Is chronic ulcerative stomatitis a variant of lichen planus,or a distinct disease?

Chronic ulcerative stomatitis is an immune‐mediated mucocutaneous disorder characterized clinically by erosions or ulcers. Most cases are limited to the mouth. The histopathological features are non‐specific or mimic those of oral lichen planus, and studies by immunofluorescent microscopy are essential for definitive diagnosis. The defining immunopathogenic mechanism is the binding of IgG to the nuclear protein deltaNp63alpha of keratinocytes in the basal and parabasal cell layers of the oral stratified epithelium. DeltaNp63alpha functions as a regulator of epithelial stem cell activity and as an antiapoptotic agent and regulates the expression of cell‐to‐cell and cell‐to‐basement membrane adhesion molecules. The autoimmune IgG‐deltaNp63alpha interaction is thought to result in damage to the structural attachment of keratinocytes to one another and to the epithelial basement membrane zone and in dysregulation of the cell cycle and apoptosis of basal keratinocytes with the development of erosions or ulcers. The aims of treatment are to suppress the pathogenic immunoinflammatory responses, to prevent local infection and to promote healing. The purpose of this article is to provide a succinct review of the diagnostic, clinical and etiopathogenic features of, and treatment guidelines for chronic ulcerative stomatitis, and to argue that this disease should be regarded as a variant of oral lichen planus, rather than as a distinct entity.     

Association of Apical Periodontitis with Cardiovascular Disease via Noninvasive Assessment of Endothelial Function and Subclinical Atherosclerosis

IntroductionChronic infections of endodontic origin might predispose to the onset of cardiovascular disease (CVD). The studies depicting the link between apical periodontitis (AP) and CVD are few, and the association is very controversial; also, the markers used are expensive, which makes them difficult to use in general practice. The purpose of this study was to investigate whether an association exists between AP and CVD using noninvasive methods (ie, flow-mediated dilatation [FMD] and carotid intima-media thickness [c-IMT]).MethodsThis cross-sectional study included 120 men between 20 and 40 years old free from periodontal disease, CVD, and traditional cardiovascular risk factors; 60 subjects had AP, and 60 acted as controls. All subjects underwent complete physical and dental examination, echocardiography, ultrasound assessment of FMD of the right brachial artery, and c-IMT. Data were analyzed using the Mann-Whitney U test and the Spearman rank correlation (r_s) test.ResultsFMD was found to be significantly impaired in patients with AP (mean = 4.9% ± 2.05%) compared with healthy controls (mean = 9.74% ± 2.59%, P = .000). The study also depicts statistically significant differences between c-IMT of the AP (mean = 0.64 ± 0.12 mm) and control (mean = 0.54 ± 0.08 mm) groups (P = .000). A significant inverse correlation between c-IMT and FMD was observed (r_s = −0.381, P = .000).ConclusionsImpaired FMD and greater c-IMT in subjects with AP suggests a potential association between endodontic infection and CVD.     

Possible roles of excess tryptophan metabolites in cancer

Tryptophan is metabolized through serotonin, indole, and kynurenine (KN) pathways. Uptake of an excess amount of tryptophan accompanied with vitamin B6 deficiency may result in the accumulation of higher concentrations of metabolites mainly from the KN pathways in the bladder. These metabolites could interact with nitrite to become mutagenic nitrosamines. They could be a promoter in the initiator–promoter model of carcinogenesis. They produced bladder cancer when implanted in the bladder. They also interact with transition metals copper or iron to form reactive radicals or reactive oxygen species (ROS). Some metabolites, 3‐hydroxy‐anthranilic acid, were autooxidized to mutagenic cinnabarinic and anthranilyl radical intermediates. These radical intermediates could also be ligands that interact with aryl hydrocarbon receptor (AhR) and induce xenobiotic metabolizing enzymes (XMEs) to metabolize contaminated carcinogens. When tryptophan is exposed to either visible or UV light, a photoproduct of 6‐formylindolo[3,2b]‐carbazole is formed, which has a very high affinity for the AhR that plays a role in carcinogenesis. This review gives an insight into various mechanisms through which tryptophan metabolites cause carcinogenesis. It could be concluded that tryptophan metabolites play a complementary role in promoting carcinogenesis along with carcinogens like aflatoxin, CCl₄, 2‐acetylaminofluorene, 4‐aminobiphenyl, 2‐naphthylamine, or N‐[4‐(5‐nitro‐2‐furyl)?2‐thiazolyl] formamide. The underlying mechanisms could be their autoxidation, exposure to either visible or UV light, interaction with nitrite or transition metals to form reactive intermediates, serving as ligands to interact with an AhR that is known to play a role in carcinogenesis through induction of XMEs. Further research is warranted.Environ. Mol. Mutagen. 52:81–104, 2011. © 2010 Wiley‐Liss, Inc.     

Rapid in-situ detection kit (RisK): Development of loop-mediated isothermal amplification (LAMP) assay for the rapid identification of selected invasive alien fish in Malaysian freshwaters

Invasive alien fish species have become a silent treat towards the ecosystem especially the native fish population in Malaysia. There has been a need to develop rapid identification methods that can aid management teams in identifying fish species that are not native to our ecosystem. Current visual identification methods are highly tedious and require time, delaying action towards curbing the invasion. The LAMP assay successfully identified six popular invasive fish species in Malaysia. None of the LAMP assays showed false positives and the Limit of Detection of the LAMP primers were highly sensitive and could detect DNA samples up to 1 × 10⁻¹⁵ ng/μl. The LAMP primers designed were highly specific to the target species and did not amplify non target species. DNA sequencing was done to ensure the accuracy of LAMP assay results. This study demonstrates that LAMP is a suitable tool in species identification efforts of invasive fish species in Malaysia.     

