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Objectives: Investigating the user acceptance and associated factors regarding the use of an unguided online-intervention in people with obesity and comorbid depressive symptoms., Methods: Quantitative longitudinal pilot study with regard to user acceptance (Baseline before access to online-intervention; Follow-up after 3 months) with n = 46 subjects., Results: Moderate (usefulness, ease of use, satisfaction) to high (ease of learning) user acceptance was reported with regard to the online-intervention. Uptake-rates were 76.1 %, completion-rates were 22.9 %. Positive associations were found e. g. for people receiving invalidity pension and personality traits., Conclusions: Online-interventions for people with obesity and comorbid depressive symptoms represent a complementary treating component. Associated factors of user acceptance should be taken into account when implementing online-interventions to support high fitting accuracy and to increase the benefit for program users., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective Patients with chronic somatic diseases such as obesity often suffer from comorbid depressive disorders and present a great challenge for the medical health care system. The study aims to investigate the user acceptance of an internet-based self-management program regarding depression (using the example of MoodGYM) from two different perspectives: (A) the perspective of patients as well as (B) the perspective of experts based on Rogers' 5 stages model of the innovation-decision process (2003). Methods This study is following a qualitative design including qualitative patient interviews (N = 7) and a focus group with medical experts (N = 12). Results Internet-based self-management programs represent a complementary treatment approach for patients and experts. Both groups see the need for combining the topics overweight, activity, depression and social interchange. Conclusion Patient and expert judgement showed a high degree of user acceptance for internet-based self-management programs regarding depression. The implementation of such programs within the medical care system of patients with obesity should take physical and social aspects of the illness into account., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Digital media offer new possibilities in rehabilitation aftercare. This study investigates the rehabilitants' willingness to use new media (sms, internet, social networks) in rehabilitation aftercare and factors that are associated with the willingness to use media-based aftercare. 92 rehabilitants (patients with obesity) filled in a questionnaire on the willingness to use new media in rehabilitation aftercare. In order to identify influencing factors, binary logistic regression models were calculated. 3 quarters of the rehabilitants (76.1%) reported that they would be willing to use new media in rehabilitation aftercare. The binary logistic regression model yielded two factors that were associated with the willingness to use media-based aftercare: the possession of a smartphone and the willingness to receive telephone counseling for aftercare. The majority of the rehabilitants was willing to use new media in rehabilitation aftercare. The reasons for refusal of media-based aftercare need to be examined more closely., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Rheumatoid arthritis is an inflammatory and disabling joint disease affecting 0.5-1.5% of the population. Although various anti-inflammatory (NSAIDs) and disease-modifying (DMARDs) drugs are in clinical use, their precise mechanisms of action are not always defined. In this report, we discuss the effects of widely used DMARDs such as gold derivatives and chloroquine on cathepsins K and S, which have been implicated as critical mediators of inflammation and joint erosion in rheumatoid arthritis. We demonstrate that clinically potent gold derivatives inhibit cathepsins K and S in in vitro and cell-based assays. An X-ray analysis of the gold thiomalate/cathepsin K complex reveals that the inhibitor is bound to the active-site cysteine residue of the protease. Chloroquine, a lysosomotropic agent of lower clinical potency than gold derivatives, inhibits neutral pH-labile cathepsins intracellularly, but does not affect the neutral pH-stable cathepsin S. The potent inhibition of cathepsins implicated in the pathogenesis of rheumatoid arthritis by gold derivatives may explain the therapeutic efficacy of these drugs.

