Patch and Photo-Patch Testing are Important in Patients with Idiopathic Photodermatoses

This number of the Revista da Sociedade Portuguesa de Dermatologia e Venereologia contains two articles dedicated to idiopathic photodermatoses, for which autoimmune reactions to an unknown endogenous chromophore are suspected to be involved – polymorphous light eruption, actinic prurigo, hydroa vacciniforme, chronic actinic dermatitis, and solar urticarial.1,2 Many of these and other photodermatoses have a very clear clinical presentation, while others may mimic allergic contact dermatitis (ACD) or photo-allergic contact dermatitis (PhACD), a classical T cell-mediated or delayed type IV hypersensitivity reaction to an exogenous chromophore applied on the skin in the presence of, or followed by exposure to ultraviolet (UV) or visible light.3,4 Allergic contact reactions can be followed by persistent photosensitivity and chronic actinic dermatitis, such as in cases of chronic ACD from certain plants, e.g., Compositae that are rich in sesquiterpene lactones,5 fragrances, lichens, and colophony,4 or in PhACD or photo-aggravated ACD from drugs like ketoprofen, etofenamate, and chlorproethazine, or even other contact allergens, such as tosylamide/formaldehyde resin, fragrances, and thiourea derivatives.4The long persistence of these chemicals in the epidermis (for up to at least 17 days in the case of ketoprofen),6 or the formation of endogenous photosensitizers might perhaps explain the progression to chronic actinic dermatitis.4In patients with idiopathic photodermatoses the use of sunscreens is mandatory, however, the sensitization risk from these chemicals may be enhanced by the previous skin inflammation and the need for repeated application for long periods.7 UV filters, which are chromophores that capture UV light, are among the most frequent causes of PhACD,8-11 namely benzophenones, dibenzoylmethane derivatives, octocrylene, and cinammates.9,10,12-14 Although more recent UV filters seem to be more photostable and less prone to induce PhACD,3 a few cases have been described,9 for example, from polysilicone-15 (Parsol®SLX).15 With regard to methylene bis-benzotriazolyl tetramethylbutylphenol (syn. bisoctrizole or Tinosorb® M), ACD from it is due to the surfactant decyl glucoside, in particular, which is added in order to stabilize the sunscreen molecule.16,17Topical drugs, such as the non-steroidal anti-inflammatory ketoprofen, piketoprofen, suprofen, etofenamate, piroxicam, and benzydamine,18 as well as phenothiazine derivatives, i.e., promethazine or chlorproethazine, and isothipendyl chlorhydrate19 are frequent causes of ACD/PhACD, either by direct application or by transfer from other individuals in close contact (consort or connubial dermatitis). Moreover, some of these chemicals, particularly ketoprofen, exhibit cross-reactions with UV filters, i.e., benzophenone(s) and octocrylene, the latter containing benzophenone residues. Also fenofibrate, a systemic drug, shares the benzophenone ring and can cross react with ketoprofen and related molecules.3,20 Furthermore, patients with PhACD from ketoprofen present with concomitant reactions to the perfume ingredient cinnamic alcohol, reactions that at present are difficult to explain by cross-reactivity.21Therefore, patch and photo-patch testing are highly recommended in patients with idiopathic and autoimmune photodermatoses, as well as in all other diseases aggravated by sunlight, in order to detect and avoid exposure to possible aggravating factors, and particularly to UV filters. Recently, recommendations for diagnostic patch testing have been issued by the European Society of Contact Dermatitis (ESCD),22 and in a cooperative effort of the ESCD and European Society of Photodermatology (ESPD), an agreement was not only reached regarding standardized protocols for photo-patch testing,23 but also on the list of 20 allergens to be included in the European baseline photo-patch tests series and an additional extended series including certain classical photo-allergens.24 Last but not least, photo-patch tests with all the patient’s own topical products and systemic photosensitizers to which the patients is exposed are strongly recommended as well, since the outcome may further contribute to the relevance of positive reactions observed, or avoid “false”- negative reactions obtained by testing standardized allergens only.24This number of the Revista da Sociedade Portuguesa de Dermatologia e Venereologia contains two articles dedicated to idiopathic photodermatoses, for which autoimmune reactions to an unknown endogenous chromophore are suspected to be involved – polymorphous light eruption, actinic prurigo, hydroa vacciniforme, chronic actinic dermatitis, and solar urticarial.1,2 Many of these and other photodermatoses have a very clear clinical presentation, while others may mimic allergic contact dermatitis (ACD) or photo-allergic contact dermatitis (PhACD), a classical T cell-mediated or delayed type IV hypersensitivity reaction to an exogenous chromophore applied on the skin in the presence of, or followed by exposure to ultraviolet (UV) or visible light.3,4 Allergic contact reactions can be followed by persistent photosensitivity and chronic actinic dermatitis, such as in cases of chronic ACD from certain plants, e.g., Compositae that are rich in sesquiterpene lactones,5 fragrances, lichens, and colophony,4 or in PhACD or photo-aggravated ACD from drugs like ketoprofen, etofenamate, and chlorproethazine, or even other contact allergens, such as tosylamide/formaldehyde resin, fragrances, and thiourea derivatives.4The long persistence of these chemicals in the epidermis (for up to at least 17 days in the case of ketoprofen),6 or the formation of endogenous photosensitizers might perhaps explain the progression to chronic actinic dermatitis.4In patients with idiopathic photodermatoses the use of sunscreens is mandatory, however, the sensitization risk from these chemicals may be enhanced by the previous skin inflammation and the need for repeated application for long periods.7 UV filters, which are chromophores that capture UV light, are among the most frequent causes of PhACD,8-11 namely benzophenones, dibenzoylmethane derivatives, octocrylene, and cinammates.9,10,12-14 Although more recent UV filters seem to be more photostable and less prone to induce PhACD,3 a few cases have been described,9 for example, from polysilicone-15 (Parsol®SLX).15 With regard to methylene bis-benzotriazolyl tetramethylbutylphenol (syn. bisoctrizole or Tinosorb® M), ACD from it is due to the surfactant decyl glucoside, in particular, which is added in order to stabilize the sunscreen molecule.16,17Topical drugs, such as the non-steroidal anti-inflammatory ketoprofen, piketoprofen, suprofen, etofenamate, piroxicam, and benzydamine,18 as well as phenothiazine derivatives, i.e., promethazine or chlorproethazine, and isothipendyl chlorhydrate19 are frequent causes of ACD/PhACD, either by direct application or by transfer from other individuals in close contact (consort or connubial dermatitis). Moreover, some of these chemicals, particularly ketoprofen, exhibit cross-reactions with UV filters, i.e., benzophenone(s) and octocrylene, the latter containing benzophenone residues. Also fenofibrate, a systemic drug, shares the benzophenone ring and can cross react with ketoprofen and related molecules.3,20 Furthermore, patients with PhACD from ketoprofen present with concomitant reactions to the perfume ingredient cinnamic alcohol, reactions that at present are difficult to explain by cross-reactivity.21Therefore, patch and photo-patch testing are highly recommended in patients with idiopathic and autoimmune photodermatoses, as well as in all other diseases aggravated by sunlight, in order to detect and avoid exposure to possible aggravating factors, and particularly to UV filters. Recently, recommendations for diagnostic patch testing have been issued by the European Society of Contact Dermatitis (ESCD),22 and in a cooperative effort of the ESCD and European Society of Photodermatology (ESPD), an agreement was not only reached regarding standardized protocols for photo-patch testing,23 but also on the list of 20 allergens to be included in the European baseline photo-patch tests series and an additional extended series including certain classical photo-allergens.24 Last but not least, photo-patch tests with all the patient’s own topical products and systemic photosensitizers to which the patients is exposed are strongly recommended as well, since the outcome may further contribute to the relevance of positive reactions observed, or avoid “false”- negative reactions obtained by testing standardized allergens only.2

