Topical corticosteroids in dental practice

Topical corticosteroids represent an important therapeutic aid in the management of a range of oral mucosal disease conditions. Like all medications, their successful use depends upon an understanding of the disease process. This includes an appropriate diagnosis, a clear view of the desirable treatment outcomes and knowledge of whether treatment is aimed at management of a chronic disease or enhanced resolution of a short-term condition. This paper reviews the use of topical corticosteroids and their possible roles in the management of oral disease.

Secretoneurin is released into human airways by topical histamine but not capsaicin

Background: The neuropeptide secretoneurin, with potential relevance to leukocyte trafficking, is present in nerves of the nasal mucosa in allergic rhinitis and may be released in response to allergen and histamine exposure. There is no information on the occurrence and mechanisms of release of secretoneurin in healthy human airways. Methods: The presence of secretoneurin in nasal biopsies and its release in response to nasal capsaicin and histamine challenges were examined. Symptoms and lavage fluid levels of fucose were recorded as markers of effects in part produced by neural activity. Bronchial histamine challenges followed by sputum induction and analysis of secretoneurin were also carried out. Results: Nerves displaying secretoneurin immunoreactivity abounded in the nasal mucosa. Nasal capsaicin challenge produced local pain (P < 0.05) and increased the levels of fucose (P < 0.05), but failed to affect the levels of secretoneurin. Nasal histamine challenge produced symptoms (P < 0.05) and increased the mucosal output of secretoneurin (P < 0.05) and fucose (P < 0.05). Bronchial histamine challenge increased the sputum levels of secretoneurin (P < 0.05). Conclusions: We conclude that secretoneurin is present in healthy human airways and that histamine evokes its release in both nasal and bronchial mucosae. The present observations support the possibility that secretoneurin is involved in histamine-dependent responses of the human airway mucosa.

Effectiveness of topical skin care provided in aged care facilities

Background The 2001 Australian census revealed that adults aged 65 years and over constituted 12.6% of the population, up from 12.1% in 1996. It is projected that this figure will rise to 21% or 5.1 million Australians by 2031. In 1998, 6% (134 000) of adults in Australia aged 65 years and over were residing in nursing homes or hostels and this number is also expected to rise. As skin ages, there is a decreased turnover and replacement of epidermal skin cells, a thinning subcutaneous fat layer and a reduced production of protective oils. These changes can affect the normal functions of the skin such as its role as a barrier to irritants and pathogens, temperature and water regulation. Generally, placement in a long-term care facility indicates an inability of the older person to perform all of the activities of daily living such as skin care. Therefore, skin care management protocols should be available to reduce the likelihood of skin irritation and breakdown and ultimately promote comfort of the older person. Objectives The objective of this review was to determine the best available evidence for the effectiveness and safety of topical skin care regimens for older adults residing in long-term aged care facilities. The primary outcome was the incidence of adverse skin conditions with patient satisfaction considered as a secondary outcome. Search strategy A literature search was performed using the following databases: PubMed (NLM) (1966–4/2003), Embase (1966–4/2003), CINAHL (1966–4/2003), Current Contents (1993–4/2003), Cochrane Library (1966–2/2003), Web of Science (1995–12/2002), Science Citation Index Expanded and ProceedingsFirst (1993–12/2002). Health Technology Assessment websites were also searched. No language restrictions were applied. Selection criteria Systematic reviews of randomised controlled trials, randomised and non-randomised controlled trials evaluating any non-medical intervention or program that aimed to maintain or improve the integrity of skin in older adults were considered for inclusion. Participants were 65 years of age or over and residing in an aged care facility, hospital or long-term care in the community. Studies were excluded if they evaluated pressure-relieving techniques for the prevention of skin breakdown. Data collection and analysis Two independent reviewers assessed study eligibility for inclusion. Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data. Results The resulting evidence of the effectiveness of topical skin care interventions was variable and dependent upon the skin condition outcome being assessed. The strongest evidence for maintenance of skin condition in incontinent patients found that disposable bodyworn incontinence protection reduced the odds of deterioration of skin condition compared with non-disposable bodyworns. The best evidence for non-pressure relieving topical skin care interventions on pressure sore formation found the no-rinse cleanser Clinisan to be more effective than soap and water at maintaining healthy skin (no ulcers) in elderly incontinent patients in long-term care. The quality of studies examining the effectiveness of topical skin care interventions on the incidence of skin tears was very poor and inconclusive. Topical skin care for prevention of dermatitis found that Sudocrem could reduce the redness of skin compared with zinc cream if applied regularly after each pad change, but not the number of lesions. Topical skin care on dry skin found the Bag Bath/Travel Bath no-rinse skin care cleanser to be more effective at preventing overall skin dryness and most specifically flaking and scaling when compared with the traditional soap and water washing method in residents of a long-term care facility. Information on the safety of topical skin care interventions is lacking. Therefore, because of the lack of evidence, no recommendation on the safety on any intervention included in this review can be made.

