Regional Institute of Public Health

Brno, Czech Republic

Regional Institute of Public Health

Brno, Czech Republic
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Klimesova V.,Charles University | Koi J.,Charles University | Palat K.,Charles University | Stolarikova J.,Regional Institute of Public Health | And 2 more authors.
Medicinal Chemistry | Year: 2012

A set of 2-benzylsulfanyl derivatives of benzothiazole was synthesized and evaluated for antimicrobial and cytotoxic activities. The biological screening on antimicrobial activity against a panel of Gram-positive and Gramnegative bacteria, yeasts and fungi identified benzylsulfanyl derivatives of benzothiazole as selective inhibitors of mycobacteria. The lead compounds in the set, dinitro derivatives exhibited significant activity against sensitive and multidrug-resistant strains of M. tuberculosis and low cytotoxicity. The QSAR study indicated that the antituberculotic activity is connected with LUMO and HOMO energies. The lower lipophilicity and the increased size of the molecule contribute to antituberculotic activity. Thus, dinitrobenzylsulfanyl derivatives of benzothiazole represent promising smallmolecule synthetic antimycobacterials. Dedicated to Professor Dr. Karel Waisser on the occasion of his 75th birthday. © 2012 Bentham Science Publishers.

PubMed | Regional Institute of Public Health, University of Hradec Kralove, University of Oslo, Gennet and 2 more.
Type: | Journal: Scientific reports | Year: 2017

Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning bins yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in nave CD4+ T-cells (decreased), intermediate CD27-CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, nave CD4+ and CD27-CD28+ over three years. Moreover, th-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background.

Kaevska M.,Veterinary Research Institute | Sterba J.,Faculty Hospital Brno | Svobodova J.,Regional Institute of Public Health | Pavlik I.,Veterinary Research Institute
Epidemiology and Infection | Year: 2014

Non-tuberculous mycobacteria are increasingly described as infectious agents in immunocompromised patients. A 17-year-old male patient suffering from secondary non-Hodgkin's lymphoma and treated with chemotherapeutic agents was admitted to hospital due to pleuropneumonia. Mycobacterium neoaurum was cultured repeatedly from his sputum and, Mycobacterium avium subsp. avium (M. a. avium) was detected by IS901 qPCR from detached fragments of his intestinal mucosa. We attempted to determine the possible sources of infection by analysing environmental samples from the closed oncology unit and conventional unit in the hospital, and from the patient's home residence and places which he frequented. The environment of the patient harboured mycobacteria (41 isolates in total); however, M. neoaurum was not recovered. M. a. avium was detected by qPCR in the environmental samples from a small flock of hens kept by his neighbour. Although it was not confirmed by DNA fingerprinting methods, the M. a. avium infection could have been acquired through the eating of incompletely cooked eggs. © 2013 Cambridge University Press.

PubMed | R.Ø.S.A., St Annes University Hospital, University of Hradec Kralove and Regional Institute of Public Health
Type: Journal Article | Journal: Journal of clinical immunology | Year: 2015

The aim of our retrospective study was to clarify fertility, pregnancy complications and outcomes in common variable immunodeficiency (CVID) females.Retrospective data were obtained from three Czech referral centres. The data were compared with data obtained from the Czech National Registry of Reproduction Health.Our cohort of patients comprised 54 women with 115 pregnancies; 88 pregnancies in 50 females were finished with live births (77 %). In only 8 women (15%) was the diagnosis of CVID established before the first pregnancy. Replacement immunoglobulin therapy was performed in 10 patients without any moderate or severe adverse effects. Compared with the Czech population, the CVID patients suffered significantly more frequently from the threat of preterm labour (p<0.0001), vaginal bleeding (p=0.0001), eclampsia/preeclampsia (p=0.009) and a higher number of stillbirths (p<0.0001). Furthermore, the frequency of babies with low birth weight (less than 2500 g) born to the CVID patients was increased compared with the normal population (p<0.0001). Serum IgG, IgA and IgM determination was done in 57 children of 50 mothers showing 13 cases of IgA deficiency (23%). There was no significant difference among the non-symptomatic, symptomatic untreated and symptomatic treated females in any of the determined gynaecological complications. The number of unsuccessful pregnancies was higher in the symptomatic untreated women.Fertility in CVID patients is not decreased, and their pregnancies could be considered more risky compared with those of the general population.

