Synthesis of terpenoid oxo derivatives with antiureolytic activity.

Urease is an important virulence factor for a variety of pathogenic bacteria strains such as Helicobacter pylori, which colonizes human gastric mucosa, and Proteus sp., responsible for urinary tract infections. Specific inhibition of urease activity could be a promising adjuvant strategy for eradication of these pathogens. Due to the interesting antiureolytic activity of carvone and the scant information regarding the inhibitory properties of corresponding monoterpenes, we decided to study selected monoterpenic ketones and their oxygen derivatives. Several monoterpenes and their terpenoid oxygen derivatives were evaluated in vitro against Sporosarcina pasteurii urease. The most effective inhibitors-derivatives of ß-cyclocitral (ester 10 and bromolactone 14)-were described with [Formula: see text] of 46.7 µM and 45.8 µM, respectively. Active inhibitors of native urease were tested against H. pylori and Proteus mirabilis whole cells. Here, the most active inhibitor, 14, was characterized with IC50 values of 0.32 mM and 0.61 mM for P. mirabilis and H. pylori, respectively. The antibacterial activity of a few tested inhibitors was also observed. Compound 14 limited the growth of E. coli ([Formula: see text]= 250 µg/mL). Interestingly, 10 was the only compound that was effective against both Gram-negative and Gram-positive bacteria. It had a [Formula: see text] of 150 µg/mL against E. coli and S. aureus. In the presented study a group of novel antiureolytic compounds was characterised. Besides carvone stereoisomers, these are the only terpenoid urease inhibitors described so far.

Frequency of infection with Helicobacter pylori isolates of different antimicrobial profiles in children and adolescents: A preliminary study.

BACKGROUND: Helicobacter pylori (H. pylori) infection can occur as a mixed infection caused by several strains of H. pylori. OBJECTIVES: The aim of the study was to determine the frequency of colonization of the gastric mucosa by strains of H. pylori with different susceptibility to antimicrobial agents. MATERIAL AND METHODS: The study was carried out on gastric biopsies taken from 54 previously untreated Polish children and adolescents. Of the 15 positive cultures, from each primary medium, 6 single H. pylori colonies were isolated, making a total of 90 isolates, and the susceptibility to metronidazole (MZ), amoxicillin (AC) and clarithromycin (CH) was determined by E-test method. The presence of the cagA gene and vacA alleles (s1, s2, m1, m2) was determined by PCR. RESULTS: Positive culture for H. pylori was noted in 15/54 (27.7%) of patients. All H. pylori isolates were susceptible to AC, 27.8% were resistant to MZ and 38.9% to CH. The results showed 7/15 (46.7%) of children were infected with H. pylori strains with antibiotic heteroresistance, resistant to CH (5/15, 33.3%) and to MZ (2/15, 13.3%). The cagA + vacA s1/m2 combination was predominant genotype among detected H. pylori strains. The isolates possessing different antimicrobial susceptibility profiles in the same patient were identified. CONCLUSIONS: Microbiological analyses confirmed the presence of isolates possessing different antimicrobial susceptibility profiles in 47% of examined children with H. pylori infection. Different antimicrobial susceptibility profiles of H. pylori isolates detected in the same patient may influence the success of eradication therapy.

The use of hyperbaric oxygen therapy in the treatment of hemorrhagic cystitis after allogeneic stem cell transplantation from an unrelated donor.

Hemorrhagic cystitis (HC) is a diffuse inflammation of the bladder of an infectious or non-infectious etiology, causing bleeding of the bladder mucosa. There are no explicit guidelines defining the appropriate treatment of HC. Hyperbaric oxygen therapy (HBO) is a non-invasive method involving the use of 100 % oxygen under increased pressure, which penetrates to poorly perfused areas. The most appropriate group for treatment with HBO is patients with BK virus-associated HC after allogenic human stem cell transplantation (alloHSCT). In this report, we present five patients after alloHSCT from a matched unrelated donor with symptoms of HC successfully treated with HBO. All patients received therapy with 100 % oxygen in a hyperbaric chamber at 2.5 atmospheres for 60 min, delivered 5 days per week. Complete response with resolution of pain and hematuria, as well as eradication of viral load, was achieved by all the patients after a mean of 13 sessions (range 11-30) of HBO. These data indicate that HBO therapy is sufficient and effective in the treatment of HC, and represents a well-tolerated procedure with good clinical and laboratory results after ineffective primary treatment.