A library of thirty two 3,4-diphenylfuranones related to both combretastatin A-4 and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was prepared. Cytotoxic effects on a panel of cancer and normal cell lines and antiinfective activity were evaluated, and the data were complemented with tests for the activation of caspase 3 and 7. High cytotoxicity was observed in some of the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one with IC50 0.12-0.23 μM, but the compounds were also highly toxic against non-malignant control cells. More importantly, notable antibacterial activity indicating G+ selectivity has been found in the 3,4-diarylfuranone class of compounds for the first time. Hydroxymethylation of furanone C5 knocked out cytotoxic effects (up to 40 μM) while maintaining significant activity against Staphylococcus strains in some derivatives. MIC95 of the most promising compound, 3-(4-bromophenyl)-5,5-bis(hydroxymethyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98 μM (0.38 μg/mL) and 3.9 μM (1.52 μg/mL) after 24 and 48 h, respectively.
- Klíčová slova
- Antibacterial, Combretafuranone, Combretastatin analogue, Cytotoxic, Furanone, Synthesis,
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- antifungální látky chemická syntéza chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- Bacteria účinky léků MeSH
- furany chemická syntéza chemie farmakologie MeSH
- houby účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- proliferace buněk účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- antifungální látky MeSH
- furany MeSH
A heart involvement known as Lyme carditis (LC), a consequence of Lyme borreliosis (LB), is relatively rare in contrast to the involvement of skin, joints and nervous system; it accounts for < 4% of all these patients in European countries. However, the diagnosis of the disease belongs to the most difficult challenges. While various forms of AV blocks dominate in the USA as confirmed by the literature, there is a clear predominance of arrhythmias of various incidence in the Czech Republic. The authors of this article focused on the form belonging to the rarest manifestations of LC, namely dilated cardiomyopathy (DCMP). The goal was to elucidate the etiological participation of Borrelia infection in the development of DCMP, which has attracted controversial opinions so far. In total, 33 patients with DCMP were enrolled in the study, 23 males and 10 females, with mean age 57.7 years (range 24-76 years). ELISA NRLB KC 90 method was used in all blood samples for detection of Borrelia infection (BI), Western blot method was used for confirmation, followed by identification of DNA of pathogenic Borreliae using PCR method. Bioptic material was examined by electronmicroscopy with an attempt to detect Spirochaetae in myocardium. 16 patients were excluded from the study owing to the absence of signs of LB. The study group included 17 patients (3 females, 13 males) with mean age 58 years (range 43-76 years), in whom the presence of Bb was proved by identification of DNA of pathogenic Borreliae or by electronmicroscopic detection of Spirochetae in myocardial bioptic sample. The findings obtained during the study confirmed that BI very probably participated in the development of dilated cardiomyopathy. It may be concluded that most of cases were either unapparent forms of LB or insufficiently treated cutaneous forms of this disease.
- MeSH
- Borrelia izolace a purifikace MeSH
- dilatační kardiomyopatie mikrobiologie MeSH
- DNA bakterií krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc komplikace MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA bakterií MeSH
BACKGROUND: Geographic differences of particular species of ticks and variant strains of Borrelias impede the comparison of local and foreign experience. The authors tried to support some literary observations with their own results and designed a study aimed at determination of anti-Borrelia antibodies (AB) in the selected population samples. The goal of the study was to find and statistically evaluate: a) difference in distribution of values of AB in the sample of probands from the risk and non-risk environment (foresters in Sumava and Prague blood donors, respectively) by means of ELISA method, b) tick bite frequency in the risk and non-risk groups, c) to determine and statistically evaluate the prevalence of probands with increased levels of antiborrelial antibodies in the local study population by ELISA method and the prevalence of probands with non-normal values found by Western blot (WB) method. METHODS AND RESULTS: In the group of Prague blood donors (control group), in total 200 probands were examined; in the risk group, 71 probands from Sumava forest were examined. Blood specimens were examined in the National Reference Laboratory for Lyme Borreliosis in Prague. In all specimens, ELISA NRLB KC90 was used. Western blot assay was used for confirmation. CONCLUSIONS: On the basis of literature review from Europe and USA, it is possible to generalize the following, despite some equivocations: 1. regional differences are not significant, with the exception of high-risk territories or "occupational exposure"; 2. there is no significant difference between males and females; 3. considerable caution is necessary in comparing the control and risk groups; prerequisite for such comparison is defining the characteristics of both groups.