Long-term variability of CO2 and O in the Mars upper atmosphere from MRO radio science data

We estimate the annual variability of CO2 and O partial density using approximately 6years of Mars Reconnaissance Orbiter (MRO) radio science data from August 2006 to January 2012, which cover three full Martian years (from the northern hemisphere summer of 28 to the northern hemisphere summer of 31). These two elements are the dominant species at the MRO periapsis altitude, constituting about 70-80% of the total density. We report the recovered annual cycle of CO2 and the annual and seasonal cycle of O in the upper atmosphere. Although no other observations are available at those altitudes, our results are in good agreement with the density measurements of the Mars Express Spectroscopy for Investigation of Characteristics of the Atmosphere of Mars, which uses stellar occultations between 60 and 130km to determine the CO2 variability, and with the Mars Global Reference Atmospheric Model 2010 for the O annual and seasonal variabilities. Furthermore, the updated model provides more reasonable MRO drag coefficients (CD), which are estimated to absorb mismodeling in the atmospheric density prediction. The higher content of dust in the atmosphere due to dust storms increases the density, so the CDs should compensate for this effect. The correlation between the drag coefficient and the dust optical depth, measured by the Mars Odyssey Thermal Emission Imaging System (THEMIS) instrument, increases from 0.4 to 0.8 with the a priori and adjusted models, respectively. The trend of CDs not only confirms a substantial improvement in the prediction of the atmospheric density with the updated model but also provides useful information for local dust storms, near MRO periapsis, that cannot be measured by the opacity level since THEMIS does not always sample the southern hemisphere evenly

