Idiopathic necrotizing dermatitis: Current management

Objectives: To identify and demonstrate necrotizing dermatitis in infancy; an uncommon, puzzling syndrome, in which anecdotal reporting and personal experience indicates that one third of cases may require skin grafting. Much informed discussion about the pathogenesis of this distressing syndrome centres on the role of spider envenomation; and in particular on the speculative role of the Australian White-tailed spider, Lampona cylindrata. Methods: We present here six cases of necrotizing dermatitis treated surgically at the Royal Children's Hospital and Mater Children's Hospital in Brisbane over the period from 1991 to 1999. Clinical history, surgical details and pathological investigations were reviewed in each case. Microbiological investigation of necrotic ulcers included standard aerobic and anaerobic culture. Result: Nocardia and Staphylococcus were cultured in two cases, but no positive bites were witnessed and no spiders were identified by either the children or their parents. All cases were treated with silver sulphadiazine creme. Two of the infants required general anaesthesia, excision debridement and split skin grafting. The White-tailed spider, Lampona cylindrata, does not occur in Queensland, but Lampona murina does; neither species has necrotizing components in its venom. Circumstantial evidence is consistent with this syndrome being due to invertebrate envenomation, possibly following arachnid bites. Conclusion: In our experience there is insufficient evidence to impute a specific genus as the cause, at this stage of scientific knowledge. If the offending creature is a spider, we calculate that the syndrome of necrotizing dermatitis occurs in less than 1 in 5000 spider bites.

Deep dermal burn injury results in scarless wound healing in the ovine fetus

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta 1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.

Urinary porphyrins as biomarkers for arsenic exposure among susceptible populations in Guizhou Province, China

Coal is widely used in PR China. Unfortunately, coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of heating, cooking and drying of food in poorly ventilated dwellings. The population at risk has been estimated to be approximately 200,000 people. Clinical symptoms of arsenicosis may include changes of skin pigmentation, hyperkeratosis of hand and feet, skin cancers, liver damage, persistent cough and chronic bronchitis. We analyzed the porphyrin excretion profile using a HPLC method in urine samples collected from 113 villagers who lived in Xing Ren district, a coal-bome arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is not prevalent. Urinary porphyrins were higher in the arsenic exposed group than those in the control group. The correlation between urinary arsenic and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed significant increases in the excretion profile of the younger age (< 20 years) arsenic-exposed group, suggesting that porphyrins could be used as early warning biomarkers of chronic arsenic exposure in humans. Greater increases of urinary arsenic and porphyrins in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. Whether elevated porphyrins could predict adverse health effects associated with both cancer and non-cancer end-points in chronically arsenic-exposed populations need further investigation. (c) 2005 Elsevier Inc. All rights reserved.

Microemulsions as topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl ester (TMZA-HE)

A prodrug, temozolomide acid hexyl ester (TMZA-HE), was identified as a skin-deliverable congener for temozolomide (TMZ) to treat skin cancers. Poor solubility and instability of TMZA-HE rendered a serious challenge for formulation of a topical preparation. Microemulsions (ME) were chosen as a potential vehicle for TMZA-HE topical preparations. ME systems were constructed with either oleic acid (OA) or isopropyl myristate (IPM) as the oil phase and tocopheryl (vitamin E) polyethylene glycol 1000 succinate (VE-TPGS) as a surfactant. Topical formulations of OA and IPM ME systems demonstrated beneficial solubilising ability and provided a stable environment for the prodrug, TMZA-HE. Significant differences between the microstructures of OA and IPM ME systems were revealed by freeze fracture electron microscopy (FFEM) and different loading abilities and permeation potencies between the two systems were also identified. In permeation studies, IPM ME systems, with inclusion of isopropyl alcohol (IPA) as a co-surfactant, significantly increased TMZA-HE permeation through silicon membranes and rat skin resulting in less drug retention within the skin, while OA ME systems demonstrated higher solubilising ability and a higher concentration of TMZA-HE retained within the skin. Therefore IPM ME systems are promising for transdermal delivery of TMZA-HE and OA ME systems may be a suitable choice for a topical formulation of TMZA-HE. © 2007 The Authors.