Taking into account a previous report of an unidentified enzyme from macrophages acting as a kininase, the ability of cysteine proteases to degrade kinins has been investigated. Wild-type fibroblast lysates from mice, by contrast with cathepsin K-deficient lysates, hydrolysed BK (bradykinin), and released two metabolites, BK-(1-4) and BK-(5-9). Cathepsin K, but not cathepsins B, H, L and S, cleaved kinins at the Gly4-Phe5 bond and the bradykinin-mimicking substrate Abz (o-aminobenzoic acid)-RPPGFSPFR-3-NO2-Tyr (3-nitrotyrosine) more efficiently (pH 6.0: kcat/K(m)=12500 mM(-1) x s(-1); pH 7.4: kcat/K(m)=6930 mM(-1) x s(-1)) than angiotensin-converting enzyme hydrolysed BK. Conversely Abz-RPPGFSPFR-3-NO2-Tyr was not cleaved by the Y67L (Tyr67-->Leu)/L205A (Leu205-->Ala) cathepsin K mutant, indicating that kinin degradation mostly depends on the S2 substrate specificity. Kininase activity was further evaluated on bronchial smooth muscles. BK, but not its metabolites BK(1-4) and BK(5-9), induced a dose-dependent contraction, which was abolished by Hoe140, a B2-type receptor antagonist. Cathepsin K impaired BK-dependent contraction of normal and chronic hypoxic rats, whereas cathepsins B and L did not. Taking together vasoactive properties of kinins and the potency of cathepsin K to modulate BK-dependent contraction of smooth muscles, the present data support the notion that cathepsin K may act as a kininase, a unique property among mammalian cysteine proteases.

The expression of MDR1b coding mRNA is increased in alveolar type II cells from juvenile rat lung in culture. Hydrogen peroxide and paraquat-induced further upregulation supporting that oxidative stress mediated mechanisms are involved in the regulation of MDR1b in rat lung. The expression rates of mRNA for catalase, Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Mn-superoxide dismutase (Mn-SOD) remains constant during culture and were not modulated by hydrogen peroxide or paraquat. Thus, antioxidative enzymes in primary A II cells from rat lung are not regulated by reactive oxygen species dependent mechanisms. Primary A II cells were substantially more sensitive towards paraquat-induced cytotoxicity and lipid peroxidation than the permanent human lung tumor cell lines H322 and H358. A 100 microM hydrogen peroxide for 2h induces substantial DNA damage which is not paralleled by an increased rate of lipid peroxidation. The expression rate of mRNA coding for catalase and Mn-SOD was not changed and almost the same is true for the activity of catalase and Cu/Zn-SOD. Only 50 microM paraquat induced a significant decrease in catalase activity and an increase in Cu/Zn-SOD activity.

The limited availability of highly selective cathepsin substrates seriously impairs studies designed to monitor individual cathepsin activities in biological samples. Among mammalian cysteine proteases, cathepsin K has a unique preference for a proline residue at P2, the primary determinant of its substrate specificity. Interestingly, congopain from Trypanosoma congolense also accommodates a proline residue in its S2 subsite. Analysis of a congopain model showed that amino acids forming its S2 subsite are identical with those of cathepsin K, except Leu67 which is replaced by a tyrosine residue in cathepsin K. Furthermore, amino acid residues of the congopain S2' binding pocket, which accepts a proline residue, are strictly identical with those of cathepsin K. Abz-HPGGPQ-EDN2ph [where Abz represents o-aminobenzoic acid and EDN2ph (=EDDnp) represents N -(2,4-dinitrophenyl)-ethylenediamine], a substrate initially developed for trypanosomal enzymes, was efficiently cleaved at the Gly-Gly bond by cathepsin K (kcat/ K(m)=426000 M(-1) x s(-1)). On the other hand, Abz-HPGGPQ-EDN2ph was resistant to hydrolysis by cathepsins B, F, H, L, S and V (20 nM enzyme concentration) and the Y67L (Tyr67-->Leu)/L205A cathepsin K mutant (20 nM), but still acted as a competitive inhibitor. Taken together, the selectivity of Abz-HPGGPQ-EDN2ph to cathepsin K primarily depends on the S2 and S2' subsite specificities of cathepsin K and the ionization state of histidine at P3. Whereas Abz-HPGGPQ-EDN2ph was hydrolysed by wild-type mouse fibroblast lysates, its hydrolysis was completely abolished in the cathepsin K-deficient samples, indicating that Abz-HPGGPQ-EDN2ph can be used to monitor selectively cathepsin K activity in physiological fluids and cell lysates.