxiliary diagnostic method. The authors of the present study describe several cases of use of the Wood's lamp where it provided valuable assistance to the dermatologist, aiming at encouraging the use of this device in the daily practice.

Photodynamic action of the red laser on Propionibacterium acnes

Abstract: Background: Photodynamic therapy is a therapeutic modality that has consolidated its activity in the photooxidation of organic matter, which arises from the activity of reactive oxygen species. Objective: To evaluate the effect of red laser 660nm with the photosensitizer methylene blue on Propionibacterium acnes in vitro. Method: The experimental design was distributed into four groups (1 - control group without the application of light and without photosensitizer, 2 - application of light, 3 - methylene blue without light, and 4 - methylene blue with light). Tests were subjected to red laser irradiation 660nm by four cycles of 5 minutes at 3-minute intervals. Results: It was evidenced the prominence of the fourth cycle (20 minutes) groups 2, 3 and 4. Study limitations: Despite the favorable results, the laser irradiation time photosensitizer associated with methylene blue were not sufficient to to completely inhibit the proliferation of bacteria. Conclusion: Further studies in vitro are recommended to enable the clinical application of this photosensitizer in photodynamic therapy.

Effect of Propionibacterium acnes (PA) injection on intervertebral disc degeneration in a rat model: Does it mimic modic changes?

INTRODUCTION: Multiple reports of bacterial isolates in human disc tissue have suggested a role of low-grade infection on intervertebral disc degeneration and modic changes (MC) generation. Animal models have been extensively used to study IDD; however, until recently, no consideration had been given to eventual infectious processes. To reproduce the phenomena by inoculating an infecting agent would support the infectious hypothesis. Therefore, we studied the effect of Propionibacterium acnes (PA) inoculation on rat-tails and determined whether it would produce MCs on the adjacent endplates. HYPOTHESIS: Disc infection with PA would accelerate IDD compared with the standard model and would also lead to MCs on the adjacent endplates. METHODS: Twelve Sprague-Dawley rats were randomized to receive a needle puncture in a caudal tail disc with either saline (control) or an inoculum of 5×107 CFU of strain 1a PA. Twelve weeks later, the rats were euthanized and the tails were analyzed. The main assessment criteria were obtained from the post-mortem MRI: T2 values of punctured discs and adjacent endplates, as well as disc volumes. A histological grading score for IDD was also used, measuring the morphology and cellularity of the nucleus and annulus, as well as endplate disruption. RESULTS: The median T2 value and disc volume were smaller in PA-punctured discs [T2 value: 30ms (23-44) vs. 61ms (38-132), respectively, P=0.01; 0.01mm3 (0.01-0.05) vs. 0.5mm3 (0.01-5.35), respectively; P=0.049]. There was no change in the adjacent endplates. There was no significant difference in histological grading between the test and control [13 (10-14) vs. 10.5 (6-13); P=0.05]. DISCUSSION: Inoculation of caudal discs with PA generated increased degeneration; however, no MCs were observed on the adjacent endplates. A better understanding of low-grade disc infections is still needed. LEVEL OF EVIDENCE: V (animal study).

Treatment of Leishmania (Leishmania) Amazonensis-Infected Mice with a Combination of a Palladacycle Complex and Heat-Killed Propionibacterium acnes Triggers Protective Cellular Immune Responses.

Palladacycle complex DPPE 1.2 was previously reported to inhibit the in vitro and in vivo infection by Leishmania (Leishmania) amazonensis. The aim of the present study was to compare the effect of DPPE 1.2, in association with heat-killed Propionibacterium acnes, on L. (L.) amazonensis infection in two mouse strains, BALB/c and C57BL/6, and to evaluate the immune responses of the treated animals. Foot lesions of L. (L.) amazonensis-infected mice were injected with DPPE 1.2 alone, or associated with P. acnes as an adjuvant. Analysis of T-cell populations in the treated mice and in untreated controls was performed by FACS. Detection of IFN-γ-secreting lymphocytes was carried out by an ELISPOT assay and active TGF-ß was measured by means of a double-sandwich ELISA test. The treatment with DPPE 1.2 resulted in a significant reduction of foot lesion sizes and parasite burdens in both mouse strains, and the lowest parasite burden was found in mice treated with DPPE 1.2 plus P. acnes. Mice treated with DPPE 1.2 alone displayed a significant increase of TCD4+ and TCD8+ lymphocytes and IFN-γ secretion which were significantly higher in animals treated with DPPE 1.2 plus P. acnes. A significant reduction of active TGF-ß was observed in mice treated with DPPE 1.2 alone or associated with P. acnes. Moreover, DPPE 1.2 associated to P. acnes was non-toxic to treated animals. The destruction of L. (L.) amazonensis by DPPE 1.2 was followed by host inflammatory responses which were exacerbated when the palladacycle complex was associated with P. acnes.

