4-Hexyl-1,3-phenylenediol, a nuclear factor-κB inhibitor, improves photodamaged skin and clinical signs of ageing in a double-blinded, randomized controlled trial.

BACKGROUND: The nuclear factor-κB (NF-κB) pathway is a key mediator of inflammation; however, few studies have examined the direct effects of NF-κB inhibition on the skin. OBJECTIVES: To investigate NF-κB activity in cultured human fibroblasts and to investigate the effects of 4-hexyl-1,3-phenylenediol (an NF-κB inhibitor) on elastin and collagen gene expression in vitro and on the clinical appearance of photodamaged skin. METHODS: The amount and activity of NF-κB in human fibroblasts obtained from donors (17-78 years old) was measured after transfection with a NF-κB reporter and a luciferase promoter system. The expression of extracellular matrix (ECM) genes was determined using quantitative polymerase chain reaction. Women with moderate skin photodamage were randomized to daily treatment with a topical lotion containing 4-hexyl-1,3-phenylenediol (n = 30) or vehicle (n = 29) for 8 weeks, with clinical assessments at baseline and weeks 2, 4 and 8. RESULTS: Fibroblasts obtained from donors older than 50 years had higher NF-κB activity compared with cells from younger donors; inhibition of the NF-κB pathway with 4-hexyl-1,3-phenylenediol enhanced the expression of ECM genes. In women, treatment for 8 weeks with 4-hexyl-1,3-phenylenediol significantly improved crow's feet fine lines, cheek wrinkles, age spots, mottled pigmentation and radiance compared with both the vehicle and baseline. Furthermore, treatment with 4-hexyl-1,3-phenylenediol resulted in a twofold greater clinical improvement in overall photodamage compared with the vehicle group. CONCLUSIONS: Inhibition of the proinflammatory NF-κB pathway resulted in increased expression of ECM proteins in vitro and significant clinical improvement in photodamaged skin.

Atypical small acinar proliferation (ASAP): Is a repeat biopsy necessary ASAP? A multi-institutional review.

BACKGROUND: Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30-40% of patients with ASAP may develop prostate cancer (PCa) within a 5-year period. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis. Our objective was to examine the association between ASAP and subsequent diagnosis of high-grade PCa and to evaluate the need for immediate repeat biopsy. METHODS: A retrospective multi-institutional review identified 264 patients who underwent prostate biopsy from 2000 to 2013 (Brown), 2008 to 2013 (University of Massachusetts) and 1994 to 2005 (Mayo) and were diagnosed with ASAP. Patients underwent transrectal ultrasound-guided biopsies for elevated PSA and/or abnormal digital rectal exam. Clinicopathologic features were assessed, including rates of subsequent PCa detection of any high-grade (Gleason 7-10) PCa. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. RESULTS: All 264 patients included underwent repeat biopsy with a median follow-up of 5.4 years (interquartile range: 4.6, 6.7). Of these patients, 89 (34%) were subsequently diagnosed with PCa including 21 (8%) with high-grade PCa. Pre-biopsy PSA was higher among patients subsequently diagnosed with (6.7 vs 5.8, P<0.001). Of those diagnosed with subsequent PCa, 69/89 (78%) had less than or equal to Gleason 3+3 disease and only 15/89 (17%) had Gleason 7 and 6/89 (6%) revealed Gleason ⩾8-10. Radical prostatectomy was performed on 36/89 (40%) patients. Surgical pathology revealed 11 patients ⩾Gleason 8-10 PCa. CONCLUSIONS: Although 34% of patients with an initial diagnosis of ASAP who had repeat biopsy were subsequently diagnosed with PCa only, only 22% (8% of the total cohort) were found to have high-grade disease. Higher PSA was associated with increased risk of identifying PCa on repeat biopsy. These findings suggest that immediate repeat biopsy may be omitted in the majority of men with ASAP.

An evaluation of tricalcium phosphate as a treatment for endodontic perforations.

In the rat, perforations of maxillary molars were created and treated with either tricalcium phosphate (Synthograft) or Cavit. At four time intervals (1 day, 1 wk, 2 wk, and 1 month), four evaluative factors (inflammation, bone resorption, cementum and dentin resorption, and epithelial proliferation) were analyzed and compared for the two materials. For the individual time periods, there were no statistically significant differences between the two materials. However, when all four time periods were combined, there was a statistically significant better result for tricalcium phosphate than for Cavit with respect to decreased inflammation (p less than 0.05).

Ultrastructure of sialadenoma papilliferum.

Sialadenoma papilliferum is a rare tumor of salivary gland origin and has been reported in the parotid and minor salivary glands of the oral cavity. This tumor is morphologically similar to the papillary syringoadenoma of the sweat gland. We report the clinical and morphologic features of five cases and review the literature. Ultrastructural examination of case 1 revealed the predominant cell type to be an oncocytic cell. These cells contained numerous mitochondria, exhibited parallel filaments within the cell cytoplasm, and were attached by desmosomes. The neoplastic cells appear to exhibit characteristic features of various cell types of the salivary gland duct apparatus.

Critical review of lymphomatoid papulosis of the oral cavity with case report.

