In Vitro Activity of Chlorhexidine Compared with Seven Antifungal Agents against 98 Fusarium Isolates Recovered from Fungal Keratitis Patients.

Fungal keratitis is a common but severe eye infection in tropical and subtropical areas of the world. In regions with a temperate climate, the frequency of infection is rising in patients with contact lenses and following trauma. Early and adequate therapy is important to prevent disease progression and loss of vision. The management of Fusarium keratitis is complex, and the optimal treatment is not well defined. We investigated the in vitro activity of chlorhexidine and seven antifungal agents against a well-characterized collection of Fusarium isolates recovered from patients with Fusarium keratitis. The fungus culture collection of the Center of Expertise in Mycology Radboudumc/CWZ was searched for Fusarium isolates that were cultured from cornea scrapings, ocular biopsy specimens, eye swabs, and contact lens fluid containers from patients with suspected keratitis. The Fusarium isolates that were cultured from patients with confirmed keratitis were all identified using conventional and molecular techniques. Antifungal susceptibility testing was performed according to the EUCAST broth microdilution reference method. The antifungal agents tested included amphotericin B, voriconazole, posaconazole, miconazole, natamycin, 5-fluorocytosine, and caspofungin. In addition, the activity of chlorhexidine was determined. The fungal culture collection contained 98 Fusarium isolates of confirmed fungal keratitis cases from 83 Dutch patients and 15 Tanzanian patients. The isolates were collected between 2007 and 2017. Fusarium oxysporum (n = 24, 24.5%) was the most frequently isolated species followed by Fusarium solani sensu stricto (n = 18, 18.4%) and Fusarium petroliphilum (n = 11, 11.2%). Amphotericin B showed the most favorable in vitro inhibition of Fusarium species followed by natamycin, voriconazole, and chlorhexidine, while 5-fluorocytosine, posaconazole, miconazole, and caspofungin showed no relevant inhibiting effect. However, chlorhexidine showed fungicidal activity against 90% of F. oxysporum strains and 100% of the F. solani strains. Our study supports the clinical efficacy of chlorhexidine and therefore warrants its further clinical evaluation for primary therapy of fungal keratitis, particularly in low and middle income countries where fungal keratitis is much more frequent and, currently, antifungal eye drops are often unavailable

Proposal, project, practice, pause: developing a framework for evaluating smart domestic product engagement

Smart homes are fast becoming a reality, with smart TVs, smart meters and other such “smart” devices/systems already representing a substantial household presence. These, which we collectively term “smart domestic products” (SDPs), will need to be promoted, adopted, and normalized into daily routines. Despite this, the marketing canon lacks a substantive discourse on pertinent research. We look to help correct this by melding ideas from organizational sociology, innovation diffusion and appropriation studies, and service dominant logic. Consequently, we suggest a framework for research that responds directly to the specific characteristics of SDPs. Using the SDP eco-system as a context, our framework emphasizes the interplay of embeddedness, practice, value and engagement. It comprises a four-stage horizontal/ longitudinal axis we describe as proposal, project, practice and pause. Cross-sectionally we focus on value, and combine aspects of existing thought to suggest how this impacts each stage of our engagement continuum. We subsequently identify perceived personal advantage as the resultant of these two axes and propose this as the key for understanding consumer and SDP sociomaterial engagement. This article also advances a definition of SDPs and ends with an agenda for further research

Vitamin A derivatives in the prevention and treatment of human cancer.

Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of vitamin A and the synthetic analogues (retinoids). Recent in-vitro work has led to the exciting proposal that protein kinase-C may be centrally involved in many of retinoids' anticancer actions including the effects on ornithine decarboxylase induction, intracellular polyamine levels, and epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural vitamin A at clinically tolerable doses has only limited activity against human neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, epidermodysplasia verruciformis, dysplastic nevus syndrome, and basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in retinoid trials. Definite retinoid activity has been documented in oral leukoplakia, laryngeal papillomatosis, superficial bladder carcinoma, cervical dysplasia, bronchial metaplasia, and preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some drug-resistant malignancies and several others that have become refractory, including advanced basal cell cancer, mycosis fungoides, melanoma, acute promyelocytic leukemia, and squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using retinoids as anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with retinoids in combination and adjuvant therapy

Identification of a 168-kDa mucosal antigen in a subset of patients with cicatricial pemphigoid.