Targeted three‐dimensional immunohistochemistry reveals localization of presynaptic proteins Bassoon and Piccolo in the rat calyx of Held before and after the onset of hearing

Bassoon and Piccolo contribute to the cytomatrix of active zones (AZ), the sites of neurotransmitter release in nerve terminals. Here, we examined the 3D localization of Bassoon and Piccolo in the rat calyx of Held between postnatal days 9 and 21, the period of hearing onset characterized by pronounced structural and functional changes. Bassoon and Piccolo were identified by immunohistochemistry (IHC) on slices of the brainstem harboring calyces labeled with membrane‐anchored green fluorescent protein (mGFP). By using confocal microscopy and 3D reconstructions, we examined the distribution of Bassoon and Piccolo in calyces delineated by mGFP. This allowed us to discriminate calyceal IHC signals from noncalyceal signals located in the spaces between the calyceal stalks, which could mimic a calyx‐like distribution. We found that both proteins were arranged in clusters resembling the size of AZs. These clusters were located along the presynaptic membrane facing the principal cell, close to or overlapping with synaptic vesicle (SV) clusters. Only about 60% of Bassoon and Piccolo clusters overlapped, whereas the remaining clusters contained predominantly Bassoon or Piccolo, suggesting differential targeting of these proteins within a single nerve terminal and potentially heterogeneous AZs functional properties. The total number of Bassoon and Piccolo clusters, which may approximate the number of AZs, was 405 ± 35 at P9 and 601 ± 45 at P21 (mean ± SEM, n = 12). Normalized to calyx volume at P9 and P21, the density of clusters was similar, suggesting that the absolute number of clusters, not density, may contribute to the functional maturation associated with hearing onset. J. Comp. Neurol. 518:1008–1029, 2010. © 2009 Wiley‐Liss, Inc.     

Induction of specific cell‐mediated immune responses and protection in BALB/c mice by vaccination with outer membrane vesicles from a Brucella melitensis human isolate

Brucellosis is a worldwide bacterial zoonosis caused by Brucella spp. No approved vaccine is available for human use against the disease. In this study, outer membrane vesicles (OMVs) from a Brucella melitensis biovar 1 human isolate obtained in Iran were used to immunize BALB/c mice (n = 12) by 2 intramuscular injections with a 2‐week interval. Another group of 12 mice was used as non‐vaccinated controls. Two weeks after the last vaccination, six mice of each group were sacrificed, and proliferation and interferon gamma (IFNγ) production responses of their splenocytes were evaluated following in vitro stimulation with killed Brucella cells. The other mice were challenged with the virulent B. melitensis isolate. Two weeks later, mice were killed and spleens were cultured to determine the number of the challenge strain. The results showed proliferative response and IFNγ production of splenocytes from vaccinated mice (stimulation index: 2.18 ± 0.57, and 1519.35 ± 10.70 pg/mL, respectively) were significantly higher than those of control mice (stimulation index: 1.02 ± 0.02, and 210.01 ± 17.58 pg/mL, respectively). Numbers of the challenge strain in spleens of vaccinated mice were also significantly less than those in the controls with 1.6 units of protection. Our study revealed vaccination with OMVs of the B. melitensis isolate could induce specific immune responses and protection against infection in the mouse model suggesting their potential application for active immunization against brucellosis.     

C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody‐mediated rejection episode: a retrospective cohort study

After kidney transplantation, C4d is an incomplete marker of acute antibody‐mediated rejection (AMR) and C1q‐binding donor‐specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q‐binding impact on allograft survival. We compared clinical, histological and serological features of C4d− and C4d+ AMR, C1q+ and C1q− DSA AMR and analysed C4d and C1q‐binding impact on allograft survival. Among 500 for‐cause kidney allograft biopsies, 48 fulfilled AMR criteria. C4d+ AMR [N = 18 (37.5%)] have significantly higher number class I DSA (P = 0.02), higher microvascular score (P = 0.02) and more transplant glomerulopathy (P = 0.04). C1q+ AMR [N = 20 (44%)] presented with significantly more class I and class II DSA (P = 0.005 and 0.04) and C4d+ staining (P = 0.01). Graft losses were significantly higher in the C4d+ group (P = 0.04) but similar in C1q groups. C4d+ but not C1q+ binding was an independent risk factor for graft loss [HR = 2.65; (1.11–6.34); P = 0.028]. In our cohort of clinical AMR, C4d+ staining but not C1q+ binding is an independent risk factor for graft loss. Allograft loss and patient survival were similar in C1q+ and C1q− AMR.     

Evaluation of C1q Status and Titer of De Novo Donor‐Specific Antibodies as Predictors of Allograft Survival

De novo donor‐specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0.01) and was more common in class II versus class I dnDSAs (p < 0.01). C1q status correlated with tubulitis (p = 0.02) and C4d status (p = 0.03) in biopsies at the time of dnDSA development, but not T cell–mediated rejection (TCMR) or antibody‐mediated rejection (ABMR). De novo DSA titer correlated with Banff g, i, t, ptc, C4d scores, TCMR (p < 0.01) and ABMR (p < 0.01). Post‐dnDSA graft loss was observed more frequently in recipients with C1q‐positve dnDSA (p < 0.01) or dnDSA titer ≥ 1:1024 (p ≤ 0.01). However, after adjustment for clinical phenotype and nonadherence in multivariate models, neither C1q status nor dnDSA titer were independently associated with allograft loss, questioning the utility of these assays at the time of dnDSA development.