Ondřej Topolčan

Cytokines as plasma markers of abdominal aortic aneurysm.

Abstract The pathogenesis of abdominal aortic aneurysms (AAA) is a complex process in which atherosclerosis and inflammation play a leading role. Cytokines are important mediators of both processes. The aim of our study was to determine whether plasma levels of cytokines which are most involved in AAA pathogenesis can be used as endogenous markers of AAA development, and thus to facilitate the decision on surgical intervention in cases when this is clinically unclear (e.g. small AAA). In the prospective study a total of 90 patients with AAA were examined. These patients were divided into the following groups according to symptoms and AAA diameter: symptomatic AAAs, including ruptures (n=16); asymptomatic AAAs (n=74); AAAs with a diameter of up to 5 cm (n=30), AAAs of 5–8 cm (n=38), and AAAs with a diameter over 8 cm (n=22). The average age of the patients was 70.7 (56–82) years. The male to female ratio was 4:1 (71:19). A control group consisted of 30 healthy individuals of similar age and sex presentation with no manifestation of atherosclerosis. Plasma levels of cytokines were assessed in venous blood by means of radio- or enzymo-immunoassay. Statistical processing of the results was conducted with ANOVA and Wilcoxon tests with Spearman correlation, where p<0.05 was considered to be statistically significant. Plasma concentrations of cytokines were significantly higher in AAA patients than in healthy individuals. In AAA patients the tumour necrosis factor-α (TNF-α) and interleukin (IL-8) levels were low in large and in symptomatic AAAs. IL-6 levels were increased with increasing AAA diameter and symptoms. IL-8 levels (p<0.05) showed a statistically significant correlation with the diameter, and TNF-α (p<0.05) with the symptoms of AAA. IL-1β, IL-2 and IL-6 did not show any significant changes with different AAA diameter or symptomatology. In Conclusion: IL-8 and TNF-α can be used as endogenous markers of the process of AAA development, in deciding for either surgical or endovascular treatment of patients when the clinical indication is not entirely clear.

Gastric lipoma presenting as upper gastrointestinal obstruction

Abstract: A 61-year-old man presented with an upper gastrointestinal obstruction caused by a submucosal gastric lipoma in the prepyloric area. The diagnosis was made coincidentally during his admission for another disease. Gastric resection was performed because of a large lipoma combined with florid gastric ulcers. The frequency of gastric lipoma, its differential diagnosis, means of diagnosis, and treatment are discussed.

Isocitrate Dehydrogenase-1 Mutations as Prognostic Biomarker in Glioblastoma Multiforme Patients in West Bohemia

Introduction. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. Recent whole-genome studies revealed novel GBM prognostic biomarkers such as mutations in metabolic enzyme IDH—isocitrate dehydrogenases (IDH1 and IDH2). The distinctive mutation IDH1 R132H was uncovered to be a strong prognostic biomarker for glioma patients. We investigated the prognostic role of IDH1 R132H mutation in GBM patients in West Bohemia. Methods. The IDH1 R132H mutation was assessed by the RT-PCR in the tumor samples from 45 GBM patients treated in the Faculty Hospital in Pilsen and was correlated with the progression free and overall survival. Results. The IDH1 R132H mutation was identified in 20 from 44 GBM tumor samples (45.4%). The majority of mutated tumors were secondary GBMs (16 in 18, 89.9%). Low frequency of IDH1 mutations was observed in primary GBMs (4 in 26, 15.3%). Patients with IDH R132H mutation had longer PFS, 136 versus 51 days (P < 0.021, Wilcoxon), and OS, 270 versus 130 days (P < 0.024, Wilcoxon test). Summary. The prognostic value of IDH1 R132H mutation in GBM patients was verified. Patients with mutation had significantly longer PFS and OS than patients with wild-type IDH1 and suffered more likely from secondary GBMs.

Changes of cytokine levels during granulocyte-colony-stimulating factor stem cell mobilization in healthy donors: association with mobilization efficiency and potential predictive significance.

BACKGROUND: Peripheral blood stem cells are an important source of hematopoietic stem cells (HSCs) for allogeneic transplantations. Some allogeneic donors mobilize HSCs poorly in response to the granulocyte—colony‐stimulating factor (G‐CSF). The estimation of the mobilization result in an individual donor is difficult due to the absence of suitable predictive factors.

Asymptomatic Abdominal Aortic Aneurysms Show Histological Signs of Progression: A Quantitative Histochemical Analysis

Objective: Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology. Methods: In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5–7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples. Results: Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular. Conclusion: Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

Overview of healthcare system in the Czech Republic

The healthcare system in the Czech Republic underwent and still is undergoing dramatic changes since the Velvet revolution in 1989. History of the Czech healthcare system, main healthcare laws, and the current status of healthcare documented in the main healthcare indicators is described based on the several main sources as well as delivery of health services and the role of the main actors in healthcare system. The material is based mainly on Czech Health Statistics 2009, and HiT Summary, Health Care Systems in Translation, 2005, public information of Ministry of Health CR.

Effects of selenium and tellurium on the activity of selenoenzymes glutathione peroxidase and type I iodothyronine deiodinase, trace element thyroid level, and thyroid hormone status in rats.

