Rev Med Liege, 2004 Nov, 59(11), 626 - 9 {Belgian consensus document on the treatment of acne}; de la Brassinne M et al.; This article describes the consensus on the treatment of acne, reached by a Belgian working group . An effective treatment has to rely as much as possible on the pathophysiologic factors: the increased production of sebum, the abnormal desquamation (retention hyperkeratosis) of the epithelium of he sebaceous gland, the proliferation of Propionibacterium acnes and inflammation . The therapeutic arsenal contains topical as well as systemic drugs . This consensus gives an overview of both modalities and an algorithm is presented describing the practical approach to acne treatment. J Clin Microbiol, 2005 Jan, 43(1), 326 - 34 Propionibacterium acnes types I and II represent phylogenetically distinct groups; McDowell A et al.; Although two phenotypes of the opportunistic pathogen Propionibacterium acnes (types I and II) have been described, epidemiological investigations of their roles in different infections have not been widely reported . Using immunofluorescence microscopy with monoclonal antibodies (MAbs) QUBPa1 and QUBPa2, specific for types I and II, respectively, we investigated the prevalences of the two types among 132 P . acnes isolates . Analysis of isolates from failed prosthetic hip implants (n = 40) revealed approximately equal numbers of type I and II organisms . Isolates from failed prosthetic hip-associated bone (n = 6) and tissue (n = 38) samples, as well as isolates from acne (n = 22), dental infections (n = 8), and skin removed during surgical incision (n = 18) were predominately of type I . A total of 11 (8%) isolates showed atypical MAb labeling and could not be conclusively identified . Phylogenetic analysis of P . acnes by nucleotide sequencing revealed the 16S rRNA gene to be highly conserved between types I and II . In contrast, sequence analysis of recA and a putative hemolysin gene (tly) revealed significantly greater type-specific polymorphisms that corresponded to phylogenetically distinct cluster groups . All 11 isolates with atypical MAb labeling were identified as type I by sequencing . Within the recA and tly phylogenetic trees, nine of these isolates formed a cluster distinct from other type I organisms, suggesting a further phylogenetic subdivision within type I . Our study therefore demonstrates that the phenotypic differences between P . acnes types I and II reflect deeper differences in their phylogeny . Furthermore, nucleotide sequencing provides an accurate method for identifying the type status of P . acnes isolates. Lancet, 2004 Dec 18, 364(9452), 2188 - 95 Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial; Ozolins M et al.; BACKGROUND: We investigated the efficacy and cost-effectiveness of five antimicrobial regimens for mild to moderate facial acne and whether propionibacterial antibiotic resistance affects treatment response . METHODS: In this randomised, observer-masked trial, 649 community participants were allocated one of five antibacterial regimens . Primary outcomes were patients' self-assessed improvement and reduction in inflamed lesions at 18 weeks . Analyses were by intention to treat . FINDINGS: Moderate or greater improvement at 18 weeks was reported in 72 (55%) of 131 participants assigned oral oxytetracycline plus topical placebo, 70 (54%) of 130 assigned oral minocycline plus topical placebo, 78 (60%) of 130 assigned topical benzoyl peroxide plus oral placebo, 84 (66%) of 127 assigned topical erythromycin and benzoyl peroxide in a combined formulation plus oral placebo, and 82 (63%) of 131 assigned topical erythromycin and benzoyl peroxide separately plus oral placebo . Most improvement occurred in the first 6 weeks . Treatment differences for the proportion of people with at least moderate improvement were: minocycline versus oxytetracycline -1.2% (unadjusted 95% CI -13.3 to 10.9); combined erythromycin and benzoyl peroxide versus oxytetracycline 11.1% (-0.7 to 22.9) and versus minocycline 12.3% (0.4 to 24.2); erythromycin and benzoyl peroxide separately versus combined formulation -3.5% (-15.2 to 8.2); benzoyl peroxide versus oxytetracycline 5.0% (-7.0 to 17.0), versus minocycline 6.2% (-5.8 to 18.2), and versus combined formulation -6.1% (-17.9 to 5.7) . Benzoyl peroxide was the most cost-effective treatment . Efficacy of both tetracyclines was reduced by pre-existing tetracycline resistance . INTERPRETATION: Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations are similar in efficacy to oral oxytetracycline and minocycline and are not affected by propionibacterial antibiotic resistance. BMC Nephrol . 2004 Dec 21;5(1):18 {Epub ahead of print} Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: A case report; Koya D et al.; {Background} The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high . Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined . {Case Presentation} Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis . He had a history of ventricular septum defect (VSD) . A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve . Specimens of blood demonstrated Propionibacterium acnes . The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days . After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved . {Conclusion} Although renal function in our case worsened despite therapy with antibiotics, a short-term and low does of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure . We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully. Prikl Biokhim Mikrobiol, 2004 Nov-Dec, 40(6), 645 - 8 {Isolation of cobalt-resistant strains of propionic acid bacteria, potent producers of vitamin B12}; In vitro activities of cefotaxime et al.; Laboratoire de Bacteriologie-Virologie, UMR-CNRS 7565, Faculte de Medecine, 54500 Vandoeuvre-les-Nancy, FranceOBJECTIVES: To evaluate the antibiotic susceptibilities of Propionibacterium acnes isolates from central nervous system (CNS) infections to agents used in current treatment regimens . METHODS: MICs of 16 reference antibiotics were determined by an agar dilution method for 24 consecutive strains of P . acnes isolated from individual patients with intracranial empyema or brain abscess . Bactericidal activities of antibiotics against P . acnes PAN14 were studied at 0.25-2 x MIC using a time-kill method . RESULTS: All of the isolates were resistant to fosfomycin, intermediate or resistant to metronidazole and susceptible to all the other antibiotics tested, except for nine strains, which were intermediate to ofloxacin . Among antibiotics tested alone in time-kill experiments, vancomycin was the most effective drug and exhibited bactericidal activity after 24 h at 1x and 2 x MIC, whereas cefotaxime and ciprofloxacin were bactericidal after 48 h at 2 x MIC . No significant bactericidal activity could be demonstrated with the other antibiotics tested alone . The addition of cefotaxime to vancomycin resulted in bactericidal activity at lower concentrations (0.5 x MIC), whereas synergy was observed between quinupristin/dalfopristin and cefotaxime at 2 x MIC . In contrast, antagonism was observed between cefotaxime and linezolid, and ciprofloxacin and clindamycin . CONCLUSION: Our data suggest that P . acnes isolates causing CNS infections remain highly susceptible to most antibiotics used for the treatment of such infections . Moreover, we showed that cefotaxime, vancomycin and ciprofloxacin possess good bactericidal activities against P . acnes, and that these activities may be enhanced when vancomycin is combined with cefotaxime or when cefotaxime is combined with quinupristin/dalfopristin. Health Technol Assess, 2005 Jan, 9(1), 1 - 212 Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne; Ozolins M et al.; OBJECTIVES: To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains . DESIGN: This was a parallel group randomised assessor-blind controlled clinical trial . It was a pragmatic design with intention-to-treat analysis . All treatments were given for 18 weeks, after a 4-week treatment free period . Outcomes were measured at 0, 6, 12 and 18 weeks . SETTING: Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England . PARTICIPANTS: Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face . INTERVENTIONS: Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR(R) (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin(R) (3% erythromycin + 5% benzoyl peroxide) b.d . + oral placebo o.d.; topical Stiemycin(R) (2% erythromycin) o.d . + topical Panoxyl(R) Aquagel (5% benzoyl peroxide) o.d . + oral placebo o.d., and topical Panoxyl(R) Aquagel (5% benzoyl peroxide) b.d . + oral placebo o.d . (the active comparator group) . MAIN OUTCOME MEASURES: The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots) . RESULTS: The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d . or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small . The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 {95% confidence interval (CI) 1.04 to 2.90} . Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor . Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039) . The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost . For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks . Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline . The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria . The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria . None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains . Systemic adverse events were more common with the two oral antibiotics . Local irritation was more common with the topical treatments, particularly benzoyl peroxide . Residual acne was present in most participants (95%) at the end of the study . CONCLUSIONS: The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal . Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly . Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks . Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy . Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne . The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance . Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions . It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life . There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective . The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face . Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e . what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability). Appl Environ Microbiol, 2004 Dec, 70(12), 7561 - 6 Effects of expression of hemA and hemB genes on production of porphyrin in Propionibacterium freudenreichii; Piao Y et al.; The genus Propionibacterium has a wide range of probiotic activities that are exploited in dairy and fermentation systems such as cheeses, propionic acid, and tetrapyrrole compounds . In order to improve production of tetrapyrrole compounds, we expressed the hemA gene, which encodes delta-aminolevulinic acid (ALA) synthase from Rhodobacter sphaeroides, and the hemB gene, which encodes porphobilinogen (PBG) synthase from Propionibacterium freudenreichii subsp . shermanii IFO12424, either monocistronically or polycistronically in strain IFO12426 . The recombinant strains accumulated larger amounts of ALA and PBG, with resultant 28- to 33-fold-higher production of porphyrinogens, such as uroporphyrinogen and coproporphyrinogen, than those observed in strain IFO12426, which harbored the shuttle vector pPK705. Appl Environ Microbiol, 2004 Dec, 70(12), 7303 - 10 Molecular and genetic characterization of propionicin F, a bacteriocin from Propionibacterium freudenreichii; Brede DA et al.; This work describes the purification and characterization of propionicin F, the first bacteriocin isolated from Propionibacterium freudenreichii . The bacteriocin has a bactericidal activity and is only active against strains of P . freudenreichii . Propionicin F appears to be formed through a processing pathway new to bacteriocins . The mass of the purified bacteriocin was determined by mass spectrometry, and the N-terminal amino acid sequence was determined by Edman degradation . Sequencing of pcfA, the bacteriocin structural gene, revealed that propionicin F corresponds to a 43-amino-acid peptide in the central part of a 255-amino-acid open reading frame, suggesting that mature propionicin F is excised from the probacteriocin by N- and C-terminal proteolytic modifications . DNA sequencing and Northern blot hybridizations revealed that pcfA is cotranscribed with genes encoding a putative proline peptidase and a protein from the radical S-adenosylmethionine family . A gene encoding an ABC transporter was also identified in close proximity to the bacteriocin structural gene . The potential role of these genes in propionicin F maturation and secretion is discussed. Clin Dermatol, 2004 Sep-Oct, 22(5), 398 - 407 Acne: topical treatment; Krautheim A et al.; Acne vulgaris is a common skin disease, affecting about 70-80% of adolescents and young adults . It is a multifactorial disease of the pilosebaceous unit.