Formulation of topical non-steroidal anti-inflammatory agents

Reversed-pahse high-performance liquid chromatographic (HPLC) methods were developed for the assay of indomethacin, its decomposition products, ibuprofen and its (tetrahydro-2-furanyl)methyl-, (tetrahydro-2-(2H)pyranyl)methyl- and cyclohexylmethyl esters. The development and application of these HPLC systems were studied. A number of physico-chemical parameters that affect percutaneous absorption were investigated. The pKa values of indomethacin and ibuprofen were determined using the solubility method. Potentiometric titration and the Taft equation were also used for ibuprofen. The incorporation of ethanol or propylene glycol in the solvent resulted in an improvement in the aqueous solubility of these compounds. The partition coefficients were evaluated in order to establish the affinity of these drugs towards the stratum corneum. The stability of indomethacin and of ibuprofen esters were investigated and the effect of temperature and pH on the decomposition rates were studied. The effect of cetyltrimethylammonium bromide on the alkaline degradation of indomethacin was also followed. In the presence of alcohol, indomethacin alcoholysis was observed and the kinetics of decomposition were subjected to non-linear regression analysis and the rate constants for the various pathways were quantified. The non-isothermal, sufactant non-isoconcentration and non-isopH degradation of indomethacin were investigated. The analysis of the data was undertaken using NONISO, a BASIC computer program. The degradation profiles obtained from both non-iso and iso-kinetic studies show that there is close concordance in the results. The metabolic biotransformation of ibuprofen esters was followed using esterases from hog liver and rat skin homogenates. The results showed that the esters were very labile under these conditions. The presence of propylene glycol affected the rates of enzymic hydrolysis of the ester. The hydrolysis is modelled using an equation involving the dielectric constant of the medium. The percutaneous absorption of indomethacin and of ibuprofen and its esters was followed from solutions using an in vitro excised human skin model. The absorption profiles followed first order kinetics. The diffusion process was related to their solubility and to the human skin/solvent partition coefficient. The percutaneous absorption of two ibuprofen esters from suspensions in 20% propylene glycol-water were also followed through rat skin with only ibuprofen being detected in the receiver phase. The sensitivity of ibuprofen esters to enzymic hydrolysis compared to the chemical hydrolysis may prove valuable in the formulation of topical delivery systems.

The role of models@run.time in supporting on-the-fly interoperability

Models at runtime can be defined as abstract representations of a system, including its structure and behaviour, which exist in tandem with the given system during the actual execution time of that system. Furthermore, these models should be causally connected to the system being modelled, offering a reflective capability. Significant advances have been made in recent years in applying this concept, most notably in adaptive systems. In this paper we argue that a similar approach can also be used to support the dynamic generation of software artefacts at execution time. An important area where this is relevant is the generation of software mediators to tackle the crucial problem of interoperability in distributed systems. We refer to this approach as emergent middleware, representing a fundamentally new approach to resolving interoperability problems in the complex distributed systems of today. In this context, the runtime models are used to capture meta-information about the underlying networked systems that need to interoperate, including their interfaces and additional knowledge about their associated behaviour. This is supplemented by ontological information to enable semantic reasoning. This paper focuses on this novel use of models at runtime, examining in detail the nature of such runtime models coupled with consideration of the supportive algorithms and tools that extract this knowledge and use it to synthesise the appropriate emergent middleware.

Towards standardization of UV eye protection:what can be learned from photodermatology?

While knowledge about standardization of skin protection against ultraviolet radiation (UVR) has progressed over the past few decades, there is no uniform and generally accepted standardized measurement for UV eye protection. The literature provides solid evidence that UV can induce considerable damage to structures of the eye. As well as damaging the eyelids and periorbital skin, chronic UV exposure may also affect the conjunctiva and lens. Clinically, this damage can manifest as skin cancer and premature skin ageing as well as the development of pterygia and premature cortical cataracts. Modern eye protection, used daily, offers the opportunity to prevent these adverse sequelae of lifelong UV exposure. A standardized, reliable and comprehensive label for consumers and professionals is currently lacking. In this review we (i) summarize the existing literature about UV radiation-induced damage to the eye and surrounding skin; (ii) review the recent technological advances in UV protection by means of lenses; (iii) review the definition of the Eye-Sun Protection Factor (E-SPF®), which describes the intrinsic UV protection properties of lenses and lens coating materials based on their capacity to absorb or reflect UV radiation; and (iv) propose a strategy for establishing the biological relevance of the E-SPF. © 2013 John Wiley & Sons A/S.