Propionibacterium acnes induces an adjuvant effect in B-1 cells and affects their phagocyte differentiation via a TLR2-mediated mechanism.

B-1 lymphocytes are present in large numbers in the mouse peritoneal cavity, as are macrophages, and are responsible for natural IgM production. These lymphocytes migrate to inflammatory foci and are also involved in innate immunity. It was also demonstrated that B-1 cells are able to differentiated into phagocytes (B-1CDP), which is characterized by expression of F4/80 and increased phagocytic activity. B-1 cell responses to antigens and adjuvants are poorly characterized. It has been shown that Propionibacterium acnes suspensions induce immunomodulatory effects in both macrophages and B-2 lymphocytes. We recently demonstrated that this bacterium has the ability to increase B-1 cell populations both in vitro and in vivo. P. acnes induces B-1CDP differentiation, increases the expression of TLR2, TLR4 and TLR9 and augments the expression of CD80, CD86 and CD40 in B-1 and B-1CDP cells. Because P. acnes has been shown to modulate TLR expression, in this study, we investigated the role of TLR2 and TLR4 in B-1 cell population, including B-1CDP differentiation and phagocytic activity in vitro and in vivo. Interestingly, we have demonstrated that TLR2 signaling could be involved in the increase in the B-1 cell population induced by P. acnes. Furthermore, the early differentiation of B-1CDP is also dependent of TLR2. It was also observed that TLR signals also interfere in the phagocytic ability of B-1 cells and their phagocytes. According to these data, it is clear that P. acnes promotes an important adjuvant effect in B-1 cells by inducing them to differentiate into B-1CDP cells and modulates their phagocytic functions both in vivo and in vitro. Moreover, most of these effects are mediated primarily via TLR2. These data reinforce the findings that such bacterial suspensions have powerful adjuvant properties. The responses of B-1 cells to exogenous stimulation indicate that these cells are important to the innate immune response.

[Bacterial resistance in acne? A meta-analysis of the controversy]. / ¿Resistencia en el acné? Un metaanálisis a propósito de la controversia.

BACKGROUND: Acne is one of the dermatological pathologies with the highest incidence around the world. It is a multifactorial disease and its treatment can be complex. Propionibacterium acnes play a key role in the inflammation of this dermatosis. Topical antibiotics, including mainly erythromycin and clindamycin, have been used, but there is controversy over their use due to the widely documented bacterial resistance. For this reason a meta-analysis of the publications over the past 10 years is presented in order to confirm this hypothesis. MATERIAL AND METHODS: A search was made of the publications over the past 10 years that included the results of antibiogams of patients with acne. MeSH type searches were performed with the terms "acne vulgaris", "Propionibacterium acnes", "topical administration", "treatment", "erythromycin", "clindamycin", "nadifloxacin", "antibacterial agent", "bacterial drug resistance" in PubMed, Ovid, EBSCO, Cochrane, ScienceDirect and ClinicalKey meta-searches. RESULTS: A total of 13 articles were found that met the inclusion criteria. The mean odds ratio (OR 1.24, 95% CI) of the articles showed a slight tendency toward resistance of Propionibacterium acnes. CONCLUSIONS: An increase in bacterial resistance to topical erythromycin and clindamycin can be confirmed, thus the use of these antibiotics is recommended in selective cases for short periods, and in combination with benzoyl peroxide for the best clinical outcome in patients with acne vulgaris.

Multicenter study for efficacy and safety evaluation of a fixeddose combination gel with adapalen 01% and benzoyl peroxide 2 5% (Epiduo® for the treatment of acne vulgaris in Brazilian population

Abstract: BACKGROUND: The current options for the treatment of acne vulgaris present many mechanisms of action. For several times, dermatologists try topical agents combinations, looking for better results. OBJECTIVES: To evaluate the efficacy, tolerability and safety of a topical, fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel for the treatment of acne vulgaris in the Brazilian population. METHODS: This is a multicenter, open-label and interventionist study. Patients applied 1.0 g of the fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel on the face, once daily at bedtime, during 12 weeks. Lesions were counted in all of the appointments, and the degree of acne severity, overall improvement, tolerability and safety were evaluated in each visit. RESULTS: From 79 recruited patients, 73 concluded the study. There was significant, fast and progressive reduction of non-inflammatory, inflammatory and total number of lesions. At the end of the study, 75.3% of patients had a reduction of >50% in non-inflammatory lesions, 69.9% in inflammatory lesions and 78.1% in total number of lesions. Of the 73 patients, 71.2% had good to excellent response and 87.6% had satisfactory to good response. In the first week of treatment, erythema, burning, scaling and dryness of the skin were frequent complaints, but, from second week on, these signals and symptoms have reduced. CONCLUSION: The fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel is effective, safe, well tolerated and apparently improves patient compliance with the treatment.