(1) The influence of androgens at the onset of adolescence leads to an enlargement of the sebaceous gland and a rise in sebum production . Additional increased proliferation and altered differentiation of the follicular epithelium eventually blocks the pilosebaceous duct, leading to development of the microcomedo as the primary acne lesion . Concomitantly and subsequently, colonization with Propionibacterium acnes increases, followed by induction of inflammatory reactions from bacteria, ductal corneocytes, and sebaceous proinflammatory agents (Fig 1).(2-5) Clin Dermatol, 2004 Sep-Oct, 22(5), 380 - 4 Acne: inflammation; Farrar MD et al.; The inflammatory stage of acne vulgaris is usually of greatest concern to the patient . A number of morphologically different inflammatory lesions may form that can be painful and unsightly . In 30% of patients, such lesions lead to scarring(1) . Inflammatory acne and acne scarring can have significant psychological effects on the patient, including depression, anxiety, and poor self-image(2) . Although inflammatory acne has been well characterized clinically, the mechanisms by which inflammatory lesions arise are still poorly understood . The human skin commensal bacterium, Propionibacterium acnes, has long been associated with inflammatory acne . This organism has been implicated over and above all of the other cutaneous microflora in contributing to the inflammatory response characteristic of acne . However, its precise role in the disease and its interaction with the human immune system remain to be elucidated. Clin Dermatol, 2004 Sep-Oct, 22(5), 360 - 6 Acne and sebaceous gland function; Zouboulis CC; The embryologic development of the human sebaceous gland is closely related to the differentiation of the hair follicle and the epidermis . The number of sebaceous glands remains approximately the same throughout life, whereas their size tends to increase with age . The development and function of the sebaceous gland in the fetal and neonatal periods appear to be regulated by maternal androgens and by endogenous steroid synthesis, as well as by other morphogens . The most apparent function of the glands is to excrete sebum . A strong increase in sebum excretion occurs a few hours after birth; this peaks during the first week and slowly subsides thereafter . A new rise takes place at about age 9 years with adrenarche and continues up to age 17 years, when the adult level is reached . The sebaceous gland is an important formation site of active androgens . Androgens are well known for their effects on sebum excretion, whereas terminal sebocyte differentiation is assisted by peroxisome proliferator-activated receptor ligands . Estrogens, glucocorticoids, and prolactin also influence sebaceous gland function . In addition, stress-sensing cutaneous signals lead to the production and release of corticotrophin-releasing hormone from dermal nerves and sebocytes with subsequent dose-dependent regulation of sebaceous nonpolar lipids . Among other lipid fractions, sebaceous glands have been shown to synthesize considerable amounts of free fatty acids without exogenous influence . Sebaceous lipids are responsible for the three-dimensional skin surface lipid organization . Contributing to the integrity of the skin barrier . They also exhibit strong innate antimicrobial activity, transport antioxidants to the skin surface, and express proinflammatory and anti-inflammatory properties . Acne in childhood has been suggested to be strongly associated with the development of severe acne during adolescence . Increased sebum excretion is a major factor in the pathophysiology of acne vulgaris . Other sebaceous gland functions are also associated with the development of acne, including sebaceous proinflammatory lipids; different cytokines produced locally; periglandular peptides and neuropeptides, such as corticotrophin-releasing hormone, which is produced by sebocytes; and substance P, which is expressed in the nerve endings at the vicinity of healthy-looking glands of acne patients . Current data indicate that acne vulgaris may be a primary inflammatory disease . Future drugs developed to treat acne not only should reduce sebum production and Propionibacterium acnes populations, but also should be targeted to reduce proinflammatory lipids in sebum, down-regulate proinflammatory signals in the pilosebaceous unit, and inhibit leukotriene B(4)-induced accumulation of inflammatory cells . They should also influence peroxisome proliferator-activated receptor regulation . Isotretinoin is still the most active available drug for the treatment of severe acne. J Cosmet Laser Ther, 2004 Sep, 6(3), 156 - 62 420 nm intense continuous light therapy for acne; Omi T et al.; BACKGROUND: Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy . However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity . Describe here is a high-intensity, narrow-band, blue light (ClearLight) system, and its therapeutic clinical effect is investigated on acne using cutaneous measurements, bacterial observations and ultrastructural changes . MATERIALS AND METHODS: A total of 28 adult healthy volunteers with facial acne (mean age 28.1 years, range 16-56 years) were recruited for this study . They were treated with a total of eight serial biweekly 15-minute treatment sessions . Clinical counts of acne, as well as moisture, sebum and pH measurements were taken between each session . Nine of the 28 patients were followed for 2-3 months after the last treatment . Detection of bacteria in acne pustules was analyzed by culture and by polymerase chain reaction (PCR) . Ultrastructural changes were examined in eight patients after four sessions of the light therapy . RESULTS: All patients completed the study . Overall, there was a 64.7% improvement in acne lesions . There were no bacterial changes before or after the therapy, although damaged Propionibacterium acnes were observed at the ultrastructural level . CONCLUSIONS: ClearLight performed eight times over 4 weeks can be useful in the treatment of acne . Further investigation will be needed to elucidate the mechanism of action of ClearLight. Am J Ophthalmol, 2004 Nov, 138(5), 878 - 9 Propionibacterium acnes endophthalmitis with bacterial sequestration in a Molteno's implant after cataract extraction; Hollander DA et al.; PURPOSE: To report a case of Propionibacterium acnes endophthalmitis following uncomplicated cataract extraction with bacterial sequestration in a preexisting Molteno's drainage implant . DESIGN: Interventional case report . METHODS: A 7-year-old girl with congenital glaucoma and a preexisting Molteno's drainage implant developed anterior nongranulomatous uveitis 4 months following cataract surgery . P . acnes endophthalmitis was diagnosed by polymerase chain reaction, Southern blot, and electron microscopy . RESULTS: Extraction of the Molteno's implant was required to control the persistent intraocular inflammation and to convert the results of polymerase chain reaction and Southern blot testing of aqueous sample for P . acnes from positive to negative . CONCLUSION: P . acnes may be sequestered in glaucoma implants, potentially requiring implant removal to treat cases of P . acnes endophthalmitis. Med Dosw Mikrobiol, 2004, 56(1), 79 - 92 {Characteristics of the Propionibacterium strains isolated from acne patients}; Bialecka A et al.; Propionibacterium acnes is a component of physiological flora of human skin . It colonizes the outlets of sebaceous glands and participates in the pathogenesis of inflammatory acne . Acne vulgaris is a common skin disease . It is found in more or less exacerbated form in approximately 85% of adolescent population . The main purpose of the research was to confirm the hypothesis of Propionibacterium bacteria participation in the aetiopathogenesis of acne vulgaris . The researches have proved the presence of Propionibacterium acnes on the surface of the skin both of people with acne-related changes and these with whom such changes were not found . Statistically significant differences were found in the number of P . acnes bacteria per 1 square centimeter of healthy and disease-affected skin as well as in the diversity of biochemical types . The highest number of P . acnes bacteria have been found in fresh changes with visible symptoms of inflammation . In order to confirm the hypothesis of the participation of Propionibacterium bacteria in the aetiopathogenesis of acne, a detailed phenotypical analysis of isolated P . acnes strains have been conducted . Type, biotype, resistance pattern, proteolytic and lipolytic properties have been determined. In Silico Biol . 2004 Sep 28;4(3):0043 {Epub ahead of print} In silico exploration of the fructose-6-phosphate phosphorylation step in glycolysis: genomic evidence of the coexistence of an atypical ATP-dependent along with a PPi-dependent phosphofructokinase in Propionibacterium freudenreichii subsp . shermanii; Meurice G et al.; We performed a detailed bioinformatic study of the catalytic step of fructose-6-phosphate phosphorylation in glycolysis based on the raw genomic draft of Propionibacterium freudenreichii subsp . shermanii (P . shermanii) ATCC9614 {Meurice et al., 2004} . Our results provide the first in silico evidence of the coexistence of genes coding for an ATP-dependent phosphofructokinase (ATP-PFK) and a PPi-dependent phosphofructokinase (PPi-PFK), whereas the fructose-1,6-bisphosphatase (FBP) and ADP-dependent phosphofructokinase (ADP-PFK) are absent . The deduced amino acid sequence corresponding to the PPi-PFK (AJ508922) shares 100% similarity with the already characterised propionibacterial protein (P29495; Ladror et al., 1991} . The unexpected ATP-PFK gene (AJ509827) encodes a protein of 373 aa which is highly similar (50% positive residues) along at least 95% of its sequence length to different well-characterised ATP-PFKs . The characteristic PROSITE pattern important for the enzyme function of ATP-PFKs (PS00433) was conserved in the putative ATP-PFK sequence: 8 out of 9 amino acid residues . According to the recent evolutionary study of PFK proteins with different phosphate donors {Bapteste et al., 2003}, the propionibacterial ATP-PFK harbours a G104-K124 residue combination, which strongly suggested that this enzyme belongs to the group of atypical ATP-PFKs . According to our phylogenetic analyses the amino acid sequence of the ATP-PFK is clustered with the atypical ATP-PFKs from group III of the Siebers classification {Siebers et al., 1998}, whereas the expected PPi-PFK protein is closer to the PPi-PFKs from clade P {Mueller et al., 2001} . The possible significance of the co-existence of these two PFKs and their importance for the regulation of glycolytic pathway flux in P . shermanii is discussed. Eur J Ophthalmol, 2004 Sep-Oct, 14(5), 442 - 4 Late onset posttraumatic Propionibacterium acnes endophthalmitis; El-Asrar AM et al.; PURPOSE: To report a case of late onset posttraumatic endophthalmitis secondary to Propionibacterium acnes infection . METHODS: Interventional case report . RESULTS: A 28-year-old man developed endophthalmitis 6 months after a penetrating trauma . The patient underwent pars plana lensectomy and vitrectomy along with injection of intravitreal antibiotics . Anaerobic cultures of the vitreous yielded P . acnes . Seven months after surgery, the eye was quiet with a best-corrected visual acuity of 20/60 . CONCLUSIONS: This case emphasizes the importance of considering P acnes when treating patients with late onset posttraumatic endophthalmitis. Cutis, 2004 Sep, 74(3), 189 - 92 The pathophysiology of acne vulgaris in children and adolescents, part 2: Tailoring treatment; Bergfeld WF; Various pathophysiologic factors are involved in the development of acne lesions, microcomedones, comedones, and inflammatory lesions . These factors include follicular hyperkeratosis, increased colonization of follicles by Propionibacterium acnes, increased sebum production, and inflammatory mediators . Optimal treatment of acne involves the use of agents that address these various underlying pathogenetic factors. Drugs, 2004, 64(21), 2389 - 97 Topical antibacterial therapy for acne vulgaris; Dreno B; Topical antibiotics and benzoyl peroxide, are the two main topical antibacterial treatments indicated for mild-to-moderate acne vulgaris . Topical antibiotics act both as antibacterial agents suppressing Propionibacterium acnes in the sebaceous follicle and as anti-inflammatory agents . Benzoyl peroxide is a powerful antimicrobial agent that rapidly destroys both bacterial organisms and yeasts . Topical clindamycin and erythromycin have been proven to be effective against inflammatory acne vulgaris in concentrations of 1-4% with or without the addition of zinc . However, none of the antibacterials tested was more effective than benzoyl peroxide, which also has the advantage of not being associated with antimicrobial resistance.Topical antibacterial therapy should be discontinued once improvement is observed . If no improvement is observed within 6-8 weeks, the agent