Clinical hospital Sestre milosrdnice

Zagreb, Croatia

Clinical hospital Sestre milosrdnice

Zagreb, Croatia
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Selanec J.,Clinic for Internal Diseases | Vrkic N.,Clinical Hospital Sestre Milosrdnice | Zupancic M.,University of Ljubljana | Trampus Bakija A.,University of Ljubljana | And 3 more authors.
Journal of Veterinary Internal Medicine | Year: 2013

Background: Babesia infections in dogs can result in a wide range of clinical and laboratory presentations, including coagulopathy. Expression of intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF) in dogs with babesiosis is unknown. Objectives: Whether inflammation in babesiosis triggers activation of ICAM-1 and the coagulation system. Animals: Twelve and 10 dogs with naturally occurring babesiosis before and after antiparasitic treatment, respectively, were compared with 10 healthy dogs. Methods: In this prospective study, diagnosis was made by blood smear examination and confirmed by PCR. C-reactive protein (CRP), soluble intercellular adhesion molecule 1 (sICAM-1), and von Willebrand factor (vWF) levels were measured by a canine ELISA kit, fibrinogen (FIB) and factor VIII activity levels were measured by coagulometric methods, and blood cell counts (WBC, RBC, PLT) were determined with an automatic analyzer. Results: Compared to healthy dogs, the CRP, sICAM-1, and FIB concentrations were significantly increased before therapy and remained high for 3 days after therapy in dogs with babesiosis. vWF activity was significantly decreased in dogs with babesiosis before treatment. FVIII activity did not differ between dogs with babesiosis and healthy dogs. WBC; RBC and PLT were significantly lower before treatment and normalized by 3 days after treatment. Conclusion and Clinical Importance: A proinflammatory condition in babesiosis appears to influence endothelial dysfunction and hemostatic activity. Although clearly beneficial for the parasite, sequestered blood cells can obstruct blood flow in small vessels, promote an inflammatory state, and could increase the severity of babesiosis. © 2013 by the American College of Veterinary Internal Medicine.


Amass L.,Schering | Pukeleviciene V.,Kaunas District Center for Addictive Disorders | Subata E.,Vilnius Center for Addictive Disorders | Pieri M.C.,SerT Polo Est | And 6 more authors.
Addiction | Year: 2012

Aims To provide controlled data on direct induction with buprenorphine/naloxone (BNX) versus indirect buprenorphine (BPN)-to-BNX induction. Design Phase 4, prospective, randomized, active-drug controlled, parallel-group trial consisting of a 2-day, double-blind, double-dummy induction phase followed by 26 days of open-label treatment with BNX. Setting Nineteen sites in 10 European countries from March 2008 to December 2009. Participants A total of 187 opioid-dependent men and women ≥15 years of age. Measurements The primary objective was assessment of patient response to direct and indirect BNX induction [proportion of patients receiving the scheduled 16-mg BNX dose on day 3 (i.e. first day post-induction)]. Secondary assessments included illicit drug use, treatment retention and compliance, withdrawal scale scores, and safety. Findings Patient response to direct- versus indirect-BNX induction was similar [direct 91.4% (85/93) versus indirect 90.4% (85/94); 95% confidence interval (CI): -7.3%, 9.2%]. Rapid dose induction (16mg of BPN equivalent on day 2) was acceptable and 72% of patients completed treatment (day 28). There were no significant differences in secondary measures across groups. An average BNX maintenance dose of 15.3mg across groups was associated with substantial reductions in illicit opioid use and no self-reported intravenous misuse. Treatment compliance and retention rates were similar (98.5% and 81.3%, respectively). Treatment-emergent adverse event rates were comparable: 75% versus 74% for direct- versus indirect-induction groups, respectively. Conclusions Direct buprenorphine/naloxone induction was a safe and effective strategy for maintenance treatment of opioid dependence. Response to high-dose direct buprenorphine/naloxone induction appears to be similar to indirect buprenorphine-to-buprenorphine/naloxone induction and was not associated with reports of intravenous buprenorphine/naloxone misuse. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.


