Docking Studies, Cytotoxicity Evaluation and Interactions of Binuclear Copper(II) Complexes with S-Isoalkyl Derivatives of Thiosalicylic Acid with Some Relevant Biomolecules.

The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5'-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1ß, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.

Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based cross-sectional study.

BACKGROUND:: Emerging epidemiological evidence suggests independent associations between psoriasis and metabolic syndrome. Objectives: The aim of the study was to examine the prevalence of metabolic syndrome and its components in patients with psoriasis, and to assess which factors may predict metabolic syndrome in these patients. METHODS:: A hospital-based, cross-sectional study with 244 psoriatic patients and 163 control subjects with skin diseases other than psoriasis was conducted at the Clinic of Dermatovenerology, Clinical Center of Serbia, Belgrade, from October 2011 to October 2012. Metabolic syndrome was defined using the revised National Cholesterol Education Program Adult Treatment Panel III. Severity of psoriasis was measured by Psoriasis Area and Severity Index and Body Surface Area. RESULTS:: The adjusted odds ratios (ORs) and 95% confidence intervals (CI) for psoriasis patients vs. non-psoriasis patients were 2.66 (95% CI, 1.58-4.42) for metabolic syndrome, 3.81 (95% CI, 2.30-6.31) for hypertension, 2.29 (95% CI, 1.39-3.78) for central obesity, 1.92 (95% CI, 1.08-3.41) for hyperglycemia, 1.87 (95% CI 1.18-2.96) for low high-density lipoprotein cholesterol level, and 1.42 (95% CI, 0.87-1.04) for hypertrigliceridemia. We failed to find any statistically significant association between the metabolic syndrome and clinical severity of psoriasis. Later onset and longer duration of psoriasis were predicting factors for metabolic syndrome in our patients. Study limitations: The cross-sectional design of the study does not allow us to draw directional causal inferences concerning the association between psoriasis and metabolic syndrome. Factors such as diet, alcohol consumption or mental health, which have not been evaluated in this study, may be confounders in this relation. CONCLUSION:: A higher prevalence of metabolic syndrome and its components in patients with psoriasis than in controls, regardless of disease severity, emphasizes the need for early treatment and follow-up of all psoriatic patients with respect to metabolic diseases.

Inzidenz von bullösen Autoimmunerkrankungen in Serbien: eine retrospektive Studie über 20 Jahre.

HINTERGRUND UND ZIELE: Die meisten früheren Arbeiten zu den klinisch-epidemiologischen Merkmalen von bullösen Autoimmunerkrankungen (AIBD) konzentrierten sich vor allem auf eine einzige Krankheitsentität oder nur eine Krankheitsgruppe; nur in wenigen Studien wurde die Inzidenz verschiedener AIBD untersucht. Bei der vorliegenden Studie war es unser Ziel, das gesamte Spektrum der AIBD zu betrachten, die Inzidenz der häufigsten AIBD zu ermitteln und die zeitlichen Trends ihres Auftretens in Zentralserbien über einen Zeitraum von 20 Jahren zu untersuchen. METHODEN: Wir rekrutierten retrospektiv 1161 AIBD-Fälle, die in Zentralserbien von Januar 1991 bis Dezember 2010 neu diagnostiziert wurden. Die Diagnose stützte sich auf eine strikte klinische, histologische und immunhistologische Beurteilung. ERGEBNISSE: Folgende Inzidenzraten wurden für die einzelnen Erkrankungen ermittelt: 4,35 pro eine Million Einwohner/Jahr (pME/Jahr) für Pemphigus, 4,47 pME/Jahr für Pemphigoid, 1,42 pME/Jahr für Dermatitis herpetiformis (DH), 0,25 pME/Jahr IgA-Dermatose und 0,08 pME/Jahr für Epidermolysis bullosa acquisita. Im betrachteten Zeitraum stieg die altersbereinigte Inzidenzrate für Pemphigus und insbesondere für Pemphigoid signifikant an, während sie für DH, allerdings nicht signifikant, abnahm. SCHLUSSFOLGERUNGEN: Unsere Studie befasst sich zum ersten Mal mit den Inzidenzraten des gesamten Spektrums der AIBD in Serbien und untersucht die zeitlichen Trends ihres Auftretens über einen Zeitraum von 20 Jahren. Nach unserem besten Wissen wurde ein ähnlicher Befund wie der unsere, dass nämlich die Inzidenzraten von Pemphigus und Pemphigoid vergleichbar sind, bisher noch nicht publiziert.

Incidence of autoimmune bullous diseases in Serbia: a 20-year retrospective study.

