Dobezylan wapnia – nowe zastosowania

Calcium dobesilate is a calcium salt of dobesilic acid which acts selectively on the capillary walls. It seems that calcium dobesilate may be effective in the treatment of diseases with vascular abnormalities. Recently, new data has been published showing significant clinical improvement in various dermatoses, namely pigmented palpable purpura, psoriasis, rosacea, actinic keratosis or even non-melanoma skin cancers. However, it should be underlined, that these reports are based on description of single subjects or small patient groups. Therefore, these observations should be confirmed by other researchers, preferably, in comparative, placebo-controlled studies to support the therapeutic activity of calcium dobesilate.Dobezylan wapnia jest solą wapniową kwasu dobezylowego wykazującą aktywność wobec ścian naczyń włosowatych. Wydaje się, że preparat ten może wykazać pozytywne efekty w leczeniu schorzeń przebiegających z udziałem zaburzeń naczyniowych. W ostatnim czasie ukazały się liczne doniesienia dokumentujące istotną poprawę kliniczną po zastosowaniu dobezylanu wapnia w przypadku niektórych dermatoz, w tym: plamicy barwnikowej, łuszczycy, trądziku różowatego, rogowacenia słonecznego, a nawet w terapii nieczerniakowych nowotworów skóry. Warto jednak zaznaczyć, że dotychczasowe obserwacje dotyczyły głównie pojedynczych pacjentów lub niewielkichgrup chorych. Konieczna jest zatem obiektywne zweryfikowanie skuteczności dobezylanu wapnia w podanych wskazaniach — najlepiej poprzez przeprowadzenie badań porównawczych, o ile to możliwe kontrolowanych placebo

Development of chemical tools to monitor human Kallikrein 13 (KLK13) activity

Kallikrein 13 (KLK13) was first identified as an enzyme that is downregulated in a subset of breast tumors. This serine protease has since been implicated in a number of pathological processes including ovarian, lung and gastric cancers. Here we report the design, synthesis and deconvolution of libraries of internally quenched fluorogenic peptide substrates to determine the specificity of substrate binding subsites of KLK13 in prime and non-prime regions (according to the Schechter and Berger convention). The substrate with the consensus sequential motive ABZ-Val-Arg-Phe-Arg-ANB-NH2 demonstrated selectivity towards KLK13 and was successfully converted into an activity-based probe by the incorporation of a chloromethylketone warhead and biotin bait. The compounds described may serve as suitable tools to detect KLK13 activity in diverse biological samples, as exemplified by overexpression experiments and targeted labeling of KLK13 in cell lysates and saliva. In addition, we describe the development of selective activity-based probes targeting KLK13, to our knowledge the first tool to analyze the presence of the active enzyme in biological samples

Determinants of psychosocial health in psoriatic patients: a multi-national study

There are limited data on the differences in the impact of psoriasis between various countries with respect to quality of life (QoL). The aim of this study was to explore the psychosocial health of patients with psoriasis in different European countries. A total of 682 patients were recruited in 13 European countries. All patients completed a questionnaire regarding socio-demographic information, negative life events, suicidal ideation and satisfaction with their dermatologist. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and QoL with the Dermatology Life Quality Index (DLQI) and EuroQoL (EQ-5D). The lowest anxiety and depression scoring was noted in patients from Denmark, the lowest level of impairment in QoL in subjects from Spain, and the highest level of impairment in QoL in patients from Italy. The most relevant parameters influencing patients' well-being were severity of pruritus and satisfaction with their dermatologist. The level of anxiety and depression symptoms correlated significantly with suicidal ideation

