Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Alternative methods to animal studies for the evaluation of topical/transdermal drug delivery systems

It is critical to develop an effective understanding of the interaction between the drug, delivery system and skin in order to predict and assess skin penetration and permeation. Experimental models for the assessment of topical and transdermal delivery systems must permit evaluation of these complex interactions. Whilst in the past, animal models were commonly used, recent regulatory guidelines, based on 3R principles (refinement, reduction, replacement), encourage the rational use of animals. Alternative methods have been proposed for use in the development of topical and transdermal delivery systems which are often used in combination. We will review the current state of the art in alternative methods for topical and transdermal delivery systems development, including technologies that can assist in the characterization of skin penetration/permeation studies

The auxin-inducible GH3 homologue Pp-GH3.16 is downregulated in Pinus pinaster root systems on ectomycorrhizal symbiosis establishment

• In an attempt to determine whether auxin-regulated plant genes play a role in ectomycorrhizal symbiosis establishment, we screened a Pinus pinaster root cDNA library for auxin-upregulated genes. This allowed the identification of a cDNA, Pp-GH3.16 , which encodes a polypeptide sharing extensive homologies with GH3 proteins of different plants. • Pp-GH3.16 was specifically upregulated by auxins and was not affected by cytokinin, gibberellin, abscisic acid or ethylene, or by heat shock, water stress or anoxia. • Pp-GH3.16 mRNAs were quantified in pine roots inoculated with two ectomycorrhizal fungi, Hebeloma cylindrosporum and Rhizopogon roseolus . Surprisingly, Pp-GH3.16 was downregulated following inoculation with both fungal species. The downregulation was most rapid on establishment of symbiosis with an indole-3- acetic acid (IAA)-overproducing mutant of H. cylindrosporum , which overproduced mycorrhizas characterized by a hypertrophic Hartig net. This indicates that, despite being auxin-inducible, Pp-GH3.16 can be downregulated on establishment of symbiosis with a fungus that releases auxin. • By contrast, Pp-GH3.16 was not downregulated in pine root systems inoculated with a nonmycorrhizal mutant of H. cylindrosporum , suggesting that the downregulation we observed in mycorrhizal root systems was a component of the molecular cross-talk between symbiotic partners at the origin of differentiation of symbiotic structures

Alkenes as Chelating Groups in Diastereoselective Additions of Organometallics to Ketones

Alkenes have been discovered to be chelating groups to Zn­(II), enforcing highly stereoselective additions of organozincs to β,γ-unsaturated ketones. ¹H NMR studies and DFT calculations provide support for this surprising chelation mode. The results expand the range of coordinating groups for chelation-controlled carbonyl additions from heteroatom Lewis bases to simple C–C double bonds, broadening the 60 year old paradigm

Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry

Objective. Digital ulcers (DUs) are frequent manifestations of systemic scleroderma (SSc). This study assessed functional limitations due to DUs among patients enrolled in the Digital Ulcer Outcome (DUO) Registry, an international, multicentre, observational registry of SSc patients with DU disease. Methods. Patients completed at enrolment a DU-specific functional assessment questionnaire with a 1-month recall period, measuring impairment in work and daily activities, and hours of help needed from others. Physician-reported clinical parameters were used to describe the population. For patients who completed at least part of the questionnaire, descriptive analyses were performed for overall results, and stratified by number of DUs at enrolment. Results. This study included 2327 patients who completed at least part of the questionnaire. For patients with 0, 1-2, and DUs at enrolment, mean overall work impairment during the prior month among employed/self-employed patients was 28\%, 42\%, and 48\%, respectively. Across all included patients, ability to perform daily activities was impaired on average by 35\%, 54\%, and 63\%, respectively. Patients required a mean of 2.0, 8.7, and 8.8 hours of paid help and 17.0, 35.9, and 63.7 hours of unpaid help, respectively, due to DUs in the prior month. Patients with DUs had more complications and medication use than patients with no DUs. Conclusion. With increasing number of DUs, SSc patients reported more impairment in work and daily activities and required more support from others