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Aim: The aim of this study was to assess coagulation markers of endothelial damage and examine new markers of endothelial activation such as matrix metalloproteinases (MMPs) in a group of healthy pregnant women. Matrix metalloproteinase (MMP)-2, in particular, plays a major role in the degradation of the extracellular matrix confirming its essential function in both the survival (angiogenesis) and death of endothelial cells. Detection of specific coagulation factors, mainly released from the vascular endothelium such as vWF, sTM (soluble thrombomodulin) and ePCR (endothelial protein C receptor) and factors dependent on endothelial activation such as t-PA and PAI-1, could provide information on possible endothelial dysfunction and help differentiate pregnant patients with an altered thrombotic state. Methods: Healthy pregnant women underwent complete assessment for endothelial damage (as vWF, vWF activity, sTM, ePCR, EMP, MMP-2, MMP-9 and TIMP-2) using the ELISA and other methods. Results and Conclusions: The results show that endothelial activation during pregnancy is different from that in other pathological conditions involving endothelial damage and typically characterized by higher levels of both coagulation endothelial markers and MMPs. In pregnancy, changes in extracellular matrix composition and matrix metalloproteinase activity also occur and promote vascular remodeling but, only in the uterus. Predisposing risk factors for epithelial dysfunction, and vascular mediators associated with vascular remodeling must be assessed from concentrations in whole blood. The levels of MMPs are not increased in the circulation and the local situation in the uterus cannot be monitored this way. However, MMP-2 processes and modulates the functions of many other vasoactive and pro-inflammatory molecules including adrenomedullin, big endothelin-1, calcitonin gene-related peptide, CCL7/MCP-3, CXCL12/SDF-1, galectin-3, IGFBP-3, IL-1 Beta, S100A8, and S100A9. These molecules represent new potential molecular markers of endothelial damage during pregnancy.

Aims: It is possible to reconstruct the elbow motion in tetraplegic patients using the posterior portion of the deltoid muscle. In this surgery however, it is a problem to achieve a firm suture between the deltoid muscle and the tendon graft which extends the muscle and is sewn in order to compensate for the plegic musculus triceps brachii function. This study assesses two methods of attachment between muscle and free tendon graft from the biomechanical point of view. Methods: The assessment was made on 7 fresh-frozen cadaveric samples where the rear portion of the deltoid muscle was sewn with the strip of fascia lata (A1-A7) and 7 samples (B1-B7) where the free tendon graft was attached with a strengthened part of deltoid fascia. The character of the attachment defect was evaluated as strength and elongation parameters using the device Zwick Z020-TND. Results: The ANOVA showed a statistically significant greater suture solidity connecting the muscle and tendon for group B (B1-B7) than group A. The deformation of the actual suture location was smaller in group B than the deformation of attachment surroundings. Conclusion: From the biomechanical solidity point of view, it is more efficient to use the strengthened fascia of the deltoid muscle on its inner side for the suture with the tendon graft for reconstruction of the elbow extension in tetraplegic patients.

The Supplement 1 of Biomedical Papers, Vol. 151 (2007) contains contributions presented at the 57th Pharmacological Days, in other words, at the 57th Czech and Slovak Pharmacological Meeting. This meeting takes place in Olomouc, on September 12–14, 2007. Palacky University at Olomouc is pleased to host this event which represents a traditional gathering of pharmacologists, toxicologists and scientists interested in fi elds overlapping with these two broadly defi ned fi elds of biomedical sciences. It is also a good tradition that this meeting is a truly Czecho-Slovakian one with participants coming from both sides of the friendly borders between Czech and Slovak Republics. Olomouc is, in many aspects, an almost ideal place for meetings of scientifi c communities. It is a city with the second oldest University in the Czech Republic (after Charles University of Prague), founded in 1573 which is also known for their famous former students, e.g. Albrecht Eusebius Valdstejn (Wallenstein) or Gregor Mendel. Its location, not much distant from Prague, Bratislava, Cracow, Vienna or Budapest makes Olomouc a lively city full of students and scholars coming from all places of the world. We believe that the 57th Pharmacological Days will off er a good opportunity for mutual exchange of ideas and for meeting of friends and coworkers.

Background: Chemokines and chemokine receptors are major mediators of leukocyte trafficking into the sites of the immune response. They participate in defence against microbial infection, in Th1/Th2 polarization of the immune response, allograft rejection and angiogenesis/angiostasis as well as in tumorigenesis and metastasis. To date, several functional polymorphisms of chemokine and chemokine receptor genes have been discovered that are able to deregulate chemokine system and, therefore, they may interfere with the pathogenesis of a large number of inflammatory and other diseases. In this review we focus on the known polymorphisms of two chemokines: CCL2, CCL5 and their corresponding receptors (CCR2, CCR5) and we also discuss their associations with susceptibility and progression to selected immune-mediated diseases. Methods And Results: Based on relevant literature this article gives a short overview of case-control and family studies regarding effect of the genetic factors on diseases such as coronary artery disease, systemic lupus erythematosus, diabetes mellitus, lung diseases and others. Conclusion: Recent advance in the identification of chemokine genetic background of the diseases could provide opportunity for pharmacological treatment. However, we need more information about posttranscriptional events to understand functional relevance of polymorphisms and to discovery new avenues to blocking disease de velopment.