International audienceThis study describes the presence of antibodies in sera from patients with cicatricial pemphigoid specific for a 168-kDa antigen expressed by buccal mucosa. Six cicatricial pemphigoid sera unreactive, with epidermal or dermal proteins in immunoblot assay were tested on mucosal protein extracts. Four of these sera labeled a mucosal 168-kDa antigen (M168) under reducing conditions. An additional cicatricial pemphigoid serum with circulating antibodies to 180-kDa bullous pemphigoid antigen (BPAg2) also labeled M168. None of these cicatricial pemphigoid sera reacted with the alpha, beta, or gamma subunits of laminin-5. Nitrocellulose elution studies showed that the M168 antigen is a basement membrane antigen and labeled the epidermal side of salt-split skin. Immunoaffinity-purified anti-M168 antibodies did not bind to the 230-kDa bullous pemphigoid antigen (BPAg1) or to the 180-kDa BPAg2. None of the control sera from healthy individuals or from bullous pemphigoid, pemphigus vulgaris, or pemphigus foliaceus patients reacted with Ml68. This study demonstrates the specificity of some cicatricial pemphigoid sera against a 168-kDa antigen that is different from the laminin-5 subunits and shares no epitopes with the antigens of bullous pemphigoid (BPAg1, BPAg2) or the epidermolysis bullosa acquisita.This study describes the presence of antibodies in sera from patients with cicatricial pemphigoid specific for a 168-kDa antigen expressed by buccal mucosa. Six cicatricial pemphigoid sera unreactive, with epidermal or dermal proteins in immunoblot assay were tested on mucosal protein extracts. Four of these sera labeled a mucosal 168-kDa antigen (M168) under reducing conditions. An additional cicatricial pemphigoid serum with circulating antibodies to 180-kDa bullous pemphigoid antigen (BPAg2) also labeled M168. None of these cicatricial pemphigoid sera reacted with the alpha, beta, or gamma subunits of laminin-5. Nitrocellulose elution studies showed that the M168 antigen is a basement membrane antigen and labeled the epidermal side of salt-split skin. Immunoaffinity-purified anti-M168 antibodies did not bind to the 230-kDa bullous pemphigoid antigen (BPAg1) or to the 180-kDa BPAg2. None of the control sera from healthy individuals or from bullous pemphigoid, pemphigus vulgaris, or pemphigus foliaceus patients reacted with Ml68. This study demonstrates the specificity of some cicatricial pemphigoid sera against a 168-kDa antigen that is different from the laminin-5 subunits and shares no epitopes with the antigens of bullous pemphigoid (BPAg1, BPAg2) or the epidermolysis bullosa acquisita

Diagnostic value of indirect immunofluorescence on sodium chloride-split skin in differential diagnosis of subepidermal autoimmune bullous dermatoses.

International audienceOBJECTIVE: To determine the diagnostic value of indirect immunofluorescence on sodium chloride-split skin (SSS) in differentiating the pemphigoid group of subepidermal autoimmune bullous dermatoses, including bullous pemphigoid (BP), cicatricial pemphigoid, and pemphigoid gestationis, from epidermolysis bullosa acquisita (EBA). DESIGN: Serum samples were tested using immunofluorescence on SSS and immunoblot assay on epidermal and dermal extracts, a recombinant protein corresponding to the C-terminal end of the 230-kd BP antigen, and purified laminin-5. SETTING: An immunodermatology laboratory. PATIENTS: One hundred forty-two serum samples from patients with BP (n = 98), cicatricial pemphigoid (n = 23), pemphigoid gestationis (n = 10), EBA (n = 10), and anti-type IV collagen (n = 1). MAIN OUTCOME MEASURES: Binding sites of serum to the epidermal and/or dermal sides of SSS were correlated with their antigenic specificities. RESULTS: Epidermal staining on SSS was highly specific for pemphigoid. Alternatively, a poor correlation was found for the dermal-reacting serum samples and the diagnosis of EBA; of the 19 serum samples with dermal staining on SSS, only 10 reacted with the EBA antigen. The remaining serum samples were from patients with cicatricial pemphigoid having antibodies to the alpha 3 or beta 3 chains of laminin-5 (n = 5) or patients with BP having antibodies to the 180-kd BP antigen (n = 2). One sample recognized exclusively a 185-kd dermal antigen corresponding to type IV collagen. One more BP serum sample with dermal staining did not recognize any dermal or epidermal antigen. CONCLUSION: In case of immunofluorescent dermal staining, the precise diagnosis should be confirmed by identification of the involved antigen, since it may reveal antibodies to laminin-5 or type XVII or IV collagen, in addition to the EBA antigen.OBJECTIVE: To determine the diagnostic value of indirect immunofluorescence on sodium chloride-split skin (SSS) in differentiating the pemphigoid group of subepidermal autoimmune bullous dermatoses, including bullous pemphigoid (BP), cicatricial pemphigoid, and pemphigoid gestationis, from epidermolysis bullosa acquisita (EBA). DESIGN: Serum samples were tested using immunofluorescence on SSS and immunoblot assay on epidermal and dermal extracts, a recombinant protein corresponding to the C-terminal end of the 230-kd BP antigen, and purified laminin-5. SETTING: An immunodermatology laboratory. PATIENTS: One hundred forty-two serum samples from patients with BP (n = 98), cicatricial pemphigoid (n = 23), pemphigoid gestationis (n = 10), EBA (n = 10), and anti-type IV collagen (n = 1). MAIN OUTCOME MEASURES: Binding sites of serum to the epidermal and/or dermal sides of SSS were correlated with their antigenic specificities. RESULTS: Epidermal staining on SSS was highly specific for pemphigoid. Alternatively, a poor correlation was found for the dermal-reacting serum samples and the diagnosis of EBA; of the 19 serum samples with dermal staining on SSS, only 10 reacted with the EBA antigen. The remaining serum samples were from patients with cicatricial pemphigoid having antibodies to the alpha 3 or beta 3 chains of laminin-5 (n = 5) or patients with BP having antibodies to the 180-kd BP antigen (n = 2). One sample recognized exclusively a 185-kd dermal antigen corresponding to type IV collagen. One more BP serum sample with dermal staining did not recognize any dermal or epidermal antigen. CONCLUSION: In case of immunofluorescent dermal staining, the precise diagnosis should be confirmed by identification of the involved antigen, since it may reveal antibodies to laminin-5 or type XVII or IV collagen, in addition to the EBA antigen