Experimental Investigation of a Domestic Refrigeration Appliance Based on Exergy Destruction

Since refrigeration appliances consume more than 15% of electrical energy over the globe, many solutions have been proposed to enhance the efficiency of these appliances. However, the solutions mostly rise the expenditure and complexity of the appliances, making these methods less feasible for manufacturing. Therefore, some inexpensive and less complicated modifications should be proposed to enhance the efficiency and performance of the appliances affordably. This paper presents a new solution using unutilized cooling capacity of evaporator for cooling compressor. The experimental exergy analysis of a domestic refrigerator in which the suction pipe absorbs heat from the compressor shell illustrates a 12.64% reduction in total irreversibility, as well as a 5% and 4% of increase in cooling capacity and coefficient of performance, respectively. Moreover, the appliance with the modified cycle needs 18.2% less refrigerant than the normal design. This idea would be an affordable and practical way to enhance the efficiency of refrigeration appliances as well as decrease the manufacturing costs. This study proposes recommended design guidelines for more efficient refrigeration appliances to be used in designing compressors

Integral and Differential Model of Hermetical Compressor Heat Losses Including Experimental Validation

The current evaluation of heating and cooling system performances has become a major issue in European buildings sector. A promising method for measuring heat pump performances on-field has been previously developed and published. However, the accuracy of the method is strongly dependent on the evaluation of heat transfer from compressor towards the ambient air. In this paper a developed compressor heat transfer model that couples integral and differential formulations is presented. The model consists of three fundamental steps: thermodynamic analysis of the compression process, detailed thermophysical flow analysis using a CFD software, and finally compressor thermal network analysis consisting of integral equations that describe heat transfer of solid-fluid interfaces. Temperature distribution of the compressor shell is the main output of the model. Internal and external thermal profiles obtained from the numerical model and experimental measurements are compared in one operating condition at two compressor speeds. The RMS errors of external profiles are 3.20 °C and 1.96 °C, at 30 rps and 60 rps, respectively. The model can be used to determine the minimum number of surface temperature sensors and their locations on the compressor shell necessary to measure heat losses on-field. More accurate evaluation of compressor heat losses towards the ambient air will improve the accuracy of the performance measurement method

A study of the structural geology of the Witteberg Group and lowermost Karoo Supergroup, Darlington Dam, Jansenville District, Eastern Cape

A number of outcrops of the Witteberg Group and lowermost Karoo Supergroup rocks were studied in the area south of the Darlington Dam, Jansenville District, with the aim of documenting structural characteristics of the area. All lithologies are folded with fold styles varying from gentle to near isoclinal (based on interlimb angle). Fold axes are either sub-horizontal or plunging at gentle to moderate angles whereas axial planes dip gently to vertically (predominantly steep to sub-vertical). Folds verge predominantly towards the north but where southward verging they are associated with faulting or strongly folded areas. Folds plunge gently to the east-southeast and west-northwest. The area consists of a large anticlinorium with both first and second order folds occurring. Eastwest striking faults occur in the study area and are classified as normal, reverse and thrust faults. A study of the joint sets shows that there are four dominant joint directions, namely 18o, 33o, 97o and 107o (in order from least to most important). An interpretation of the tectonic history is presented in which the relationships between faults and folds show that faults formed during and after folding. Folding, and reverse and thrust faulting, occurred during the compressional events that formed the Cape Fold Belt, whereas the normal faults formed during the relaxation of these compressional forces or during the break-up of Gondwana