Background: Both patients and psychotherapists can experience strong emotional reactions towards each other in what are termed transference and countertransference within therapy. In the first part of this review, we discuss transference issues. Although not usually part of the obvious language of cognitive behavioral therapy (CBT), examination of the cognitions related to the therapist, is an integral part of CBT, especially in working with difficult patients. In the second part, we cover counter-transference issues. We describe schematic issues that give rise to therapist counter-transference and explain how this interacts in different types of patient therapist encounter. We also examine ways in which the therapist can use CT to help him/her modify the countertransference and, in the process, assist the patient. Methods: PUBMED data base was searched for articles using the key words "therapeutic relations", "transference", "countertransference", "cognitive behavioral therapy", "cognitive therapy", "schema therapy", "dialectical behavioral therapy". The search was repeated by changing the key word. No language or time constraints were applied. The lists of references of articles detected by this computer data base search were examined manually to find additional articles. We also used the original texts of A. T. Beck, J. Beck, M. Linehan, R. Leahy, J. Young and others. Basically this is a review with conclusions about how therapists can manage transference issues. Results: Transference. The therapist should pay attention to negative or positive reactions towards him/ her but should not deliberately provoke or ignore them. He/she should be vigilant for signs of strong negative emotions, such as a disappointment, anger, and frustration experienced in the therapeutic relationship by the patient. Similarly he/ she should be alert to exaggerated positive emotions such as love, excessive idealization, praise or attempts to divert the attention of therapy onto the therapist. These reactions open space for understanding the patient's past and actual relations outside the therapy. Countertransference. The therapist should be aware of countertransference schemas as they apply to him/her. He/she should monitor his/her own feelings that indicate countertransference. Further, the assistance of and discussion with supervisors and colleagues is useful in regard to countertransference even in experienced therapists. Countertransference can be used as an open window into the interpersonal relations of the patient. Conclusions: Both the literature and our experience underscore the importance of careful and open examination of both transference and counter-transference issues in CBT and their necessary incorporation in the complete management of all patients undergoing CBT.

Background: The purpose of this paper is to describe two cases of desquamative gingivitis (DG) that were treated with a topic gel containing clobetasol propionate and Calendula officinalis L in an acetate tray over two years. Methods: Two patients with a diagnosis of lichen planus presenting as DG who had undergone previous treatments for this condition with no significant results, were treated by a handling gel containing clobetasol, nystatin, Calendula oficcinalis L and pectin in custom trays. Results: Both patients had remission of symptoms while using the trays and after they stopped the treatment, the symptomatic outbreaks were delayed and presented as less severe symptoms in the two years follow-up. The treatment is aimed primarily at reducing the length and severity of symptomatic outbreaks desquamative gingivitis Conclusion. This handling gel using a tray may be an efficacious treatment of desquamative gingivitis.

Aims: The human fetal period of life is when there is complete development of the dermatoglyphic pattern. However, to date not enough is known about the differentiation of the papillary terrain during prenatal life and which mechanisms are involved in this differentiation. The aims of the present study are to contribute to the clarification of the embryogenesis of the papillary ridges and to compare their development on the hands and feet. Methods: The hands and feet of 35 human embryos and fetuses were examined in the present study. We used a new and original method of orientation. The right hand with right foot or left hand with left foot of each embryo/fetus were placed together into one paraffin block. Three different planes of orientation were used. Results: Volar pad development and papillary ridge formation are identical on hands and feet, but the developmental stages on feet lag one week behind those of hands. Papillary ridge embryogenesis follows the cranio-caudal developmental direction. After developmental week 14 the configuration of the future dermatoglyphic pattern has already ocurred at the dermo-epidermal junction. We consider the 6th month of prenatal development to be the gestational age when the papillary ridge development is completed. Conclusion: Our observations lead to the conclusion that the increased vascularization of dermis considerably affects papillary ridge formation.

This Supplement to the BIOMEDICAL PAPERS, Volume 150 (Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub), is devoted to the 33rd Congress of the Czech Society of Pathologists and the 2nd Satelite Symposium & Workshop on Molecular Pathology held at the Regional Centre Olomouc & Faculty of Medicine, Palacký University Olomouc, May 4–6, 2006.

