Jana Vranova

Role of duodenal iron transporters and hepcidin in patients with alcoholic liver disease

Patients with alcoholic liver disease (ALD) often display disturbed iron indices. Hepcidin, a key regulator of iron metabolism, has been shown to be down‐regulated by alcohol in cell lines and animal models. This down‐regulation led to increased duodenal iron transport and absorption in animals. In this study, we investigated gene expression of duodenal iron transport molecules and hepcidin in three groups of patients with ALD (with anaemia, with iron overload and without iron overload) and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in duodenal biopsies by using real‐time PCR and Western blot. Serum hepcidin levels were measured by using ELISA. Serum hepcidin was decreased in patients with ALD. At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly increased in ALD. This pattern was even more pronounced in the subgroups of patients without iron overload and with anaemia. Protein expression of FPN1 paralleled the increase at the mRNA level in the group of patients with ALD. Serum ferritin was negatively correlated with DMT1 mRNA. The down‐regulation of hepcidin expression leading to up‐regulation of iron transporters expression in the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol consumption very probably causes suppression of hepcidin expression in patients with ALD.

High prevalence of HFE gene mutations in patients with porphyria cutanea tarda in the Czech Republic.

Background  Iron overload and hepatitis C virus (HCV) infection are independent factors which are thought to play a role in the pathogenesis of porphyria cutanea tarda (PCT).

Comprehensive treatment of temporomandibular joint disorders.

Abstract Aims: Changing lifestyles, decreasing physical activity, which is increasing the number of degenerative joint diseases of various etiology, and certain dental procedures are increasing the number of patients complaining of pain in their temporomandibular joints. The aim of the study was to assess the benefits of comprehensive physiotherapy sessions in order to decrease the number of temporomandibular joint problems, thereby improving the patient’s quality of life. Methodology: An examination by a dentist determined each patient’s treatment plan, which consisted of a medical exam, physical therapy and education. Each form of treatment was applied 10 times at intervals of 7–14 days. The main goal of the therapeutic physical education was to redress the muscle imbalance in the mandibular joint. This was achieved by restoring balance between the masticatory muscles, along with releasing the spastic shrouds found in the masticatory muscles. The aim of education was to teach the patient exercises focused on the temporomandibular joint and masticatory muscles. The intensity of the exercises and their composition were individually adjusted and adapted to their current state. Physical therapy consisted of the application of pulsed magnetic therapy, laser therapy, and non-invasive positive thermotherapy. Results: The above procedure was conducted on a therapeutic group of 24 patients (3 men and 20 women). In the course of therapy, there were no complications, and all patients adhered to the prescribed regime. None reported any side effects. The mean treatment duration was 123±66 days. The outcome of the therapy was evaluated as described in the methodology, the degree of pain affecting the joint, and the opening ability of the mouth. In both parameters, there was a significant decline in patient pain. Conclusions: In a study devoted to tactics of rehabilitation treatment for temporomandibular joint disorders, the need for comprehensive long-term therapy, involving education, and learning proper chewing habits was made apparent for recovery and pain reduction. A priority in physical therapy, and combinations of pulsed magnetic therapy and hyperthermia-positive peloids, are also beneficial.

Incidence of cutaneous malignant melanoma in the Czech Republic: the risks of sun exposure for adolescents.

The Czech Republic reported one of the highest incidence rate in cutaneous melanoma (CM) in Europe and because this incidence has been increasing, mainly among young people, the main goal of our study was to establish sun exposure behavior risk factors for CM formation and to evaluate whether the young generation of Czechs is exposed to a higher risk of CM than the older generation. A questionnaire-based case-control study was conducted. We obtained 978 completed questionnaires: 216 from patients with CM and 762 from healthy respondents. The healthy individuals were further divided to adolescents (n = 460) and older respondents (n = 302). Three logistic regression models were developed: 1. patients with CM vs. healthy older respondents, 2. adolescents vs. healthy older respondents, and 3. patients with CM vs. adolescents. The main risk factors for all three models were the number of sunburn episodes and the use of the sunscreen in the childhood. The most alarming results for adolescents included: all day sun exposure, including times of maximum risk (11 AM to 3 PM), inadequate use of sunscreen in adulthood, and frequent mountain holidays. Our results show that sun-safety in the young generation is satisfactory, when the responsibility for sun exposure behavior is in the hands of their parents; however, when children become adolescents, they become immune to sun-safety and risk prevention campaigns and their behavior becomes much more risky. Our results further suggest the sun-safety campaigns need to be modified in such a way as to have greater impact and influence on adolescent sun-risk behaviors.