should be discontinued and a therapeutic switch considered . The primary limitation of benzoyl peroxide for some acne vulgaris patients is cutaneous irritation or dryness.Antibacterial therapy can be used in combination with other agents . Combining topical antibiotics and topical retinoids may enhance the efficacy, since the retinoid will improve the penetration of the antibiotic . Combining a topical antibiotic with benzoyl peroxide may increase the bactericidal effect of the antibiotic and reduce the potential for bacterial resistance . Topical and oral antibacterials should not be used in combination for the treatment of acne vulgaris, since this association may increase the risk of bacterial resistance. Pathobiology, 2004, 71(5), 246 - 52 Involvement of CD14 in lipopolysaccharide- induced liver injury in mice pretreated with Propionibacterium acnes; Uchida T et al.; OBJECTIVE: The aim of this study was to elucidate the role of CD14 in the Propionibacterium acnes-lipopolysaccharide (LPS) system . METHODS AND RESULTS: CD14 transgenic mice (M14M), which expressed heterotopic CD14 and showed decreased responses to LPS in vivo, were used . Seven days after priming, the size of granulomas induced by an intraperitoneal administration of P . acnes in the M14M mice was smaller than that in the nontransgenic mice . The number of CD14-positive cells in granulomas was also decreased in the M14M mice compared to the nontransgenic mice . An LPS challenge induced apoptotic and necrotic changes in hepatocytes in the nontransgenic mice but not in the M14M mice . Seven days after priming, tumor necrosis factor-alpha expression was found in monocytic cells in granulomas and Kupffer cells in the nontransgenic mice and was significantly upregulated after LPS injection, whereas the expression was very weak in these cells in the M14M mice . CONCLUSIONS: CD14 plays a role in the P . acnes-LPS system in both priming and induction phases. Cutis, 2004 Aug, 74(2), 92 - 7 The pathophysiology of acne vulgaris in children and adolescents, Part 1; Bergfeld WF; Microcomedones, the earliest lesions of acne, appear at adrenarche, which typically occurs at about 8 years of age when androgens of adrenal origin begin to stimulate follicular hyperkeratosis and sebaceous hyperplasia in pilosebaceous units on the face . Comedones appear about 2 years later, when androgens of gonadal origin are produced and colonization of follicles by Propionibacterium acnes increases . Inflammatory lesions, such as pustules, papules, and nodules, are the result of the host's immune responses to P acnes; the proinflammatory cytokines are released by immunocompetent leukocytes that are recruited in response to this bacterium and its metabolic by-products . Androgens also affect the barrier function of the skin, and disturbances of barrier function may stimulate epidermal DNA synthesis . This leads to epidermal hyperplasia, which may also contribute to follicular hyperkeratosis in acne . Optimal treatment for this disorder will address these various pathophysiologic factors. Br J Dermatol, 2004 Sep, 151(3), 616 - 22 Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action; Pollock B et al.; BACKGROUND: Acne affects 83-95% of 16-year-olds of both sexes, and many seek help from a clinician . Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne . OBJECTIVES: To study the efficacy of aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P . acnes and on sebum excretion . METHODS: Ten patients (nine men and one woman, age range 16-40 years) with mild to moderate acne on their backs were recruited . Each patient's back was marked with four 30-cm2 areas of equal acne severity . Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site . At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P . acnes swabs performed . ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 h . Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm(-2), 15 J cm(-2)) . Each patient was treated weekly for 3 weeks . At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P . acnes swabs were repeated . RESULTS: There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites . No statistically significant reduction in P . acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site . CONCLUSIONS: ALA-PDT is capable of clinically improving acne . An alternative mode of action for ALA-PDT other than direct damage to sebaceous glands or photodynamic killing of P . acnes is suggested from the results of this study. Gastroenterology, 2004 Sep, 127(3), 892 - 902 Inducible histamine protects mice from P . acnes-primed and LPS-induced hepatitis through H2-receptor stimulation; Yokoyama M et al.; BACKGROUND & AIMS: Inducible histamine and histamine H2-receptors have been suggested to be involved in innate immune response . METHODS: We examined a functional role of inducible histamine in the protection against hepatic injury and lethality in Propionibacterium acnes -primed and lipopolysaccharide-induced hepatitis, using histidine decarboxylase knockout and H2-receptor knockout mice . RESULTS: Lipopolysaccharide challenge after Propionibacterium acnes priming increased histidine decarboxylase activity in the liver of wild-type mice, associated with a marked elevation of histamine turnover . Histidine decarboxylase-like immunoreactivity was observed in CD68-positive Kupffer cells/macrophages . Treatment of wild-type mice with famotidine or ranitidine but not d -chlorpheniramine augmented hepatic injury and inhibited the survival rate significantly . The same dose of Propionibacterium acnes and lipopolysaccharide induced severe hepatitis and high lethality in histidine decarboxylase knockout and H2-receptor knockout mice; the former were rescued by the subcutaneous injection of histamine . Immunohistochemical study supported the protective role of histamine against the apoptosis of hepatocytes . Histamine suppressed the expression of IL-18 and tumor necrosis factor alpha in the liver, leading to the reduced plasma levels of cytokines including IL-18, TNF-alpha, IL-12, IFN-gamma, and IL-6 . CONCLUSIONS: These findings as a whole indicated that endogenously produced histamine in Kupffer cells/macrophages plays a very important role in preventing excessive innate immune response in endotoxin-induced fulminant hepatitis through the stimulation of H2-receptors. J Microbiol, 2004 Jun, 42(2), 117 - 25 Antibody response to crude cell lysate of propionibacterium acnes and induction of pro-inflammatory cytokines in patients with acne and normal healthy subjects; Basal E et al.; Propionibacterium acnes (P . acnes) plays an important role in the disease pathogenesis of acne vulgaris, a disorder of pilosebaceous follicles, seen primarily in the adolescent age group . In the present study, the presence of antibodies against P . acnes (MTCC1951) were detected in acne patient (n=50) and disease free controls (n=25) using dot-ELISA and Western blot assay . The ability of P . acnes to induce pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs), obtained from acne patients and healthy subjects, were also analysed . The patients (n=26) who were culture positive for skin swab culture, were found to have a more advanced disease and higher antibody titres (1:4000 to > 1:16000) compared to the P . acnes negative patients (n=24) and normal controls (n=25) . An analysis of patients' sera by western blot assay recognized a number of antigenic components of P . acnes, ranging from 29 to 205 kDa . The major reactive component was an approximately 96 kDa polypeptide, which was recognised in 92% (24 of 26) of the patients sera . Further, the P . acnes culture supernatant, crude cell lysate and heat killed P . acnes whole cells, obtained from 72-h incubation culture, were observed to be able to induce significant amounts of IL-8 and tumor necrosis factor alpha (TNF-alpha) by the PBMCs in both the healthy subjects and patients, as analysed by cytokine-ELISA . The levels of cytokines were significantly higher in the patients than the healthy subjects . A major 96 kDa polypeptide reactant was eluted from the gel and was found to cause dose dependent stimulation of the productions of IL-8 and TNF-alpha . Thus, the above results suggest that both humoral and pro-inflammatory responses play major roles in the pathogenesis of acne. J Dairy Res, 2004 Aug, 71(3), 367 - 71 Influence of manufacturing conditions on the conjugated linoleic acid content and the isomer composition in ripened French Emmental cheese; Gnadig S et al.; In a study of the evolution of conjugated linoleic acid (CLA) during cheese production, the influence of Emmental cheese processing on the CLA content and the CLA isomer composition was evaluated . The use of raw and thermised milk, changes of processing temperature and the effect of propionic acid bacteria (PAB) were investigated . The content of CLA in raw milk was 8.6 +/- 1.9 mg/g fat and in the ripened cheese at 70 d was 8.6 +/- 1.6 mg/g fat, under normal processing conditions . No changes in the CLA content and CLA isomer composition were observed during Emmental cheese manufacturing process . Changes in cooking and moulding temperatures did not influence the CLA content . CLA content of cheese made from microfiltered milk with two different Propionibacterium freudenreichii strains was very close to cheeses made without PAB . CLA levels seem to be stable in this type of dairy product under the conditions examined. Hepatology, 2004 Sep, 40(3), 555 - 64 Selective priming to Toll-like receptor 4 (TLR4), not TLR2, ligands by P . acnes involves up-regulation of MD-2 in mice; Romics L Jr et al.; Lipopolysaccharide (LPS) triggers cytokine production through Toll-like receptor 4 (TLR4), which shares downstream signaling pathways with TLR2 . We investigated the roles of TLR2 and TLR4 in Propionibacterium acnes (P . acnes)-primed, LPS-induced liver damage using selective TLR ligands . Stock LPS induced interleukin 8 in both TLR4- and TLR2-expressing human embryonic kidney (HEK) 293 cells . Purified LPS (TLR4 ligand) activated HEK/TLR4 cells, while peptidoglycan and lipoteichoic acid (TLR2 ligands) activated HEK/TLR2 cells, respectively . In mice, P . acnes priming resulted in increased liver messenger RNA (mRNA) and serum levels of tumor necrosis factor alpha, interleukin 12, and interferon gamma (IFN-gamma) by both stock LPS and purified LPS challenges compared with nonprimed controls . In contrast, P . acnes failed to sensitize to TLR2 ligands (peptidoglycan + lipoteichoic acid) . In the liver, P . acnes-priming was associated with up-regulation of TLR4 and MD-2 proteins, and subsequent LPS challenge further increased MD-2 and CD14 mRNA levels . The lack of sensitization to TLR2 ligands by P . acnes correlated with no increase in hepatic TLR1 or TLR6 mRNA . In vitro, P . acnes pretreatment desensitized RAW macrophages to a secondary stimulation via both TLR2 and TLR4 . However, IFN-gamma could selectively prevent desensitization to TLR4 but not to TLR2 ligands . Furthermore, P . acnes induced production of IFN-gamma in vivo as well as in isolated splenocytes . In vitro, P . acnes-primed Hepa 1-6 hepatocytes but not RAW macrophages produced increased MD-2 and CD14 mRNA levels after an LPS challenge . In conclusion, P . acnes priming to selective TLR4-mediated liver injury is associated with up-regulation of TLR4 and MD-2 and is likely to involve IFN-gamma and prevent TLR4 desensitization by P . acnes . Eur J Pediatr Surg, 2004 Aug, 14(4), 245 - 9 Distal catheter obstruction from non-infectious cause in ventriculo-peritoneal shunted children; Arnell K et al.; In hydrocephalic children, ventriculo-peritoneal shunting is the preferred treatment with few complications . However, an obviously non-infectious peritoneal reaction to the cerebrospinal fluid (CSF) may occasionally lead to shunt malfunction . In eight hydrocephalic children, shunt malfunction with distal catheter complication was found with abdominal pseudocyst formation in seven cases and accumulation of the CSF in one . All children had a normal CSF cell count and glucose concentration, and white cell count, and C-reactive protein in peripheral blood were normal . No CSF infection could be detected despite prolonged aerobic and anaerobic cultures . After initial externalisation of the shunt and subsequent routine administration of antibiotics because infection initially was suspected, ventriculo-peritoneal shunting was attempted one to three times with identical failure before successful conversion to a ventriculo-atrial system . At laparotomy the peritoneum and intestinal serosa were hyperaemic and oedematous in all patients, five of whom also had pseudocysts and two of whom also had intra-abdominal adhesions . Four children had a revision 6-24 years after the ventriculo-atrial conversion due to short atrial catheter with distal obstruction . In three of them, the distal catheter was successfully replaced into the peritoneal cavity . The fourth child, however, developed an infectious abdominal pseudocyst with adhesions due to a then undetected Propionibacterium acnes infection . After externalisation and antibiotics, a new ventriculo-atrial shunt was inserted . At follow-up between 5 months to nearly 6 years later, the three children with peritoneal catheters did not show any signs of shunt malfunction or abdominal problems . Thus hydrocephalic children may develop shunt malfunction with distal catheter obstruction due to a still unexplained, transient, non-infectious peritoneal reaction leading to abdominal pseudocyst formation or accumulation of CSF . In some children, however, it may later be possible to replace the distal catheter into the peritoneal cavity, if no infection is involved. EMBO J, 2004 Sep 15, 23(18), 3621 - 31 Epub 2004 Aug 26. Transcarboxylase 5S structures: assembly and catalytic mechanism of a multienzyme complex subunit; Hall PR et al.; Transcarboxylase is a 1.2 million Dalton (Da) multienzyme complex from Propionibacterium shermanii that couples two carboxylation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate to yield propionyl-CoA and oxaloacetate . Crystal structures of the 5S metalloenzyme subunit, which catalyzes the second carboxylation reaction, have been solved in free form and bound to its substrate pyruvate, product oxaloacetate, or inhibitor 2-ketobutyrate . The structure reveals a dimer of beta(8)alpha(8) barrels with an active site cobalt ion coordinated by a carbamylated lysine, except in the oxaloacetate complex in which the product's carboxylate group serves as a ligand instead . 