Aim: To determine the accuracy of the modified Mallampati test for predicting difficult tracheal intubation. Design: A cross-sectional, clinical, observational, non-blinded study. A quality analysis of anesthetic care. Setting. Operating theatres and department of anesthesiology in a university hospital. Material and methods: Following the local ethics committee approval and patients' informed consent to anesthesia, all adult patients (> 18 yrs) presenting for any type of non-emergency surgical procedures under general anesthesia requiring endotracheal intubation were enrolled. Prior to anesthesia, Samsoon and Young's modification of the Mallampati test (modified Mallampati test) was performed. Following induction, the anesthesiologist described the laryngoscopic view using the Cormack-Lehane scale. Classes 3 or 4 of the modified Mallampati test were considered a predictor of difficult intubation. Grades 3 or 4 of the Cormack-Lehane classification of the laryngoscopic view were defined as impaired glottic exposure. The sensitivity, specificity, positive and negative predictive value, relative risk, likelihood ratio and accuracy of the modified Mallampati test were calculated on 2x2 contingency tables. Results: Of the total 1,518 patients enrolled, 48 had difficult intubation (3.2%). We failed to detect as many as 35.4% patients in whom glottis exposure during direct laryngoscopy was inadequate (sensitivity 0.646). Compared to the original article by Mallampati, we found lower specificity (0.824 vs. 0.995), lower positive predictive value (0.107 vs. 0.933), higher negative predictive value (0.986 vs. 0.928), lower likelihood ratio (3.68 vs. 91.0) and accuracy (0.819 vs. 0.929). Conclusion: When used as a single examination, the modified Mallampati test is of limited value in predicting difficult intubation.

Background: Breast cancer treatment trends are currently based on tailored therapies using tumor and patient biomarkers. Lapatinib is the first dual inhibitor of HER1 (EGFR, ErbB1) and HER2 (ErbB2, Neu) tyrosine kinases to be used in clinical practice. However, only HER2 is currently used for therapy indications and new predictors for the treatment with lapatinib are sought. Methods and results: This minireview focuses on lapatinib and its role in breast cancer treatment. Preclinical and clinical studies as well as pharmacological characteristics are briefly reviewed while the focus is on efficacy assessment including predictive factors for therapy outcome. Conclusion: Lapatinib (Tykerb/Tyverb) was Food and Drug Administration (FDA) approved in 2007 for use in combination with capecitabine for the treatment of HER2-positive advanced or metastatic breast cancer in patients who had received previous treatment (including anthracycline, taxane and trastuzumab containing regimens) and in 2010 for use in combination with letrozole for postmenopausal women with hormonal receptor positive and HER2- positive metastatic breast cancer. In contrast to trastuzumab (Herceptin), lapatinib is orally administered and it targets both HER2 and HER1 receptors. As a synthetic and oral tyrosine kinase inhibitor (TKI), it is convenient, cheaper and easier to produce than monoclonal antibodies. The recommended dosage is not dependent on body weight either. Lapatinib plasma level measurement could be an approach to tailored therapy for further optimizing the dose and prolonging this efficient therapy. New lapatinib response predictors are being evaluated. At this time, only HER2 amplification/overexpression is used to choose lapatinib therapy candidates. Further studies on concurrent HER1 fluorescent in situ hybridization (FISH)/immunohistochemistry (IHC) assessment and/or microarray analyses may produce new data on the predictive role of the HER1 (EGFR) gene/protein. PTEN loss and PIK3CA gene mutations are other markers that may predict lapatinib poor response.

Aim: To determine the incidence of postoperative nausea and vomiting (PONV), identify risk factors, assess treatment and its effectiveness. Design: A prospective, observational, questionnaire- and interview-based study. Setting. Standard and intensive care units of the following university hospital departments: abdominal, thoracic and vascular surgery; gynecology; plastic and esthetic surgery; urology; and traumatology. Material and methods: Adult patients scheduled for elective surgery who gave informed consent were enrolled. A questionnaire-based study was performed on the first postoperative day. The collected data relevant to PONV were statistically analyzed. Conclusion: The incidence of PONV was significantly lower than generally presumed and was related to the patient gender, type of surgery and overall health status. PONV was more frequent in obese patients and when drugs antagonizing opioids or muscle relaxants were used. Early administration of antiemetic agents led to considerably less discomfort.

Background: Phase II biotransformation reactions (also 'conjugation reactions') generally serve as a detoxifying step in drug metabolism. Phase II drug metabolising enzymes are mainly transferases. This review covers the major phase II enzymes: UDP-glucuronosyltransferases, sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases (mainly thiopurine S-methyl transferase and catechol O-methyl transferase). The focus is on the presence of various forms, on tissue and cellular distribution, on the respective substrates, on genetic polymorphism and finally on the interspecies differences in these enzymes. Methods and Results: A literature search using the following databases PubMed, Science Direct and EBSCO for the years, 1969-2010. Conclusions: Phase II drug metabolizing enzymes play an important role in biotransformation of endogenous compounds and xenobiotics to more easily excretable forms as well as in the metabolic inactivation of pharmacologically active compounds. Reduced metabolising capacity of Phase II enzymes can lead to toxic effects of clinically used drugs. Gene polymorphism/ lack of these enzymes may often play a role in several forms of cancer.