New insights into the etiology of preeclampsia:identification of key elusive factors for the vascular complications

The incidence of preeclampsia is reduced by a third in smokers, but not in snuff users. Soluble Flt-1 (sFlt-1) and soluble endoglin (sEng) are increased prior to the clinical onset of preeclampsia. Animals exposed to high circulating levels of sFlt-1 and sEng elicit severe preeclampsia-like symptoms. Smokers have reduced circulating sFlt-1 and cigarette smoke extract decreases sFlt-1 release from placental villous explants. An anti-inflammatory enzyme, heme oxygenase-1 (HO-1) and its metabolite carbon monoxide (CO), inhibit sFlt-1 and sEng release. Women with preeclampsia exhale less CO than women with normal pregnancies and HO expression decreases as the severity of preeclampsia increases. In contrast, sFlt-1 levels increase with increasing severity. More importantly, chorionic villous sampling from women at eleven weeks gestation shows that HO-1 mRNA expression is decreased in women who go on to develop preeclampsia. Collectively, these facts provide compelling evidence to support the proposition that the pathogenesis of preeclampsia is largely due to loss of HO activity. This results in an increase in inflammation and excessive elevation of the two key anti-angiogenic factors responsible for the clinical signs of preeclampsia. These findings provide strong evidence for a protective role of HO-1 in pregnancy and identify HO as a target for the treatment of preeclampsia. The cardiovascular drugs, statins, stimulate HO-1 expression and inhibit sFlt-1 release in vivo and in vitro, thus, they have the potential to ameliorate early onset preeclampsia. The StAmP trial is underway to address this and if positive, its outcome will lead to the very first therapeutic intervention to prolong affected pregnancies.

Em Algorithm for MLE of a Probit Model for Multiple Ordinal Outcomes

The correlated probit model is frequently used for multiple ordered data since it allows to incorporate seamlessly different correlation structures. The estimation of the probit model parameters based on direct maximization of the limited information maximum likelihood is a numerically intensive procedure. We propose an extension of the EM algorithm for obtaining maximum likelihood estimates for a correlated probit model for multiple ordinal outcomes. The algorithm is implemented in the free software environment for statistical computing and graphics R. We present two simulation studies to examine the performance of the developed algorithm. We apply the model to data on 121 women with cervical or endometrial cancer. Patients developed normal tissue reactions as a result of post-operative external beam pelvic radiotherapy. In this work we focused on modeling the effects of a genetic factor on early skin and early urogenital tissue reactions and on assessing the strength of association between the two types of reactions. We established that there was an association between skin reactions and polymorphism XRCC3 codon 241 (C>T) (rs861539) and that skin and urogenital reactions were positively correlated. ACM Computing Classification System (1998): G.3.

Antimicrobial activity of a chlorhexidine intravascular catheter site gel dressing

Objectives: The antimicrobial efficacy of a chlorhexidine gluconate (CHG) intravascular catheter gel dressing was evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and an extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Chlorhexidine deposition on the skin surface and release from the gel were determined. Methods: The antimicrobial efficacy was evaluated in in vitro studies following microbial inoculation of the dressing and application of the dressing on the inoculated surface of a silicone membrane and donor skin [with and without a catheter segment and/or 10% (v/v) serum] on diffusion cells. Antimicrobial activity was evaluated for up to 7 days. Chlorhexidine skin surface deposition and release were also determined. Results: MRSA and E. coli were not detectable within 5 min following direct inoculation onto the CHG gel dressing. On the silicone membrane, 3 log and 6 log inocula of MRSA were eradicated within 5 min and 1 h, respectively. Time to kill was prolonged in the presence of serum and a catheter segment. Following inoculation of donor skin with 6 log cfu of MRSA, none was detected after 24 h. Chlorhexidine was released from the gel after a lag time of 30 min and increasing amounts were detected on the donor skin surface over the 48 h test period. The CHG gel dressing retained its antimicrobial activity on the artificial skin for 7 days. Conclusions: The CHG intravascular catheter site gel dressing had detectable antimicrobial activity for up to 7 days, which should suppress bacterial growth on the skin at the catheter insertion site, thereby reducing the risk of infection. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Secretion of tumor necrosis factor by human leukocytes stimulated with shark cartilage

