Disrupted intracellular redox balance of the diplomonad fish parasite Spironucleus vortens by 5-nitroimidazoles and garlic-derived compounds.

The 5-nitroimidazole, metronidazole, has traditionally been employed in veterinary medicine to treat a range of infections including the diplomonad fish parasite Spironucleus. This study aims to determine the mode of action of metronidazole on Spironucleus vortens, including the specific mechanism of activation of the pro-drug and subsequent cellular targets of the drug metabolites. Due to the ban on use of metronidazole in the treatment of production animals in Europe and USA, garlic-derived compounds were also investigated as natural alternatives to metronidazole chemotherapy. Scanning electron microscopy (SEM) provided an overview of gross cellular damage caused by metronidazole and garlic derivatives. Proteomic analyses by 2D gel electrophoresis identified the proteins involved in specific covalent adduct formation with nitroimidazoles. Furthermore, thioredoxin reductase (TrxR) activity and non-protein thiol concentration were assayed in extracts of S. vortens before and after treatment with nitroimidazoles and garlic-derivatives. Metronidazole and garlic-derived compounds caused severe damage of trophozoites indicated by membrane blebbing and lysed cell debris. Analysis of the S. vortens proteome identified several proteins capable of specific nitroimidazole binding, including; uridine phosphorylase, enolase, protein disulphide isomerase, aminoacyl-histidine dipeptidase and malic enzyme. Of the compounds tested, metronidazole and the garlic-derived compound ajoene were the most effective at inhibiting TrxR activity and depleting non-protein thiols. These data suggest TrxR-mediated activation of nitroimidazoles, leading to depletion of non-protein thiols. Redox imbalance due to antioxidant failure is implicated as the mode of action of nitroimidazoles and garlic-derived compounds, ultimately leading to cell death. Possible synergy between garlic derivatives and metronidazole should be further investigated in vitro in order to determine their theoretical implications.

Comparison of the respiratory depressant effects of halothane and isoflurane in routine surgery.

Respiratory depression has been studied in 21 patients anaesthetized with either halothane and nitrous oxide, or isoflurane and nitrous oxide while undergoing routine surgery. Spontaneous ventilation was preserved and the end-tidal concentrations of the two volatile anaesthetics were at approximately equal MAC-multiples. The minute volume of pulmonary ventilation was not significantly different for the two anaesthetics, but tidal volume was significantly greater and frequency significantly lower with isoflurane. Arterial and end-tidal PCO2 were consistently lower in the patients receiving isoflurane, the difference being significant in many of the sub-groups. There was no evidence of a progressive increase in PCO2 with either anaesthetic during surgery lasting up to 225 min. Mean values for PCO2, however, tended to be well above the normal reference range, with mean arterial PCO2 in the range 7.2-8.6 kPa.

An end-tidal sampler for use with slow response analysers during anaesthesia.

An end-tidal sampler is described which can be used during anaesthesia with spontaneous respiration at rates of at least 60 b.p.m. It can be used with slow response analysers such as refractometers and fuel cells to indicate end-tidal concentrations. It can also be used to extend the scope of those breath-to-breath analysers which have a response time which is too slow for the respiratory rates which may occur during anaesthesia with spontaneous breathing. Using the device, mean PCO2 of the samples was 0.13 kPa less than the corresponding values for the end-expiratory PCO2 measured by conventional breath-by-breath analysis. Full response was achieved in 12 breaths.

A system for storage of references. A method of storage and retrieval of references on a personal microcomputer.

A computer program, written in BBC BASIC, for storage and retrieval of literature references on a personal microcomputer fitted with floppy disc drives is described. The storage capacity is 425 references per 100K disc. A versatile search function allows ready access to references by matching any number of combinations of the following 10 items: authors, name, year and volume of journal, pages, reference number, and up to four key words. The resulting bibliographic list can be formatted to any desired house style. There is a facility for sorting the list into alphabetical order of the authors and the use of a wordprocessor for special print styles on any BBC compatible printer. These two features make retyping the list unnecessary. A search can be done manually, while browsing through the references. Advantages of this system over the existing packages are discussed. The program is totally run by on-screen menus, and it is easy to use, even by a novice.