Background: The introduction of the calcineurin inhibitors (CI) cyclosporine and tacrolimus into immunosuppressive protocols initiated a new era in organ transplantation with excellent short-term graft survival. Nevertheless, the chronic nephrotoxicity of these drugs represents a significant adverse factor limiting their long-term use. Patients treated with a CI can be at risk for developing renal failure and this problem is especially pronounced in patients after renal transplantation. Methods and Results: In a review paper we summarize the clinical aspects, histological manifestations and pitfalls of diagnostics of acute and chronic CI nephrotoxicity in patients after kidney transplantation. We look in detail at the disputed relationship between blood concentrations of cyclosporine and tacrolimus and histological manifestation of toxicity and summarize data showing that for toxic effects, local renal exposure to CI and their metabolites can play a more significant role than systemic exposure. We also include recent views on the pathophysiologic and molecular mechanisms underlying these changes; factors influencing local susceptibility to CI nephrotoxicity are discussed, including variability of expression and activity of P-glycoprotein and cytochrome P450. Last but not least we summarize our own experience with clinically manifest and subclinical forms of nephrotoxicity and their impact on the progression of chronic graft changes. Conclusions: Owing to their unique effects, CI remain the cornerstone of most immunosuppressive protocols for renal transplantation. Together with optimization of local kidney exposure to CI and their metabolites, efforts to reduce systemic levels as much as possible are the most important preventive measure for reducing toxic renal graft damage.

Introduction: The cerebellum is a very complex structure with many motor/non-motor functions and direct and indirect connections with almost the entire central nervous system. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological method for studying, diagnosing, and treating disorders of the nervous system. The aim of the present review is to summarise the research and potential clinical uses of cerebellar TMS. Methods: PubMed literature search using the key words "cerebellum TMS". Results: TMS of the cerebellum is used in two types of protocols. The first type involves the separate stimulation of the cerebellum while tracking its clinical or electrophysiological influence on motor and non-motor functions. The second involves stimulation of the cerebellum as a conditioning stimulus before stimulating the motor cortex, to monitor the electrophysiological impact of cerebellar stimulation on the motor cortex. Most studies are performed on small groups of healthy volunteers; isolated studies are performed on patients with neurological disorders (spinocerebellar ataxia, migraine, dystonia, Miller Fisher syndrome). It has been shown that cerebellar TMS is able to influence motor systems, memory, and perception of time, and there is evidence of its electrophysiological effects in the frontal cortex. Conclusion: Published studies suggest that cerebellar TMS is currently only important in research. There is not yet any clear or reliable evidence of the therapeutic effects of cerebellar TMS. However, its use as a treatment method can be anticipated.

Aims: Cytokine levels in nasal secretions reflect the inflammatory status of the nasal and paranasal sinus mucosa and the development of mucosal disease. The results of previous investigations suggest that macrolide antibiotics can be effective in treatment of chronic rhinosinusitis and nasal polyposis. The aim of this prospective study was to compare the immunomodulatory and clinical effects of long-term low-dose macrolide treatment of nonatopic and atopic patients with nasal polyposis. Methods: Forty (n = 40) patients with nasal polyposis, 22 allergic and 18 nonallergic were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory Th1 cytokines TNF-α and IL-1β, Th2 cytokines IL-4, IL-5 and IL-6, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using flow cytometric method. We also scored each of the 40 patients before and after therapy according to nasal symptom score and endoscopic score. Results: Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-α (p<0.01) in nasal secretions in nonallergic patients. In subjects with nasal polyposis and allergy, we found decreased levels of IL-8 (p<0.01), IL-6 (p<0.05) and IL-1β (p<0.01). Macrolide therapy decreased the size of polyps in 45.45% of nonatopic and in 50% of atopic patients. After macrolide treatment, we found 67.83% patients in nonallergic group and 55.55% patients in allergic group with improved nasal symptoms. Conclusions: Long-term low-dose treatment with CAM was effective in the management of nasal polyposis. Our results showed that macrolide treatment of nasal polyposis have different immunomodulatory and similar clinical effects in allergic and nonallergic patients.

Background: Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. Magnetic nanoparticles for cancer therapy and diagnosis have been developed on the basis of their unique physico-chemical properties not present in other materials. Their versatility is widely exploited in such diverse techniques as cell and macromolecule separation and purification, immunoassays, targeted drug delivery, controlled material release, electromagnetic hyperthermia, gene therapy, or magnetic resonance imaging. In this review we concentrate on the physical principles of magnetic drug targeting and biomedical applications of this technique. Methods and results: We examined several databases, PubMed, ISI Web of Knowledge, and Scopus, for the period 1985-2009, with specific attention to studies that used targeting of magnetic nanoparticles especially in the therapy and diagnostics of tumors. We have also presented several of our own results on theoretical simulations of magnetic particle motion in external magnetic field. Conclusions: We found growing number of published papers in this field of nanomedicine, showing the almost unlimited potential of magnetic nanoparticles in the field of experimental and clinical oncology.