5S and human pyruvate carboxylase (PC), an enzyme crucial to gluconeogenesis, catalyze similar reactions . A 5S-based homology model of the PC carboxyltransferase domain indicates a conserved mechanism and explains the molecular basis of mutations in lactic acidemia . PC disease mutations reproduced in 5S result in a similar decrease in carboxyltransferase activity and crystal structures with altered active sites. J Cataract Refract Surg, 2004 Aug, 30(8), 1790 - 4 Unusual anaerobic bacteria in keratitis after laser in situ keratomileusis: diagnosis using molecular biology methods; Ferrer C et al.; Laser in situ keratomileusis (LASIK) was performed in the left eye of a 57-year-old man for residual ametropia after phacoemulsification . The patient was given topical tobramycin and a corticosteroid for 1 week postoperatively . Fifteen days later, he developed 3 corneal infiltrates beneath the flap with a gas bubble, suggesting an anaerobic infection . Tobramycin and ofloxacin were administered every 2 hours, but the condition worsened . Corneal scrapings were taken from beneath the flap for microbiological cultures and a polymerase chain reaction (PCR) test . The PCR amplification was negative for fungi and mycobacteria and positive for bacterial DNA . Sequence analysis showed Propionibacterium granulosum as the causal agent, but cultures were negative . Treatment with vancomycin and cefazolin led to clinical improvement, with resolution of corneal infiltrates . Anaerobic microorganisms can cause keratitis after LASIK . Polymerase chain reaction amplification and DNA typing can help detect microorganisms involved in these ocular infections. Heart . 2004 Sep;90(9):e56. Propionibacterium acnes endocarditis on an annuloplasty ring in an adolescent boy; Vanagt WY et al.; Propionibacterium acnes, a constituent of the human cutaneous flora, infected both the native mitral valve and a Carpentier mitral annuloplasty ring in an adolescent patient . In the case of culture negative endocarditis, the incubation period of blood cultures should be prolonged to identify this pathogen. Appl Biochem Biotechnol, 1999 Feb, 76(2), 99 - 106 On-Line Dialysis of Organic Acids from a Propionibacterium freudenreichii Fermentation: Evaluation of a New pH Control Strategy; Da Costa JP et al.; The efficiency of an ion exchange system coupled to a bioreactor to extract on-line inhibitory organic acids produced was evaluated . Batch fermentations without dialysis and fed-batch experiments with and without dialysis of Propionibacterium freudenreichii were conducted . It was possible to keep the propionic acid concentration in the reactor at a low level to avoid complete growth inhibition . Improvements in biomass and propionic acid productivities were achieved when the dialysis system was used . The performance of the dialysis system was improved when a new pH control strategy evaluated in this study was used. Am J Clin Dermatol, 2004, 5(4), 261 - 5 Benzoyl peroxide-based combination therapies for acne vulgaris: a comparative review; Taylor GA et al.; Benzoyl peroxide, with its broad-spectrum antimicrobial activity, is among the most widely used topical agents in the treatment of inflammatory acne vulgaris . Benzoyl peroxide is marketed either alone or in combination with other topical antibiotics; namely, erythromycin and clindamycin . The combination products confer specific advantages over benzoyl peroxide alone, particularly in decreasing the in vivo follicular counts of Propionibacterium acnes, the anaerobic bacterium implicated in the pathogenesis of acne . In addition, the topical treatment of inflammatory acne has been complicated by the development of P acnes resistance to topical erythromycin and clindamycin . Combination products containing benzoyl peroxide and the topical antibiotics have been shown to both: (i) prevent the development of antibiotic resistance in acne patients; and (ii) confer significant clinical improvement to patients who have already developed antibiotic resistance. Eur J Pharmacol, 2004 Aug 2, 496(1-3), 189 - 95 In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp; Park J et al.; 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. Science, 2004 Jul 30, 305(5684), 671 - 3 The complete genome sequence of Propionibacterium acnes, a commensal of human skin; Bruggemann H et al.; Propionibacterium acnes is a major inhabitant of adult human skin, where it resides within sebaceous follicles, usually as a harmless commensal although it has been implicated in acne vulgaris formation . The entire genome sequence of this Gram-positive bacterium encodes 2333 putative genes and revealed numerous gene products involved in degrading host molecules, including sialidases, neuraminidases, endoglycoceramidases, lipases, and pore-forming factors . Surface-associated and other immunogenic factors have been identified, which might be involved in triggering acne inflammation and other P . acnes-associated diseases. Am J Pathol, 2004 Aug, 165(2), 631 - 9 Indigenous pulmonary Propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice; Nishiwaki T et al.; Although many cases of sarcoidosis are self-limiting with spontaneous remission, uncontrolled pulmonary granulomatosis with fibrosis produces intolerable long-term respiratory symptoms in a minority of patients . Individuals with chronic pulmonary sarcoidosis require an alternative therapy to corticosteroidal treatment because of its insufficient effectiveness . Although many researchers have considered infection as the triggering factor for this disease, the mechanisms by which the candidate causative organisms induce this disorder remain unclear . We report here that extrapulmonary sensitization to Propionibacterium acnes, which is one of the candidates to date, induced pulmonary Th-1 granulomas mainly in the subpleural and peribronchovascular regions often observed in sarcoidosis . These granulomas appear to be caused by indigenous P . acnes pre-existing in the lower respiratory tract of the normal lung, which is believed to be germ-free, and by an influx of P . acnes-sensitized CD4(+) T cells from the circulation . Importantly, the eradication of indigenous P . acnes with antibiotics alleviated the granulomatous lung disease . This is the first report to present clear evidence of the contribution of an indigenous pulmonary bacterium to the formation of granulomatous lesions in the lung . We propose that treatment targeting indigenous P . acnes in the lung may be a possible remedy for pulmonary sarcoidosis. Scand J Clin Lab Invest, 2004, 64(5), 451 - 6 Biosynthesis of 32P-labelled hydroxocobalamin and a study of its behaviour in rats; Grasbeck R et al.; Using Propionibacterium freudenreichii and 32P-ATP, batches of 32P-labelled cobalamin (Cbl) were biosynthesized with a maximum specific activity of 61 microCi/mg, i.e . about 100 times higher than previously reported . Pharmacological doses mixed with 57Co-Cbl were injected subcutaneously in the form of hydroxo-Cbl into rats subsequently killed 5-20 days later . The two labelled Cbls were distributed in approximately the same way, the highest concentration being found in kidney (typical for rats) and about one-fifth of that in liver . These findings tallied with previous observations with radioactive cyano-Cbl and microbiological assay . In all injected rats, the 57Co/32P ratio was lower in liver than in kidney . Drugs eradicating the intestinal flora had no influence . In rats receiving the vitamin orally, the ratio was higher in liver than in kidney . All of our findings could be due to formation of a cobinamide-like compound lacking phosphorus . It is concluded that we have produced radiophosphorus-labelled Cbl that enables studies in vivo. Curr Opin Pediatr, 2004 Aug, 16(4), 385 - 91 Acne update: 2004; Smolinski KN et al.; PURPOSE OF REVIEW: Acne vulgaris is a common skin disorder among children and young adults that carries enormous financial and psychosocial impact . Contemporary therapies attempt to address factors underlying acne as a disorder of the pilosebaceous unit . These longstanding paradigms regarding pathogenesis and treatment continue to evolve in light of recent work on this ubiquitous disease . RECENT FINDINGS: This review focuses on new literature that has emerged regarding the biology of the folliculosebaceous unit, the identification of particular mediators responsible for inflammatory acne, the use of topical and systemic retinoids in acne therapy, and approaches to address the emergence of antibiotic-resistant Propionibacterium acnes strains . In addition, the use of several novel therapeutic avenues is discussed, including combination therapies, lipoxygenase inhibitors, and lasers . SUMMARY: As the understanding of the factors that initiate and exacerbate acne vulgaris continues to increase, so does the diversity of therapeutic options . Rational use of available treatment options based on the type and severity of acne lesions is a key component of successful acne therapy and allows the physician who treats adolescents with acne to provide optimum care. J Clin Neurosci, 2004 Aug, 11(6), 677 - 9 Propionibacterium acnes causing delayed subdural empyema - a case report and review of literature; Ghalayini SR et al.; The authors report a patient who presented with a delayed subdural empyema caused by Propionibacterium acnes following excision of a meningioma . This organism should be suspected in all patients with delayed empyema especially in the presence of implants and immunosuppression . The main features of this pathogen is discussed . Surgical drainage and high-dose intravenous penicillin should be the recommended therapy. Immunol Lett, 2004 Jun 15, 94(1-2), 47 - 55 Roles of CD14 in LPS-induced liver injury and lethality in mice pretreated with Propionibacterium acnes; Shuto Y et al.; The mechanism of the liver damage and lethality in Propionibacterium acnes (P . acnes)-LPS system remains obscure . To examine the role of CD14 in the system, M14M mice, in which CD14 was expressed heterotopically under the control of the metallothionein promoter were used . The production of soluble CD14 (sCD14) was increased by both P . acnes - priming and LPS challenge (1 microg per mouse) in both nontransgenic and M14M mice, although the plasma level was much higher in M14M nontransgenic than mice . The size of granulomas induced by an intraperitoneal administration of P . acnes in M14M mice 7 days after priming was smaller than that in nontransgenic mice . An LPS challenge induced apoptotic and necrotic changes in hepatocytes in nontransgenic mice but not in M14M mice . The challenge dose resulted in almost 90% lethality in nontransgenic mice but not in M14M mice 24h after challenge . TNF-alpha, IFN-gamma, IL-12, IL-18 and inducible nitric oxide synthase (iNOS) mRNA expressions produced by LPS challenge in M14M mice were low compared with those in nontransgenic mice . IL-18 mRNA expression was upregulated in P . acnes-primed nontransgenic mice but not in M14M mice . These results suggest that the high sCD14 concentration may account for less marked liver damage in M14M mice . Increase in the challenge dose of LPS (2 microg per mouse) resulted in increased lethality of M14M mice without liver damage . The levels of endothelial cell leukocyte adhesion molecule (ELAM)-1 mRNA expression in several organs in M14M mice 1-3h after LPS challenge were, however, lower than those in nontransgenic mice . The high sCD14 concentration may stimulate endothelial cell activation, which may account for lethality