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Background: Photodynamic therapy (PDT) is a new modality in cancer treatment. It is based on the tumour-selective accumulation of a photosensitizer followed by irradiation with light of a specific wavelength. PDT is becoming widely accepted owing to its relative specificity and selectivity along with absence of the harmful side-effects of chemo and radiotherapy. There are three known distinct mechanisms of tumour destruction following PDT, generation of reactive oxygen species which can directly kill tumour cells, tumour vascular shutdown which can independently lead to tumour destruction via lack of oxygen and nutrients and thirdly enhanced antitumour immunity. Methods: A review based on the literature acquired from the PubMed database from 1983 with a focus on the enhanced antitumour immunity effects of PTD. Results and conclusion. Tumour cell death is accompanied by the release of a large number of inflammatory mediators. These induce a non-specific inflammatory response followed by gradual adaptive antitumour immunity. Further, a combination of PDT with the immunological approach has the potential to improve PDT efficiency and increase the cure rate. This short review covers specific methods for achieving these goals.

Background: Merkel cell carcinoma (MCC) is a rare potentially fatal skin tumour affecting older mainly white people and younger immunosuppressed individuals. While uncommon, the incidence is increasing relative to melanoma and with twice the lethality. The benign appearance of the tumour usually on exposed skin parts, contrasting with its extensive microscopic invasion, can delay timely diagnosis. Recurrent MCC is currently attributed to the recently discovered Merkel cell polyomavirus This brief review of MCC covers the history, epidemiology,etiology,clinical and histological features, treatment and prognosis. Methods: Literature search using PubMed and search words Merkel cell carcinoma (MCC), etiology, treatment for the years 1972 to 2010. Results and conclusion. Merkel cell carcinoma is a rare malignancy with uncertain prognosis. Due to the uncommon occurrence and dearth of randomized studies, there is no agreement on optimal treatment. The tumor has only recently been included in the international classification of tumors (NCCN). The treatment approaches found to be best are radical surgery of primary tumor, drainage of lymph node extension and possibly adjuvant loco-regional radiotherapy. The basis of successful treatment however, remains prevention regular dermatological examination in immunosuppressed patients and early initiation of combination therapy, based on radical surgery supplemented by radiotherapy and palliative chemotherapy in the last resort.

Background: Acute myeloid leukemia (AML) shows a high degree of heterogeneity owing to a variety of mutations and the mechanisms of leukemogenesis. This heterogeneity is often not reflected in standard treatment approaches which while providing predictable outcomes in the majority of patients fail in particular cases even with high-dose multiagent chemotherapy regimens. Further, the unselective effect of chemotherapy leads to high treatment-related toxicity and the enormous risk of infection during prolonged pancytopenia, preventing further dose escalation. Objectives: Cytokines play a role in leukemogenesis, AML cell persistence and treatment outcome. In this review we highlight cytokine dependent mechanisms essential for AML cell survival and the role of single cytokines in leukemogenesis and allogeneic transplantation-related phenomena. Cytokine-related mechanisms of leukemogenesis, AML cell persistence and resistance to chemotherapy are complex. Modulation of the cytokine network can disrupt signalling pathway activation and overcome the high resistance to treatment. It may also increase the selectivity of AML treatment, reduce the overall treatment-related toxicity and improve outcomes of AML treatment in all age groups of patients. Conclusions: This review provides a deeper insight into these processes with focus on the most vulnerable step. Special attention is paid to the possibility of selective influence on defined cell populations for therapeutic target. We believe that modulating cytokine-dependent processes in AML is an approach that could be included in standard chemotherapeutic regimens for improving overall treatment outcome.

Background: The prevailing recommendation for the elderly is to live in their own homes as long as conditions allow. With this emphasis on the natural living environment, it is imperative to closely monitor both the general health and nutritional needs of the elderly in community settings. Aim: The aim of the study was to compare three nutritional status screening and evaluation tools of the elderly in their homes. Methods: Testing of measuring instruments, MNA, SGA, and MUST took place in the homes of 120 seniors in selected areas of the Czech and Slovak Republics. The study included 120 seniors. For testing of the relationships and dependencies, Pearson's correlation coefficient, t and Fisher tests were used. The level of statistical significance was α = 0.05. Results: All tests were to a large degree correlated (p_MNA = 0.0049; p_MUST = -0.537; p_SGA = -0.578) with the body mass index of the seniors. Simultaneously, it was confirmed that the tools for assessing nutritional status in the study showed significant differences regarding the classification of patients at risk of malnutrition and/or malnourished patients. Conclusions: Based on the findings, we conclude that MNA appeared to be a more appropriate tool for nutritional assessment of the elderly living in their homes. SGA and MUST provided rather subjective evaluation of the nutritional status and did not furnish an in-depth categorization of malnutrition.