BACKGROUND: The latest Paradigm 722 insulin pump, Medtronic MiniMed, USA, enables daily reading of 288 interstitial fluid glucose concentrations determined by a sensor inserted into subcutaneous tissue; the sensor signals are transmitted into the insulin pump, enabling the patient to see real-time glucose concentration on the display and adapt further treatment. AIMS: To assess the evolution of HbA1c over the course of a 3-month period in two cohorts of persons with type 1 (n=39) or type 2 (n=3) diabetes (PWD): 1) PWD on Paradigm 722 using sensors for continuous glucose monitoring (CGM group), 2) PWD on other types of insulin pumps performing intensive self-monitoring as before (3 to 6 times/d) on glucometer Linus, Wellion, Agamatrix (control group). METHODS: Compliant PWDs using insulin pump with insulin aspart for several previous months were included in the study. Seventeen were put on Paradigm 722 with CGM and 25 were included in the control group. Paired t-test and the statistical program SPSS v.15.0 were used to analyze the data. RESULTS: There was no significant difference in age between the two groups (P=0.996), in diabetes duration (P=0.482) or in daily insulin dose (P=0.469). In the CGM group (but not in the control group) HbA1c/IFCC dropped from 6.98±0.43 % to 5.98±0.36 % (P=0.006) within 1 month and remained reduced. CONCLUSION: The use of the Paradigm 722 insulin pump with CGM resulted in significant improvement in HbA1c which appeared within one month and remained throughout the whole 3-month study period. No significant improvement in HbA1c was seen in the control group.

Background: We analyzed data gathered from initial and repeated prostate biopsies at the University Hospital in Olomouc, Czech Republic. We evaluated the diagnostic yield of repeated transrectal ultrasound (TRUS) guided biopsies. We also assessed whether the result of the repeated biopsy depended on the benign diagnosis of the previous biopsy. Methods: From June 2006 till December 2008, the total of 794 men underwent a TRUS guided biopsy. The following parameters were recorded for each patient: age, total Prostatic Specific Antigen (PSA) level, free PSA level, digital rectal examination record, total prostate volume, and the histo-pathological evaluation. For patients undergoing a repeated biopsy, the histo-pathological result of the previous biopsy was also available, as well as the total number of previous biopsies and the time since the last biopsy. These data were analyzed using standard statistical methods. Results: Initial biopsy was positive for prostate cancer in 157 out of 566 men (27.7%). The total PSA level was confirmed to be a significant (P < 0.001) predictor of prostate cancer. The ratio of free PSA to total PSA (the socalled PSA index) was found to be significantly lower (P < 0.001) for patients suffering from adenocarcinoma. A total of 191 men underwent a repeated biopsy. The repeated biopsy was positive for adenocarcinoma in 39 cases (20.4%). Although this yield is lower, the significance is at the threshold (P = 0.04700). In the group of rebiopted men, total PSA level and PSA index were again significant (P = 0.0024 and P = 0.0015 respectively) predictive factors for prostate carcinoma. The diagnostic yield of repeated biopsy was assessed with respect to the most common types of the benign findings in the previous biopsy - adenomyomatous hyperplasia, inflammation, high grade prostatic intraepithelial neoplasia, and suspected adenocarcinoma. No significant difference in the diagnostic yield was found (P = 0.38431). Conclusions: Total PSA level and PSA index are the most significant precursors of adenocarcinoma in both initial and repeated biopsy. The histo-pathological result of a repeated biopsy was found to be independent of the type of benign diagnosis of the previous biopsy. A substantial number of prostate cancer is diagnosed in repeated biopsies which advocates for the indication of a repeated biopsy in case of a negative result of the initial one.

Background: Variants of the immune response genes (IRG) are considered a potential source of interindividual differences in both innate and adaptive immune responses. A large number of gene polymorphisms have been reported as alternative forms of the IRG nucleotide sequence with important functional consequences for the structure/expression of immune response molecules. Accordingly, IRG polymorphisms are considered responsible for various monogenic diseases. They may also affect individual predisposition to complex diseases or modify their clinical course. Methods and Results: In this review we define IRG polymorphism including its potential functionality. Common approaches used for the investigation of IRG polymorphisms are next briefly described. We then review current approaches (including genome - wide studies) for assessing the importance of particular IRG variants in the susceptibility to and clinical course of complex diseases. Finally, based on our own experience and on the literature, we illustrate current knowledge of the genetic component of two selected complex diseases (sarcoidosis and coronary artery disease). Conclusions: Despite major advances in genotyping technology and general knowledge of the implications of IRG in the susceptibility to complex diseases, the potential clinical application of these approaches still faces major challenges.

