Inhibition of ultraviolet B-mediated activation of nuclear factor kappaB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, possesses significant anti-inflammatory and cancer chemopreventive properties. Studies have shown the photochemopreventive effects of green tea and EGCG in cell culture, animal models, and human skin. The molecular mechanism(s) of photochemopreventive effects of EGCG are incompletely understood. We recently showed that EGCG treatment of the normal human epidermal keratinocytes (NHEK) inhibits ultraviolet (UV)B-mediated activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we evaluated the effect of EGCG on UVB-mediated modulation of the nuclear factor kappa B (NF-kappaB) pathway, which is known to play a critical role in a variety of physiological functions and is involved in inflammation and development of cancer. Immunoblot analysis demonstrated that the treatment of NHEK with EGCG (10-40 microM) for 24 h resulted in a significant inhibition of UVB (40 mJ/cm(2))-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha, in a dose-dependent manner. UVB-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha was also observed in a time-dependent protocol (15 and 30 min, 1, 2, 3, 6, 12 h post-UVB exposure). Employing immunoblot analysis, enzyme-linked immunosorbent assay, and gel shift assay, we demonstrate that EGCG treatment of the cells resulted in a significant dose- and time-dependent inhibition of UVB-mediated activation and nuclear translocation of a NF-kappaB/p65. Our data suggest that EGCG protects against the adverse effects of UV radiation via modulations in NF-kappaB pathway, and provide a molecular basis for the photochemopreventive effect of EGCG.     

The modified Palmer lateral approach for calcaneal fractures: wound healing and postoperative computed tomographic evaluation of fracture reduction

In 32 consecutive intra-articular calcaneal fractures (28 patients, 4 bilateral), open treatment was done using the modified Palmer lateral approach and the reduction was assessed with postoperative radiography and computed tomography (CT) (coronal and axial images, 1-2 days after surgery). Retrospective analysis of the available radiographs and CT scans was done in 27 fractures (25 patients, 2 bilateral) to assess accuracy of reduction achieved; in five fractures the studies were not available. Sanders classification was type I in 2 (7%), type II in 20 (74%), and type III in 5 (19%) fractures; the calcaneocuboid joint was involved in 9 (33%) fractures. Reduction included elevation of the depressed lateral side of the posterior facet, reduction of the neck (anterior third of calcaneus) to the body (middle third of calcaneus), realignment of the posterior tuberosity, and reduction of lateral wall blowout; internal fixation was done with cannulated screws. Mean (+/-SD) values of the following displacement parameters were significantly improved after surgery: B?hler's angle, posterior facet angle, lateral posterior facet articular depression, heel width (coronal CT), and calcaneal height. There was no significant difference between preoperative and postoperative values of mean angle of Gissane, posterior tuberosity position, and body width and length on axial CT. One (3%) of the 32 fractures was associated with preoperative (traumatic) full-thickness skin necrosis at the sinus tarsi that required free muscle flap coverage. One (3%) postoperative wound healing complication occurred, consisting of wound dehiscence and drainage at the central portion of the surgical wound in a smoker, which resolved with dressing changes and antibiotics. In conclusion, the modified Palmer lateral approach enabled open reduction of major features of calcaneal fractures with less soft-tissue risk than more extensile approaches.     

