The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats.

It has been reported previously that the density of angiotensin II receptors is increased in the rat liver in experimentally-induced fibrosis. We hypothesized that pharmacological blockade of angiotensin receptors may produce beneficial effects in models of liver fibrosis. In this study, we used the widely used thioacetamide (TAA)-induced model of liver fibrosis (300 mg/L TAA ad libitum for 12 weeks). Rats received daily injections (i.p), lasting 4 weeks of the angiotensin II type 1 receptor antagonists, losartan 30 mg/kg (TAA + L) or telmisartan 10 mg/kg (TAA + T) and were compared to rat that received TAA alone. Chronic treatment with losartan and telmisartan was associated with a significant reduction in the activity of alkaline phosphatase, and decreased concentrations of tumor necrosis factor-alpha and transforming growth factor beta-1 compared to controls. We also found a significant reduction interleukin-6 in rats receiving telmisartan (P < 0.05) but not losartan. Both treatments increased the concentration of liver glutathione along with a concomitant decrease of GSSG compared to controls. In addition, increased paraoxonase 1 activity was observed in the serum of rats receiving telmisartan group compared to the TAA alone controls. Finally, histological evaluation of liver sections revealed losartan and telmisartan treatment was associated with reduced inflammation and liver fibrosis. Taken together, these results indicate that both telmisartan and losartan have anti-inflammatory and anti-oxidative properties in the TAA model of liver fibrosis. These finding add support to a growing body of literature indicating a potentially important role for the angiotensin system in liver fibrosis and indicate angiotensin antagonists may be useful agents for fibrosis treatment.

Streptococcus suis in invasive human infections in Poland: clonality and determinants of virulence and antimicrobial resistance.

The purpose of this study was to perform an analysis of Streptococcus suis human invasive isolates, collected in Poland by the National Reference Centre for Bacterial Meningitis. Isolates obtained from 21 patients during 2000-2013 were investigated by phenotypic tests, multilocus sequence typing (MLST), analysis of the TR9 locus from the multilocus variable number tandem repeat (VNTR) analysis (MLVA) scheme and pulsed-field gel electrophoresis (PFGE) of SmaI-digested DNA. Determinants of virulence and antimicrobial resistance were detected by polymerase chain reaction (PCR) and analysed by sequencing. All isolates represented sequence type 1 (ST1) and were suggested to be serotype 2. PFGE and analysis of the TR9 locus allowed the discrimination of four and 17 types, respectively. Most of the isolates were haemolysis- and DNase-positive, and around half of them formed biofilm. Genes encoding suilysin, extracellular protein factor, fibronectin-binding protein, muramidase-released protein, surface antigen one, enolase, serum opacity factor and pili were ubiquitous in the studied group, while none of the isolates carried sequences characteristic for the 89K pathogenicity island. All isolates were susceptible to penicillin, cefotaxime, imipenem, moxifloxacin, chloramphenicol, rifampicin, gentamicin, linezolid, vancomycin and daptomycin. Five isolates (24 %) were concomitantly non-susceptible to erythromycin, clindamycin and tetracycline, and harboured the tet(O) and erm(B) genes; for one isolate, lsa(E) and lnu(B) were additionally detected. Streptococcus suis isolated in Poland from human invasive infections belongs to a globally distributed clonal complex of this pathogen, enriched in virulence markers. This is the first report of the lsa(E) and lnu(B) resistance genes in S. suis.

Protective effects of melatonin against thioacetamide-induced liver fibrosis in rats.

The aim of this study was to determine the effect of melatonin on thioacetamide (TAA) induced liver fibrosis in rats. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and proinflammatory cytokines: interleukin 6 (IL-6), interleukin-1beta (IL-1ß), tumour necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-ß) and platelet-derived growth factor (PDGF). Parameters of oxidative stress: oxidised glutathione (GSSG), reduced glutathione (GSH) and presaged activity of paraoxonase 1 (PON-1), an antioxidative enzyme were determined. Inflammatory changes and fibrosis extent were evaluated histologically. Experiments were carried out in Wistar rats. Animals were divided into 4 groups: I - controls, water ad libitum for 12 weeks, group II - TAA, 300 mg/L ad libitum for 12 weeks, III - melatonin, 10 mg/kg b.w. intraperitoneally (i.p.) daily for 4 weeks, IV - TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. i.p. daily for 4 weeks. Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin compared to the group receiving only TAA. Immunoenzymatic findings on effect of melatonin on concentration of proinflammatory cytokines confirmed these data. Biochemical examinations in liver homogenates revealed statistically significant improvement (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin. Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was increased in liver homogenates and serum in the group receiving TAA followed by melatonin compared to the TAA group without melatonin treatment. Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis.