Duodenal expression of iron transport molecules in patients with hereditary hemochromatosis or iron deficiency

Disturbances of iron metabolism are observed in chronic liver diseases. In the present study, we examined gene expression of duodenal iron transport molecules and hepcidin in patients with hereditary hemochromatosis (HHC) (treated and untreated), involving various genotypes (genotypes which represent risk for HHC were examined), and in patients with iron deficiency anaemia (IDA). Gene expressions of DMT1, ferroportin, Dcytb, hephaestin, HFE and TFR1 were measured in duodenal biopsies using real‐time PCR and Western blot. Serum hepcidin levels were measured using ELISA. DMT1, ferroportin and TFR1 mRNA levels were significantly increased in post‐phlebotomized hemochromatics relative to controls. mRNAs of all tested molecules were significantly increased in patients with IDA compared to controls. The protein expression of ferroportin was increased in both groups of patients but not significantly. Spearman rank correlations showed that DMT1 versus ferroportin, Dcytb versus hephaestin and DMT1 versus TFR1 mRNAs were positively correlated regardless of the underlying cause, similarly to protein levels of ferroportin versus Dcytb and ferroportin versus hephaestin. Serum ferritin was negatively correlated with DMT1 mRNA in investigated groups of patients, except for HHC group. A decrease of serum hepcidin was observed in IDA patients, but this was not statistically significant. Our data showed that although untreated HHC patients do not have increased mRNA levels of iron transport molecules when compared to normal subjects, the expression is relatively increased in relation to body iron stores. On the other hand, post‐phlebotomized HHC patients had increased DMT1 and ferroportin mRNA levels possibly due to stimulated erythropoiesis after phlebotomy.

Correlation of NT-proBNP, proANP and novel biomarkers: Copeptin and proadrenomedullin with LVEF and NYHA in patients with ischemic CHF, non-ischemic CHF and arterial hypertension

Cardiol 2010;56:117–24. [11] Rittger H, Rieber J, Kogler K, et al. Clinical outcome and quality of life after interventional treatment of left main disease with drug-eluting-stents in comparison to CABG in elderly and younger patients. Clin Res Cardiol 2011;100:439–46. [12] White AJ, Kedia G, Mirocha JM, et al. Comparison of coronary artery bypass surgery and percutaneous drug-eluting stent implantation for treatment of left main coronary artery stenosis. JACC Cardiovasc Interv 2008;1:236–45. [13] Wu X, Chen Y, Liu H, et al. Comparison of long-term (4-year) outcomes of patients with unprotected left main coronary artery narrowing treated with drug-eluting stents versus coronary-artery bypass grafting. Am J Cardiol 2010;105:1728–34. [14] Lee MS, Yang T, Dhoot J, Liao H. Meta-analysis of clinical studies comparing coronary artery bypass grafting with percutaneous coronary intervention and drug-eluting stents in patients with unprotected left main coronary artery narrowings. Am J Cardiol 2010;105:1070–5. [15] Shewan LG, Coats AJ. Ethical authorship and publishing. Int J Cardiol 2010;144:1–2.

