Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects

Our previous studies and other published reports on the chemical warfare agent sulfur mustard (SM) and its analog 2-chloroethyl ethyl sulfide (CEES) have indicated a role of oxidative stress in skin injuries caused by these vesicating agents. We examined the effects of the catalytic antioxidant AEOL 10150 in the attenuation of CEES-induced toxicity using our established skin injury models (skin epidermal cells and SKH-1 hairless mice) to validate the role of oxidative stress in the pathophysiology of mustard vesicating agents. Treatment of mouse epidermal JB6 and human HaCaT cells with AEOL 10150 (50 μM) 1 h post-CEES exposure resulted in significant (p < 0.05) reversal of CEES-induced decreases in both cell viability and DNA synthesis. Similarly, AEOL 10150 treatment 1 h after CEES exposure attenuated CEES-induced DNA damage in these cells. Similar AEOL 10150 treatments also caused significant (p < 0.05) reversal of CEES-induced decreases in cell viability in normal human epidermal keratinocytes. Cytoplasmic and mitochondrial reactive oxygen species measurements showed that AEOL 10150 treatment drastically ameliorated the CEES-induced oxidative stress in both JB6 and HaCaT cells. Based on AEOL 10150 pharmacokinetic studies in SKH-1 mouse skin, mice were treated with a topical formulation plus subcutaneous injection (5 mg/kg) of AEOL 10150 1 h after CEES (4 mg/mouse) exposure and every 4 h thereafter for 12 h. This AEOL 10150 treatment regimen resulted in over 50% (p < 0.05) reversal of CEES-induced skin bi-fold and epidermal thickness, myeloperoxidase activity, and DNA oxidation in mouse skin. Results from this study demonstrate the potential therapeutic efficacy of AEOL 10150 against CEES-mediated cutaneous lesions, supporting AEOL 10150 as a medical countermeasure against SM-induced skin injuries.     

Sebaceous carcinoma in solid organ transplant recipients: The elegant path from epidemiology to etiology

Sebaceous carcinoma (SC) is a rare skin cancer associated with rapid progression and relatively poor survival, particularly in solid organ transplant recipients (SOTRs). Immunosuppressive regimens place SOTRs at substantially increased risk of a variety of skin cancers; recent research has shown a 25-fold increase in SC in the SOTR population, especially among lung recipients, older males, those with longer time since transplant, and patients undergoing induction therapy with thymoglobulin. The potential etiologic mechanisms underlying SC are multifaceted and complex. Immunosuppression creates a microcosm through which to view causative factors for carcinogenesis which has implications in elucidating mechanistic etiologies for SC far beyond the SOTR population, since not all cancers are more common in immunosuppressed patients. Research integrating the role of oncogenic viruses, underlying medical conditions, genetic risk factors, toxicity of prophylactic medications, drug-induced photosensitization, and T-cell deficiency/dysfunction is needed to better elucidate the factors underlying SC in immunosuppressed hosts. In this report, we integrate current research regarding SC in SOTR patients using the causal pie/sufficient-component cause model. In doing so, we provide a paradigm through which to view future research regarding the etiology of SC.     

Thermal body patterns for healthy Brazilian adults (male and female)

The aim of this study was to establish the skin temperature (T_sk) thermal profile for the Brazilian population and to compare the differences between female and male Brazilian adults. A total of 117 female and 103 male were examined with a thermographic camera. The T_sk of 24 body regions of interest (ROI) were recorded and analyzed. Male T_sk results were compared to female and 10 ROI were evaluated with respect to the opposite side of the body (right vs. left) to identify the existence of significant contralateral T_sk differences (ΔT_sk). When compared right to left, the largest contralateral ΔT_sk was 0.3 °C. The female vs. male analysis yielded significant differences (p<0.05) in 13 of the 24 ROI. Thigh regions, both ventral and dorsal, had the highest ΔT_sk by sex (≈1.0 °C). T_sk percentile below P₅ or P₁₀ and over P₉₀ or P₉₅ may be used to characterize hypothermia and hyperthermia states, respectively. Thermal patterns and T_sk tables were established for Brazilian adult men and women for each ROI. There is a low T_sk variation between sides of the body and gender differences were only significant for some ROIs.     

