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.Propionibacterium acnes is an opportunistic pathogen implicated in late-stage prosthetic joint infections, acne vulgaris, endocarditis, endophthalmitis, osteomyelitis, and shunt-associated central nervous system infections (2,5,7,33). Currently, routine diagnostic practices may underestimate the clinical importance of this anaerobic organism due to inefficient detection and isolation procedures, along with the traditionally held view that, due to its low virulence, its presence in clinical samples reflects contamination. While the opportunistic pathogenic potential of coagulase-negative staphylococci (CoNS), such as Staphylococcus epidermidis, is well recognized, the importance of P. acnes may still be overlooked (13), despite the fact that it produces more kinds of putative virulence determinants than CoNS (5, 38). This fact is illustrated by recent studies in which P. acnes was recovered as frequently as CoNS from the prosthetic hips of patients undergoing revision arthroplasty (33, 34).As a member of the resident human microbiota, P. acnes is found predominantly in the sebaceous gland-rich areas of the skin in adults (5, 25). It has, however, also been isolated from the conjunctiva, the mouth, and the large intestine (7). It accounts for approximately half of the total skin microb...
The modification of proteins by nonenzymatic glycation leading to accumulation of advanced glycation end products (AGEs) is a well-established phenomenon of aging. In the eyes of elderly patients, these adducts have been observed in retinal pigment epithelium (RPE), particularly within the underlying pentalaminar substrate known as Bruch's membrane. AGEs have also been localized to age-related subcellular deposits (drusen and basal laminar deposits) and are thought to play a pathogenic role in progression of the major sight-threatening condition known as age-related macular degeneration (AMD). The current study has quantified AGEs in Bruch's membrane from postmortem eyes and established age-related correlations. In particular, we investigated the potential of confocal Raman microscopy to identify and quantify AGEs in Bruch's membrane in a nondestructive, analytical fashion. Bruch's membrane and the innermost layers of the underlying choroid (BM-Ch) were dissected from fresh postmortem eye-cups (n=56). AGE adducts were quantified from homogenized tissue using reverse-phase HPLC and GC/MS in combination with immunohistochemistry. For parallel Raman analysis, BM-Ch was flat-mounted on slides and evaluated using a Raman confocal microscope and spectra analyzed by a range of statistical approaches. Quantitative analysis showed that the AGEs pentosidine, carboxymethyllysine (CML), and carboxyethyllysine (CEL) occurred at significantly higher levels in BM-Ch with age (P<0.05-0.01). Defined Raman spectral "fingerprints" were identified for various AGEs and these were observed in the clinical samples using confocal Raman microscopy. The Raman data set successfully modeled AGEs and not only provided quantitative data that compared with conventional analytical approaches, but also provided new and complementary information via a nondestructive approach with high spatial resolution. It was shown that the Raman approach could be used to predict chronological age of the clinical samples (P<0.001) and a difference in the Raman spectra between genders was highly significant (P<0.000001). With further development, this Raman-based approach has the potential for noninvasive examination of AGE adducts in living eyes and ultimately to assess their precise pathogenic role in age-related diseases.
Light microscopic studies comparing sperm parameters show little association between diabetes and male fertility. However, with the introduction of new analytical techniques, evidence is now emerging of previously undetectable effects of diabetes on sperm function. Specifically, a recent study has found a significantly higher sperm nuclear DNA fragmentation in diabetic men. As advanced glycation end products (AGEs) are important instigators of oxidative stress and cell dysfunction in numerous diabetic complications, we hypothesized that these compounds could also be present in the male reproductive tract. The presence and localization of the most prominent AGE, carboxymethyl-lysine (CML), in the human testis, epididymis and sperm was determined by immunohistochemistry. Parallel ELISA and Western blot analyses were performed to ascertain the amount of CML in seminal plasma and sperm from 13 diabetic and nine non-diabetic subjects. CML immunoreactivity was found throughout the seminiferous epithelium, the nuclei of spermatogonia and spermatocytes, in the basal and principle cells cytoplasm and nuclei of the caput epididymis and on most sperm tails, mid pieces and all cytoplasmic droplets. The acrosomal cap, especially the equatorial band, was prominently stained in diabetic samples only. The amount of CML was significantly higher (p = 0.004) in sperm from non-diabetic men. Considering the known detrimental actions of AGEs in other organs, the presence, location and quantity of CML, particularly the increased expression found in diabetic men, suggest that these compounds may play a hitherto unrecognized role in male infertility.
Suppression of angiogenesis during diabetes is a recognized phenomenon but is less appreciated within the context of diabetic retinopathy. The current study has investigated regulation of retinal angiogenesis by diabetic serum and determined if advanced glycation end products (AGEs) could modulate this response, possibly via AGE-receptor interactions. A novel in vitro model of retinal angiogenesis was developed and the ability of diabetic sera to regulate this process was quantified. AGE-modified serum albumin was prepared according to a range of protocols, and these were also analyzed along with neutralization of the AGE receptors galectin-3 and RAGE. Retinal ischemia and neovascularization were also studied in a murine model of oxygen-induced proliferative retinopathy (OIR) in wild-type and galectin-3 knockout mice (gal3 ؊/؊ ) after perfusion of preformed AGEs. Serum from nondiabetic patients showed significantly more angiogenic potential than diabetic serum (P < 0.0001) and within the diabetic group, poor glycemic control resulted in more AGEs but less angiogenic potential than tight control (P < 0.01). AGE-modified albumin caused a dose-dependent inhibition of angiogenesis (P < 0.001), and AGE receptor neutralization significantly reversed the AGE-mediated suppression of angiogenesis (P < 0.01). AGE-treated wild-type mice showed a significant increase in inner retinal ischemia and a reduction in neovascularization compared with non-AGE controls (P < 0.001). However, ablation of galectin-3 abolished the AGE-mediated increase in retinal ischemia and restored the neovascular response to that seen in controls. The data suggest a significant suppression of angiogenesis by the retinal microvasculature during diabetes and implicate AGEs and AGEreceptor interactions in its causation. Diabetes 53: 785-794, 2005
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