BACKGROUND AND OBJECTIVES: While most previous surveys on the clinico-epidemiological features of autoimmune bullous diseases (AIBDs) have predominantly focused on a single disease entity or just one disease group, there have been only few studies examining the incidence of various AIBDs. In the present study, we set out to determine the spectrum of AIBDs, to estimate the incidence of the most common AIBDs, and to examine their temporal trends in Central Serbia over a period of 20 years. METHODS: We retrospectively recruited 1,161 new AIBD cases diagnosed in Central Serbia during the period from January 1991 to December 2010. The diagnosis was based on strict clinical, histological, and immunohistological evaluation. RESULTS: The incidence rates were: 4.35 per million population/year (pmp/year) for pemphigus, 4.47 pmp/year for pemphigoid, 1.42 pmp/year for dermatitis herpetiformis (DH), 0.25 pmp/year for linear IgA disease, and 0.08 pmp/year for epidermolysis bullosa acquisita. In the period observed, age-adjusted incidence rates significantly increased for pemphigus and particularly for pemphigoid, whereas they decreased, albeit not significantly, for DH. CONCLUSIONS: For the first time, our study evaluates the incidence rates of the entire spectrum of AIBDs in Serbia, and examines their temporal trends over a 20-year period. To the best of our knowledge, our finding of similar incidence rates for pemphigus and pemphigoid has previously not been reported.

Pemphigus herpetiformis - a case report of a rare form of pemphigus and review of the literature.

Introduction: Pemphigus herpetiformis is the rare variant of pemphigus with characteristic clinical features, histopathological findings different from the convectional pemphigus, and immunological findings consistent with pemphigus. Case report: We presented a 65-year-old woman with initial pruritus followed by pruritic urticarial papules and plaques, some with annular rings of tense vesicles on the periphery, on the trunk and extremities, with no mucous lesions. Histopathological examination demonstrated spongiosis and intraepidermal vesicles in the mid or subcorneal epidermis in some biopsy specimen, with neutrophil and eosinophil infiltrate. Direct immunoflorescent microscopy revealed intercellular IgG deposition, most prominent in the upper layers of epidermis. Indirect immunoflorescent microscopy showed intercellular binding of IgG autoantibodies in the patient's sera. Initially the patient was threated with systemic corticosteroids and azathioprine, but dapson provided complete clinical remission. Conclusion: This entity was established 40 years ago, and around 100 patients have been reported worldwide. It is important to be aware of this particular form of pemphigus because clinical presentation, course of the disease and therapeutic approach are different from conventional forms of pemphigus.

Assessment of quality of life in patients with psoriasis: a study from Serbia.

BACKGROUND: Psoriasis has a substantial impact on patients' quality of life. OBJECTIVES: The aims of this study were to assess the impact of the clinical severity of psoriasis on patients' quality of life and to determine the effects of psoriasis-related stress on patients' everyday life. METHODS: The cross-sectional study was conducted at the Institute of Dermatovenereology, Clinical Center of Serbia, Belgrade. The study included 201 patients (124 men and 77 women), aged 18-70 with a diagnosis of psoriasis, hospitalized or treated as outpatients during 2009. For the assessment of patients' quality of life, the psoriasis disability index (PDI) was used. The stress related to psoriasis was measured with the psoriasis life stress inventory (PLSI) and disease severity with the psoriasis area and severity index (PASI). RESULTS: We found moderate correlation between PLSI and all PDI subscales and overall score (correlation coefficients ranged from 0.334 to 0.521). The correlation between PASI and PDI subscales was weak, while we failed to find any significant correlation between PASI and the PLSI. The results of multiple regression analysis indicated that stress, more severe disease, and lower educational level are significant determining factors of a poorer quality of life in patients with psoriasis. CONCLUSION: Our results support the importance of assessing the quality of life in psoriasis and effects of stress in patients' adjustment to their condition and may have important implications for a psychological stress management approach in the clinical management of psoriasis.

Regressing anaplastic CD30-positive large-cell lymphoma of the skin.

Originally believed to be of histiocytic origin, regressing primary cutaneous anaplastic large-cell lymphoma is a CD30 (Ki 1) positive T-cell lymphoma with histologic high grade malignancy, but with an often favorable clinical course with regression of individual lesions. We present a case of a 69-year-old white woman with an 8-month history of noduloulcerative lesions on her right lower leg, otherwise in good general health. The clinical, histologic, and immunohistochemical findings pointed to CD30 positive primary cutaneous anaplastic large-cell lymphoma. There were no signs of generalization, lymph node or internal organ involvement. After 2 years of activity, the disease regressed. During the 10-year follow-up period, no signs of disease reactivation were noted. Accurate recognition of this lymphoma is important to avoid unnecessary aggressive treatments.

CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD.

For circulating lymphocytes to migrate to inflammatory sites, they must first adhere to the target tissue endothelium with sufficient strength to overcome the shear forces of blood flow. We previously reported that dermal papillary vessels in acute graft-versus-host disease (aGVHD) support shear-resistant lymphocyte adherence. We now identify the relevant adhesion molecule(s) directing this binding, showing that interactions between lymphocyte CD44 and hyaluronic acid (HA) expressed on dermal vessels in aGVHD alone confer this shear-resistant attachment. Native HA deposits on vascular endothelium support lymphocyte adherence, whereas HA immobilized on plastic does not. HA expressed at dermal endothelium in aGVHD is thus specialized to support lymphocyte adherence under flow conditions, and CD44-HA interactions may contribute to lymphocytotropism to skin in aGVHD.