Hubka V.,Charles University | Mencl K.,Pardubice Regional Hospital Inc. | Skorepova M.,Charles University | Lyskova P.,Regional Institute of Public Health | Zalabska E.,Pardubice Regional Hospital Inc.
Medical Mycology | Year: 2011

Chaetomium species have been rarely described as aetiological agents of invasive and dermatomycotic infections in humans. The majority of cases have been reported within the last two decades. Treatment failed in most of these cases. In this paper we present two cases in which Chaetomium spp. can be clearly identified as an aetiological agent in pathological conditions. In the first report, we describe a new aetiological agent, Chaetomium brasiliense, which was implicated in a case of otitis externa in a patient with spinocellular carcinoma basis cranii. The patient had been repeatedly treated for relapsing otitis externa and had previously undergone surgery several times for otitis media. The fungal aetiology was confirmed by repeated positive culture and histologic studies. The second case involved onychomycosis with strikingly brown nail discoloration due to Chaetomium globosum in an otherwise healthy patient. The nail lesion was successfully cured by oral terbinafine. The determination of both species was supported by sequencing of rDNA regions. The morphological aspect of Chaetomium spp. identification is also discussed. In vitro antifungal susceptibility tests demonstrated that both isolates were susceptible to terbinafine and azole derivates except fluconazole. Amphotericin B was effective only against the C. brasiliense strain. We review the literature to summarize clinical presentations, histologic findings, and treatment strategies. © 2011 ISHAM.

Petrlikova E.,Charles University | Waisser K.,Charles University | Divisova H.,Charles University | Husakova P.,Charles University | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2010

New 3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium and two strains of Mycobacterium kansasii. The antimycobacterial activity increased with the replacement of the carbonyl group by the thiocarbonyl group in the starting 3-(4-alkylphenyl)-2H-1, 3-benzoxazine-2,4(3H)-diones. The most active derivatives were more active than isonicotinhydrazide (INH). Free-Wilson analysis was also carried out and the activity contribution was examined. © 2010 Elsevier Ltd. All rights reserved.

Novotna E.,Charles University | Waisser K.,Charles University | Kunes J.,Charles University | Palat K.,Charles University | And 4 more authors.
Archiv der Pharmazie | Year: 2014

New quaternary ammonium salt-type compounds with lipophilic cholesterol and terpene moieties were synthesized. The compounds showed promising antibacterial and antimycobacterial activities. Those compounds containing the cholesterol moiety showed significant activity against Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium. On the contrary, the antimycobacterial activity increased with the presence of the terpene unit in the molecule. New quaternary ammonium salt-type compounds with lipophilic cholesterol and terpene moieties were synthesized, yielding new potential disinfectants with broad-spectrum activity. Compounds containing the cholesterol moiety showed significant activity against Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas compounds with the terpene unit displayed increased antimycobacterial activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PubMed | Regional Institute of Public Health, Military Health Institute and Charles University
Type: | Journal: European journal of medicinal chemistry | Year: 2016

Two new classes of antitubercular agents, namely 5-alkylsulfanyl-1-(3,5-dinitrophenyl)-1H-tetrazoles and 2-alkylsulfanyl-5-(3,5-dinitrophenyl)-1,3,4-oxadiazoles, and their structure-activity relationships are described. These compounds possessed excellent activity against Mycobacterium tuberculosis, including the clinically isolated multidrug (MDR) and extensively drug-resistant (XDR) strains, with no cross resistance with first or second-line anti-TB drugs. The minimum inhibitory concentration (MIC) values of the most promising compounds reached 0.03M. Furthermore, these compounds had a highly selective antimycobacterial effect because they were completely inactive against 4 gram positive and 4 gram negative bacteria and eight fungal strains and had low invitro toxicity for four mammalian cell lines, including hepatic cell lines HepG2 and HuH7. Although the structure-activity relationship study showed that the presence of two nitro groups is highly beneficial for antimycobacterial activity, the analogues with a trifluoromethyl group instead of one of the nitro groups maintained a high antimycobacterial activity, which indicates the possibility for further structural optimization of this class of antitubercular agents.

Sak B.,Academy of Sciences of the Czech Republic | Brady D.,University of Glasgow | Pelikanova M.,University of South Bohemia | Kvetonova D.,Academy of Sciences of the Czech Republic | And 7 more authors.
Journal of Clinical Microbiology | Year: 2011

In the present population-based study, we determined the prevalences of the most common human-pathogenic microsporidia, Encephalitozoon spp. and Enterocytozoon bieneusi, in asymptomatic healthy people living in the Czech Republic. A total of 382 males and females (ages, 1 to 84 years) living in the Czech Republic, of whom 265 were Czech nationals and 117 were foreign students, were included in a study testing for the presence of microsporidia by use of coprology and molecular methods. Single-species infections with Enterocytozoon bieneusi or an Encephalitozoon sp. were detected for 9 and 136 individuals, respectively. Moreover, coinfections were detected for 14 individuals. Four genotypes of 3 human-pathogenic Encephalitozoon spp. and 7 E. bieneusi genotypes, including 3 novel genotypes, were detected. Some of these were reported in humans for the first time. The highest prevalence was recorded for individuals older than 50 years and for loose, unformed stool samples. These findings clearly show that exposure to microsporidia is common among immunocompetent people and that microsporidiosis is not linked to any clinical manifestation in healthy populations. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

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