Background: Dental implants are a suitable option for the replacement of some or all missing teeth. Their main function is to secure the stability of the artificial tooth. The implant material interacts with several cell types including osteoblasts, gingival fibroblasts, periodontal ligament fibroblasts and monocytes. The most common material used is pure titanium which is corrosion resistant and has an elasticity modulus similar to that of bone. In recent years, diverse modified titanium surfaces have also been developed. The wound healing around the implant is a complex process that determines how well the host can heal and accept the implanted material. For this reason, search for markers of the biocompatibility of these new materials is paramount. To identify markers found to be suitable for studying the biocompatibility of dental implants. Methods: Review of Pubmed and Web of Science databases for the years 1958-2010. Conclusions: The surface of dental implant material should enhance firm attachment of the implant to junctional epithelium, soft connective tissue and bone. For the purposes of dental implant biocompatibility studies, a number of markers produced by osteoblasts or by cells of periodontal ligament have been proposed. In general, the most typical markers for osteoblasts and fibroblasts are alkaline phosphatase and collagen I, respectively. The involvement of both cell types in the inflammatory response is primarily evaluated by determination of tumour necrosis factor α and proinflammatory interleukins.

Background: Ellipticine and doxorubicin are antineoplastic agents, whose action is based mainly on DNA damage such as intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts. The key target to resolve which of these mechanisms are responsible for ellipticine and doxorubicin anticancer effects is the development of suitable methods for identifying their individual DNA-damaging effects. Here, the ³²P-postlabeling method was tested to detect covalent DNA adducts formed by ellipticine and doxorubicin. Methods: The standard procedure of ³²P-postlabeling assay, this procedure under ATP-deficient conditions, the version using extraction of adducts with n-butanol and the nuclease P1 enrichment version were used to analyze ellipticineand/ or doxorubicin-derived DNA adducts. Results: Two covalent ellipticine-derived DNA adducts, which are associated with cytotoxicity of ellipticine to human UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines, were detected by the ³²P-postlabeling method. These adducts are identical to those formed by the ellipticine metabolites, 13-hydroxy- and 12-hydroxyellipticine. In contrast, no covalent adducts formed by doxorubicin in DNA of these neuroblastoma cells and in DNA incubated with this drug and formaldehyde in vitro were detectable by the ³²P-postlabeling assay. Conclusions: The results presented in this paper are the first to demonstrate that in contrast to covalent DNA adducts formed by ellipticine, the adducts generated by formaldehyde-mediated covalent binding of doxorubicin to DNA are not detectable by the ³²P-postlabeling assay. No DNA adducts were, detectable either in vitro, in incubations of DNA with doxorubicin or in DNA of neuroblastoma cells treated with this drug. The results also suggest that covalent binding of ellipticine to DNA of UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines is the predominant mechanism responsible for the cytotoxicity of this drug. To understand the mechanisms of doxorubicin anticancer effects on neuroblastoma cells, development of novel methods for identifying covalent doxorubicin-derived DNA adducts is the major challenge for further research.

Aim: The aim of this study was to investigate the oral health status of women with high-risk pregnancies. Methods: A case-control study of 142 pregnant women was conducted. The case group included 81 pregnant women with high-risk pregnancies, while 61 women with normal pregnancies served as controls. The following variables were recorded for each woman: age, general health status, DMF, CPITN, and PBI index, amounts of Streptococcus mutans in the saliva and dental treatment needs. The Mann-Whitney test, Kruskal-Wallis test, t-test and chi-squared test were used for statistical analyses. Results: Statistically significant differences were detected between the PBI indices and dental treatment needs of the two groups. Out of the entire study cohort, 77% of the women in the case group and 52% of the women in the control group required dental treatment. Conclusion: In this study, women with complications during pregnancy had severe gingivitis and needed more frequent dental treatment than those in the control group.