A 60-year-old woman was referred to the Department of Dental Medicine at Long Island Jewish Medical Center for evaluation of multiple lesions of the tongue. She reported a long history of recurrent papular cutaneous eruptions that waxed and waned. A biopsy specimen of one of the cutaneous lesions was diagnosed as lymphomatoid papulosis. Sporadic, recurrent oral ulcers that resolved spontaneously were noted 10 to 14 days before the initial visit. These ulcers had recurred for the past 17 years. The most recent oral lesion was an erythematous, irregular, solitary ulcerated area on the middle third dorsum of tongue. The area quickly enlarged, ultimately developing extensive surface necrosis. Shortly after, a similar lesion on the posterior dorsum of the tongue developed. Biopsy specimens of the former lesion showed numerous, large, atypical, pleomorphic, and hyperchromatic cells with abundant mitoses. The large, atypical cells were immunohistochemically proven to be T lymphocytes. A diagnosis of lymphomatoid papulosis was made. Two weeks later, the tongue lesions had spontaneously and totally resolved. The clinical, histomorphologic, and immunohistochemical features, as well as gene rearrangement studies of this rare entity, are presented.

Polymorphous low-grade adenocarcinoma: flow cytometric, p53, and PCNA analysis.

Polymorphous low-grade adenocarcinoma of minor salivary glands (terminal duct carcinoma, lobular carcinoma) was first defined more than a decade ago. A 17% recurrence rate and a 9% metastasis rate have been reported. Fifteen formalin-fixed, paraffin-embedded archival cases were analyzed. Ploidy and proliferative activity were evaluated with flow cytometric analysis. Demonstration of an abnormal p53 gene product and proliferative cell nuclear antigen analyses were also performed with routine immunohistochemical procedures. The purpose of this investigation was to evaluate these parameters and determine if a correlation existed. Flow cytometry was performed on 10 cases; 3 showed an aneuploid cell line (mean, S-phase diploid tumor cells 5.9%; S-phase aneuploid 26.7%). Products of a mutation of the p53 tumor suppressor gene have been noted to accumulate in salivary gland tumors, both benign and malignant. Qualitative assessment revealed p53 positive staining in 4 of 15 tumors; positive cells comprised 5% to 10% of the tumor. The percentage of tumor cells positive for proliferative cell nuclear antigen staining ranged from 0.5% to 70%. There was no correlation between proliferative activity as determined by proliferative cell nuclear antigen when compared with results of flow cytometric analysis except for one case that exhibited p53 staining, a 26% proliferative cell nuclear antigen fraction, and a distinct aneuploid cell line.

Heterotopic oral gastrointestinal cyst: report of 2 cases and review of the literature.

Oral heterotopic gastrointestinal cyst is a rare entity occurring in infants and children and showing a predilection for males. The cyst usually appears as an asymptomatic swelling in the floor of the mouth. Difficulty in feeding, swallowing, respiration, and speech have been reported in approximately 30% of those affected. The tongue-in particular, its anterior aspectis involved in up to 60% of reported cases. The clinical, radiographic, and histopathologic features of cases of heterotopic gastrointestinal cyst involving the anterior tongue in a 2-year-old girl and the anterior floor of the mouth in a 2-month-old boy are presented, and theories of pathogenesis are discussed.

Diagnosis and treatment of common oral lesions found in the elderly.

A wide variety of oral lesions are recognized in the geriatric patient. The most common lesions include neoplasia, immunologic based mucosal disease, hematological disorders, oral manifestation of systemic disease, and conditions characterized by oral or facial pain. Diagnostic and treatment considerations for leukoplakia, carcinoma, metastatic disease, candidiasis, herpes zoster, plasmacytoma, myeloma, lymphoma, several of the more common vesiculoulcerative mucosal diseases and idiopathic burning mouth syndrome are presented.

Differential levels of elastin fibers and TGF-ß signaling in the skin of Caucasians and African Americans.

BACKGROUND: While skin color is the most notable difference among ethnic skins the current knowledge on skin physiological and aging properties are based mainly on Caucasian skin studies. OBJECTIVE: To evaluate histological differences in elastin fiber network and differential responsiveness to TGF-ß in skin of Caucasians and African Americans. METHODS: These studies were undertaken using human skin biopsies, primary dermal fibroblasts, Western blot analyses, immunofluorescence microscopy, cDNA array and quantitative real-time PCR. RESULTS: In Caucasian subjects, tropoelastin expression and elastin fibers in photoprotected skin was substantially less than in age-matched African American skin. Expression of tropoelastin in photoexposed skin of African American was similar to their photoprotected skin, suggesting that photoexposure did not affect elastin fibers in African American skin to the same extent as Caucasian skin. An elevated level of TGF-ß1 present in media from dermal fibroblasts derived from African American skins correlated well with the higher levels of TGF-ß mRNA in African American skins analyzed by cDNA array. Treatment with TGF-ß1 resulted in a considerably higher induction of elastin mRNA in dermal fibroblasts from African Americans than from Caucasian fibroblasts, indicative of enhanced TGF-ß signaling in African American skins. Furthermore, UVA exposure decreased levels of elastin mRNA in Caucasian fibroblasts compared to African Americans fibroblasts. CONCLUSION: These results suggest that there are ethnic differences in the elastin fiber network and in TGF-ß signaling in African American and Caucasian skin, and that African American have less UV dependent loss of elastin than Caucasian which may contribute to the different perceived aging phenotypes.