To assess the role of shark cartilage as an immune modulator, acid, salt-soluble, and phosphate-buffered saline extracts were prepared from three different commercial sources (SL, TL, FDC) of cartilage and used to stimulate human leukocytes in vitro. Duplicate leukocyte cultures were set up, each containing 50 $\mu$l of endotoxin-free extract, 200 $\mu$l of cell suspension (2.4-2.5 $\times$ 10$\sp5$ cells) and 100 $\mu$l of medium and incubated at 37$\sp\circ$C. Cultures stimulated with LPS (5 $\mu$g/ml) or medium served as the positive and negative controls, respectively. Culture supernatants were assayed for TNF$\alpha$ by ELISA. Cartilage extracts stimulated cells to release significant levels of TNF$\alpha$ (p $<$.005); the highest response was obtained with the acid extract of SL cartilage. In comparison, response to corresponding extracts of bovine cartilage was lower (p $<$.05). The stimulatory activity was reduced (85%) following proteolytic digestion, and lost when extract was heated (60$\sp\circ$C, 20 min) or treated with urea (6M), suggesting that the active component(s) is a protein. ^

Inducible Overexpression of Endothelin-3 in a Transgenic Mouse Leads to Hyperpigmentation That Decreases Over Time

Endothelin-3 (Edn3) has been shown to be an essential environmental cue in melanocyte development. Edn3 and its receptor, EdnrB, are allelic to mouse mutations occurring at the lethal spotting and piebald loci, respectively; these mutations result in hypopigmentation phenotypes. Mutations in the genes for both Edn3 and EdnrB are implicated in human pigmentation disorders such as Waardenburg-Shah syndrome, which is characterized by pigmentation defects, deafness, and megacolon. In this study, a tetracycline-inducible transgenic mouse model that overexpresses Edn3 under the control of the Keratin 5 promoter was shown to produce a hyperpigmentation phenotype that decreases over time. The expression pattern of transgenic Edn3 and its effects on the melanocyte population were examined in transgenic embryos, postnatal skin, and the skin of adult mice that exhibit faded hyperpigmentation. These studies suggest that overexpression of Edn3 in this model is restricted primarily to the roof plate of the neural tube and surface ectoderm in the developing embryo and to keratinocytes in the epidermis of postnatal mice. A decline in transgenic expression and a reduction in the dermal melanocytes and free melanin that characterize the phenotype in juvenile mice were shown to correlate with the fading of the hyperpigmentation phenotype. Transgenic mice in which transgenic expression was repressed (resulting in the disappearance of the hyperpigmentation phenotype) also exhibited a decrease in the dermal melanocyte population. The Edn3-overexpressing mice used in this study might be helpful m understanding human skin conditions characterized by dermal melanocytosis.

Love comes in at the eye

LOVE COMES IN AT THE EYE relates the story of Marshall Craig, a Midwesterner transplanted to South Florida who turns 35 in the course of the book. Marshall is an assistant curator for a Miami art museum, a man who has been obsessed with--as he calls it--a greed for seeing from a young age. His fascination with the surface of appearance of things is exacerbated by his precocious studies in art and its histories. Marshall views himself as marked by his red hair and freckled skin, as someone whose chances of attracting a partner into a meaningful relationship have been diminished by his looks. He is colored by his image of himself as unattractive and most importantly, convinced that his romantic life would be more successful, more vibrant, if he'd been graced with the face and figure of, say, a Velazquez. When Marshall meets a Cuban-born man from Atlanta, he is transfixed by the conviction that this is the man the universe has selected for him. The thrust of the story goes beyond boy-meets/loses/gets-boy to an exploration of said boy coming to terms with his definition of self. In a pivotal span of six months, the book explores Marshall's obsessions with seeing and how they define his vision of reality, the emphasis placed on beauty in gay culture, the tentative beginnings of a relationship as it takes root and grows, and finally, the inexplicable, magical forces that direct our romantic destinies.