Aim: The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model. Methods: The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used. Results: The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative. Conclusions: The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

Background: Experimental, epidemiological and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFAs) in preventing inflammation and cancer of the colon. This review covers the unsaturated docosahexaenoic fatty acid (DHA), describes some of its important cellular and molecular mechanisms, its interaction with another dietary lipid, butyrate and with endogenous apoptotic regulators of the tumour necrosis factor (TNF) family. We also discuss the clinical impact of this knowledge and the use of these lipids in colon cancer prevention and treatment. Results: From the literature, DHA has been shown to suppress the growth, induce apoptosis in colon cancer cells in vitro and decrease the incidence and growth of experimental tumours in vivo. Based on these data and our own experimental results, we describe and discuss the possible mechanisms of DHA anticancer effects at various levels of cell organization. We show that DHA can sensitize colon cancer cells to other chemotherapeutic/chemopreventive agents and affect the action of physiological apoptotic regulators of the TNF family. Conclusion: Use of n-3 PUFAs could be a relatively non-toxic form of supportive therapy for improving colon cancer treatment and slowing down or preventing its recurrence. However, it is necessary to use them with caution, based on solid scientific evidence of their mechanisms of action from the molecular to the cellular and organism levels.

Aims: The aim of this review was to summarize recent knowledge of the structure and function of a transcriptional repressor, B lymphocyte induced maturation protein 1 (BLIMP1) and its participation in the pathogenesis of B lymphomas. Methods and results: This review summarizes the structure and function of BLIMP1, its major target genes and its role as a tumour suppressor in B cell lymphomas. We review our recent data implicating the loss of BLIMP1α as an important step in the pathogenesis of the Epstein-Barr virus (EBV) associated B cell lymphomas. Conclusions: BLIMP1 is a transcriptional repressor essential for the differentiation of germinal centre (GC) B cells to plasma cells. The loss of BLIMP1 in GC B cells could contribute to the pathogenesis of EBV-associated lymphomas by preventing plasma cell differentiation and viral replication.

Aim: The aim of this study was to evaluate TSPY (testis specific protein on the Y chromosome) gene and 5'UTR (UnTranslated Region) polymorphisms in men with impaired fertility compared to fertile controls. Methods: We analyzed 72 infertile men and 31 fertile controls usingconventional sequencing analysis to find crucial SNPs (single nucleotide polymorphism) and other changes. Results: The most remarkable changes were found in the 1^st exon only. In one half of the both infertile men and fertile controls, the most frequent finding was 26 SNPs with a similar pattern. In the other half we found highly relevant changes, generating a stop codon in the first third of exon 1. Early termination cut down the protein by 78.5%. This kind of change was not found in the fertile controls. No correlation was found between the spermiogram and the changes leading to the stop codon. The distribution of men with deletions, insertion and higher gene copy number was not statistically different. Conclusion: The changes found in exon 1 in infertile men could fundamentally affect the process of spermatogenesis. These findings could significantly enhance our understanding of the molecular-genetic causes of male infertility.

Background: ADAM33 and STAT6 belong to the candidate genes that have been commonly associated with asthma, bronchial hyperresponsiveness or IgE levels. Our objective was to assess the association of 11 SNPs of the ADAM33 and 6 of the STAT6 and their haplotypes with IgE levels and asthma. We also evaluated the possible role of parental origin of haplotypes on IgE levels. Methods: We enrolled 109 children with asthma and 45 healthy controls. Genotyping was performed by TaqMan probes and confirmed by sequencing. Haplotype construction was based on the knowledge of parental genotypes and also inferred by using the EM algorithm and Bayes' theorem. Results: None of the SNPs were associated with elevated IgE level or asthma. We found that the most frequent STAT6 haplotype ATTCAA (built from rs324012, rs324011, rs841718, rs3024974, rs3024974, rs4559 SNPs, respectively) was associated with elevated total IgE levels (P=0.01) and this haplotype was predominantly transmitted paternally (P<0.001). We compared our results with those of studies performed on German and Australian Caucasian populations and found that rs324011, rs3024974 and rs4559 SNPs in STAT6 should have a major effect on IgE levels. Therefore, we suggest the TCA haplotype alone (built from rs324011, rs3024974 and rs4559 SNPs, respectively) in STAT6 is associated with total IgE elevation. Conclusions: The influence of paternal origin of the STAT6 haplotype on IgE levels is surprising but the exact role of possible paternal imprinting in STAT6 regulation should be investigated and confirmed in future studies.