Background: Intensive selfmonitoring is an important and cost-demanding part of diabetes treatment. Continuous glucose monitoring (CGM) using transcutaneous sensors offers "real time" information on glycemia. In the present study, we assessed the therapeutic efficacy of CGM on metabolic control using two different statistical methods: linear regression and "survival analysis". Objectives: (1) to assess the therapeutic efficacy of CGM on metabolic control using two different statistical methods: linear regression and survival analysis; (2) to demonstrate the particular advantages of each statistical method. Methods: A total of 42 persons with diabetes mellitus treated by means of an insulin pump participated in this study. According to the means of selfmonitoring persons with diabetes were divided into two groups: 1. intervention group of 17 persons using CGM, 2. control group of 25 persons using a glucometer. Each person was followed for a period of three months. At the beginning of the study and at the end of each month HbA1c was determined. Results: Both the regression analysis and survival analysis brought evidence of significant changes of the HbA1c in either of the groups. The method of linear regression enables to analyse the evolution of HbA1c in each individual person followed by comparison of the groups. The survival analysis demonstrated that the probability of HbA1c decrease to the predefined level as well as its further maintaining at this level was higher in the CGM group. The mean time interval necessary to HbA1c decrease was shorter in the CGM group. Conclusions: The efficacy of CGM was demonstrated. In addition to linear regression, survival analysis appears to be an useful complementary method in the statistical evaluation of the treatment efficacy.

BACKGROUND: Ingestion of aristolochic acid (AA) is associated with the development of aristolochic acid nephropathy (AAN), which is characterized by chronic renal failure, tubulointerstitial fibrosis and urothelial cancer. AA may also cause another type of kidney fibrosis with malignant transformation of the urothelium, called Balkan Endemic Nephropathy (BEN). The compound predominantly responsible for the nephropathy and urothelial cancer of AA, is aristolochic acid I (AAI) which is a genotoxic mutagen after metabolic activation The activation pathway involves reduction of the nitro group to a cyclic N-acylnitrenium ion that can form covalent DNA adducts. These specific DNA adducts have been detected in experimental animals exposed to AAI, and in urothelial tissues from AAN patients. In rodent tumours induced by AAI, 7-(deoxyadenosin-N⁶-yl)aristolactam I was the most abundant DNA adduct formed and associated with activation of ras oncogenes through a characteristic transversion mutation. Such A:T→T:A mutations have been identified in TP53 of urothelial tumour DNA of an AAN patient and in several patients suffering from BEN along with specific AA-DNA adducts. Understanding which enzymes are involved in AAI activation to species forming DNA adducts and/or detoxification to its O-demethylated metabolite aristolochic acid Ia (AAIa) is important in order to assess susceptibility to this carcinogen. METHODS AND RESULTS: A literature search. CONCLUSIONS: The most important human enzymes activating AAI by simple nitroreduction in vitro are hepatic and renal cytosolic NAD(P)H:quinone oxidoreductase, hepatic microsomal cytochrome P450 (CYP) 1A2 and renal microsomal NADPH:CYP reductase as well as cyclooxygenase which is highly expressed in urothelial tissue. However, the contribution of most of these enzymes to the development of AAN and BEN diseases is still unclear. Hepatic CYP enzymes were found to detoxify AAI to AAIa in mice, and thereby protect the kidney from injury. CYP enzymes of the 1A subfamily seem to play a major role in this process in mouse liver. Likewise, among human CYP enzymes, CYP1A1 and 1A2 were found to be the most efficient enzymes participating in AAI oxidation to AAIa in vitro. Nevertheless, which CYPs are the most important in this process in both animal models and in humans have not been entirely resolved as yet. In addition, the relative contribution of enzymes found to activate AAI to species responsible for induction of urothelial cancer in humans remains still to be resolved.

Aims: Stuttering is a serious health and social problem that can distinctively affect not only the mental development of an individual but also his life possibilities, including social fulfilment and his general life prospects. The etiology of stuttering is however unknown and that is why it is not possible to treat it causally. This pilot study takes into account the hypothesis of bronchial constriction as a negative factor in stuttering and investigates the effect of the long-acting bronchodilator formoterol fumarate on stuttering in 42 patients. Methods: Patients were divided in 2 groups - A (school children and juveniles) and B (adults 18-25 resistant to other treatment). The medicine was administered once a day in the morning in a dose of 12 µg for the total period of 6 months. The prime outcome parameter - severity of stuttering - was evaluated using the ordinary scale (McGill Pain Questionnaire). The evaluation was done by an examining physician during visits to the centres and by the patients themselves (in cases of the youngest with the assistance of a parent) in a daily diary. Results: A non-parametric pair test (Wilcoxon signed rank test) was used to compare the average marks in the whole set of patients. During the six moth period of administration of Foradil® the speech fluency improved. The average number of dysfluent words decreased from 10.5 ± 1.3 to 6.6 ±0.97. Conclusion: The average mark of speech fluency evaluated by the physicians between the period of non use of Foradil® and the six month period after the use of Foradil® improved from 2.95 ± 0.76 to 1.95 ± 0.56 (as proved by the chi-square test, p<0.0001). The evaluation of speech fluency of balbuties uses the logopedic practices. Other clinical evaluations of speech fluency are not known.