Ansari M.,University of Edinburgh | Mckeigue P.M.,University of Edinburgh | Skerka C.,Leibniz Institute for Natural Product Research and Infection Biology | Hayward C.,University of Edinburgh | And 29 more authors.
Human Molecular Genetics | Year: 2013

It is a longstanding puzzle why non-coding variants in the complement factor H (CFH) gene are more strongly associated with age-related macular degeneration (AMD) than functional coding variants that directly influence the alternative complement pathway. The situation is complicated by tight genetic associations across the region, including the adjacentCFH-related genes CFHR3 and CFHR1, which may themselves influence the alternativecomplementpathwayandare contained within acommondeletion (CNP147) which is associated with protection against AMD. It is unclear whether this association ismediated through a protective effect of low plasma CFHR1 concentrations, high plasma CFH or both. We examined the triangular relationships of CFH/CFHR3/ CFHR1 genotype, plasma CFH or CFHR1 concentrations and AMD susceptibility in combined case-control (1256 cases, 1020 controls) and cross-sectional population (n 5 1004) studies and carried out genome-wide association studies of plasma CFH and CFHR1 concentrations. A non-coding CFH SNP (rs6677604) and the CNP147deletion were strongly correlated both with each otherandwith plasmaCFHandCFHR1concentrations. The plasma CFH-raising rs6677604 allele and raised plasma CFH concentration were each associated withAMD protection. In contrast, the protective association of the CNP147 deletion with AMD was not mediated by low plasma CFHR1, since AMD-free controls showed increased plasma CFHR1 compared with cases, but it maybe mediated by the association of CNP147 with raised plasma CFH concentration. The results are most consistent with a regulatory locus within a 32 kb region of the CFH gene, with amajor effect on plasma CFH concentration and AMD susceptibility. ©The Author 2013.


Emanuele E.,University of Pavia | Bertona M.,University of Pavia | Altabas K.,Clinical Hospital Sestre Milosrdnice | Altabas V.,Clinical Hospital Sestre Milosrdnice | Alessandrini G.,Dermatology Clinics
Clinical, Cosmetic and Investigational Dermatology | Year: 2012

Purpose: Acne vulgaris is a skin disorder of the sebaceous follicles, involving hyperkeratinization and perifollicular inflammation. Aberrant extracellular matrix remodeling due to matrix metalloproteinases (MMPs) has been associated with the presence of acne conditions. Given the complex pathophysiology of acne, novel topical therapies should include combination products that target multiple pathogenetic mechanisms. In this pilot study we investigated the changes in gene expression of extracellular MMPs, the tissue inhibitors of metalloproteinases, and proinflammatory molecules after 45 days of topical application of a combination product containing nicotinamide, retinol, and 7-dehydrocholesterol in 16 patients with inflammatory acne on their back. Materials and methods: Skin biopsies were obtained before and after treatment for gene expression studies. Results: Quantitative real-time polymerase chain reaction revealed a significant downregulation of MMP-1, MMP-2, MMP-9, MMP-14, interleukin-6, monocyte chemoattractant protein-1, and macrophage migration inhibitory factor. In contrast, the tissue inhibitors of metalloproteinases and transforming growth factor-β1 were significantly upregulated. The gene expression findings correlated well with the clinical treatment response. Conclusions: The combination of nicotinamide, retinol, and 7-dehydrocholesterol appears to be effective for acne treatment from both clinical and molecular standpoints. © 2012 Emanuele et al, publisher and licensee Dove Medical Press Ltd.


Pavic I.,Clinical Hospital Sestre Milosrdnice | Pavic P.,Elementary School Trilj | Palcic I.,Clinical Hospital Sestre Milosrdnice | Nenadic N.,Srebrnjak Childrens Hospital
International Journal of Environmental Health Research | Year: 2012

Passive smoking has been found to be associated with a large number of disorders of passive smokers. It seems that the children are the most susceptible population for harmful effects of passive smoke exposure. The aim of this study was to evaluate the effect of passive smoking on children's functional abilities. The target population was 199 children who were 13-15 years old at the time of the study. For the assessment of motor skills 6-min run test was used. Children exposed to passive smoking by their mothers had statistically significant lower functional abilities (r =0.7029; 95% CI 0.7707 to 0.6194; p < 0.0001). We also found statistically significant difference if the both parents are smokers (r =0.3343; 95% CI 0.4595 to 0.1961; p < 0.0001). The results of our study did not show statistically significant difference if the children are exposed to cigarette smoke by their fathers (r = 0.03139; 95% CI 0.1171 to 0.1785; p = 0.6792). Public health preventive actions should go toward minimizing the exposure of children to passive smoking by counseling the smoking parents that quitting smoking provides enormous health benefits not only to them but also to their children. © 2012 Copyright Taylor and Francis Group, LLC.