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.

Aim: We evaluated the effects of botulinum toxin type A (BTA) - abobotulinumtoxinA on passive motion resistance (PMR) values of lower limbs affected muscles and on the functional motor status in children with spastic cerebral palsy (CP). Methods: In Group I (28 lower limbs with spastic muscles), and in Group II (14 lower limbs with dynamic spastic equinus) BTA was administered. Physical therapy was prescribed for 16 weeks. We estimated PMR using the Modified Ashworth Scale. Achieved functional motor level was evaluated by Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM). Parameters were assessed before treatment and after 3,8,16 weeks and 6 months respectively. Results: In Group I, PMR was significantly lower for hip adductors and knee extensors over 3-16 weeks, and for ankle joint extensors in both groups. There were significant differences for both groups in frequencies of GMFCS values after 16 weeks from BTA application. There was a significant increase in GMFM scores after 8 and 16 weeks from BTA application in both groups of patients. Conclusions: BTA treatment in CP children is followed by reduction in PMR values and improvement in functional motor status.

Background: Lately, more and more preparation of various cocktails or mixtures of bioactive modulators have been introduced. Their true activity is, however, rarely tested. Aim: To compare six commercially available, glucan-based immunostimulators. Methods: Immunological effects of tested combinations were measured by evaluation of phagocytosis of synthetic particles by peripheral blood neutrophils, production of IL-2 by mouse splenocytes, production of superoxide anion and nitrite oxide, antibody response to imunization with ovalbumin, and NK cell activity. Results: Our results showed that with the exception of the highest doses (phagocytosis) and superoxide anion and nitrite oxide production, only RVB 300 showed significant immunostimulative activity. Conclusion: Based on our results, we can conclude that most of the tested natural immunomodulators have limited, if any, biological effects. Only RVB 300 significantly stimulated all six tested immunological reactions.

Aims: The impact of ApoE polymorphism on angiographic parameters was assessed in patients referred for coronary angiography. Methods: Elective coronary angiography was performed in 671 subjects (525 men, 146 women, mean age 60±10 years) with symptoms of ischemic heart disease. The patients were divided into: no CAD group (smooth coronary vessels, n=83), one-vessel (n=155), two-vessel (n=170) and three-vessel disease (n=196). Patients with stenoses 0-50% were excluded. Within patients with CAD, we evaluated overall extent of CAD measured by the number of stenotic segments according to AHA (1 segment vs. 2-3 vs. ≥4), and the severity of the most serious stenosis (in percent). ApoE genotype was determined using real-time PCR. Results: The frequency of ε2/ε3 genotype (n=56) was lower in the three-vessel disease group compared to one-vessel disease (OR=0.25, P=0.0019), two-vessel disease (OR=0.31, P=0.0114) or no CAD group (OR=0.24, P=0.0057). Frequency of ε2/ε3 decreased with the number of affected segments (1 vs. ≥4: OR=0.35, P=0.0143). The ε3/ε4+ε4/ε4 genotypes (n=123) were more frequent in CAD patients altogether compared with no CAD group (OR=2.30, P=0.019), while no impact of the ε4 allele on angiographic parameters within the CAD patients was detected. In ε2/ε3 carriers with CAD, lower LDL-cholesterol, total cholesterol and lower use of lipid-lowering drugs were observed. Conclusions: The results show predominantly focal form of CAD in patients with ε2/ε3 genotype. Lower LDL-cholesterol and total cholesterol may play the key role, although other contributing factors are discussed.