Epidermal penetration of a therapeutic peptide by lipid conjugation; Stereo-selective peptide availability of a topical diastereomeric lipopeptide

In inflammatory disorders (e.g. psoriasis), local concentrations of human neutrophil elastase (HNE), also known as polymorphonuclear leukocyte elastase (HLE), possibly overwhelm its natural inhibitors leading to extracellular matrix degradation. Elevated levels of HNE have been reported in a variety of inflammatory disorders, including psoriasis. Peptidic HNE inhibitors have a common hydrophobic sequence (Ala-Ala-Pro-Val). This peptide sequence inhibits HNE competitively; however the stratum corneum presents an effective barrier to the delivery of this tetrapeptide across the skin. The current work investigates the delivery of the modified peptide whereby the tetrapeptide was lipidated to enhance its ability to penetrate the stratum The tetrapeptide Was Coupled to a racaemic mixture of a short chain lipoamino acid (LAA) resulting in two diastereomers of the lipoamino acid-modified tetrapeptide. The penetration of the lipopeptide mixture was assessed across human epidermis in vitro. The percentage of applied dose penetrating to the receptor over 8 h following administration was 2.53% for the D-LAA conjugate and 1.47% for the L-diastereomer, compared to 0% for the peptide. The D-diastereomer appears to be relatively stable but the L-diastereomer appears to degrade releasing possibly the tetrapeptide and peptide fragment(s). Therefore the results clearly indicate that coupling the tetrapeptide to a short chain LAA enhances its delivery across human epidermis.

Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia

center dot PURPOSE: To evaluate topical interferon alfa-2b (IFN-alpha 2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). center dot DESIGN: Prospective, noncomparative, interventional consecutive case series. center dot METHODS: Ten patients with recalcitrant OSSN were treated with topical IFN-alpha 2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow,up of six months. center dot RESULTS: Eight of 10 patients achieved clinical resolution from topical IFN-alpha 2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha 2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). center dot CONCLUSIONS: Topical IFN-alpha 2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision. (Am J Ophthalmol 2006; 142:568-571. (c) 2006 by Elsevier Inc. All rights reserved.)

A systematic review of topical skin care in aged care facilities

This systematic review aimed to evaluate the best available evidence regarding the effectiveness of topical skin care interventions for residents of aged care facilities. Introduction. Natural changes to skin, as well as increased predisposition to pressure sores and incontinence, means residents of aged care facilities readily require topical skin care. A range of interventions exist that aim to maintain or improve the integrity of skin of older adults. Methods. Pubmed, Embase, Current Contents, CINAHL and The Cochrane Library databases were searched, as well as Health Technology Assessment websites up to April 2003. Systematic reviews and randomized or non-randomized controlled trials were evaluated for quality and data were independently extracted by two reviewers. Results. The effectiveness of topical skin interventions was variable and dependent on the skin condition being treated. Studies examined the effectiveness of washing products on incontinence irritated skin. Disposable bodyworns may prevent deterioration of skin condition better than non-disposable underpads or bodyworns. Clinisan, a no-rinse cleanser may reduce the incidence of incontinence associated pressure ulcers when compared with soap and water. Conclusion. In general the quality of evidence for interventions to improve or maintain the skin condition in the older person was poor and more research in this area is needed. Relevance to Clinical Practice. Skin care is a major issue for nurses working with older people. On the basis of this review no clear recommendations can be made. This lack of strong evidence for nurses to base effective practice decisions is problematic. However, the 'best' evidence suggests that disposable bodyworns are a good investment in the fight against skin deterioration. No rinse cleansers are to be preferred over soap and the use of the bag bath appears to be a useful practice to reduce the risk of dry skin ( a risk factor for breaches in skin integrity).