Trissoralen um medicamento de baixa dosagem: estudos termoanalíticos da compatibilidade do fármaco-excipientes e determinação de parâmetros de qualidade para cápsulas magistrais

The trioxsalen (Tri) is a low-dose drug used in the treatment of psoriasis and other skin diseases. The aim of the study was applying the thermal analysis and complementary techniques for characterization, evaluation of the trioxsalen stability and components of manipulated pharmaceutical formulations. The thermal behavior of the Tri by TG/DTG-DTA in dynamic atmosphere of synthetic air and nitrogen showed the same profile with a melting peak followed by a volatilization-related event. From the curves TG / DTG is observed a single stage of mass loss. By heating the drug in the stove at temperatures of 80, 240 and 260 °C, it had no change in chemical structure through the techniques of XRD, HPLC, MIR, OM and SEM. From the non-isothermal and isothermal TG kinetic studies was possible to calculate the activation energy and reaction order for the Tri. The drug showed good thermal stability. Studies on drug-excipient compatibility showed interaction of trissoralen with sodium lauryl sulfate 1:1. There was no interaction with aerosol, pregelatinized starch, sodium starch glycolate, cellulose, croscarmellose sodium, magnesium stearate, lactose and mannitol.The characterization of three trioxsalen formulations at concentrations of 2.5, 5, 7.5, 10, 12.5 and 15 mg was performed by DSC, TG / DTG, XRD, NIR and MIR. The PCA classification method based on spectral data from the NIR and MIR of trissoralen formulations allows successful differentiation into three groups. The formulation 3 was the one that best showed analytical profile with the following composition of aerosil excipients, pre-gelatinized starch and cellulose. The activation energy of the volatilization process of the drug was determined in binary mixtures and formulation 3 through fitting and isoconversional methods. The binary mixture with sodium starch glycolate and lactose showed differences in kinetic parameters compared to the drug isolated. The thermoanalytical techniques (DSC and TG / DTG) were shown to be promising methodologies for quantifying trioxsalen obtained by the linearity, selectivity, no use solvents, without sample preparation, speed and practicality.

Caldo de cana desidratado na ração de codornas de corte

In order to evaluate the effect of levels of dehydrated cane juice sugar (DCJS) (0.0, 1.5, 3.0 and 4.5%) in the diet of European quail (Coturnix coturnix coturnix) on performance on performance, carcass characteristics and economical at 22 days of age indices, 192 quails cutting, were distributed in a completely randomized design with four treatments and six replicates of eight birds each There was no significant difference to the performance of quail in any of the periods. Quadratic effects of levels of DCJS on carcass weight (y = 173.71 + 4.2767x – 1.2644x², R² = 0.99), thigh-thigh more about (y = 36,055 + 1,1263x – 0,2256x², R² = 0.91) and abdominal fat (y = 3,3295 - + 0.8903x 0,19x2, R ² = 0,97) where the optimum levels were estimated 1,69; 2.50 and 2.34%, respectively. There was a linear effect descending of DCJS levels on weight breast with skin (y = 66.267 – 0.5653x, R² = 0.83) and without skin (y = 60.286 – 0.7193x, R² = 0.58). In economic analysis, one can observe higher profit to the producer with the use of conventional feed. However, between the levels of inclusion of sugar cane juice is observed that the level of 1.5% DCJS obtained the best results in economic analysis, obtaining only a difference of relative gross margin of 0.47% compared to conventional. It is recommended 1.69 and 2.50% DCJS for higher carcass, thigh + drumstick weight and lower percentage of abdominal fat quails, respectively.