Background: Historically, metastatic colorectal carcinoma was regarded as a tumor that is relatively resistant to cytotoxic-agents. Due to the limited number of treatment options, methods have been investigated to enhance selectivity. One method for enhancing selectivity is anatomical targeting, including hepatic arterial infusion (HAI). Methods: A comprehensive review of the literature. Results: Early studies with HAI used fluoropyrimidines, 5-fluorouracil or floxuridine. Several randomized trials comparing the HAI of fluoropyrimidines with systemic administration of fluoropyrimidines or best supportive care that were conducted in the 1980s and early 1990s demonstrated a superior objective response rate, but usually not a prolongation of survival in patients treated with HAI. The current standard of first line systemic chemotherapy of metastatic colorectal carcinoma is combination chemotherapy (fluoropyrimidines, oxaliplatin and/or irinotecan) administered with targeted agents. A number of trials have reported promising activity of the HAI of oxaliplatin and/or irinotecan with fluoropyrimidines, but only pilot studies are available for the combination of HAI of cytotoxic agents with targeted drugs. Factors that limit the effectiveness and utilization of HAI include catheter or port system related complications, the presence of extrahepatic metastases, or increased risk of hepatic toxicity. Conclusions: HAI could be considered in clinical practice in different settings, including patients after liver resection, as second line therapy in patients failing standard front line regimens and as neodjuvant therapy to convert to resectability. Future studies should specifically concentrate on identifying regimens that would result in increased cure rates in patients with isolated hepatic metastases. For this reason, exploiting anatomical selectivity may still be a useful approach, even in the era of targeted therapy.

Aims: We report a case of multi-recurrent herpes zoster in a 53-year-old Caucasian woman treated repeatedly at the Faculty Hospital Hradec Kralove, Czech Republic over the years 2009 - 2011. Methods: Specific PCR methods targeting single nucleotide polymorphisms (SNPs) in open reading frames (ORF) 38, 54 and 62 were utilized to determine vaccine or wild type varicella-zoster (VZV) strains followed by SNPs analysis using two amplicons in ORF 22 and/or ORF 21/ORF 50. Additional genotyping in ORF 1, 6, 9 and 28 was subsequently performed due to the unusual results. Results: Three sets of clinical specimens from one patient (from hospital visits 2, 3 and 4) were analyzed and the presence of an unusual wild-type strain of VZV was discovered. The VZV strain isolated from the lesions bears a combination of markers characteristic both for Mosaic 2 (M2) and European 1 (E1) wild-type VZV strains. Conclusion: This is the first report of atypical wild-type VZV strain circulating currently in Czech Republic.

Background: Calciphylaxis is a potentially fatal complication of persistent secondary hyperparathyroidism; its cause is still not clear. Unfortunately there is no close relation in severity of clinical picture, serological and pathological alteration. For this reason the prognosis is difficult to establish. Administration of sodium thiosulphate may reduce the precipitation of calcium crystals and improve the general clinical conditions before surgical parathyroidectomy, which seems the only therapeutic approach able to reduce the mortality risk in these patients. Methods and Results: A 60 year old female patient suffering from End Renal Stage Disease, on haemodialysis from 2001 due to the onset of haemolytic uremic syndrome, underwent a kidney transplant in April 2008. After transplantation there was a recurrence of the haemolytic uremic syndrome, with temporary worsening of the graft. Six months later there was a definite loss of graft and return to dialysis treatment. On April 2010 a severe systemic calciphylaxis related to secondary hyperparathyroidism was diagnosed. The patient underwent parathyroidectomy but, because of the unimproved clinical picture, treatment with sodium thiosulphate was initiated. There was only improvement in cutaneous lesions. The worsening general clinical condition of the patient caused death due to general septic complications. Conclusions: The coexistence of haemolytic uremic syndrome and secondary hyperpathyroidism makes the prognosis poor and, in this case, therapy, which counteracts calcium crystals precipitation, has no effect. Preventive parathy­roidectomy can be considered as the only possible treatment.