- MeSH
- Borrelia burgdorferi komplex imunologie MeSH
- dárci krve * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- protilátky bakteriální krev MeSH
- rizikové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- protilátky bakteriální MeSH
The relatively low percent of patients affected with the cardiac form of Lyme borreliosis is difficult to diagnose, especially if the disease manifests itself in ways other than atrio-ventricular blockade. The advanced stage of Lyme carditis manifesting as dilated cardiomyopathy is a special case of this affliction. The authors of this report present clinical experience with an attempt to support the working hypothesis about involvement of Lyme borreliosis infection in the development of dilated cardiomyopathy. The patients were clinically examined thoroughly with special attention to the cardiovascular system. In addition to the basic clinical methods, the following procedures have been employed: dynamic Holter's electrocardiography, exercise ECG test, coronarography, and myocardial biopsy. From laboratory methods pertaining to the detection of Borrelia, ELISA method, Western blot, PCR, electron microscopy and histopathological analysis were used. In all three cases, clinical and laboratory findings provided the evidence of the borreliosis infection involvement in the development of dilated cardiomyopathy.
- MeSH
- dilatační kardiomyopatie diagnóza etiologie patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc komplikace diagnóza patologie MeSH
- myokard patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- MeSH
- dějiny 20. století MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemocnice univerzitní dějiny MeSH
- senioři MeSH
- vnitřní lékařství dějiny MeSH
- Check Tag
- dějiny 20. století MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Česká republika MeSH
A significant part of patients with carotid artery stenosis is operated on without preoperative angiography, to reduce the risks and cost of such examination. Duplex ultrasound often cannot reliable visualise the proximal parts of the aortic arch vessels. We evaluated the ability of duplex ultrasound to identify those types of lesions and ascertain their prevalence. We analysed retrospectively carotid duplex scans and carotid angiography in 448 carotid arteries. 17 significant proximal lesions (3.89%) were identified on the duplex scan and confirmed by angiography. Lesions of the proximal parts of the aortic arch vessels are rare and may be reliably detected by duplex ultrasound.
- MeSH
- arteria carotis communis diagnostické zobrazování MeSH
- dospělí MeSH
- duplexní dopplerovská ultrasonografie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- rentgendiagnostika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stenóza arteria carotis diagnostické zobrazování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
A long-term prospective study of patients with confirmed non-cardiac form of Lyme disease (n=221) over a mean follow-up period of 40.6 months is reported. The study revealed no case of Borrelia-related cardiac involvement developed after several years in patients who had received antibiotic therapy in the early period. Therefore, these patients do not need follow-up by a cardiologist.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc komplikace farmakoterapie MeSH
- mladiství MeSH
- myokarditida diagnóza mikrobiologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The article summarizes basic characteristics of Lyme borreliosis, its incidence, epidemiology, pathogenesis and clinical image. Particular attention is given to the review of papers aimed at the cardiac abnormalities--the Lyme carditis. Though they are not very frequent, due to the variability of their clinical course and due to various forms, which are difficult to diagnose, they can represent a specific problem. Major part of the article is given to the authors' own experience with the dilated cardiomyopathy of the Borrelia origin and namely to the perspective study of the patients after the skin form of the disease erythema migrans, who were treated "lege artis" in the early phase of the disease with antibiotics. Authors were interested how many of those patients would develop later the cardiac abnormalities.