Improvements in colorectal cancer screening programmes – quantitative immunochemical faecal occult blood testing – how to set the cut-off for a particular population

OBJECTIVE The aim of the study was to determine the optimum cut-off value of the quantitative immunochemical test (q-FIT) OC-Sensor for colorectal cancer and advanced adenomatous polyps in a particular population. METHODS 815 patients were referred for colonoscopy and were offered two q-FIT examinations at two different colonoscopy centers. The patients were classified according to the colonoscopic findings. Test sensitivity, specificity, and accuracy were statistically evaluated using one test and two tests at the levels of 50, 75, 100, 125, and 150 ng/mL of faecal hemoglobin in those patients with advanced polyps and colorectal cancer. The optimum cut-off test level for clinically significant neoplasia was determined using one test. RESULTS The optimum cut-off value of q-FIT OC-Sensor for the detection of clinically significant neoplasia in our particular population was determined as 75 ng/mL using one test. This value provides an optimum proportion of 73% sensitivity (±95% CI 60.3% - 83.4%) and 90% specificity (±95% CI 86.8% - 92.8%), PPV and NPV were determined as 54.76% and 95.43% respectively. CONCLUSIONS The first step in the implementation of q-FIT test in the screening program in our country is to determine the optimum cut-off level for a population, and to estimate the number of tests performed with respect to the optimum cost effectiveness and economical climate. Using one test, the optimum level of q-FIT OC-Sensor® in the Czech Republic was determined as 75 ng/mL. This study could serve as a model for further studies in other countries, where screening does not yet exist.

Hemangioma Curative Effect of PDL, Alexandrite, Er:YAG and CO2 Lasers

OBJECTIVE Hemangioma is a mesenchymal benign tumor formed by blood vessels. Anomalies affect up to 10% of children and they are more common in females than in males. The aim of this study was to evaluate hemangioma treatment using four different types of lasers, namely, alexandrite, Er:YAG, CO(2), and pulsed dye laser (PDL). BACKGROUND DATA The argon laser was the first to be used for dermatological patients, namely, with port wine stains (PWS) in the late 1960s and early 1970s. A variety of different lasers and light sources were useful in the treatment of vascular lesions, e.g., KTP, Nd:YAG, CO(2), PDL, and Er:YAG. METHODS A group of 869 consecutive patients with hemangioma was retrospectively reviewed. The patients including in our study were divided into four groups according to the type of laser used: Alexandrite laser (n=85, 58 women and 20 men), CO(2) laser (n=78, 58 women and 20 men), Er:YAG laser (n=105, 87 women and 18 men), and PDL laser (n=601, 453 women and 148 men). All patients were treated in one session without anesthesia application. The ablative systems vaporized the tissues until the hemangioma was removed. The non-ablative systems used one shot, which destroyed the hemangioma blood vessels. RESULTS For the treatment efficacy analysis, the following factors were evaluated: therapeutic effect (yes vs. no), loss of pigment (yes vs. no), and appearance of scar (yes vs. no). From results it was evident that the therapeutic effect of all the lasers except alexandrite was very high; almost 100%. In the CO(2) and the Er:YAG laser groups a high percentage of side effects was also observed. Exposure to these lasers caused loss of pigment and scar formation in many cases. The best therapeutic effect, with only minor side effects, has been achieved with the PDL laser. CONCLUSION It was confirmed that PDL (595 nm, 1.5 ms, 7 mm, 9 - 11 J/cm(2)) had optimal effect without scars. Er:YAG or CO(2) laser radiation with specific characteristics was also useful for small superficial lesions.

Expression of selected proteins in breast cancer brain metastases

The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.

Fabrication of biodegradable textile scaffold based on hydrophobized hyaluronic acid

In this work, we report on the preparation of a novel biodegradable textile scaffold made of palmitoyl-hyaluronan (palHA). Monofilament fibres of palHA with a diameter of 120μm were prepared by wet spinning. The wet-spun fibres were subsequently processed into a warp-knitted textile. To find a compromise between swelling in water and degradability of the final textile scaffold, a series of palHA derivatives with different degrees of substitution of the palmitoyl chain was synthesized. Freeze-drying not only provided shape fixation, but also speeded up scaffold degradation in vitro. Fibronectin, fibrinogen, laminin and collagen IV were physically adsorbed on the textile surface to enhance cell adhesion on the material. The highest amount of adsorbed cell-adhesive proteins was achieved with fibronectin (89%), followed by fibrinogen (81%). Finally, textiles modified with fibronectin or fibrinogen both supported the adhesion and proliferation of normal human fibroblasts in vitro, proving to be a useful cellular scaffold for tissue engineering.