AIMS: To judge whether and how the character of the visual stimulus and type of cognitive task affects brain event-related potentials (ERPs). METHODS: ERPs to three types of visual stimuli (white blank oval on a dark background, unfolded cube and net of sixteen small squares) were recorded from nine scalp sites and saved on a computer. Special software was used for off-line analysis of the ERPs. RESULTS: The presentation of each of the three visual stimuli used was followed by ERPs consisting of two negative (N160, N340) and one positive (P220) components. The character of the stimulus did not affect the latency of ERPs components. However, the type of visual stimuli affected the amplitude. The most conspicuous changes were shown by the N340 ERPs component. Its average amplitude in comparison with reference amplitude was always significantly higher during the first cognitive task ("Choose the cube that can be folded up from the unfolded cube!") and significantly lower than reference amplitude during the second cognitive task ("Complete the missing part of a figure with the appropriate item!"). It was also shown that subjective personality traits such as nervousness, spontaneous aggressivity and emotional lability had an influence on the recovery phase of the experiment affecting the average amplitude of N340 CONCLUSION: The results revealed that the cognitive processes underlying successful resolution of two pictorial cognitive tasks affected differently the activity of systems giving rise to visual ERPs.

Background: Cholinesterases are a group of serine hydrolases that split the neurotransmitter acetylcholine (ACh) and terminate its action. Of the two types, butyrylcholinesterase and acetylcholinesterase (AChE), AChE plays the key role in ending cholinergic neurotransmission. Cholinesterase inhibitors are substances, either natural or man-made that interfere with the break-down of ACh and prolong its action. Hence their relevance to toxicology and pharmacology. Methods and Results: The present review summarizes current knowledge of the cholinesterases and their inhibition. Particular attention is paid to the toxicology and pharmacology of cholinesterase-related inhibitors such as nerve agents (e.g. sarin, soman, tabun, VX), pesticides (e.g. paraoxon, parathion, malathion, malaoxon, carbofuran), selected plants and fungal secondary metabolites (e.g. aflatoxins), drugs for Alzheimer's disease (e.g. huperzine, metrifonate, tacrine, donepezil) and Myasthenia gravis (e.g. pyridostigmine) treatment and other compounds (propidium, ethidium, decamethonium). Conclusions: The crucial role of the cholinesterases in neural transmission makes them a primary target of a large number of cholinesterase-inhibiting drugs and toxins. In pharmacology, this has relevance to the treatment of neurodegenerative disorders.

Backround. The treatment of personality disorder is repeatedly reported as less successful than the treatment of patients without personality disorder. Most clinicians believe that anxiety disorder in tandem with a personality disorder often leads to longer treatment, worsens the prognosis, and thus increases treatment costs. Our study was designed to compare the short-term effectiveness of therapy in patients suffering from social phobia with and without personality disorder. Method: The specific aim of the study was to assess the efficacy of a 6 week therapeutic program designed for social phobia (SSRIs and CBT) in patients suffering from social phobia with comorbid personality disorder (17 patients) and social phobia without comorbid personality disorder (18 patients). The patients were regularly assessed in weeks 0, 2, 4 and 6 using the CGI (Clinical Global Improvement) for severity, LSAS (Liebowitz Social Anxiety Scale), and in self-assessments BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory). Results: Patients in both groups improved their scores in most of the assessment instruments used. A combination of CBT and pharmacotherapy proved to be the most effective treatment for patients suffering with social phobia with or without comorbid personality disorder. Treatment efficacy in patients with social phobia without personality disorder was significantly better than in the group with social phobia comorbid with personality disorder for CGI and specific inventory for social phobia - LSAS. The scores on the subjective depression inventory (BDI) also showed significantly greater decrease over the treatment in the group without personality disorder. The treatment effect between groups did not differ in subjective general anxiety scales BAI. Conclusion: Our study showed that patients suffering from social phobia and comorbid personality disorder showed a smaller decrease in specific social phobia symptomatology during treatment compared than patients with social phobia without personality disorders. However, a significant decrease in symptomatology occurred in personality disorder patients as well.

Aim: Acute interstitial pneumonia is characterized by rapid progressive dyspnoea degenerating into respiratory failure requiring mechanical ventilation. Acute interstitial pneumonia (AIP) and idiopathic pulmonary fibrosis (IPF) are separate clinic/pathological entities although overlap may be present. It is well-known that patients with IPF have increased risk of lung carcinoma; Adenocarcinoma in connection with IPF is less common. Moreover the subtype of adenocarcinoma, diffuse bronchoalveolar carcinoma has not yet been described. Case report: We report the case of 45 yr old former hockey player with increased bilateral reticular shadowing on chest radiograph, dyspnoea, velcro-like crackles, restrictive respiratory disease and mixed high-resolution computed tomography finding. During brief in-patient treatment the patient developed acute respiratory failure accompanied by multiorgan failure and disseminated coagulopathy. Deterioration of the microcirculation was followed by loss of peripheral vascular resistance, which was irreversible even with normalization of the blood gases achieved by extracorporeal membrane oxygenation. At autopsy, bronchoalveolar carcinoma in usual interstitial pneumonia (UIP) combined with areas of alveolar damage with hyaline membranes was found. Conclusion: This case alerts clinicians to unusual idiopathic pulmonary fibrosis manifestations and its complications. Close collaboration between clinicians, pathologists and laboratory physicians is highly recommended for early diagnosis and appropriate treatment.