BACKGROUND: Molecular genetic methods were implemented in the detection of thrombophilic disorders in the 1990's with the discovery of coagulation inhibitors antithrombin III (AT III), protein C (PC) and S (PS). The discovery of the molecular cause of activated protein C (APC) resistance by Bertina in 1994 greatly expanded their utilization. METHODS AND RESULTS: Currently, a broad group of molecular genetic markers with a clearly demonstrated risk of thrombophilia are used - mutation of FV Leiden 506R/Q, mutation of prothrombin (F II) 20210G/A, mutation of methylenetetrahydrofolate reductase (MTHFR) 677C/T in homozygous form, mutation of plasminogen activator inhibitor (PAI-1) 4G/5G, mutations of single coagulation inhibitors as well as a number of polymorphisms with controversial thrombophilic risk such as F XIII Val34Leu, platelet glycoproteins, endothelial protein C receptor and thrombomodulin. Another area utilizing molecular genetic methods is research of the pathophysiology of individual coagulation processes. To date, the greatest advances in regard to APC resistance have been achieved here. Although the molecular cause of APC resistance was clearly demonstrated in the 1990's, its clinical variability has not yet been fully explained. The same is true for the second most widespread mutation, prothrombin gene mutation, where only the latest research has hinted at a possible mechanism of expression of the genetic changes in the actual coagulation process. CONCLUSIONS: The future of molecular genetic methods is in achieving a complex understanding of the pathophysiology of thrombophilia and not only in its utilization as a method for detecting many polymorphisms with a very low risk of thrombosis.

BACKGROUND: Bacterial strains that are oxacillin and methicillin-resistant, historically termed methicillin-resistant Staphylococcus aureus (MRSA) are resistant to all β-lactam agents, including cephalosporins and carbapenems. MRSA are pathogenic and have a number of virulence factors that enable them to result in disease. They are transmissible and important causes of nosocomial infections worldwide. An MRSA outbreak can occur when one strain is transmitted to other patients or through close contacts of infected persons in the community. Hospital-associated MRSA (HA-MRSA) isolates are also frequent causes of healthcare-associated bloodstream and catheter-related infections. Community-associated MRSA (CA-MRSA) isolates are often only resistant to beta-lactam agents and erythromycin but they are an emerging cause of community-associated infections, ecpecially skin and soft tissue infections (SSTI) and necrotizing pneumonia. METHODS: Current possibilities for detecting MRSA strains in the laboratory are reviewed and discussed in the context of the recent literature. RESULTS AND CONCLUSION: The active surveillance and prevention of MRSA occurence and spreading in hospitals are discussed in the context of recent literature.

AIMS: To analyze the event-related desynchronization/synchronization (ERD/ERS) attended with the mental load arising while solving two cognitive tasks. The features of the presented visual stimulus determined the type of cognitive task that should be solved. METHODS: For each experimental task and everybody's subject FFT Analysis module calculated the total power histograms from a fixed frequency band (3-20 Hz or 8-13 Hz) for each 3-second EEG sample with 50 % overlay and all electrodes. From the histograms the software derived two FFT single values - The average Total Power (TP) and Frequency at Maximum Power (FMP). RESULTS: It has been shown that during the solution of cognitive tasks the marked changes of ongoing EEG activity appeared. The short lasting and localized amplitude decrease in rhythmic activity (ERD) and the change of EEG frequency were among the most frequent. The ERD extent was determined by an informational content of processed visual stimuli and by the site of scalp-recording electrode. A higher mental load related to the solution of cognitive tasks shifted the average FM to lower frequencies. CONCLUSION: The suitability of an analysis of ongoing EEG activity to uncover differences in people's brain activation patterns when engaged in performing cognitively demanding tasks was proved.