without liver damage in M14M mice . Thus, CD14 is involved in both the priming and induction phases as well as lethality in P . acnes-LPS system. Cutis, 2004 Jun, 73(6 Suppl), 6 - 10 Antibiotic resistance in the topical treatment of acne vulgaris; Leyden JJ; Topical antimicrobial agents are the first line of treatment in mild to moderate acne vulgaris . The primary pathogenic agent implicated in the development of inflammatory acne is Propionibacterium acnes . P acnes also may play a secondary role in noninflammatory acne or comedogenesis . Over the past 20 years, concern has grown about the gradual worldwide increase in the prevalence of antibiotic-resistant P acnes strains . Factors associated with the development of resistant P acnes following treatment with topical antibiotics, clinical relevance of antibiotic resistance, and strategies to reduce the incidence of P acnes resistance are discussed in this review. J Cosmet Laser Ther, 2004 Jun, 6(2), 91 - 5 The role of pulsed light and heat energy (LHE) in acne clearance; Elman M et al.; BACKGROUND: Propionibacterium acnes synthesize and store a large amount of porphyrins . Once the porphyrin is exposed to visible light it becomes chemically active and transfers to an excited state, resulting in the formation of singlet oxygen, which combines with cell membranes to destroy the P . acnes . This process is dependent on the rate of production of excited porphyrin molecules, which is influenced by the concentration of porphyrins, the concentration of photons, the temperature, and the wavelength of the photons . METHODS: Nineteen patients with mild to moderate acne underwent bi-weekly treatments for 4 weeks using the ClearTouch system . During each treatment, pulses of light and heat were applied . Each pulse used an average energy density of 3.5 J/cm(2), a pulse width of 35 ms, and a wavelength between 430 and 1100 nm . RESULTS: At the end of the eighth treatment, acne clearance for the non-inflammatory and inflammatory lesions was 63 +/- 21% and 50 +/- 32%, respectively . One month after the last treatment, the acne clearance for non-inflammatory and inflammatory lesions was 79 +/- 22% and 74 +/- 20%, respectively, with further improvement in acne clearance at 2 months after the last treatment (85 +/- 17% and 87 +/- 25%, respectively) . CONCLUSION: ClearTouch pulsed light and heat energy (LHE) technology is effective and safe for the treatment of acne vulgaris. J Eur Acad Dermatol Venereol, 2004 Jul, 18(4), 450 - 4 Evidence for diversity within Propionibacterium acnes: a comparison of the T-cell stimulatory activity of isolates from inflammatory acne, endocarditis and the laboratory; Jappe U et al.; BACKGROUND: Propionibacterium acnes is primarily associated with the pathogenesis of acne vulgaris but reports are increasing in number implicating P . acnes in other diseases such as abscess formation, meningitis and endocarditis . The pathogenicity of P . acnes is thought to be partly due to the interaction of the bacterium with the immune system . Historically, investigations have focused on humoral and cell-mediated immune responses to P . acnes antigens without attention to the possibility that different antigens may be expressed by different isolates . OBJECTIVE: Investigations were performed to determine whether there were differences between a laboratory strain of P . acnes (P-37) and fresh clinical isolates in their ability to stimulate naive and adult lymphocytes . MATERIAL AND METHODS: The fresh isolates were collected from a patient with inflammatory acne and a patient with P . acnes-induced prosthetic valve endocarditis . The lymphocyte transformation assay was used to detect responses to whole-cell suspensions of stationary phase P . acnes isolates during 7 days of incubation . RESULTS: The acne isolate was significantly more stimulatory for cord blood mononuclear cells (CBMNCs) than the laboratory isolate (P . acnes P-37) at day 4 of incubation . There were no significant differences between the three strains at any other time points . However, the isolate cultivated from inflammatory acne was significantly more stimulatory for peripheral blood mononuclear cells (PBMNCs) from acne donors than the endocarditis isolate or the laboratory strain at most time points . There were no significant differences between the endocarditis strain and the laboratory strain . CONCLUSION: It can be hypothesized that in case of P . acnes-induced endocarditis lymphocyte stimulation is a disadvantage for the microorganism and therefore a lack of lymphocyte stimulation may be relevant to the pathogenesis of endocarditis. Org Biomol Chem, 2004 Jun 21, 2(12), 1777 - 81 Epub 2004 May 20. Determination of the binding specificity of the 12S subunit of the transcarboxylase by saturation transfer difference NMR; Peikert C et al.; In this study we present the characterization of the interaction of biotin and methylmalonyl-CoA (MMCoA) with the carboxyltransferase subunit (12S) from the transcarboxylase (TC) from Propionibacterium shermanii . This biotin dependent multienzyme complex catalyses the transfer of carbon dioxide from methylmalonyl-CoA (MMCoA) to pyruvate . The Saturation Transfer Difference NMR (STD) technique was performed to determine the binding epitope from biotin and MMCoA to the 12S subunit . We could show by titrations during STD experiments that biotin and MMCoA bind cooperatively in one binding pocket. Int J Dermatol, 2004 Feb, 43(2), 103 - 7 Propionibacterium acnes biotypes and susceptibility to minocycline and Keigai-rengyo-to; Higaki S et al.; BACKGROUND: Propionibacterium acnes is the predominant organism in acne lesions, but the sensitivity of different biotypes of P . acnes to therapeutic agents has seldom been reported . METHODS: To characterize biotypes of P . acnes and to measure the effects of Keigai-rengyo-to (KRT) and minocycline (MINO) on clinical P . acnes isolates . RESULTS: Propionibacterium acnes biotype III (BIII) is the most common form of identified acne lesion, followed by P . acnes biotype I . BIII was isolated from mild, moderate and severe severity and the average lipase activity of BIII was higher than that of Biotypes I, II, IV and V . No significant differences in the decrease of free fatty acid production elicited by KRT or by MINO were found between BIII and the other biotypes . The degree of decreased butyric acid production was greater than that of propionic acid production in the medium supplemented with MINO . The percent decrease of butyric acid production elicited by 1 mg/mL of KRT was the same as that elicited by 0.1 microg/mL of MINO . Among biotypes of P . acnes, the minimal inhibitory concentrations of agents tested were generally higher in erythritol-positive biotypes than in erythritol-negative biotypes . CONCLUSION: The high frequency of BIII might be responsible for the severity of acne in patients . It seems that if the same concentrations of MINO and KRT are used, the antilipase activity of MINO is stronger than that of KRT . Minocycline also has a direct anti-lipase activity against P . acnes . The mechanism underlying the influence of erythritol on the susceptibility of P . acnes to these agents remains unknown. Am J Clin Dermatol, 2004, 5(2), 79 - 84 Topical antibacterial treatments for acne vulgaris : comparative review and guide to selection; Tan HH; Topical antibacterial agents are an essential part of the armamentarium for treating acne vulgaris . They are indicated for mild-to-moderate acne, and are a useful alternative for patients who cannot take systemic antibacterials . Topical antibacterials such as clindamycin, erythromycin, and tetracycline are bacteriostatic for Propionibacterium acnes, and have also been demonstrated to have anti-inflammatory activities through inhibition of lipase production by P . acnes, as well as inhibition of leukocyte chemotaxis . Benzoyl peroxide is a non-antibiotic antibacterial agent that is bactericidal against P . acnes and has the distinct advantage that thus far, no resistance has been detected against it . Combined agents such as erythromycin/zinc, erythromycin/tretinoin, erythromycin/isotretinoin, erythromycin/benzoyl peroxide, and clindamycin/benzoyl peroxide are increasingly being used and have been proven to be effective . They generally demonstrate good overall tolerability and are useful in reducing the development of antibacterial resistance in P . acnes . The selection of a topical antibacterial agent should be tailored for specific patients by choosing an agent that matches the patient's skin characteristics and acne type . Topical antibacterial agents should generally not be used for extended periods beyond 3 months, and topical antibacterials should ideally not be combined with systemic antibacterial therapy for acne; in particular, the use of topical and systemic antibacterials is to be avoided as far as possible. Antonie Van Leeuwenhoek, 2004 Jul, 86(1), 77 - 85 Purification and characterisation of lipoglycan macroamphiphiles from Propionibacterium acnes; Whale GA et al.; Lipidated macroamphiphiles such as the lipoteichoic acids and mycobacterial lipoarabinomannans are cell envelope components of Gram-positive bacteria that have been extensively associated with the pathogenesis of disease . In order to study such associations, purification of these macroamphiphiles is essential for resolving their structures and diverse biological effects . We describe herein a method for purification of lipoglycan components from Propionibacterium acnes . This method uses the existing phenol-water extraction, followed by hydrophobic interaction chromatography and an additional purification step that utilises preparative electrophoresis for the separation of two lipoglycan components . Analysis of these lipoglycans revealed evidence for a lipid anchor based on fatty acids whilst the polysaccharide moiety contained significant amounts of mannose, glucose and galactose, together with an amino sugar suspected of being a diaminohexuronic acid . These latter components have been previously identified as components of the P . acnes cell wall polysaccharide . Consequently, it is proposed that there may be a relationship between the structures of these distinctive cell envelope polymers. J Med Dent Sci, 2003 Dec, 50(4), 265 - 74 Pulmonary granulomas caused experimentally in mice by a recombinant trigger-factor protein of Propionibacterium acnes; Minami J et al.; Etiology of sarcoidosis remains unknown . A trigger factor from Propionibacterium acnes causes a cellular immune response in some sarcoid patients but not in nonsarcoid subjects . We examined whether experimentally induced hypersensitivity to the trigger factor gives rise to granulomas . Female C57BL/6 mice primed intravenously with P . acnes or not were sensitized with recombinant-protein RP35, a fragment of P . acnes trigger factor, and complete Freund's adjuvant . In controls, RP35 was replaced with P . acnes or one of two control proteins . In primed and unprimed mice, pulmonary granulomas were found in some of the mice sensitized with RP35 or P . acnes but in no control-protein-sensitized mice . Detection of pulmonary granulomas (25-57%) did not differ significantly between mice sensitized with RP35 or P . acnes, primed or not . No difference in popliteal lymph-node-cell reactivity and serum antibodies to these two antigens was found between mice with and without pulmonary granulomas . P . acnes was cultured from the lungs of 8 (33%) of 24 untreated mice . The recombinant trigger-factor protein of P . acnes caused pulmonary granulomas in primed and unprimed mice sensitized with the protein and adjuvant . Sarcoid granulomas may form during hypersensitivity to antigens of P . acnes indigenous to the affected organ. Shanghai Kou Qiang Yi Xue, 1998 Sep, 7(3), 143 - 6 {A bacteriology analysis from infected root canals of human deciduous teeth}; Hu YW et al.; OBJECTIVE: To provide a basis for therapy and prevention, the flora of infected root canals of human deciduous teeth was analyzed.METHODS: By immediate-enzyme method, the bacteria compositions of 22 cases with infected root canals of deciduous teeth, including 8 cases with acute periapical inflammation and 14 with chronic ones, were examined . RESULTS: Among 240 strains bactera, 200 strains were obligate anaerobes, belonging to the genera peptostreptococcus, bacteriodes, veillonella, eubacterrum, propionibacterium, actinomyces and fusobacterium . Bacteriodes and eusobacterium especially B . gingivalis and F . nucleatum have been more frequently isolated from root canals with acute periapical inflammation than that with chronic ones (P<0.05) . In chronic cases, veillonella especially V . parvula, were more frequently isolated than acute inflammation . CONCLUSION: Periaplcal inflammation of deciduous teeth was mixed polymicrobial infections regardless of acute or chronic cases and anaerobic bacteria were dominated . B . gingivalis and F . nucleatum probably were related to acute periapical inflammation of deciduous teeth . The effect of V . parvula