Background: Routine medical microbiology diagnostics relies on conventional cultivation followed by phenotypic techniques for identification of pathogenic bacteria and fungi. This is not only due to tradition and economy but also because it provides pure culture needed for antibiotic susceptibility testing. This review focuses on the potential of High Resolution Melting Analysis (HRMA) of double-stranded DNA for future routine medical microbiology. Methods and Results: Search of MEDLINE database for publications showing the advantages of HRMA in routine medical microbiology for identification, strain typing and further characterization of pathogenic bacteria and fungi in particular. The results show increasing numbers of newly-developed and more tailor-made assays in this field. For microbiologists unfamiliar with technical aspects of HRMA, we also provide insight into the technique from the perspective of microbial characterization. Conclusions: We can anticipate that the routine availability of HRMA in medical microbiology laboratories will provide a strong stimulus to this field. This is already envisioned by the growing number of medical microbiology applications published recently. The speed, power, convenience and cost effectiveness of this technology virtually predestine that it will advance genetic characterization of microbes and streamline, facilitate and enrich diagnostics in routine medical microbiology without interfering with the proven advantages of conventional cultivation.

Background: The current diagnosis of stroke relies on clinical examination by a physician supplemented by various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in acute settings to diagnosis stroke, differentiate between stroke types, and ideally predict an initial/recurring stroke would be extremely valuable. The diagnosis of stroke is currently hampered by delay due to lack of a suitable tool for rapid, accurate and analytically sensitive biomarker - based testing. There is a clear need for further assay development and clinical validation in this area (acute stroke setting) in order to improve patient outcomes and quality of life. Visinin like protein 1 (VILIP-1) is a newly discovered CNS-abundant protein which has shown promise in experimental studies, for early stroke diagnosis. However, to date there is no clinical study that has measured VILIP-1 in sera as a marker of stroke. Aim: To develop an assay for the determination of VILIP-1 in human serum, and to investigate its clinical relevance as a marker of ischemic stroke. Design and methods. A new sandwich ELISA was developed, introduced and clinically tested. Mean spiking recovery was 98%. The mean recovery for dilution linearity was 93%. The limit of detection of the assay was 0.01 mcg/l; the intraassay and interassay coefficient of variation (CV) were always less than 10%. The study was approved by the Ethics Commission of the Hospital Šternberk, Czech Republic. A total of 17 healthy individuals (9 men and 8 women, age 64.0 ± 13.0) and 16 individuals with ischemic stroke (10 men and 6 women, age 63.0±11.5) were recruited for our study. The criteria of stroke were proposed by the National Czech Standard. All individuals had blood samples drawn, and VILIP-1 analysis and CT and/or MRI were performed. Results: VILIP-1 serum level significantly differentiated healthy subjects from patients with stroke (P<0.01). All individuals with stroke had VILIP-1 serum values higher than > 0.05 mcg/l, healthy had values below this value. The diagnostic efficacy of serum VILIP-1 was very significant (sensitivity 100%, specificity 100% at 0.093 mcg/l VILIP-1 serum values, AUC 1.0 (CI 0.93-1.0, P<0.01), Chi-squared in the frequency table was 33 (P<0.01). Conclusion: We have introduced a new analytical tool for the study of VILIP-1. Our results support the hypothesis that serum VILIP-1 may be associated with ischemic stroke. The ELISA VILIP-1 assay offers a new research tool for the diagnosis and pathophysiology of stroke and other CNS diseases.

