Priprava i in vitro karakterizacija plutajućih zrnaca acetohidroksamske kiseline za iskorjenjivanje H. pylori

Gellan based floating beads of acetohydroxamic acid (AHA) were prepared by the ionotropic gellation method to achieve controlled and sustained drug release for treatment of Helicobacter pylori infection. The prepared beads were evaluated for diameter, surface morphology and encapsulation efficiency. Formulation parameters like concentrations of gellan, chitosan, calcium carbonate and the drug influenced the in vitro drug release characteristics of beads. Drug and polymer interaction studies were carried out using differential scanning calorimetry. Chitosan coating increased encapsulation efficiency of the beads and reduced the initial burst release of the drug from the beads. Kinetic treatment of the drug release data revealed a matrix diffusion mechanism. Prepared floating beads showed good antimicrobial activity (in vitro H. pylori culture) as potent urease inhibitors. In conclusion, an oral dosage form of floating gellan beads containing AHA may form a useful stomach site specific drug delivery system for the treatment of H. pylori infection.Metodom ionotropskog želiranja pripravljena su plutajuća zrnca acetohidroksamske kiseline (AHA) na bazi gelana za kontrolirano i usporeno oslobađanje ljekovite tvari, namijenjena za liječenje infekcija uzrokovanih Helicobacter pylori. Pripravljenim zrncima proučavani su dijametar, površinska morfologija i sposobnost inkapsuliranja. Koncentracija gelana, kitozana, kalcijeva karbonata i ljekovite tvari utjecala je na oslobađanje in vitro. Interakcija između ljekovite tvari i polimera praćena je diferencijalnom pretražnom kalorimetrijom. Oblaganje zrnaca kitozanom povećalo je učinkovitost inkapsuliranja i smanjilo početno naglo oslobađanje. Oslobađanje ljekovite tvari slijedilo je mehanizam difuzije matriksa. Plutajuća zrnca s AHA pokazala su antimikrobno djelovanje in vitro na kulturi H. pylori kao snažni inhibitori ureaze. Može se zaključiti da su plutajuća zrnca s AHA na bazi gelana pogodna za specifičnu isporuku u želucu te korisna u terapiji infekcija uzrokovanih H. pylori

13[C]-Urea Breath Test as a Novel Point-of-Care Biomarker for Tuberculosis Treatment and Diagnosis

BACKGROUND: Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeled substrates and detection of labeled products in exhaled breath using portable infrared spectrometers. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether mycobacterial urease activity could be utilized in such a breath test format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent bronchoscopic infection with either Mycobacterium bovis or Mycobacterium tuberculosis. Rabbits were treated with 25 mg/kg of isoniazid (INH) approximately 2 months after infection when significant cavitary lung pathology was present. [(13)C] urea was instilled directly into the lungs of intubated rabbits at selected time points, exhaled air samples analyzed, and the kinetics of delta(13)CO(2) formation were determined. Samples obtained prior to inoculation served as control samples for background (13)CO(2) conversion in the rabbit model. (13)CO(2), from metabolic conversion of [(13)C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15 minutes of administration. Analyses showed a rapid increase in the rate of (13)CO(2) formation both early in disease and prior to treatment with INH. Following INH treatment, all evaluable rabbits showed a decrease in the rate of (13)CO(2) formation. CONCLUSIONS/SIGNIFICANCE: Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of unlabeled urea, which would prevent the delta(13)CO(2) signal from urease-positive gastrointestinal organisms

Eradicating Helicobacter pylori reduces hypergastrinaemia during long term omeprazole treatment

Background—Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man. 
Aims—To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment. 
Methods—Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment. 
Results—In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing a median increase of 68% (p<0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95). 
Conclusion—Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long term proton pump inhibitor treatment. 

 Keywords: hypergastrinaemia; Helicobacter pylori; omeprazol