Anetoderma arising in cutaneous B-cell lymphoproliferative disease

Anetoderma is circumscribed atrophy of the skin due to a localized deficiency in elastic tissue. It can follow inflammatory skin diseases of several types, and occasionally is present in the skin around neoplasms. There are a few reports of anetoderma in the lesional skin of cutaneous lymphoma. We report on two patients who presented with multiple lesions of anetoderma and who later proved to have low-grade cutaneous B-cell lymphomas. One patient (Patient 1) is a 39-year-old man and the other patient is a 26-year-old woman who is a renal transplant recipient (Patient 2). Some biopsy specimens from the anetodermic skin of Patient 1 appeared to show an urticarial reaction, although plasma cells were present. A large nodule showed lymphoid follicles surrounded by plasmacytoid lymphocytes, with loss of elastic tissue in the adjacent dermis. The plasmacytoid cells stained overwhelmingly for lambda light chain, and staining of the urticarial lesions from this patient also showed a marked majority of lambda positive cells. Immunoglobulin heavy chain gene (IgH) rearrangements showed a dominant clonal pattern in the nodular lesion. We classified the disease in Patient 1 as marginal zone lymphoma and the disease in Patient 2 as a post-transplant lymphoproliferative disorder. Because of the intimate association of anetoderma and cutaneous B-cell lymphoproliferative disorders in these two patients, it seems possible that anetoderma could result from either a local effect of the neoplastic cells or associated inflammatory cells, especially neutrophils as in Case 1. The infiltrates of Case 1 had many interstitial neutrophils and only a few clonal plasmacytoid lymphocytes, indicating that this presentation of B-cell lymphoma can be a diagnostic pitfall. Given these two cases and similar ones in the literature, biopsy of lesional skin in anetoderma should be performed to ensure that lymphomatous infiltrates are not present. Even if plasma cells are sparse, studies to detect clonality are appropriate. Cutaneous B-cell lymphoma can be added to the list of associations of elastolysis and cutaneous lymphoma, which includes granulomatous slack skin (T-cell lymphoma) and cutis laxa (myeloma).     

A literature review on oral basaloid squamous cell carcinomas,with special emphasis on etiology

In the recent years, basaloid squamous cell carcinomas (BSCCs) have gained attention because of (1) observation of a relative increase in the number of tumors arising particularly in head and neck sites, (2) identification of human papillomavirus (HPV) in BSCCs arising predominantly in the oropharynx, and (3) controversies that exist regarding the biological aggressiveness of the tumor. The objective of the present review was to address the issues mentioned above by focusing primarily on oral BSCCs, using literature that has been published in the English language up to 2013. According to the literature review, oral BSCCs were found to be relatively more common in elderly patients with a mean age of 64 years. A male predominance with a male/female ratio of 3:1 was observed. The predominant site was the tongue, with almost half of the reported cases occurring at this site, followed by the floor of the mouth and palate. With reference to habit history, majority were found to be tobacco and alcohol users. However, only 3 studies revealed data on HPV status of purely oral BSCC, and according to the results of these studies, of the 17 tumors tested, 4 had harbored high-risk HPV. Furthermore, most oral BSCCs were in an advanced clinical stage, namely, stage III or IV with T3 or T4 lesions and cervical lymph node metastasis at initial presentation, whereas 41% of patients had presented with local recurrences and 45% had died of the disease. In conclusion, although, the present literature review found enough evidence to consider tobacco and alcohol as risk factors for the development of oral BSCC, steps should be taken to fill the gap in our knowledge that exist with reference to contribution of oncoviruses, particularly HPV in the etiology of oral BSCC.     

Erythema annulare centrifugum as the presenting sign of Pseudomonas aeruginosa sepsis in a newborn

We report a case of erythema annulare centrifugum (EAC) with neonatal onset. The patient presented on the fourth day of life with erythematous papules that enlarged centrifugally to form annular or policyclic plaques on anterior surface of trunk and legs without signs of systemic toxicity. Subsequently, she developed sepsis and disseminated intravascular coagulation and died on the sixth day of life. Blood culture grew Pseudomonas aeruginosa. The coexistence of P. aeruginosa sepsis with the clinical appearance of erythema annulare centrifugum strongly suggests a pathogenetic effect of the microorganism on the skin eruption. To the best of our knowledge, this is the first report of EAC with P. aeruginosa sepsis in a newborn.     

Effects of nebulized corticosteroids therapy on hypothalamic–pituitary–adrenal axis in young children with recurrent or persistent wheeze

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic–pituitary–adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6–24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 μg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.     

Reconnection of severed nerve axons with polyethylene glycol

Severed medial giant axons in crayfish can be rejoined in vitro with polyethylene glycol (PEG) to produce axoplasmic continuity and through transmission of action potentials. Severed axon-like processes of a mammalian neuroblastoma/glioma cell line seem to be rejoined to the cell body using PEG in tissue culture. Our data suggest that PEG might be used to rejoin severed axons in vivo in various organisms.