Background: Exposure to high concentrations of oxygen radicals, the lack of nucleus and mitochrondria, inability to synthesise new protein and degradation of detoxifying enzymes makes red blood cells (RBCs) uniquely vulnerable to oxidative stress. This review summarizes the changes in biochemical parameters that primarily contribute to alterations in red blood cells during oxidative stress. Methods: PubMed, Science Direct and Springer online databases and updates from the Indian Council of Medical Research (ICMR). Results and Conclusion. As one of the first cells to be affected by changes in the redox status of the body, alterations in red blood cells are widely used in first step-diagnoses of a number of pathological conditions. The information presented in this review provides an update on biomarkers of redox balance in red blood cells. These biomarkers may be used for assessment of oxidative stress during human health and disease.

Background: In 1928, the first antibiotic, penicillin, was discovered. That was the beginning of a great era in the development and prescription of antibiotics. However, the introduction of these antimicrobial agents into clinical practice was accompanied by the problem of antibiotic resistance. Currently, bacterial resistance to antibiotics poses a major problem in both hospital and community settings throughout the world. Methods and results: This review provides examples of modern genetic methods and their practical application in the field of extended-spectrum β-lactamase detection. Since extended-spectrum β-lactamases are the main mechanism of Gram-negative bacterial resistance to oxyimino-cephalosporins, rapid and accurate detection is requested in common clinical practice. Conclusions: Currently, the detection of extended-spectrum β-lactamases is primarily based on the determination of bacterial phenotypes rather than genotypes. This is because therapeutic decisions are based on assessing the susceptibility rather than presence of resistance genes. One of the main disadvantages of genetic methods is high costs, including those of laboratory equipment. On the other hand, if these modern methods are introduced into diagnostics, they often help in rapid and accurate detection of certain microorganisms or their resistance and pathogenic determinants.

Background: There is currently limited data on which drug should be used to improve blood pressure control in patients with resistant hypertension. Recent observational trials reported spironolactone as having good effects. This study is designed to assess the effect of the addition of 25 mg of spironolactone on blood pressure (BP) in patients with resistant arterial hypertension. Methods: Patients with office systolic BP > 140 mmHg or diastolic BP > 90 mmHg despite treatment with at least 3 antihypertensive drugs including a diuretic, are enrolled in this double-blind, placebo-controlled, multicentre trial. Patients are randomly assigned to receive spironolactone or a placebo at a ratio of 1:1 by the method of simple randomisation. Our primary endpoints are to show a statistically significant difference in the fall of mean day-time systolic and diastolic BP by ambulatory blood pressure monitoring (ABPM), between the spironolactone and placebo groups, after 8 weeks of treatment. Secondary outcomes are changes of serum potassium, natrium, creatinine, body weight, casual blood pressure in office, difference in the fall of mean night-time and 24-hour ABPM BP and treatment response depending on different baseline levels of aldosterone and aldosterone/PRA ratio. This study is registered with ClinicalTrials.gov, No. NCT00524615. Discussion. If spironolactone proves effective, it might become the standard of treatment in patients with resistant arterial hypertension.

Background: Obstructive sleep apnea (OSA) can activate pathological routes which can lead to insulin resistance, development of atherosclerosis and hypertension. The combination of hypertension and OSA has an additive effect on the development of atherosclerosis. As a number of studies have revealed, that the incidence of OSA in patients with myocardial infarction is likely to be high. Methods and results: We present a patient with acute myocardial infarction and no classical coronary artery disease risk factors: non-smoker, normal blood pressure, normal total and low-density lipoprotein cholesterol levels, borderline high-density lipoprotein cholesterol level, with good physical activity, no diabetes mellitus, no abdominal obesity, a negative family history. The only risk factor was untreated obstructive sleep apnea. The course of disease was complicated by subsequent in-stent restenosis and progression of atherosclerotic plaques, which led to the need for acute coronary artery bypass graft surgery complicated by consecutive in-anastomosis stenosis despite maximum cardiovascular therapy. One year of continuous positive airway pressure treatment was needed to stabilize his health condition, which is now stable for up to two years. Conclusions: Given the complicated course of ischemic heart disease in patients with OSA, we believe that OSA diagnosis would be advisable each time these patients with symptoms of myocardial infarction, ischemic heart disease and OSA are examined. Even more important, however, is proper treatment of the OSA when it is present.