- MeSH
- dilatační kardiomyopatie diagnóza mikrobiologie MeSH
- lidé MeSH
- lymeská nemoc komplikace diagnóza MeSH
- myokarditida diagnóza mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
Multipotential neural crest cells (NCCs) originate by an epithelial-mesenchymal transition (EMT) during vertebrate embryogenesis. We show for the first time that the key hematopoietic factor c-Myb is synthesized in early chick embryos including the neural tissue and participates in the regulation of the trunk NCCs. A reduction of endogenous c-Myb protein both in tissue explants in vitro and in embryos in ovo, prevented the formation of migratory NCCs. A moderate over-expression of c-myb in naive intermediate neural plates triggered the EMT and NCC migration probably through cooperation with BMP4 signaling because (i) BMP4 activated c-myb expression, (ii) elevated c-Myb caused accumulation of transcripts of the BMP4 target genes msx1 and slug, and (iii) the reduction of c-Myb prevented the BMP4-induced formation of NCCs. The data show that in chicken embryos, the c-myb gene is expressed prior to the onset of hematopoiesis and participates in the formation and migration of the trunk neural crest.
- MeSH
- antisense oligonukleotidy MeSH
- crista neuralis cytologie imunologie fyziologie MeSH
- elektroporace MeSH
- epitel fyziologie MeSH
- kostní morfogenetické proteiny fyziologie MeSH
- kostní morfogenetický protein 4 MeSH
- kuřecí embryo MeSH
- messenger RNA metabolismus MeSH
- mezoderm fyziologie MeSH
- protoonkogenní proteiny c-myb antagonisté a inhibitory genetika imunologie fyziologie MeSH
- rodina transkripčních faktorů Snail MeSH
- specificita protilátek MeSH
- transkripční faktor MSX1 biosyntéza genetika MeSH
- transkripční faktory biosyntéza genetika MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antisense oligonukleotidy MeSH
- kostní morfogenetické proteiny MeSH
- kostní morfogenetický protein 4 MeSH
- messenger RNA MeSH
- protoonkogenní proteiny c-myb MeSH
- rodina transkripčních faktorů Snail MeSH
- transkripční faktor MSX1 MeSH
- transkripční faktory MeSH
OBJECTIVE: The objective of the work was to test whether differently formulated hypotheses, when using correct statistical methods, and the same data lead to the same results. The work pertains to the interpretation of the prevalence of antiborrelia antibody levels in more or less high risk populations. GROUP: A group of 200 blood donors from Prague (100 men, mean age 33.5 years and 100 women mean age 24.4 years) and 71 subjects with a higher risk of contact with ticks infected with Borrelia burgdorferi--forestry workers from the Sumava mountains (39 men, mean age 40.6 years and 32 women, mean age 44.5 years). METHOD: In all participants antiborrelia antibodies class IgM and IgG were assessed and using the Western blot method the presence of specific antigens was examined. The blood samples of all probands were analyzed in the national reference laboratory for Lyme borreliosis CEM in the National Institute of Public Health in Prague. To test the hypothesis on the difference of groups as regards the frequency of positive antibody levels the chi square test was used. For testing the hypothesis on the difference of the groups as regards antibodies irrespective of normal laboratory values the non-parametric method--the Mann-Whitney test was used. RESULTS: The group of Prague blood donors and forestry workers from the Sumava mountains do not differ as to the individual frequency of positive antibody values assessed by the ELISA method in class IgM and IgG but they differ in class IgM assessed by the Western blot method. Both groups differ moreover markedly in the general distribution of antibodies unrelated to normal laboratory values assessed by the ELISA method in class IgM, in class IgG the distribution does not differ. CONCLUSION: We provided evidence that when using a different formulation of the hypothesis while using correct statistical methods identical data can be differently interpreted. Thus in the interpretation of the prevalence of antiborrelia antibody levels in healthy populations with a different risk--even if the two groups do not differs as to the frequency of positive findings, there is a significant statistical difference in their distribution.
- MeSH
- Borrelia burgdorferi imunologie MeSH
- dárci krve MeSH
- dospělí MeSH
- lidé MeSH
- lymeská nemoc epidemiologie MeSH
- nemoci z povolání epidemiologie MeSH
- protilátky bakteriální krev MeSH
- séroepidemiologické studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- protilátky bakteriální MeSH