AIM: A prospective study investigated survival of patients with stage IIIA non-small-cell-lung cancer (NSCLC) treated with a combination of neoadjuvant and adjuvant chemotherapy. METHODS: Consecutive chemo-naive patients with potentially operable stage IIIA NSCLC received carboplatin-based neoadjuvant treatment. Tumor cells harvested during surgery underwent methylthiazolyl tetrazolium blue (MTT) cytotoxic assay. After surgery, adjuvant chemotherapy was selected, where possible, according to MTT results. RESULTS: A total of 65 patients were evaluated (31 received carboplatin/vinorelbine, 34 carboplatin/paclitaxel). The overall response rate was 67.7 % (95% confidence interval [CI]: 56.3-79.1 %) with downstaging in 52.3 % (95% CI: 40.2-64.5 %) and no significant differences between regimens. Median follow-up was 86 months: median overall survival (OS) was 32.1 months (95% CI: 7.4-46.5), median time to progression was 25.1 months (95% CI: 15.1-34.9 months) and five-year overall survival was 35.7 % (95% CI: 23.7-47.7 %). Forty-seven patients (72.3 %) underwent surgery and 43 patients received adjuvant chemotherapy. Five-year survival after tumor resection was 49.5 % (95% CI: 34.2-64.8%), median OS was 59.0 months (95% CI: 34.2-83.1) and median disease free survival after surgery was 57.3 months (95% CI: 29.5-84.4). With MTT-directed therapy, median OS was 85.1 months (95% CI: 15.4-148.6) and the 5-year survival rate was 57.0 % (95% CI: 34.5-79.5 %); the trend for longer survival failed to reach statistical significance. CONCLUSIONS: A combination of carboplatin-based neoadjuvant chemotherapy, surgical resection and adjuvant chemotherapy achieved satisfactory survival rates in stage IIIA NSCLC, especially in patients with complete resection of tumor and those given MTT-directed adjuvant treatment. Our results suggest MTT testing may help optimise adjuvant chemotherapy.

Background: Discovery of uncoupling protein 2 (UCP2) in 1997 and demonstration of its wide tissue expression has triggered an important question about controlled oxidative phosphorylation uncoupling and the physiological function of this process. Uncoupling protein 2 (UcP2) is a mitochondrial protein that can influence the mitochondrial membrane potential and hence the production of reactive oxygen species by mitochondria. It is also thought to be involved in apoptotic signaling pathways and it has been suggested to be important in cardio- and neuroprotection. Methods and results: We examined the recent literature (2003-2007) in the MedLine database for evidence linking p38, one of the stress-related protein kinases, with modulation of UCP2 expression in the heart. While two reports clearly demonstrate p38 as down-regulating UcP2 expression, only circumstantial evidence exists for cardiomyocytes. Conflicting results on p38-regulated cardiomyocyte survival after ischemia leave an open venue for hypotheses on the differential regulation of protein expression, including UCP2. Conclusions: Reviewing the evidence connecting UCP2 and its cytoprotective activities, we propose a tissue specific link that may explain the variable influence of p38 via modulation of UCP2 expression.

AIMS: The goal of this study was to investigate the effect of chronic smoking on arterial stiffness at a peripheral site using pulse wave analysis. METHODS: Forty two non-smokers (17 males, 25 females) of average age 20.2 ± 1.3 year and forty five smokers (19 males, 26 females) of average age 24.3 ± 2.4 year were included in the study. Four parameters, SI (stiffness index), RI (reflection index), CT (crest time) and IWD (interwave distance) were evaluated by means of an adapted device based on pletysmographic principles that transform volume changes to voltage changes. RESULTS: SI corresponding to pulse wave velocity was 0.64 m/s higher in smokers than in non-smokers (7.25 ± 0.53 m/s versus 7.89 ± 0.73 m/s, P < 0.001). RI was significantly higher in smokers (42.49 ± 6.71 %, versus 35.46 ± 0.06 %, P < 0.001) than in non-smokers. IWD for non-smokers was 8.01 ± 0.13 %, in smokers we found a 16 % increase to 9.21 ± 0.83 % (P < 0.001). We detected a small increase in CT in smokers compared to non-smokers (0.09 ± 0.01 s versus 0.10 ± 0.01 s, P < 0.005). CONCLUSIONS: Chronic tobacco smoking is associated with endothelial dysfunction. In smokers we found increased values for all assessed parameters. Our results suggest that the negative effect of cigarette smoking on the vascular system can be found even in young smokers who have been smoking for less than 10 years.

Background: Aurora kinases are a recently discovered family of kinases (A, B & C) consisting of highly conserved serine\threonine protein kinases found to be involved in multiple mitotic events: regulation of spindle assembly checkpoint pathway, function of centrosomes and cytoskeleton, and cytokinesis. Aberrant expression of Aurora kinases may lead to cancer. For this reason the Aurora kinases are potential targets in the treatment of cancer. In this review we discuss the biology of these kinases: structure, function, regulation and association with cancer. Methods and Results: A literature search. Conclusion: Many of the multiple functions of mitosis are mediated by the Aurora kinases. Their aberrant expression can lead to the deregulation of cell division and cancer. For this reason, the Aurora kinases are currently one of the most interesting targets for cancer therapy. Some Aurora kinase inhibitors in the clinic have proven effectively on a wide range of tumor types. The clinical data are very encouraging and promising for development of novel class of structurally different Aurora kinase inhibitors. Hopefully the Aurora kinases will be potentially useful in drug targeted cancer treatment.