中国林蛙蝌蚪肠道及皮肤微生物多样性分析

肠道及皮肤微生物群落对宿主的健康有着至关重要的影响.本研究使用16S rRNA基因测序技术研究中国林蛙(Rana chensinensis)Gosner38期蝌蚪肠道和皮肤共生微生物群落组成之间的差异.在门水平上,林蛙蝌蚪肠道中的优势门为变形菌门(Proteobacteria)、厚壁菌门(Firmicutes)和拟杆菌...     

Characterization of performance of multihole nozzle in cryospray

Present study deals with improvement in conventional technique of spraying liquid nitrogen on cancerous lesions to improve its efficacy. It is an attempt to demarcate the variation in outcome when cryogen is sprayed through customised multi-hole nozzle (MHN). Influence of mass flow rate on cryoablation while varying the number of holes in MHNs is analysed experimentally. Another section of study focuses on the impact of the rate of evaporation of cryogen when margin among the holes is changed. Total 6 MHNs are fabricated while changing their geometrical parameters. Single freeze-thaw cycle is carried out to spray liquid nitrogen on tissue mimicking gel with a spraying distance of 18 mm. Temperature profile captured through infrared images advocates that lethal area formed through the application of MHNs with 5 holes is larger than MHNs with 4 holes on the surface of gel. It reflects the influence of central hole on necrosis. In order to necrotize lesion through freezing, the most desired cooling rate (CR) varies from 50^∘C/min to 200^∘C/min. It is achieved up to a depth of 2 mm below the gel surface and in a radius of 10 mm from the centre of spray (CS) for all MHNs, except 4C. Most optimised margin in terms of cryoablation is also estimated in the study. MHN with 1.5 mm margin provides the most optimised results in terms of cryoablation when MHNs with the central hole are considered while MHN with 1 mm margin provides most optimised result when MHNs without central hole are considered. On the basis of observations made through thermal images it can be said that multiple freezing fronts are not observed on the gel surface which aids in the formation of lone giant ice ball. This provides an extra edge to the treatment methodology because alteration in the dimensions of necrotic zone can be made by changing the duration of spray. Larger lateral spread of necrotic zone will also reduce the number of sittings required for the treatment of larger lesions.     

Orally active antioxidative copper(II) aspirinate: synthesis, structure characterization, superoxide scavenging activity, and in vitro and in vivo antioxidative evaluations

Ever since it was proposed that reactive oxygen species (ROS) are involved in the pathogeneses of various diseases, superoxide dismutase (SOD)-mimetic complexes have been intensively studied. We prepared copper(II) aspirinate [Cu₂(asp)₄] from Cu(II) and aspirin, which has been in use for many years as an antipyretic, an analgesic, and an anti-inflammatory agent. However, Cu₂(asp)₄ has been found to have additional activities, including anti-inflammatory, antiulcer, anti-ischemic/reperfusion agent, anticancer, antimutagenic, and antimicrobial activities. The activity of copper salicylate [Cu(sal)₂] was also compared with that of Cu₂(asp)₄. The structure of the Cu₂(asp)₄ was determined using X-ray structure analysis. Its SOD-mimetic activity was determined using cytochrome c, electron spin resonance (ESR) spectroscopy, and ESR spin trap methods. The activity of Cu₂(asp)₄ was slightly greater than CuSO₄ and copper acetate [Cu(ace)₂] and slightly less than that of Cu(sal)₂. The in vitro antioxidant activity, evaluated in human epithelial or transformed neoplastic keratinocyte cells, HaCaT, and normal dermal fibroblasts in terms of cell survival following ultraviolet B (UVB) irradiation, was significantly increased in the presence of Cu₂(asp)₄, Cu(sal)₂, and CuSO₄. Further, ROS generation following UVA irradiation in the skin of hairless mice following oral treatment with Cu₂(asp)₄ for three consecutive days was significantly suppressed compared to the vehicle- or Cu(ace)₂-treated mice. On the basis of these results, Cu₂(asp)₄ was observed to be a potent antioxidative compound possessing antioxidative activity in biological systems. In conclusion, Cu₂(asp)₄ is a potent antioxidative agent that may be useful for future treatment of diseases resulting from ROS.     