Brailo V.,University of Zagreb | Vucicevic-Boras V.,University of Zagreb | Lukac J.,Clinical hospital Sestre milosrdnice | Biocina-Lukenda D.,University of Split | And 3 more authors.
Medicina Oral, Patologia Oral y Cirugia Bucal | Year: 2012

Objectives: The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral cancer and healthy controls. Study design: Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay. Results: Salivary IL-1β and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (p<0.05). No differences in concentrations of salivary TNF-α between either of the groups were observed. Serum concentrations of IL-1β were below level of detection in all but two participants. No significant differences between the groups were observed in serum concentrations of IL-6. Serum TNF-α was significantly higher in control subjects than in oral cancer patients. Conclusions: Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies. © Medicina Oral S. L.


PubMed | Clinical Hospital Center Zagreb, Ruder Boskovic Institute and Clinical Hospital Sestre milosrdnice
Type: Journal Article | Journal: Immunobiology | Year: 2016

Dipeptidyl peptidase 9 (DPP9) is a relatively new member of the DPPIV family of prolyl dipeptidases which is ubiquitously expressed. Its role in regulation of immune responses and proliferation of epithelial carcinoma cells was reported. There is no data on possible role of DPP9 expressed in skin epithelial cells (keratinocytes) and in dermal fibroblasts.Transcriptional and protein expression of DPP9 and DPPIV was examined in fibroblasts and keratinocytes isolated from normal human skin. Localization of DPP9 and its sub-localization in Golgi were determined by immunocytochemistry staining. DPPIV-like enzyme activity was determined in cell lysates and in isolated cell fractions containing membranes (M), cytosol (C) and content of organelles/endosomes/vesicles (V). Relative contribution of DPPIV and DPP8/9 enzyme activity in these fractions was determined by using selective inhibitors: sitagliptin (selective for DPPIV) and 1G244 (selective for DPP9 and a highly homologous DPP8). Possible roles of DPP8/9 via its enzyme activity were analysed by assessment of survival and proliferative capacity of fibroblasts and HaCaT cells of keratinocyte origin in the presence of the inhibitors. Possible role of DPP9 in cell migration and/or adhesion was analysed in fibroblasts and HaCaT cells after DPP9 gene silencing.Fibroblasts and keratinocytes exerted comparable level of DPP9 both at transcriptional and protein level. Fibroblasts strongly expressed DPPIV, whereas in keratinocytes DPPIV expression was low. DPP9 expression was found in cytosol and in perinuclear area of some fibroblasts, or in scattered pattern of keratinocytes, as well as in nuclei of some cells. Only low level of DPP9 sub-localization within Golgi was observed in fibroblasts and keratinocytes. DPPIV-like enzyme activity was about 5 times higher in lysates of fibroblasts than of HaCaT cells. In fibroblasts DPPIV-like enzyme activity was mainly (65%) found in the fraction containing cell membranes (M) and was predominantly (86.9%) due to DPPIV. In contrast, in HaCaT cells the DPPIV-like enzyme activity was mainly (84.2%) found in cytosol (C) and was predominantly (95.6%) due to DPP8/9. Survival and the proliferative capacity were significantly diminished in the presence of 10M 1G244, both in fibroblasts and in HaCaT cells, suggesting possible role of DPP8/9 enzyme activity in regulation of survival and proliferation of these cells. DPP9 gene silencing resulted in decreased adhesion of fibroblasts, as well as in decreased migration of fibroblasts and HaCaT cells. Accumulation of DPP9 on the edges of plasma membranes of fibroblasts and keratinocytes adhering to surface supports the idea of possible role of DPP9 in cell adhesion.This is the first study showing protein expression, sub-localization and possible biological roles of DPP9 expressed in isolated human skin cells. The data may be relevant for development of new drugs against skin diseases by targeting DPP9 expressed in the skin cells.


