Chronic ulcerative stomatitis: A comprehensive review and proposal for diagnostic criteria

Chronic ulcerative stomatitis (CUS) is an immune‐mediated disorder characterized by oral erosions and ulcers usually refractory to conventional treatments. The disease often involves middle‐aged and older women with painful lesions sometimes resembling those of erosive oral lichen planus (OLP). The most affected sites are the buccal mucosa, the gingiva and the tongue, but the skin is involved in 22.5% of cases. Histopathologic features in CUS are non‐specific and indistinguishable from those of OLP, with the exception of the presence of a mixed infiltrate composed of lymphocytes and plasma cells. Direct immunofluorescence (DIF) analysis reveals the presence of stratified epithelium‐specific antinuclear antibodies (SES‐ANA) in the lower third of the epithelium. The IgG antibodies detected on DIF are directed against the ?Np63α isoform of p63 expressed in the nuclei of the epithelial basal cells. A distinguishing feature of CUS is the low response to conventional corticosteroid therapy and the good outcome with hydroxychloroquine at the dosage of 200 mg/day or higher dosages. This paper presents a comprehensive review of CUS and is accompanied by a new case report (the 73rd case) and a proposal for updated diagnostic criteria.     

Investigation of the molecular reactivity of bioactive oxiranylmethyloxy anthraquinones

The design of a multitarget and multifunctional small molecule containing two functional groups reacting through different mechanisms represents an attractive goal for the medicinal chemist. The preparation of two bifunctional oxiranylmethyloxy anthraquinones, previously investigated as anticancer agents, is described here. These compounds combine a planar, DNA‐intercalating and pro‐oxidant anthraquinone scaffold and the alkylating epoxide functions which can covalently react with the nucleic acid. Their multilevel molecular reactivity was studied through a combination of analytical techniques: The DNA‐binding properties were investigated using a mass spectrometry‐based binding assay and by nuclear magnetic resonance, highlighting the formation of a covalent adduct with a nucleobase. Moreover, the contribution of the pro‐oxidant redox cycling was evaluated.     

Janus-faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection

We have generated unique asymmetric liposomes with phosphatidylserine (PS) distributed at the outer membrane surface to resemble apoptotic bodies and phosphatidic acid (PA) at the inner layer as a strategy to enhance innate antimycobacterial activity in phagocytes while limiting the inflammatory response. Results show that these apoptotic body-like liposomes carrying PA (ABL/PA) (i) are more efficiently internalized by human macrophages than by nonprofessional phagocytes, (ii) induce cytosolic Ca(2+) influx, (iii) promote Ca(2+)-dependent maturation of phagolysosomes containing Mycobacterium tuberculosis (MTB), (iv) induce Ca(2+)-dependent reactive oxygen species (ROS) production, (v) inhibit intracellular mycobacterial growth in differentiated THP-1 cells as well as in type-1 and -2 human macrophages, and (vi) down-regulate tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, IL-18, and IL-23 and up-regulate transforming growth factor (TGF)-β without altering IL-10, IL-27, and IL-6 mRNA expression. Also, ABL/PA promoted intracellular killing of M. tuberculosis in bronchoalveolar lavage cells from patients with active pulmonary tuberculosis. Furthermore, the treatment of MTB-infected mice with ABL/PA, in combination or not with isoniazid (INH), dramatically reduced lung and, to a lesser extent, liver and spleen mycobacterial loads, with a concomitant 10-fold reduction of serum TNF-α, IL-1β, and IFN-γ compared with that in untreated mice. Altogether, these results suggest that apoptotic body-like liposomes may be used as a Janus-faced immunotherapeutic platform to deliver polar secondary lipid messengers, such as PA, into phagocytes to improve and recover phagolysosome biogenesis and pathogen killing while limiting the inflammatory response.     

Evaluating the Prognostic Value of Positron‐Emission Tomography Myocardial Perfusion Imaging Using Automated Software to Calculate Perfusion Defect Size

Background:

Myocardial perfusion imaging by positron‐emission tomography (PET MPI) is regarded as a valid technique for the diagnosis of coronary artery disease (CAD), but the incremental prognostic value of PET MPI among individuals with known or suspected CAD is not firmly established.

Hypothesis:

Myocardial perfusion defect sizes as measured by PET MPI using automated software will provide incremental prognostic value for cardiac and all‐cause mortality.

Methods:

This study included 3739 individuals who underwent rest‐stress rubidium‐82 PET MPI for the evaluation of known or suspected CAD. Rest, stress, and stress‐induced myocardial perfusion defect sizes were determined objectively by automated computer software. Study participants were followed for a mean of 5.2 years for cardiac and all‐cause mortality. Cox proportional hazards models were developed to evaluate the incremental prognostic value of PET MPI.

Results:

A strong correlation was observed between perfusion defect sizes assessed visually and by automated software (r = 0.76). After adjusting for cardiac risk factors, known CAD, noncoronary vascular disease, and use of cardioprotective medications, stress perfusion defect size was strongly associated with cardiac death (P < 0.001). Rest perfusion defects demonstrated a stronger association with cardiac death (P < 0.001) than stress‐induced perfusion defects (P = 0.01), yet both were highly significant. Similar patterns held for all‐cause death.

Conclusions:

The current study is the largest to date demonstrating PET MPI provides incremental prognostic value among individuals with known or suspected CAD. Automated calculation of perfusion defect sizes may provide valuable supplementary information to visual assessment. This work was partially funded by a predoctoral fellowship grant awarded to the first author by the American Heart Association's Founders' Affiliate. Additional funding was provided by Niagara Falls Memorial Medical Center, Positron Corporation, the University at Buffalo, and Niagara University. The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

Clinical evaluation on porcelain laminate veneers bonded with light-cured composite: results up to 7?years

The purpose of this study was to evaluate the clinical performance of laminate porcelain veneers bonded with a light-cured composite. Thirty patients were restored with 119 porcelain laminate veneers. The veneers were studied for an observation time of 7 years. Marginal adaptation, marginal discoloration, secondary caries, color match, and anatomic form were clinically examined following modified United States Public Health Service (USPHS) criteria. Each restoration was also examined for cracks, fractures, and debonding. Pulp vitality was verified. In addition, plaque and gingival indexes and increase in gingival recession were recorded. Survival rate evaluating absolute failures and success rate describing relative failures were statistically determined, using both restoration and patient-related analyses. On the basis of the criteria used, most of the veneers rated Alfa. After 7 years, the results of the clinical investigation regarding marginal adaptation and marginal discoloration revealed only 2.5% and 4.2% Bravo ratings, respectively, among the 119 initially placed veneers. Using the restoration as the statistical unit, the survival rate was 97.5%, with a high estimated success probability of 0.843 after 7 years. Using the patient as the statistical unit, the survival rate was 90.0% and the estimated success probability after 7 years was 0.824. Gingival response to the veneers was all in the satisfactory range. Porcelain laminate veneers offer a predictable and successful treatment modality giving a maximum preservation of sound tooth. The preparation, cementation, and finishing procedures adopted are considered key factors for the long-term success and aesthetical result of the veneer restorations.