Recent trends in epidemiology of invasive pneumococcal disease in Poland.

The objectives of this study were to assess the current incidence of invasive pneumococcal disease (IPD) in Poland (2011-2013), where mass vaccination has not been implemented, and to characterize the Streptococcus pneumoniae isolates responsible for invasive infections by determining their serotype distribution and antimicrobial resistance patterns. For all isolates identification, serotyping and antimicrobial minimal inhibitory concentrations determination were performed based on routine techniques. The highest incidence rates were observed among adults older than 85 years old (4.62/100,000) and children under 1 year of age (4.28/100,000). The general case fatality ratio (CFR) was 25.4%, with the highest CFR in the age group ≥85 years old (59.7%). The most common serotypes were 3, 14, 19A, 4, 9V, 19F, 1, and 23 F (61.3% of all isolates). The 10- and 13-valent pneumococcal conjugated vaccines (PCV) covered 46.0 and 71.8% of all IPD cases, 61.4 and 79.5% of cases in children under two years, and 60.4 and 78.6% of cases involving children under five years of age, respectively. The PCV13 and 23-valent polysaccharide vaccine covered 68.7 and 86.0% of cases in adults >65 years old, respectively. Decreased susceptibility was noted for penicillin (24.8%), cefotaxime (10.0%), meropenem (5.0%), rifampicin (0.8%), chloramphenicol (4.3%), erythromycin (29.7%) and clindamycin (25.6%). Multi-drug resistance characterized 21.6% of the pneumococci tested. Despite deficiencies in the Polish surveillance system and strong underestimation of IPD cases, results of the study showed good theoretical coverage of PCV, which should encourage inclusion of anti-pneumococcal conjugate vaccine into the national immunization program.

High abundance and diversity of antimicrobial resistance determinants among early vancomycin-resistant Enterococcus faecium in Poland.

The purpose of this study was to investigate the clonal structure, antimicrobial resistance phenotypes and their determinants among early vancomycin-resistant Enterococcus faecium (VREm) isolates in Poland. Two hundred and eighty-one VREm isolates collected between 1997 and 2005 were studied. VREm isolates were characterised by multilocus sequence typing (MLST). The presence of antimicrobial resistance determinants, transposon-specific genes, IS16 and esp Efm was checked by polymerase chain reaction (PCR). Ciprofloxacin and ampicillin resistance determinants were investigated by sequencing. Two hundred and twenty-two (79 %) and 59 (21 %) VREm isolates were vanA- and vanB-positive, respectively. Among 135 representative isolates, MLST yielded 33 different sequence types (STs), of which 29 were characteristic of hospital-associated E. faecium; 128 (94.8 %) and 123 (91.1 %) isolates harboured the IS16 and esp Efm genes, and all 135 isolates were resistant to ciprofloxacin and ampicillin. Resistance to tetracycline (71.1 % isolates) was mostly associated with tetM (75.0 %) and the concomitant presence of the Tn916 integrase gene. High-level resistance to streptomycin (93.3 % of isolates) and high-level resistance to gentamicin (94.1 % of isolates) were due to ant(6')-Ia and aac(6')-Ie-aph(2″) genes, respectively, the latter of which is known to be located on various Tn4001-type transposons. Fifteen combinations of mutations in the quinolone-determining regions of GyrA and ParC were identified, including changes not previously reported, such as S83F and A84P in GyrA. Twenty-three variants of the penicillin-binding protein PBP5 occurred in the studied group, and novel insertions at amino acid positions 433 and 568 were identified. This analysis revealed the predominance of hospital-associated strains of E. faecium, carrying an abundant and divergent range of resistance determinants among early VREm isolates in Poland.

Employment opportunities with international agencies, mission organisations and government hospitals.

This article describes work with aid agencies in different developing countries. In addition to providing anaesthesia, the aim should be to increase resources and sustainability of local practice, irrespective of the duration of the visit. This article describes the background to some of the international aid agencies and our experience working with the International Committee of the Red Cross, Médecins Sans Frontières, and Response International, as well as various other mission organisations.

Synthesis of 3-aryl-2-thiohydantoin- and 3-arylhydantoin-5-acetic acids and screening of some of their pharmacological properties.

Seven 3-aryl-2-thiohydantoin-5-acetic acids were obtained from asparagine and arylisothiocyanates. After desulphuration of these compounds by monochloroacetic acid seven 3-arylhydantoin-5-acetic acids were obtained. The structure of these compounds was confirmed by their IR spectra. None of the compounds neither showed the anticonvulsive activity in the electroconvulsions and pentylenetetrazole tests nor inhibited the prostaglandin synthetase.