PubMed | Clinical Hospital Center Zagreb, Ruder Boskovic Institute, Private Gynaecological Clinic and Clinical Hospital Sestre milosrdnice
Type: Journal Article | Journal: PloS one | Year: 2015

Change in the host and/or human papillomavirus (HPV) DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RAR2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP). The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.


Berardesca E.,San Gallicano Dermatological Institute | Bertona M.,University of Pavia | Altabas K.,Clinical Hospital Sestre Milosrdnice | Altabas V.,Clinical Hospital Sestre Milosrdnice | Emanuele E.,University of Pavia
Molecular Medicine Reports | Year: 2012

The exposure of human skin to ultraviolet radiation (UVR) results in the formation of DNA photolesions that give rise to photoaging, mutations, cell death and the onset of carcinogenic events. Photolyase (EC 4.1.99.3) is a DNA repair enzyme that reverses damage caused by exposure to UVR. We sought to investigate whether addition of photolyase enhances the protection provided by a traditional sunscreen (SS), by reducing the in vivo formation of cyclobutane-type pyrimidine dimers (CPDs) and UVR-induced apoptosis in human skin. Ten volunteers (Fitzpatrick skin type II) were exposed to solar-simulated (ss) UVR at a three times minimal erythema dose for 4 consecutive days. Thirty minutes prior to each exposure, the test materials [vehicle, SS (sun protection factor 50) alone, and SS plus photolyase from Anacystis nidulans] were applied topically to three different sites. One additional site was left untreated and one received ssUVR only. Biopsy specimens were taken 72 h after the last irradiation. The amount of CPDs and the extent of apoptosis were measured by ELISA. Photolyase plus SS was superior to SS alone in reducing both the formation of CPDs and apoptotic cell death (both P<0.001). In conclusion, the addition of photolyase to a traditional SS contributes significantly to the prevention of UVR-induced DNA damage and apoptosis when applied topically to human skin.


Emanuele E.,University of Pavia | Altabas V.,Clinical Hospital Sestre Milosrdnice | Altabas K.,Clinical Hospital Sestre Milosrdnice | Berardesca E.,San Gallicano Dermatological Institute
Journal of Drugs in Dermatology | Year: 2013

The exposure to ultraviolet radiation (UVR) is one of the most important risk factors for skin aging and increases the risk of malignant transformation. Telomere shortening and an altered expression of the proto-oncogene c-FOS are among the key molecular mechanisms associated with photoaging and tumorigenesis. Photolyase from A. nidulans and endonuclease from M. luteus are xenogenic DNA repair enzymes which can reverse the molecular events associated with skin aging and carcinogenosis caused by UVR exposure. Therefore, the purpose of this study was to investigate whether the topical application of preparations containing DNA repair enzymes may prevent UVR-induced acute telomere shortening and FOS gene hyperexpression in human skin biopsies. Twelve volunteers (Fitzpatrick skin types I and II) were enrolled for this experimental study, and six circular areas (10 mm diameter) were marked out on the nonexposed lower back of each participant. One site was left untreated (site 1: negative control), whereas the remaining five sites (designated sites 2-6) were exposed to solar-simulated UVR at 3 times the MED on four consecutive days. Site 2 received UVR only (site 2: positive control), whereas the following products were applied to sites 3-6, respectively: vehicle (moisturizer base cream; applied both 30 minutes before and immediately after each irradiation; site 3); a traditional sunscreen (SS, SPF 50) 30 minutes before irradiation and a vehicle immediately after irradiation (site 4); a SS 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 5); a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 6). Skin biopsies were taken 24 h after the last irradiation. The degree of telomere shortening and c-FOS gene expression were measured in all specimens. Strikingly, the combined use of a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation completely abrogated telomere shortening and c-FOS gene hyperexpression induced by the experimental irradiations. We conclude that the topical application of preparations containing both photolyase from A. nidulans and endonuclease from M. luteus may be clinically useful to prevent skin aging and carcinogenesis by abrogating UVR-induced telomere shortening and c-FOS gene hyperexpression. Copyright © 2013.

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