Diversity and Emotion: The New Frontiers in Organizational Behavior Research

This article provides a review of recent developments in two topical areas of research in contemporary organizational behavior: diversity and emotions. In the section called “Diversity,”we trace the history of diversity research, explore the definitions and paradigms used in treatments of diversity, and signal new areas of interest. We conclude that organizational behavior in the 21st century is evolving to embrace a more eclectic and holistic view of humans at work. In the section called “Emotions,” we turn our attention to recent developments in the study of emotions in organizations. We identify four major topics: mood theory, emotional labor, affective events theory (AET), and emotional intelligence, and argue that developments in the four domains have significant implications for organizational research, and the progression of the study of organizational behavior. As with the study of diversity, the topic of emotions in the workplace is shaping up as one of the principal areas of development in management thought and practice for the next decade. Finally, we discuss in our conclusion how these two areas are being conceptually integrated, and the implications for management scholarship and research in the contemporary world.

Erluanbi, Southern Taiwan

Erluanbi is the most southern tip of Taiwan (Formosa) where the Taiwan (Formosa) Strait meets the Pacific Ocean. The Erluanbi national park is renown for its lighthouse, and its coral reef, and it hosts also some prehistoric sites bating back to 5,000 to 6,500 years. The Erluanbi (or Eluan Pi) lighthouse was completed in 1883, following requests from the American and Japanese governments to the Chinese government after several ship wrecks in the 1860s. Chinese troops were sent to protect the lighthouse construction from attacks by local tribesmen, and the lighthouse was surrounded a small fort with cannons and a ditch to protect it. It is a rare example of a fortified lighthouse in the world. The lighthouse itself is 21.4 m high and its light is 56.4 m above high water. The light flashes every 10 seconds and its range is 27.2 nautical miles. The surrounding Erluanbi national park is located on a raised coral reef with some huge fringing reef : e.g., the "sea pavillon". With the topical oceanic climate, the elevated reef hosts an unique vegetation and ecology. Since 1956, numerous prehistoric artefacts were uncovered including stone slab coffins and pottery (plain and painted), that encompassed at least four cultural stages from BC 4,500 to AD 800.

Targeting local tissues by transdermal application: Understanding drug physicochemical properties that best exploit protein binding and blood flow effects

The targeting of topically applied drug molecules into tissues below a site of application requires an understanding of the complex interrelationships between the drug, its formulation, the barrier properties of the skin, and the physiological processes occurring below the skin that are responsible for drug clearance from the site, tissue, and/or systemic distribution and eventual elimination. There is still a certain amount of controversy over the ability of topically applied drugs to penetrate into deeper tissues by diffusion or whether this occurs by redistribution in the systemic circulation. The major focus of our work in this area has been in determining how changes in drug structure and physicochemical properties, such as protein binding and lipophilicity, affect drug clearance into the local dermal microcirculation and lymphatics, as well as subsequent distribution into deeper tissues below an application site. The present study outlines our recent thinking on the drug molecule optimal physical attributes, in terms of plasma and tissue partitioning behaviour, that offer the greatest potential for deep tissue targeting. Drug Dev. Res. 46:309-315, 1999. (C) 1999 Wiley-Liss, Inc.

Absorption of sunscreens across human skin: an evaluation of commercial products for children and adults

Aims Topical sunscreens are routinely applied to the skin by a large percentage of the population. This study assessed the extent of absorption of a number of common chemical sunscreen agents into and through human skin following application of commercially available products. Methods Sunscreen products were applied to excised human epidermis in Franz diffusion cells with the amount penetrating into and across the epidermis assessed by h.p.l.c. for 8 h following application. Results All sunscreen agents investigated penetrated into the skin (0.25 g m(-2) or 14% of applied dose), but only benzophenone-3 passed through the skin in significant amounts (0.08 g m(-2) or 10% of the applied dose). With one exception, suncreen agents in corresponding products marketed for adults and children had similar skin penetration profiles. Conclusions Whilst limited absorption across the skin was observed for the majority of the sunscreens tested, benzophenone-3 demonstrated sufficiently high penetration to warrant further investigation of its continued application.