Quantity and quality of retrograde menstruation: a case control study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to test the hypothesis that menstruation is associated with a higher concentration of endometrial cells in peritoneal fluid(PF) and with increased white and red blood cell concentration in PF when compared to nonmenstrual phases of the cycle.</p> <p>Methods</p> <p>PF was obtained at laparoscopy from 107 women with endometriosis (n = 59) and controls with a normal pelvis (n = 48) during the luteal (n = 46), follicular (n = 38) or menstrual (n = 23) phase of the cycle. Endometriosis was classified according to the classification of the American Society for Reproductive Medicine (rAFS into minimal (n = 25), mild(n = 20), moderate(n = 6) and severe(n = 8) disease. Cell counts (leucocytes, erythrocytes, thrombocytes) were determined on a cell counter. In a subset of 32 patients (13 controls and 19 women with endometriosis), PF was fixed, processed and thinlayers were prepared and stained with Papanicolaou method and with immunocytochemistry using monoclonal antibodies against cytokeratin 7(CK 7), CK 8/18, Ber-Ep4, vimentin, calretinin and CD68. Ber-Ep4 is a marker for cells with epithelial origin (in some cases for mesothelial cells as well). CD68 is specific for cells from monocyte/macrophage lineage; CK7 and CK8/18 are markers for both endometrial epithelial and mesothelial cells, whereas calretinin and vimentin are markers for both endometrial stromal and mesothelial cells.</p> <p>Results</p> <p>In comparison with the nonmenstrual phase of the cycle, analysis of PF during menstruation showed an increased concentration of leucocytes (3.3 &#215; 10⁹/L vs 0.8 &#215; 10⁹/L, P = 0.03), erythrocytes (0.3 &#215; 10¹²/L vs 0.02 &#215; 10¹²/L, P = 0.006), hematocrit (0.03 L/L vs 0.003 L/L, P = 0.01) and hemoglobin (0.8 g/dL vs 0.1 g/dL, P = 0.01). Mesothelial cells stained positively with CK7, CK8/18, vimentin, and calretinin. Cells positive for Ber-Ep4 were not observed, except in 2 patients with endometriosis investigated during menses. In all patients 50-98% of single cells were strongly positive for both vimentin and CD68.</p> <p>Conclusion</p> <p>When compared to nonmenstrual phases of the cycle, menstruation is associated with an increased concentration of red and white blood cells in PF. However, the presence of EM cells that are detectable by immunohistochemistry in PF is low during all phases of the cycle, including menstruation.</p

Boosting the synthesis of pharmaceutically active abietane diterpenes in S. sclarea hairy roots by engineering the GGPPS and CPPS genes

Abietane diterpenoids (ADs), synthesized in the roots of different Salvia species, such as aethiopinone, 1-oxoaethiopinone, salvipisone, and ferruginol, have a variety of known biological activities. We have shown that aethiopinone has promising cytotoxic activity against several human tumor cell lines, including the breast adenocarcinoma MCF7, HeLa, epithelial carcinoma, prostate adenocarcinoma PC3, and human melanoma A375. The low content of these compounds in natural sources, and the limited possibility to synthesize them chemically at low cost, prompted us to optimize the production of abietane diterpenoids by targeting genes of the methylerythritol phosphate (MEP) pathway, from which they are derived. Here, we report our current and ongoing efforts to boost the metabolic flux towards this interesting class of compounds in Salvia sclarea hairy roots (HRs). Silencing the gene encoding the ent-copalyl-diphosphate synthase gene (entCPPS), acting at the lateral geranylgeranyl pyrophosphate (GGPP) competitive gibberellin route, enhanced the content of aethiopinone and other ADs in S. sclarea HRs, indicating indirectly that the GGPP pool is a metabolic constraint to the accumulation of ADs. This was confirmed by overexpressing the GGPPS gene (geranyl-geranyl diphosphate synthase) which triggered also a significant 8-fold increase of abietane diterpene content above the basal constitutive level, with a major boosting effect on aethiopinone accumulation in S. sclarea HRs. A significant accumulation of aethiopinone and other AD compounds was also achieved by overexpressing the CPPS gene (copalyl diphosphate synthase) pointing to this biosynthetic step as another potential metabolic target for optimizing the biosynthesis of this class of compounds. However, by co-expressing of GGPPS and CPPS genes, albeit significant, the increase of abietane diterpenoids was less effective than that obtained by overexpressing the two genes individually. Taken together, the results presented here add novel and instrumental knowledge to a rational design of a hairy root-based platform to yield reliable amounts of aethiopinone and other ADs for a deeper understanding of their molecular pharmacological targets and potential future commercialization

Scalable fabrication of efficient p-n junction lead sulfide quantum dot solar cells

Nowadays, the best lead sulfide (PbS) colloidal quantum dot (CQD) solar cells are primarily demonstrated in the n-p structure, while the p-n structure is significantly less developed. This technological gap between the n-p and p-n structures is much more distinct than in cases of other solution-processable photovoltaic technologies like perovskites and polymers. Here, we propose a scalable fabrication strategy for efficient PbS QD solar cells with p-n structure. An industrially suited blade-coating technique has been used to deposit both n-type and p-type QD layers. The obtained solar cells demonstrated power conversion efficiency of 9%, thus, commensurate to the record device efficiency with this architecture fabricated with a non-scalable technique. The availability of both p-n and n-p structures fabricated from scalable methods may promote the future integration of the PbS QDs into tandem devices together with other solution-processable materials to exploit the most prominent benefits of the PbS QDs, such as infrared absorption.</p