Volatile biomarkers of Pseudomonas aeruginosa in cystic fibrosis and noncystic fibrosis bronchiectasis.

AIMS: The purpose of this study was to determine whether volatile organic compounds specific to Pseudomonas aeruginosa could be detected in clinical sputum specimens. METHODS AND RESULTS: Patients were recruited from specialist bronchiectasis and cystic fibrosis clinics. The gold standard for diagnosing Ps. aeruginosa infection was a positive sputum culture. About 72 sputum headspace samples taken from patients at risk of or known to have prior Ps. aeruginosa infection were analysed by solid phase micro-extraction mass spectrometry. 2-nonanone was a marker in Ps. aeruginosa in sputum headspace gas with sensitivity of 72% and specificity of 88%. A combination of volatile compounds, a sputum library of 17 compounds with 2-nonanone, increased sensitivity in the detection of Ps. aeruginosa to 91% with specificity of 88%. CONCLUSIONS: In contrast to the 48-hour turnaround for classical microbiological culture, these results were available within 1-2 h. These data demonstrate the potential for rapid and accurate diagnosis of Ps. aeruginosa infection from sputum samples. SIGNIFICANCE AND IMPACT OF THE STUDY: 2-Nonanone is a compound requiring further study in the exhaled breath as it may improve diagnostic of Ps. aeruginosa infection when combined with other reported volatile markers.

Isoenzyme profile of lactate dehydrogenase in the cranial cervical sympathetic ganglion under normal conditions and during synaptic blockade.

The isoenzyme profile of lactate dehydrogenase in the cranial cervical sympathetic ganglion of rabbits was studied under normal conditions and during blockade of nicotinic cholinergic synapses. Under normal conditions this profile was presented by 5 isoforms of the enzyme (lactate dehydrogenases 1, 2, 3, 4, and 5). Activity of H-isoforms prevailed. Blockade was accompanied by heterotropic allosteric inhibition of lactate dehydrogenase isoforms. H- and M-isoforms underwent simultaneous changes. Activity of H-isoforms sharply decreased. However, the ratio between lactate dehydrogenases 1 and 2 during complete or partial blockade did not differ from that observed in experiments with the intact ganglion. M-isoforms (lactate dehydrogenases 4 and 5) disappeared during partial blockade. Activity of hybrid lactate dehydrogenase 3 significantly decreased and was undetected during partial and complete blockade, respectively. Our results indicate that enzyme activity and isoenzyme profile of lactate dehydrogenase are determined by function of nicotinic synapses.

Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil.

In vitro anticholinesterase activities of eight commercially available terpenoid constituents of Salvia lavandulaefolia have been investigated. These included 1,8-cineole, camphor, alpha-pinene, beta-pinene, borneol, caryophyllene oxide, linalool and bornyl acetate. Dose-dependent inhibition of acetylcholinesterase (AChE) by these chemical constituents was determined using the method of Ellman [Biochem. Pharmacol. 7 (1961) 88]. The IC50 value of 1,8-cineole was 0.06+/-0.01 mg/ml similar to that of the essential oil (0.05+/-0.01 mg/ml). Analyses of the expected inhibitions based on the prediction of a zero interactive response of a combination at its naturally occurring ratios were carried out in comparison with observed inhibition. Minor synergy was apparent in 1,8-cineole/alpha-pinene and 1,8-cineole/caryophyllene oxide combinations, with interaction indexes not exceeding 0.5. In contrast, a combination of camphor and 1,8-cineole was antagonistic with an interaction index of 2. A combination of all eight compounds was zero interactive. A combination of six constituents, excluding 1,8-cineole and camphor, was used to compare the method of expected response of a combination with a method of summation. These findings reveal that the inhibitory activity of the oil results from a complex interaction between its constituents, which produce both synergistic and antagonistic responses between the component terpenes. Understanding such interactions is important in comparing species on the basis of chemical composition.

Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers.

Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults.

Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties.

Melissa officinalis (Lemon balm) is a herbal medicine that has traditionally been attributed with memory-enhancing properties, but which is currently more widely used as a mild sedative and sleep aid. In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness, and dose-dependent decrements in timed memory task performance. However, the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties. The current study involved an initial screening of samples of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties. The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a randomized, placebo-controlled, double-blind, balanced crossover study. Following the in vitro analysis, 20 healthy, young participants received single doses of 600, 1000, and 1600 mg of encapsulated dried leaf, or a matching placebo, at 7-day intervals. Cognitive performance and mood were assessed predose and at 1, 3, and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond-Lader visual analog scales, respectively. In vitro analysis of the chosen extract established IC(50) concentrations of 0.18 and 3.47 mg ml(-1), respectively, for the displacement of [(3)H]-(N)-nicotine and [(3)H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue. However, no cholinesterase inhibitory properties were detected. The most notable cognitive and mood effects were improved memory performance and increased 'calmness' at all postdose time points for the highest (1600 mg) dose. However, while the profile of results was overwhelmingly favorable for the highest dose, decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose. These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer's disease. The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation.

[Transcutaneous transvenous occlusion of patent ductus arteriosus]. / Chreskozhnaia transvenoznaia okkliuziia otkrytogo arterialnogo protoka.

Transvenous closure is described of the patent ductus arteriosus with a conical device that consists of polyurethane foam mounted on a stainless steel flame. Since 1981, the procedure has been performed in 273 patients in Russia. Permanent complete ductus closure was achieved in 258 (95%) patients. In eight cases (3%), the occlusion was incomplete. Complications occurred in 10 patients (4%), seven of whom required emergency surgery. The new technique combines certain advantages of both alternative methods. The conical shape of the occlusion device is well suited for the anatomic structure of the ductus. The possibility of selecting the size of the device permits reduction in the rate of incomplete closure while still taking advantage of transvenous delivery to avoid entryside problems. In the initial 10 years of experience, the described technique proved effective, safe, and applicable in the vast majority of patients older than 2 years.

[The effect of weightlessness on amphibians. The ultimobranchial body]. / Vliianie nevesomosti na amfibii. Ul'timobrankhial'naia zheleza.

C-cells of Pleurodeles waltilii ultimobranchial bodies (ULT) were studied after a series of two-week spaceflight on the biosatellites. It was shown that under conditions of weightlessness the hypertrophy of ULT and calcitonin secretion activation occurred. Calcitonin accumulated into the ULT which resulted in metaplasia of the surrounding tissues, organ calcification and C-cells death. After landing, the regenerative processes which were not manifest in weightlessness occurred. They were similar to those of embryonic development of the organ.