Tellurium (Te) and selenium (Se) belong chemically to the VIa group of elements. Se represents an essential element closely related to thyroid function. Te has growing application in industrial processes. Little is known about the Te biological activity, particularly with respect to potential chemical interactions with Se-containing components in the organism. In this study, female Wistar rats (body weight: 115-120 g) received sodium selenite pentahydrate (10 mg/L) or sodium tellurite (9.4 mg/L) in drinking water for 6 wk. Additional groups of rats received their combination with zinc sulfate heptahydrate (515 mg/L). The stimulation of 5’-DI-I activity due to selenite (to 158%, p<0.01) or tellurite treatment (to 197%, p<0.01) was seen; however, no effect on glutathione peroxidase was demonstrated in this experiment. An elevation of T4, T3, and rT3 serum levels was measured in the Se+Te-treated group; T4 and rT3 levels were elevated in the Te+Zn-treated group. Te accumulates in the thyroid gland and influences the zinc thyroid level. Te treatment alone and in combination with Se or Zn decreased the iodine thyroid concentration to 65-70% of the control value. Further studies are needed to clarify the nature and effects of these events.

Serum Vitamin D Status, Vitamin D Receptor Polymorphism, and Glucose Homeostasis in Healthy Subjects

Low vitamin D status has been frequently associated with impaired glucose metabolism. We examined associations between 25-hydroxyvitamin D (25-OH-D) and several parameters of glucose homeostasis in virtually healthy subjects, and explored possible interaction with vitamin D receptor (VDR) polymorphism. Nondiabetic subjects without chronic medication or any known significant manifest disease were selected from large general-population based population survey. Insulin sensitivity and β cell secretion were calculated by homeostasis model assessment (HOMA) and soluble isoform of receptor for advanced glycation end-products (sRAGE) using commercial ELISA. Subjects were also genotyped for rs2228570 polymorphism of VDR. After adjustment for potential confounders, we observed a significant relationship between 25-OH-D and fasting glycemia (β coefficient=-5.904; p=0.002) or insulin sensitivity (β=0.042; p=0.001), but not with β cell secretion or sRAGE. We found also an interaction with VDR polymorphism. Subjects with low 25-OH-D and AA genotype had significantly lower insulin sensitivity than those with GG genotype plus highest 25-OH-D concentrations (107.3% vs. 183.9%, p=0.021). In conclusion, low vitamin D status was in virtually healthy subjects associated with decreased insulin sensitivity, namely in those with GG genotype of rs2228570 VDR polymorphism.

Synergistic effect of low K and D vitamin status on arterial stiffness in a general population

Both vitamins K and D are nutrients with pleiotropic functions in human tissues. The metabolic role of these vitamins overlaps considerably in calcium homeostasis. We analyzed their potential synergetic effect on arterial stiffness. In a cross-sectional study, we analyzed aortic pulse wave velocity (aPWV) in 1023 subjects from the Czech post-MONICA study. Desphospho-uncarboxylated matrix γ-carboxyglutamate protein (dp-ucMGP), a biomarker of vitamin K status, was measured by sandwich ELISA and 25-hydroxyvitamin D3 (25-OH-D3) by a commercial immunochemical assay. In a subsample of 431 subjects without chronic disease or pharmacotherapy, we detected rs2228570 polymorphism for the vitamin D receptor. After adjustment for confounders, aPWV was independently associated with both factors: dp-ucMGP [β-coefficient(S.E.M.)=13.91(4.87); P=.004] and 25-OH-D3 [0.624(0.28); P=.027]. In a further analysis, we divided subjects according to dp-ucMGP and 25-OH-D3 quartiles, resulting in 16 subgroups. The highest aPWV had subjects in the top quartile of dp-ucMGP plus bottom quartile of 25-OH-D3 (i.e., in those with insufficient status of both vitamin K and vitamin D), while the lowest aPVW had subjects in the bottom quartile of dp-ucMGP plus top quartile of 25-OH-D3 [9.8 (SD2.6) versus 6.6 (SD1.6) m/s; P<.0001]. When we compared these extreme groups of vitamin K and D status, the adjusted odds ratio for aPWV≥9.3 m/s was 6.83 (95% CI:1.95-20.9). The aPWV was also significantly higher among subjects bearing the GG genotype of rs2228570, but only in those with a concomitantly poor vitamin K status. In conclusion, we confirmed substantial interaction of insufficient K and D vitamin status in terms of increased aortic stiffness.

18F-Fluorocholine PET/MRI in Restaging of Prostatic Carcinoma in Relation to PSA Level and Detection of Active Disease

Aim: To evaluate our own experience with 18F- fluoromethylcholine-(FCH)-positron-emission tomography combined with magnetic resonance imaging (PET/MRI) in restaging of patients with prostatic carcinoma and elevated serum prostate-specific antigen (PSA) level. Patients and Methods: The analysis was performed on a sample of 100 male patients who underwent 18F-FCH-PET/MRI, with a mean age of 63.2 years (range=47-78 years). The imaging was performed using an integrated PET/MRI hybrid system after intravenous application of 18F-FCH at a dose of 1.25 MBq/kg. The number and sites of pathological accumulation of FCH related to local recurrence, nodal spread and skeletal metastases were compared to corresponding MRI findings; furthermore, the relation of PSA level and presence of FCH accumulation in tumorous tissue was assessed; finally we correlated the findings of different sites of metastatic involvement. Results: In patients with a PSA level up to 2 ng/ml, accumulation in tumorous tissue of local recurrence or metastases was found in 83.33% in cases of biochemical relapse, and in patients with PSA level above 5 ng/ml in 100% of cases. In general, we found any finding explained rise of PSA level in 94% of patients. Conclusion: 18F-FCH-PET/MRI using an integrated system with 1,25 MBq/kg dosing of FCH is a valuable tool in evaluation of restaging in patients with prostatic carcinoma, with high detection rate even in those with a low serum PSA level.