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Summary: Background: Chronic skin ulcers are a major complication and a therapeutic challenge in patients with diabetes mellitus. Glucose‐induced accumulation of reactive oxygen species (ROS) is considered to be an important pathogenetic factor in diabetes. Objectives: To characterize the impact of high glucose (HG) on normal human keratinocytes (NHKs) and examine if Lys‐d‐Pro‐Thr (KdPT), a tripeptide derived from α‐melanocyte‐stimulating‐hormone, has protective effects. Methods: We investigated the key functions of NHKs under HG conditions with or without KdPT in vitro as well as ex vivo employing a skin organ culture model. Results: HG impaired metabolic activity, cell proliferation, viability and migration of NHKs. As shown by atomic force microscopy HG altered the biophysical properties of NHKs, i.e. cell size and elasticity. Glucotoxicity in NHKs was paralleled by the induction of intracellular ROS and endoplasmic reticulum stress. KdPT attenuated HG‐induced oxidative stress and antagonized the effects of glucose on cell viability, metabolic activity and migration. Importantly, KdPT also antagonized the suppressive effect of HG on epidermal migration in wounded human skin organ cultures. Conclusions: Our findings highlight a novel effect of KdPT that could be exploited for the future therapy of diabetic skin ulcers. What's already known about this topic?Chronic skin ulcers are a major therapeutic challenge in patients with diabetes mellitus.Impairment of keratinocyte function is considered to be a key factor in impaired wound healing in patients with diabetes mellitus.Oxidative stress is increased in patients with diabetes mellitus. What does this study add?Insight into the precise impact of hyperglycaemic stress on cell viability, proliferation, migration, apoptosis, autophagy, oxidative and endoplasmic stress as well as on biomechanical properties of epidermal keratinocytes.Demonstration that a skin organ culture model can be used to examine the effect of hyperglycaemic stress ex vivo.Analysis of the effects of a small melanocortin‐derived peptide, Lys‐d‐Pro‐Thr (KdPT), on glucotoxicity of epidermal keratinocytes in vitro and in a skin organ culture model. What is the translational message?Better understanding of the pathobiology of glucotoxicity on epidermal keratinocytes.Demonstration that KdPT may be a drug candidate for preclinical studies on diabetic wound healing. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Cervical necrotizing fasciitis (CNF) can develop from odontogenic infections that spread to the deep fascial planes of the neck. This polymicrobial infection is rapidly progressive, destructive, and often fatal. Prompt diagnosis, recognition of acuity, aggressive, repeated surgical treatment, and medical management contribute to improved survival. Nevertheless, the progression of the disease to descending mediastinitis and septic shock leads to a poor prognosis and decreased survival. A comprehensive review of the current data regarding CNF was conducted using MEDLINE, PubMed, Scopus, and Google Scholar. The diagnostic elements, comorbid conditions, treatment modalities, complications, and survival rates were analyzed. CNF has a reported mortality rate of 7% to 20%, depending on the extent of neck involvement. When the disease progresses into the thorax, such as in the subset of patients with CNF complicated by descending necrotizing mediastinitis (DNM) of odontogenic origin, the mortality rate increases to 41%. This is greater than the reported mortality rate of 22% for DNM in cardiothoracic studies. When DNM is present, the risk of developing septic shock appears to be much greater, 22% versus 7%. In the presence of CNF, DNM, and sepsis, the mortality rate increases to 64%. Those who survive CNF complicated by DNM and sepsis have truly beaten the odds. CNF is an uncommon, but potentially fatal, condition that oral and maxillofacial surgeons might be called on to manage emergently. Treatment includes surgery and medical intensive care. Surgeons offer the best odds of patient survival by following these basic principles: airway security, early aggressive incision and drainage plus debridement with thoracotomy, as needed, close surveillance with computed tomography, and a low threshold for retreatment. In immunocompromised patients, even greater vigilance is required. Antibiotic therapy should be adjusted as cultures and sensitivities become available. Advances in interventional radiology might lead to improved survival by allowing guided minimally invasive drainage in critically ill patients who cannot tolerate additional surgical insult. Despite the technologic advances in diagnosis and treatment, CNF complicated by DNM mediastinitis and sepsis still results in astoundingly high mortality. [ABSTRACT FROM AUTHOR]

PURPOSE: The objective of the present study was twofold: first, to assess aspirates for use in cytokine profiling and second, to initiate pilot analyses to determine whether the cytokine profiling can serve as an aid in the diagnosis of jaw lesions. MATERIALS AND METHODS: The aspirates from 12 benign odontogenic cysts and tumors of the jaw were collected and randomized, and a formal incisional biopsy was performed to establish the tissue diagnosis. The biopsies revealed keratocystic odontogenic tumor, ameloblastoma, and dentigerous cyst. The cystic aspirate was analyzed using the Q-Plex Human Cytokine Screen to detect cytokine expression and determine the level of expression for each pathologic entity. An array of 16 cytokines was investigated, including interleukin (IL)-1[alpha], IL-1[beta], IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-23, interferon-[gamma], tumor necrosis factor (TNF)-[alpha], and TNF-[beta]. Tables were developed to determine the ratio of expression for the candidate cytokine pairs that were differentially expressed among the 3 pathologic entities encountered. One-way analysis of variance was used to search for significant differences in the ratio of expression of the candidate pairs among the 3 entities. RESULTS: Cytokines expressed by the 3 distinct jaw lesions were detected in the aspirate without the need for tissue biopsy. Cytokine profiling of these entities is possible owing to differential expression of the various cytokines studied. The ratio of expression was significant (P < .05) for 15 pairs of cytokines: IL-5/IL-1[alpha], IL-4/IL-2, IL-8/IL-4, TNF-[beta]/IL-6, IL-23/IL-6, TNF-[alpha]/IL-23, TNF-[alpha]/TNF-[beta], TNF-[alpha]/IL-8, TNF-[beta]/IL-5, TNF-[beta]/TNF-[alpha], TNF-[beta]/IL-13, IL-12/IL-23, IL-13/IL-15, IL-15/IL-2, and IL-6/IL-2. A comparison of the mean values indicated a 'high/low' expression value for each lesion type for the 15 cytokine pairs. CONCLUSIONS: Cytokines, expressed by the 3 groups of jaw lesions, can be detected in the cystic aspirate, and a comparison of the ratio of the expression of the aspirates demonstrated a differential expression pattern of cytokines among the 3 groups. These ratios could assist in establishing a prompt and accurate diagnosis of lesions that might be difficult to discern clinically and radiographically. The use of a simple, minimally invasive aspiration procedure can help to establish an accurate diagnosis. [ABSTRACT FROM AUTHOR]