Mathematical models in percutaneous absorption

A number of mathematical models have been used to describe percutaneous absorption kinetics. In general, most of these models have used either diffusion-based or compartmental equations. The object of any mathematical model is to a) be able to represent the processes associated with absorption accurately, b) be able to describe/summarize experimental data with parametric equations or moments, and c) predict kinetics under varying conditions. However, in describing the processes involved, some developed models often suffer from being of too complex a form to be practically useful. In this chapter, we attempt to approach the issue of mathematical modeling in percutaneous absorption from four perspectives. These are to a) describe simple practical models, b) provide an overview of the more complex models, c) summarize some of the more important/useful models used to date, and d) examine sonic practical applications of the models. The range of processes involved in percutaneous absorption and considered in developing the mathematical models in this chapter is shown in Fig. 1. We initially address in vitro skin diffusion models and consider a) constant donor concentration and receptor conditions, b) the corresponding flux, donor, skin, and receptor amount-time profiles for solutions, and c) amount- and flux-time profiles when the donor phase is removed. More complex issues, such as finite-volume donor phase, finite-volume receptor phase, the presence of an efflux. rate constant at the membrane-receptor interphase, and two-layer diffusion, are then considered. We then look at specific models and issues concerned with a) release from topical products, b) use of compartmental models as alternatives to diffusion models, c) concentration-dependent absorption, d) modeling of skin metabolism, e) role of solute-skin-vehicle interactions, f) effects of vehicle loss, a) shunt transport, and h) in vivo diffusion, compartmental, physiological, and deconvolution models. We conclude by examining topics such as a) deep tissue penetration, b) pharmacodynamics, c) iontophoresis, d) sonophoresis, and e) pitfalls in modeling.

Local inflammation is crucial for T cell mediated rejection of skin graft expressing foreign antigen

Most of the skin grafts from (K14hGH.FVB C57BL/6) F1 mice, which express foreign antigen (human growth hormone, hGH) in skin keratinocytes driven by keratin 14 promoter, were spontaneously rejected by syngeneic wild type F1 recipients and hGH-specific immune responses such as antibody and hGHspecific T cells were generated in these recipients. Interestingly, a 2nd F1 hGH-expressing skin graft was rejected by graft primed recipients, but was not rejected from such recipients if CD4+ or CD8+ T cells were depleted prior to the placement of the 2nd graft. Surprisingly, this 2nd graft retained healthy even after CD4+ or CD8+ T cells were allowed to recover so that the animal could reject a freshly placed 3rd F1 hGH-expressing graft. Furthermore, inflammatory response induced by topical treatment with imiquimod could lead to the rejection of some well-healed 2nd grafts. This result indicates that both CD4+ and CD8+ T cells are required for the rejection and the ability of effector T cells to reject a graft is determined by local factors in the graft which are presumably determined by inflammation induced by surgery or imiquimod treatment. Taken together, our results suggest that in addition to CD4+ and CD8+ T cells, local environmental factors induced by inflammation are also crucial for effector T cell functions leading to graft destruction. The understanding of these local factors will lead to more effective immunotherapy for established, epithelial cancer in the future.

Targeted drug delivery to the skin and deeper tissues: Role of physiology, solute structure and disease

1. Drug delivery through the skin has been used to target the epidermis, dermis and deeper tissues and for systemic delivery, The major barrier for the transport of drugs through the skin is the stratum corneum, with most transport occurring through the intercellular region, The polarity of the intercellular region appears to be similar to butanol, with the diffusion of solutes being hindered by saturable hydrogen bonding to the polar head groups of the ceramides, fatty acids and other intercellular lipids, Accordingly, the permeability of the more lipophilic solutes is greatest from aqueous solutions, whereas polar solute permeability is favoured by hydrocarbon-based vehicles. 2. The skin is capable of metabolizing many substances and, through its microvasculature, limits the transport of most substances into regions below the dermis. 3. Although the flux of solutes through the skin should be identical for different vehicles when the solute exists as a saturated solution, the fluxes vary in accordance with the skin penetration enhancement properties of the vehicle. It is therefore desirable that the regulatory standards required for the bioequivalence of topical products include skin studies. 4. Deep tissue penetration can be related to solute protein binding, solute molecular size and dermal blood flow. 5. Iontophoresis is a promising area of skin drug delivery, especially for ionized solutes and when a rapid effect is required. 6. In general, psoriasis and other skin diseases facilitate drug delivery through the skin. 7. It is concluded that the variability in skin permeability remains an obstacle in optimizing drug delivery by this route.