on chronic periapical innammation of deciduous teeth should not be neglected. Appl Environ Microbiol, 2004 Apr, 70(4), 2240 - 4 Prevalence of the genes encoding propionicin T1 and protease-activated antimicrobial peptide and their expression in classical propionibacteria; Faye T et al.; The purpose of this study was to investigate the frequency of production of the bacteriocin propionicin T1 and the protease-activated antimicrobial peptide (PAMP) and their corresponding genes in 64 isolates of classical propionibacteria . This study revealed that these genes are widespread in Propionibacterium jensenii and Propionibacterium thoenii but absent from the remaining species of classical propionibacteria that were studied . The pro-PAMP-encoding gene (pamA) was found in 63% of the P . jensenii strains and 61% of the P . thoenii strains, and all of these strains displayed PAMP activity . The propionicin T1-encoding gene (pctA) was present in 89% of the P . thoenii strains and 54% of the P . jensenii strains . All P . thoenii strains containing the pctA gene exhibited antimicrobial activity corresponding to propionicin T1 activity, whereas only 38% of the pctA-containing P . jensenii strains displayed this activity . Sequencing of the pctA genes revealed the existence of two allelic variants that differed in a single nucleotide in six strains of P . jensenii; in these strains the glycine at position 55 of propionicin T1 was replaced by an aspartate residue (A variant) . No strains harboring the A variant showed any antimicrobial activity against propionicin T1-sensitive bacteria . An open reading frame (orf2) located immediately downstream from the pctA gene was absent in three strains containing the G variant of propionicin T1 . Two of these strains showed low antimicrobial activity, while the third strain showed no antimicrobial activity at all . The protein encoded by orf2 showed strong homology to ABC transporters, and it has been proposed previously that this protein is involved in the producer immunity against propionicin T1 . The limited antimicrobial activity exhibited by the strains lacking orf2 further suggests that this putative ABC transporter plays an important role in propionicin T1 activity. FEBS Lett, 2004 Mar 26, 562(1-3), 22 - 6 A thermostable manganese-containing superoxide dismutase from pathogen Chlamydia pneumoniae; Yu J et al.; The gene CP0718 encoding a putative manganese-containing superoxide dismutase of Chlamydia pneumoniae AR39 was cloned and expressed in Escherichia coli . Characterization showed that the expressed protein with a monomeric molecular mass of 23.1 kDa had superoxide dismutase (SOD) activity and the cofactor of CpSOD was a bivalent manganese cation . It is unexpected that this enzyme was hyperthermostable, and maintained about 90% activity after incubation at 70 degrees C for 60 min . Manganese binding residues found in the SOD sequences from different species are conserved in CpSOD . Bioinformatics analysis compared with Propionibacterium shermanii MnSOD was performed to elucidate the CpSOD hyperthermostability based on amino acid sequences. Br J Dermatol, 2004 Mar, 150(3), 421 - 8 Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P . acnes GroEL; Graham GM et al.; BACKGROUND: Keratinocytes form the first line of defence in the skin and alert the host to danger by the production of a number of cytokines and chemokines . However, the interaction of commensal microorganisms with keratinocytes has not been well studied . OBJECTIVES: To investigate the effect of viable and nonviable cells of Propionibacterium acnes in both exponential and stationary growth phases, and of P . acnes GroEL on cytokine production by human primary keratinocytes . METHODS: Actively proliferating or contact-inhibited keratinocytes were cocultured with viable or formaldehyde-killed P . acnes cells in either the exponential or stationary phase of growth . Culture supernatants were assayed by enzyme-linked immunosorbent assay for the cytokines interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor (GM-CSF) . Keratinocytes were also stimulated with different concentrations of P . acnes GroEL and supernatants assayed for cytokines . RESULTS: Viable P . acnes in the stationary phase of growth stimulated keratinocyte monolayers to produce significantly higher amounts of IL-1alpha, TNF-alpha and GM-CSF than unstimulated keratinocytes . Viable exponential-phase bacteria stimulated production of significantly higher amounts of TNF-alpha and GM-CSF but these levels were significantly lower than those for stimulation with stationary-phase bacteria . Nonviable P . acnes from either growth phase was not able to stimulate cytokine production . P . acnes GroEL at concentrations in the range 0.05-1.0 micro g mL(-1) was able to induce increased production of cytokines by keratinocytes in a dose-dependent manner . This was analogous to stimulation with Escherichia coli GroEL . CONCLUSIONS: Stimulation of cytokine production by P . acnes and P . acnes GroEL may be important in the pathogenesis of inflammatory acne vulgaris and may have wider implications for the immunomodulation of the human immune system by commensal skin microorganisms. J Agric Food Chem, 2004 Mar 24, 52(6), 1749 - 52 Enrichment of conjugated linoleic acid in oats (Avena sativa L.) by microbial isomerization; Vahvaselka M et al.; A method for microbial isomerization of oat linoleic acid to conjugated linoleic acid (CLA) was developed . The method includes hydrolysis of oat lipids in aqueous flour slurries by the endogenous oat lipase . Then, the flour slurry containing free linoleic acid is utilized as a substrate for the isomerization reaction carried out by resting cells of Propionibacterium freudenreichii ssp . shermanii . The isomerization reaction progressed most effectively when, after the lipid hydrolysis period, the pH of the slightly acidic oat slurry was elevated to 8.0-8.5 and maintained at this range . With slurries containing 5% (w/v) oat flour, the amounts of CLA formed per dry matter were up to 10.1 mg/g corresponding to 102 mg/g lipids or 0.44 mg/mL slurry . Increments in the flour content up to 15% increased the volumetric production of CLA to 0.85 mg/mL . The proportion of the cis-9,trans-11 isomer was 80% of the total CLA formed . CLA could be concentrated into the solid material of the oat slurry by acidification. Eur J Clin Microbiol Infect Dis, 2004 Apr, 23(4), 310 - 6 Epub 2004 Mar 13. Risk factors for mortality in patients with anaerobic bacteremia; Wilson JR et al.; Risk factors for mortality in anaerobic bacteremia have been incompletely defined . The aims of the present study were to determine clinical significance by pathogen for a broad range of obligate anaerobic organisms isolated from blood, and to define the factors independently associated with mortality among those with clinically significant bacteremia . All patients who had anaerobic bacteria isolated from blood over a 19-month period (from 1 September 1998 to 1 April 2000) at two urban teaching hospitals were included in this study . Each case was analyzed for clinical significance by means of a retrospective medical record review using predetermined definitions . Information was collected on a broad range of clinical and microbiological factors, which were evaluated for their association with mortality using a Cox proportional hazards model . Among 166 patients with obligate anaerobic bacteria isolated from blood, 73 (44%) were deemed to have clinically significant bacteremia . Clinical significance ranged from 0% (0/53) for Propionibacterium spp . to 96% (43/45) for Bacteroides spp . The crude mortality rate in patients with clinically significant anaerobic bacteremia was 25% (18/73) . Mortality was significantly associated with age, polymicrobial infection, and underlying heart, kidney or liver disease in univariate analysis . Only the presence of liver disease (relative risk, 5.3; 95% confidence interval, 1.7-16.0; P=0.003) and patient age (relative risk, 1.06/y; 95% confidence interval, 1.0-1.1; P=0.005) remained significant in multivariate analysis . Among patients with anaerobic bacteremia, clinical significance varies markedly by pathogen and mortality is independently associated with age and underlying liver disease. Phytother Res, 2004 Feb, 18(2), 180 - 3 Antibacterial activity of ent-kaurene diterpenoids from Rabdosia rosthornii; Kubo I et al.; Biological activities of ent-kaurene diterpenoids, rosthornins A-D, isolated from the ether extract of the dried leaves of Rabdosia rosthornii (Diels) Hara (Labiatae) were tested . They exhibited antibacterial activity specifically against Gram-positive bacteria, among which Propionibacterium acnes was noted to be the most susceptible . Drugs Exp Clin Res, 2003, 29(4), 157 - 9 Propionibacterium acnes lipase in seborrheic dermatitis and other skin diseases and Unsei-in; Higaki S et al.; We examined Propionibacterium acnes lipase in skin diseases and Unsei-in . Butyric acid production in axillary seborrheic dermatitis (ASD) was higher than in other dermatitis, and that in acne vulgaris (AV) was significantly higher than in controls . P . acnes lipase is the pathogenic factor in AV and fatty acids produced by lipase might be the pathogenic factor in ASD . Unsei-in suppressed P . acnes lipase probably because some ingredients have antimicrobial and anti-inflammatory activities. Z Naturforsch {C}, 2004 Jan-Feb, 59(1-2), 93 - 8 In situ assessment of porphyrin photosensitizers in Propionibacterium acnes; Ramberg K et al.; Porphyrins are known to be efficient photosensitizer molecules and the combined action of light and porphyrins in Propionibacterium acnes have a lethal action on the cells . Identification and quantification of in situ porphyrins in P . acnes have been done using an integrating sphere connected to an ordinary absorption spectrophotometer, and the amounts of porphyrins in the cells were quantified by measuring scattering free absorption spectra of the cell suspensions . The concentration of porphyrins in P . acnes cells were increased in either of two ways; by the addition of delta-aminolevulinic acid (ALA), which lead to the formation of coproporphyrin III under the incubation conditions used in these experiments, or by the addition of protoporphyrin IX (PPIX) to the cell suspension . In the latter case, PPIX molecules are taken up by the cells in a membrane-mediated uptake mechanism, and accumulate in the cells either on a monomeric or a particular aggregate form . The fraction of porphyrins on aggregate form increased with increasing PPIX additions . In the case of ALA induced porphyrin production, only monomeric porphyrins were stored in the cells . In both cases, the cells have a limited binding capacity of monomeric porphyrins, which is estimated to be 3 x 10(5) molecules/cell, or one porphyrin molecule to every 100st lipid molecule in the cell membrane. Int J Food Microbiol, 2004 Mar 1, 91(2), 195 - 204 Enhancement of trehalose production in dairy propionibacteria through manipulation of environmental conditions; Cardoso FS et al.; We have shown that the ability to produce trehalose is widespread within the genus Propionibacterium . Eighteen strains isolated from dairy sources were screened for trehalose synthesis; the effect of environmental conditions on trehalose production was evaluated in Propionibacterium freudenreichii ssp . shermanii NIZO B365, a strain that accumulated high amounts of this disaccharide . Lactose was the best carbohydrate source for trehalose production, whereas lactate, the substrate that led to the highest specific growth rate, was a poor precursor . Trehalose was consumed after exhaustion of the carbon source in the medium, suggesting its role as a reserve compound . The production of trehalose was not affected by lowering the growth temperature from 30 to 20 degrees C . On the other hand, the maximum trehalose accumulation increased from about 200 to 400 mg of trehalose/g of cell protein upon decreasing the pH from 7.0 to 4.7, by increasing the concentration of NaCl to 2% (w/v), or during growth under aerobic conditions (50% air saturation, 24 microM O(2), pH 7.0) . In the absence of NaCl, trehalose accumulated concomitantly with growth, but an increase in salinity triggered a high trehalose production already in the early exponential growth phase . The data provide evidence for a dual function of trehalose as a reserve compound and as a stress-response metabolite . Moreover, P . freudenreichii ssp . shermanii NIZO B365 was able to produce high levels of trehalose in skim milk, which is promising for the implementation of fermented dairy products. Acta Crystallogr D Biol Crystallogr, 2004 Mar, 60(Pt 3), 521 - 3 Epub 2004 Feb 25. Expression and crystallization of several forms of the Propionibacterium shermanii transcarboxylase 5S subunit; Hall PR et al.; The dimeric outer 5S subunit of transcarboxylase has been expressed in three different forms and crystallized: native 5S, 5S-His(6) and selenomethione-5S-His(6) . All the crystals