Determinants of psychosocial health in psoriatic patients: A multinational study

There are limited data on the differences in the impact of psoriasis between various countries with respect to quality of life (QoL). The aim of this study was to explore the psychosocial health of patients with psoriasis in different European countries. A total of 682 patients were recruited in 13 European countries. All patients completed a questionnaire regarding sociodemographic information, negative life events, suicidal ideation and satisfaction with their dermatologist. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and QoL with the Dermatology Life Quality Index (DLQI) and EuroQoL (EQ-5D). The lowest anxiety and depression scoring was noted in patients from Denmark, the lowest level of impairment in QoL in subjects from Spain, and the highest level of impairment in QoL in patients from Italy. The most relevant parameters influencing patients’ well-being were severity of pruritus and satisfaction with their dermatologist. The level of anxiety and depression symptoms correlated significantly with suicidal ideation

Determinants of psychosocial health in psoriatic patients: A multinational study

There are limited data on the differences in the impact of psoriasis between various countries with respect to quality of life (QoL). The aim of this study was to explore the psychosocial health of patients with psoriasis in different European countries. A total of 682 patients were recruited in 13 European countries. All patients completed a questionnaire regarding sociodemographic information, negative life events, suicidal ideation and satisfaction with their dermatologist. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and QoL with the Dermatology Life Quality Index (DLQI) and EuroQoL (EQ-5D). The lowest anxiety and depression scoring was noted in patients from Denmark, the lowest level of impairment in QoL in subjects from Spain, and the highest level of impairment in QoL in patients from Italy. The most relevant parameters influencing patients’ well-being were severity of pruritus and satisfaction with their dermatologist. The level of anxiety and depression symptoms correlated significantly with suicidal ideation

Determinants of Psychosocial Health in Psoriatic Patients: A Multi­national Study

There are limited data on the differences in the impact of psoriasis between various countries with respect to quality of life (QoL). The aim of this study was to explore the psychosocial health of patients with psoriasis in different European countries. A total of 682 patients were recruited in 13 European countries. All patients completed a questionnaire regarding socio-demographic information, negative life events, suicidal ideation and satisfaction with their dermatologist. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and QoL with the Dermatology Life Quality Index (DLQI) and EuroQoL (EQ-5D). The lowest anxiety and depression scoring was noted in patients from Denmark, the lowest level of impairment in QoL in subjects from Spain, and the highest level of impairment in QoL in patients from Italy. The most relevant parameters influencing patients' well-being were severity of pruritus and satisfaction with their dermatologist. The level of anxiety and depression symptoms correlated significantly with suicidal ideation.Peer reviewedFinal Published versio

Kallikrein-Related Peptidase 14 Activates Zymogens of Membrane Type Matrix Metalloproteinases (MT-MMPs)—A CleavEx Based Analysis

Kallikrein-related peptidases (KLKs) and matrix metalloproteinases (MMPs) are secretory proteinases known to proteolytically process components of the extracellular matrix, modulating the pericellular environment in physiology and in pathologies. The interconnection between these families remains elusive. To assess the cross-activation of these families, we developed a peptide, fusion protein-based exposition system (Cleavage of exposed amino acid sequences, CleavEx) aiming at investigating the potential of KLK14 to recognize and hydrolyze proMMP sequences. Initial assessment identified ten MMP activation domain sequences which were validated by Edman degradation. The analysis revealed that membrane-type MMPs (MT-MMPs) are targeted by KLK14 for activation. Correspondingly, proMMP14-17 were investigated in vitro and found to be effectively processed by KLK14. Again, the expected neo-N-termini of the activated MT-MMPs was confirmed by Edman degradation. The effectiveness of proMMP activation was analyzed by gelatin zymography, confirming the release of fully active, mature MT-MMPs upon KLK14 treatment. Lastly, MMP14 was shown to be processed on the cell surface by KLK14 using murine fibroblasts overexpressing human MMP14. Herein, we propose KLK14-mediated selective activation of cell-membrane located MT-MMPs as an additional layer of their regulation. As both, KLKs and MT-MMPs, are implicated in cancer, their cross-activation may constitute an important factor in tumor progression and metastasis.Dentistry, Faculty ofMedicine, Faculty ofOther UBCNon UBCBiochemistry and Molecular Biology, Department ofOral Biological and Medical Sciences (OBMS), Department ofReviewedFacult