Two Specific Strains of <Emphasis Type="Italic">Histoplasma capsulatum</Emphasis> causing Mucocutaneous Manifestations of Histoplasmosis: Preliminary Analysis of a Frequent Manifestation of Histoplasmosis in Southern Brazil

Objectives  Skin lesions, uncommon in US cases (<10%), occur in 38–85% of cases reported from Latin America. Although these differences may reflect reporting bias, delayed diagnosis, or differences in host immune response among different ethnic groups, they also could result from genetic differences changing the pathobiology of the organism. It is possible that genetic differences among strains of H. capsulatum may influence the pathogenesis and clinical manifestations of histoplasmosis. Methods  We examined the clinical features of patients with mucocutaneous manifestations of histoplasmosis and performed genetic analysis based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes of H. capsulatum isolates of patients. Two pairs of PCR primers were designed to develop and amplify the ITS regions of H. capsulatum, 5′-TACCCGGCCACCCTTGTCTA-3′ and 5′-AGCGGGTGGCAAAGCCC-3′. These primers were based on the ITS sequence of Ajellomyces capsulatus, the ascomycetous teleomorph form of H. capsulatum, deposited in the GenBank (accession number U18363). Eight patients attending a tertiary-care hospital in southern Brazil were enrolled into the study. All case patients had skin cultures growing H. capsulatum at the mycology laboratory. Results  Six of eight (75%) patients were HIV-positive and presented involvement of multiples organs by H. capsulatum. Two HIV-negative patients did not present evidence of involvement of other organs besides mucosa and skin. ITS sequencing of a DNA H. capsulatum fragment of 485-bp from isolates of 8 patients revealed two distinct strains. The 2 distinct fragments (Hc1, Hc2) differed from each other at 7 positions in the ITS regions. They were identical to strains of H. capsulatum isolated in patients from Colombia and Argentina, but different from strains isolated in US. Hc1 and Hc2 were isolated in 5 patients and 3 patients, respectively, with mucocutaneous manifestations of histoplasmosis. Both Hc1 and Hc2 strains were isolated in HIV-infected and non-HIV-infected patients. Conclusions  Mucocutaneous manifestations of histoplasmosis, which are frequently seen in Brazilian patients were caused by 2 specific strains in our institution. Those strains have been isolated in patients with these particular clinical features of histoplasmosis in Latin America. Our study suggests that unique pathogenic characteristics among the Latin American species of H. capsulatum might explain its increased dermatotropism.     

Utilization of chlorhexidine gluconate to evaluate a nonhuman primate skin-degerming model

We have developed a nonhuman skin-degerming model to predict the in vivo effectiveness of topical antimicrobial formulations. The model incorporates a balanced, randomized, complete block design and uses the hands of anesthetized cynomolgus monkeys as treatment sites to measure product effectiveness. Two different 4% chlorhexidine gluconate formulations were evaluated in the primate model and then retested in a human skin-degerming model of identical design. Statistical analysis of the data revealed no significant differences between the two models with regard to the response exhibited by each to the test formulations.     

Effect of strain rate on the fracture behaviour of skin

The effect of strain rate on the stress-strain behaviour of skin is studied. It is observed that the plastic set in the skin is dependent on strain rate. The scanning electron micrographs of the fractured skin sample shows thicker fibrils and thinner one at low strain rates. The plastic flow is clearly brought out in the stress-strain curves at different strain rates. The stress relaxation behaviour at any given strain is clearly brought out in the 3-dimensional plot.     

Stage of pregnancy dictates heterothermy in temperate forest-dwelling bats

Bats face high energetic requirements, as powered flight is costly and they have a disadvantageous surface-to-volume-ratio. To deal with those requirements energy saving mechanisms, such as heterothermy (torpor), have evolved. Torpor during pregnancy, however, reduces rates of foetal development and consequently prolongs pregnancy. Therefore, heterothermy has a great effect on reproduction, as an unhindered parturition can only be assured by high body temperatures. Regardless of these adverse affects of torpor the energetic requirements of bats during reproduction urge for energy savings and bats are known to enter torpor during pregnancy. The species in the current study differ in their torpor patterns and thus their heterothermic strategy. However, we hypothesized, that species-specific heterothermic behaviour should be revoked at the end of pregnancy. We analyzed skin temperatures of Myotis bechsteinii, Myotis nattereri and Plecotus auritus during pregnancy and found no differences in torpor depth between species during the last phase of pregnancy. Furthermore, we could show that individuals entered torpor frequently during pregnancy and only minimized torpor during the last stage of pregnancy. This suggests that close to the end of pregnancy, heterothermy is restricted but not species-specific and the required energy is allocated otherwise.