have an orthorhombic space group, but while native 5S forms primitive orthorhombic crystals, 5S-His(6) crystals are either C-centered or primitive and SeMet-5S-His(6) crystals are C-centered . Crystallization of native 5S requires the addition of lithium sulfate, whereas this salt prevented crystallization of 5S-His(6) . All 5S crystals diffract to approximately 2.0 A resolution with synchrotron radiation . Efforts are under way to solve the structure of SeMet-5S-His(6) using MAD. Arch Dermatol, 2004 Feb, 140(2), 210 - 4 Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis; Westerhof W et al.; BACKGROUND: Progressive macular hypomelanosis is a common hypopigmentation mainly on the central parts of the trunk, predominantly in young adults, especially women . It is often mistaken for pityriasis versicolor and pityriasis alba . It occurs in all races and has been described in many parts of the world . We discovered follicular red fluorescence restricted to lesional skin . We suspected a relation with a porphyrin-producing bacteria residing in sebum of the pilosebaceous duct, and we therefore performed a study in 8 patients.Observation In all biopsy specimens taken from lesional skin of 8 women, we could demonstrate gram-positive bacteria in the pilosebaceous duct, and a mild perifollicular lymphocytic infiltrate was seen . In all but 1 patient, Propionibacterium acnes was yielded from cultured biopsy specimens taken from follicular lesional skin . Healthy follicular skin did not show bacteria in histological sections, and cultures did not yield anaerobic bacteria . CONCLUSIONS: There seems to be a relation between the presence of P acnes and the hypopigmented macules . We propose that a factor is produced by these strains of P acnes, which interfere with melanogenesis . Based on these observations, we are undertaking a clinical trial to find a treatment for this troubling, intractable disease. Int Endod J, 2004 Jan, 37(1), 61 - 9 Resolution of persistent periapical infection by endodontic surgery; Ferreira FB et al.; AIM: To examine the surfaces of a root tip removed during surgical endodontic treatment for the presence of microorganisms . SUMMARY: The present clinical case illustrates an endodontic retreatment of a maxillary premolar tooth with a fistula and periapical reaction . The case was under treatment for 1 year, during which an intracanal medicament was replaced several times . As the lesion did not decrease and exudate was persistent through the fistula and root canal, root end resection with root end filling was performed . Microbiological samples were collected from the fistula, where Propionibacterium acnes, a species associated with endodontic failures, was detected by appropriate anaerobic technique . The resected root apex was observed by scanning electron microscopy (SEM), which revealed cocci and fungal forms surrounding one of the foramina . After 12 months, the periapical lesion had reduced. J Natl Cancer Inst, 2004 Feb 4, 96(3), 201 - 9 Mobilization of dendritic cell precursors into the circulation by administration of MIP-1alpha in mice; Zhang Y et al.; BACKGROUND: Dendritic cells (DCs) play a central role in immune responses and may be useful adjuvants for tumor vaccine therapy . We previously reported that F4/80(-)B220(-)CD11c(+) DC precursors expressing the CC chemokine receptors CCR1 and CCR5 are mobilized rapidly into the circulation in mice injected with Propionibacterium acnes and are recruited into inflammatory tissue by macrophage inflammatory protein 1alpha (MIP-1alpha), which binds to CCR1 and CCR5 . Here we investigate the mechanisms of DC precursor mobilization and the antitumor effect of these cells in mice . METHODS: Numbers of DC precursors in peripheral blood were determined in P . acnes-treated mice (groups of 10 C57BL/B6 {B6} wild-type mice, CCR1(-/-) mice, CCR5(-/-) mice, and B6 mice treated with antibody to MIP-1alpha or control antibody) and in B6 mice injected with recombinant MIP-1alpha . MIP-1alpha-mobilized DC precursors matured by treatment with granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor-alpha and pulsed with B16 melanoma lysates were assayed for their ability to confer protective immunity against tumor challenge in vivo and to induce cytotoxic T lymphocytes against B16 tumor cells in vitro . RESULTS: The recruitment of DC precursors into the circulation by P . acnes administration was higher in B6 mice (12.6%, 95% confidence interval {CI} = 9.1% to 16.1%) than in CCR1(-/-) (9.0%, 95% CI = 7.5% to 10.5%), CCR5(-/-) (6.3%, 95% CI = 5.2% to 7.3%), or anti-MIP-1alpha antibody-treated (6.6%, 95% CI = 5.7% to 7.5%) mice . Injection of MIP-1alpha also mobilized DC precursors into the circulation (13.1%, 95% CI = 10.8% to 15.6%) . Matured MIP-1alpha-mobilized-DC precursors pulsed with B16 tumor lysates elicited B16-specific antitumor immunity in vitro and in vivo . CONCLUSIONS: MIP-1alpha and its receptors are important in recruiting DC precursors into the circulation . DC precursors mobilized rapidly by MIP-1alpha may provide sufficient useful DC precursors for DC-based vaccination in cancer treatment. Arch Microbiol, 2004 Mar, 181(3), 215 - 30 Epub 2004 Jan 17. Mass spectrometry proteomic analysis of stress adaptation reveals both common and distinct response pathways in Propionibacterium freudenreichii; Leverrier P et al.; Microorganisms used in food technology and probiotics are exposed to technological and digestive stresses, respectively . Traditionally used as Swiss-type cheese starters, propionibacteria also constitute promising human probiotics . Stress tolerance and cross-protection in Propionibacterium freudenreichii were thus examined after exposure to heat, acid, or bile salts stresses . Adapted cells demonstrated acquired homologous tolerance . Cross-protection between bile salts and heat adaptation was demonstrated . By contrast, bile salts pretreatment sensitized cells to acid challenge and vice versa . Surprisingly, heat and acid responses did not present significant cross-protection in P . freudenreichii . During adaptations, important changes in cellular protein synthesis were observed using two-dimensional electrophoresis . While global protein synthesis decreased, several proteins were overexpressed during stress adaptations . Thirty-four proteins were induced by acid pretreatment, 34 by bile salts pretreatment, and 26 by heat pretreatment . Six proteins are common to all stresses and represent general stress-response components . Among these polypeptides, general stress chaperones, and proteins involved in energetic metabolism, oxidative stress response, or SOS response were identified . These results bring new insight into the tolerance of P . freudenreichii to heat, acid, and bile salts, and should be taken into consideration in the development of probiotic preparations. Microb Pathog, 2004 Mar, 36(3), 171 - 4 Studies on the cytotoxic effects of Propionibacterium acnes strains isolated from cornea; Csukas Z et al.; Eukaryotic tissue culture appears to be a suitable model for measuring the bacterial cytotoxic effect . Propionibacterium acnes strains were isolated from corneal tissue removed by keratoplastic surgery from patients with corneal dystrophy or bullous keratopathy . The cytotoxic effect of the filtrates of 10 P . acnes strains were studied by means of measuring the decrease of the mitochondrial dehydrogenase activities of viable epithelial (HeLa) and fibroblastic (BHK-21) cell cultures . A time and concentration dependent, reversible cytotoxic effect was detected in both tissue types . The results also showed that strains of P . acnes are capable of surviving anaerobic conditions for as long as 8 months and suggest that production cytotoxic effects during the long persistence it may harm human tissue. J Vasc Surg, 2003 Dec, 38(6), 1384 - 9 Multiple bacteria in aortic aneurysms; Marques da Silva R et al.; OBJECTIVE: The purpose of the present study was to reexamine the possibility that bacteria, particularly anaerobes, are present in aortic aneurysms . METHODS: From December 2000 to November 2001, 53 samples from aneurysm walls were collected from 49 patients during reconstructive surgery . The tissue specimens were sectioned and cultured under anaerobic conditions . Twenty-eight specimens were also subjected to scanning or transmission electron microscopy . RESULTS: Anaerobic cultivation yielded bacteria in 14 of the 53 samples (26.4%) . All bacteria were gram-positive cocci or rods from nine genera and 12 species . Five cultures (35%) were mixed, containing two bacterial species . Mixed aerobic and anaerobic species were found in four samples (28.5%) . Anaerobic bacteria were recovered from 10 of 14 positive cultures (71%) . Among anaerobes found were Propionibacterium acnes, Propionibacterium granulosum, Actinomyces viscosus, Actinomyces naeslundii, and Eggerthella lenta . Coaggregating bacteria of different sizes and structure were found on the aneurysm walls and inside the intravascular plaque at electron microscopy . Bacteria were found in 20 of the 28 samples (71%) examined with scanning or transmission electron microscopy . CONCLUSION: Multiple bacteria, many of which did not belong to the indigenous skin microflora, colonize aortic aneurysms . It is not clear whether the bacteria contribute to weakening of the aortic wall by eliciting inflammation or whether they are secondary colonizers of aneurysms. Skinmed, 2003 Jul-Aug, 2(4), 234 - 45 Subantimicrobial dose doxycycline for acne and rosacea; Bikowski JB; Acne vulgaris and rosacea present therapeutic challenges due to their chronicity, potential for disfigurement, and psychosocial impact . Although pathophysiologically distinct, both conditions have major inflammatory components . Consequently, topical and systemic antimicrobial agents are routinely prescribed for extended periods . Emergence of resistant strains of Propionibacterium acnes, adverse events, and compliance issues associated with chronic systemic tetracycline use have led to new treatment approaches . At subantimicrobial doses, tetracyclines reduce inflammation via anticollagenolytic, antimatrix-degrading metalloproteinase, and cytokine down-regulating properties . Subantimicrobial dose (SD) doxycycline (Periostat 20 mg) has clinical utility in periodontitis and has been investigated in a double-blind, placebo-controlled trial in the treatment of moderate facial acne as well as in an open label study in the treatment of rosacea . The results of subantimicrobial dose doxycycline treatment in early trials support its benefits and further investigation in acne and rosacea. Dermatology, 2003, 207(4), 343 - 8 Is androgenetic alopecia a photoaggravated dermatosis? Trueb RM. Progressive thinning of the scalp hair in androgenetic alopecia (AGA) results in a gradual decline in natural protection of the scalp from ultraviolet radiation (UVR) . A number of pathologic conditions of the scalp are evidently related to UVR, particularly photosensitive diseases and disorders of the chronically photodamaged bald scalp . The most important chronic effects of UVR are photocarcinogenesis and solar elastosis . Besides these, erosive pustular dermatosis and 'red scalp' are distinct disorders peculiar to the balding scalp . While the consequences of sustained UVR on the unprotected scalp are well appreciated, the effects of UVR on hair loss have widely been ignored . However, clinical observations and theoretical considerations suggest that UVR may have negative effects: acute telogen effluvium from UVR has been described, and the production of porphyrins by Propionibacterium sp . in the pilosebaceous duct, with photoactivation of porphyrins leading to oxidative tissue injury, has been implicated in follicular microinflammation . Alternatively, keratinocytes themselves may respond to physicochemical stress from UVR, besides irritants and pollutants, by producing radical oxygen species and nitric oxide and by releasing proinflammatory cytokines, eventually leading to injury of the putative site of follicular stem cells in the superficial portion of the hair follicle . Since all of these processes involved in hair loss share the common feature that they are induced or exacerbated by exposure to sunlight, it is proposed that AGA is a photoaggravated dermatosis that requires photoprotection . Am J Clin Dermatol, 2003, 4(12), 813 - 31 Is antibiotic resistance in cutaneous propionibacteria clinically relevant? : implications of resistance for acne patients and prescribers; Eady AE et al.; It is well recognized that some patients with acne do not respond adequately to antibiotic therapy . It is important to distinguish antibiotic recalcitrant acne which we would suggest represents acne that shows a diminished response to treatment irrespective of the cause as opposed to 'antibiotic-resistant acne' which is acne that is less responsive to treatment as a direct consequence of skin colonization with resistant propionibacteria . Here we show that antibiotic-resistant acne is not just a theoretical possibility but a real phenomenon that could have important consequences for patients and prescribers . The relationship between skin colonization by antibiotic-resistant propionibacteria and treatment outcomes is a complex one that is explained at the follicular level by physiological differences affecting local drug concentrations . A systematic review of the literature on antibiotic-resistant propionibacteria revealed methodological shortcomings in studies of their prevalence and a paucity of evidence on their clinical significance . Despite the elucidation of resistance mechanisms in cutaneous propionibacteria, our continuing inability to distinguish between strains of Propionibacterium acnes means that we still do not fully understand how resistance spreads, although person-to-person transfer is most likely . Finally, we present a decision tree for acne management in an era of prudent antimicrobial prescribing that provides an alternative to existing treatment algorithms by placing topical retinoids and not antibiotics at the cornerstone of acne management. Surgery, 2003 Nov, 134(5), 818 - 26 Effects of OPC-6535 on lipopolysaccharide-induced acute liver injury in the rat: involvement of superoxide and tumor necrosis factor-alpha from hepatic macrophages; Hasegawa T et al.; BACKGROUND: The objective of this study was to investigate the effects of OPC-6535 on Propionibacterium acnes-primed and lipopolysaccharide-induced liver injury in the rat . METHODS: P . acnes was administered intravenously to the rat at 16 mg/kg 7 days before the experiments . In liver perfusion experiments, lipopolysaccharide was mixed in perfusion buffer at 2.5 microg/mL . The chemiluminescence method and histochemical reduction of nitro blue tetrazolium were used for detecting superoxide . Release of cytokines into the perfusate was examined . In in vivo experiments, lipopolysaccharide was administered intravenously to the rat at 200 microg/kg . Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were determined in the plasma, and myeloperoxidase activity was measured in the liver tissue . OPC-6535 was given intravenously at 1 mg/kg 30 minutes before lipopolysaccharide challenge, and was then, in perfusion experiments, added to the buffer at 10 micromol/L . RESULTS: In perfusion experiments, P . acnes and lipopolysaccharide caused dramatic production of superoxide, tumor necrosis factor-alpha (TNF-alpha) and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) . Superoxide was mainly from hepatic macrophages . Treatment with OPC-6535 suppressed superoxide and TNF-alpha but did not affect GRO/CINC-1 . In in vivo experiments, P . acnes and lipopolysaccharide increased the level of TNF-alpha, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase activity in the liver . OPC-6535 reduced TNF-alpha, AST, and ALT, but did not affect GRO/CINC-1 or myeloperoxidase . CONCLUSION: Attenuation of liver injury by OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF-alpha production by hepatic macrophages in P . acnes- and lipopolysaccharide-treated rats. Sarcoidosis Vasc Diffuse Lung Dis, 2003 Oct, 20(3), 197 - 203 Propionibacterium acnes DNA detected in bronchoalveolar lavage cells from patients with sarcoidosis; Hiramatsu J et al.; BACKGROUND AND AIM OF THE WORK: The causes of sarcoidosis are unknown . Propionibacterium acnes is so far the only bacterium to be found in sarcoid lymph nodes . We attempted to detect P . acnes DNA in cells recovered by bronchoalveolar lavage (BAL) from patients with sarcoidosis . METHODS: BAL cells from 30 patients with histologically proven sarcoidosis and 30 controls with other lung diseases were examined by a nested polymerase chain reaction (PCR) for 16S rRNA of P . acnes . BAL cells from three recent sarcoid patients and two control patients were also examined by in situ PCR to locate P . acnes DNA . Clinical findings in sarcoid patients with and without positive results by PCR were compared . RESULTS: P . acnes DNA was detected in BAL cells from 21 (70%) sarcoid patients and 7 (23%) control patients . In situ signals of P . acnes DNA were detected in the cytoplasm of 0.2% to 2.8% of alveolar macrophages from sarcoid patients, but from no cells of the control patients . Gallium-67 uptake by lung parenchyma was found in about half of the sarcoid patients with P . acnes DNA, but in none of the other sarcoid patients . More of these patients with such DNA had lung parenchymal shadows in chest X-ray films and were in more advanced stages of the disease than the other sarcoid patients . CONCLUSIONS: Detection of P . acnes DNA in BAL cells was significantly more common in the patients with confirmed sarcoidosis . Detection was associated with some indices of disease activity in the lung. Clin Microbiol Infect, 2003 Nov, 9(11), 1125 - 7 Molecular diagnosis of a vascular prosthesis infection, due to Propionibacterium acnes, by amplification and sequencing of 16S rDNA; Le Page L et al.; We describe a case of indolent vascular prosthesis infection due to Propionibacterium acnes . The microorganism was identified only by amplification and sequencing of 16S rDNA, while standard cultures remained negative . This observation underscores the usefulness of molecular techniques for the diagnosis of infection caused by fastidious microorganisms. FEMS Microbiol Lett, 2003 Nov 7, 228(1), 51 - 5 Analysis of clinical isolates of Propionibacterium acnes by optimised RAPD; Perry AL et al.; Random amplification of polymorphic DNA (RAPD) was evaluated as a genotypic method for typing clinical strains of Propionibacterium acnes . RAPD can suffer from problems of reproducibility if parameters are not standardised . In this study the reaction conditions were optimised by adjusting template DNA concentration and buffer constituents . All isolates were typeable using the optimised RAPD protocol which was found to be highly discriminatory (Simpson's diversity index, 0.98) and reproducible . Typing of P . acnes by optimised RAPD is an invaluable tool for the epidemiological investigation of P . acnes for which no other widely accepted method currently exists. Eur J Pharm Biopharm, 2003 Nov, 56(3), 407 - 12 Hydrogel patches containing triclosan for acne treatment; Lee TW et al.; Adhesive hydrogel patches containing Triclosan (TS) were prepared as an anti-acne dosage form . Sodium polyacrylate and carboxymethylcellulose (sodium salt) were used as matrix polymers, and Al(3+), produced by the reaction of dihydroxy aluminum aminoacetate and L(+)-tartaric acid, was employed as a crosslinking agent for the negatively charged polymers . The crosslinking reactions were done at 25, 40 and 50 degrees C for predetermined time intervals . The semi-solid gels were obtained only when the reaction period was more than 12 h, but the polymer gels were fluidic with a shorter reaction . The swelling ratios increased as the reaction period was prolonged and the reaction temperature increased, indicating that the degree of the crosslinking is proportional to the reaction period and the temperature . On a scanning electron microphotograph, the crosslinked gel exhibited a honeycomb-like structure having pores of a few micrometers . The adhesive force of a patch, which could be easily attached to and peeled off facial skin, was 45.5 gmf and it increased by adding poly acrylic acid into the patch formulations . Propionibacterium acnes (ATCC 6919) growth inhibition area around the patch was not significant on an agar plate when TS content was 0.01 wt.%, but the antibacterial activity was apparent when the content was 0.05 wt.% . In vitro permeation revealed that up to 5 wt.% of Transcutol (TC) content in patch, TC, a permeation enhancer, significantly increased the amount of TS transported into hairless mouse skins but it did not substantially accelerate TS transportation into the receptors of Franz diffusion cells . Since our patches for the treatment of acne was aimed to localize TS into skins, TC content of 5 wt.% seems to be adequate for the dermal delivery of TS . The model patches in this study would be applicable to facial skins for the treatment of acne. Vet Q, 2003 Sep, 25(3), 131 - 6 First cases of animal diseases published since 2000 . 3 . Cattle; Elsinghorst TA; In this third article of a series of papers listing first case reports of animal diseases published since 2000, the following seven cases of cattle diseases are discussed: AL amyloidosis . Canola oil intoxication . Disseminated intracytoplasmic neuronal vacuolation . Encephalomyelitis associated with Akabane virus infection in adult cows . Lower limb deformity: "mirror image duplication of the plantar/palmar half of the distal portion of the digit" . Lupinus argenteus intoxication . Novel Propionibacterium infection . After a short introduction, the bibliographical data, the abstract of the author(s), and some additional information derived from the article are given . The article will be regularly updated adding overlooked as well as new first reports. Eur Radiol, 2003 Oct, 13(10), 2304 - 8 Epub 2003 Mar 13. Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up; Kirchhoff T et al.; Propionibacterium acnes (P . acnes) is suspected to be involved in the pathophysiology of SAPHO syndrome, since it has been isolated repeatedly through open surgical bone biopsy . This study demonstrates the role of MRI in identifying inflamed bone areas in patients with SAPHO syndrome and the role of CT-guided bone biopsies in obtaining samples from these areas for microbiological and histopathological investigations, thus obviating open surgery . Fourteen consecutive patients with SAPHO syndrome were investigated by MRI to identify acute inflammatory changes in hyperostotic periarticular bone . The CT-guided biopsies for microbiological investigations were taken from the areas identified . Patients positive for P . acnes were started on long-term antibiotic therapy according to antibiotic susceptibility . On MRI the inflammatory changes appeared as hyperintense areas on fat-saturated T2 fast-spin-echo (FSE) images and showed signal increase on fat-saturated T1 SE images after Gd-DTPA . With MR localization CT-guided bone biopsies yielded P . acnes in 8 patients . No bacteria could be isolated from the remaining 6 patients . Acute inflammatory bone changes in SAPHO syndrome are well localized by MRI . With MR localization, CT-guided bone biopsies offer a minimally invasive alternative to open surgery in the detection of . P . acnes leading to the institution of a specific antibiotic therapy. Biol Pharm Bull, 2003 Oct, 26(10), 1393 - 7 Influence of histamine in a liver injury model induced by Propionibacterium acnes and lipopolysaccharide; Kurihara H et al.; In normal mice, plasma histamine levels were 29.4+/-10.1 pmol/ml . When 0.1 microg of lipopolysaccharide (LPS) was intravenously injected into Propionibacterium acnes (P . acnes)-primed ICR mice, histamine levels increased remarkably to 61.2+/-15.9 pmol/ml (p<0.001) . An increase was also observed in liver tissues . Oral administration of histidine at 200 mg/kg once daily for 5 d before intravenous LPS injection increased the plasma alanine aminotransferase (ALT) activity to 2936.5+/-356.3 IU/l, a significant change compared with the controls (2244.8+/-425.5 IU/l, p<0.05) . The 24 h survival rate after LPS injection was 72.7% in the mice treated with 50 mg/kg of ranitidine, in contrast with 50% in the control group although the treatment did not significantly decrease the plasma ALT activity . On the other hand, 50 mg/kg of pyrilamine significantly reduced plasma ALT activity (p<0.001) . The results suggested that histamine levels are related to hepatic damage in the P . acnes plus LPS induction of liver injury. Dermatol Nurs, 2003 Aug, 15(4), 359 - 62 Antibiotic resistance of Propionibacterium acnes in acne vulgaris; Swanson JK; Acne vulgaris is a common skin disease affecting all ages . Antibiotics remain the most common prescribed agent for the treatment of acne . Improper use of antibiotics in the dermatological setting needs to be evaluated to prevent the increasing prevalence of antibiotic resistance. J Leukoc Biol, 2003 Dec, 74(6), 1056 - 63 Epub 2003 Nov 21. TNF revisited: TNF-independent antitumor activity in sera of mice sensitized with Propionibacterium acnes and challenged with lipopolysaccharide; Schwamberger G et al.; Sera of mice sensitized with bacteria and subsequently challenged with lipopolysaccharide promote hemorrhagic necrosis of tumors in vivo and display cytotoxic activity against tumor cells in vitro, which has been attributed to the induction of tumor necrosis factor (TNF) . Here, we describe the induction of a previously unrecognized antitumor activity in such sera, which is distinct from TNF but displays tumor-specific cytocidal activity in vitro as well as potent tumor-regressing activity in vivo . Biochemical analysis of this activity yielded a molecular mass of approximately 150 kDa, closely resembling a novel tumoricidal factor of murine macrophages (Mphi) termed MTC 170 (Mphi tumor cytotoxin, approximate m