Antifungal mode of action of triforine

Rapidly growing mycelia of Aspergillus fumigatus treated with 10 μg/ml triforine (N,N′-bis-(1-formamido-2,2,2-trichloroethyl)-piperazine) showed little or no inhibition in dry weight increase prior to 2 h. By 2.5–3 h, triforine inhibited dry weight increase by 85%. The effects of triforine on protein, DNA, and RNA syntheses corresponded to the effect on dry weight increase both in time of onset and magnitude. Neither glucose nor acetate oxidation were inhibited by triforine.Ergosterol synthesis was almost completely inhibited by triforine even in the first hour after treatment. Inhibition of ergosterol synthesis was accompanied by an accumulation of the ergosterol precursors 24-methylenedihydrolanosterol, obtusifoliol, and 14α-methyl-Δ^{8, 24 (28)}-ergostadienol. Mycelia treated with 5 μg/ml of triarimol (α-(2,4-dichlorophenyl)-α-phenyl-5-pyrimidinemethanol) also accumulated the same sterols as well as a fourth sterol believed to be Δ^{5, 7}-ergostadienol.Identification of 4,4-dimethyl-Δ^{8, 24 (28)}-ergostadienol in untreated mycelia indicates that the C-14 methyl group is the first methyl group removed in the biosynthesis of ergosterol by A. fumigatus. The lack of detectable quantities of 4,4-dimethyl-Δ^{8, 24 (28)}-ergostadienol in triforine or triarimol-treated mycelia and the accumulation of C-14 methylated sterols in treated mycelia suggests that both fungicides inhibit sterol C-14 demethylation. The accumulation of Δ^{5, 7}-ergostadienol in triarimol-treated mycelia further implies that triarimol also inhibits the introduction of the sterol C-22(23) double bond.Two strains of Cladosporium cucumerinum tolerant to triforine and triarimol were also tolerant to the fungicide S-1358 (N-3-pyridyl-S-n-butyl-S′-p-t-butylbenzyl imidodithiocarbonate).     

Etude des phénomènes de sorption entre deux triazines herbicides et des acides humiques

A study of sorption phenomena between two triazine herbicides and humic acids Terbutryne is very readily adsorbed by humic acids while atrazine is only slightly adsorbed and this only in an acid environment. The influence of pH on adsorption and the competitive effect of the cations Ca²⁺, Al³⁺ and Fe³⁺ shows that the proton form of the molecules of the two herbicides can be adsorbed by an ion exchange-type mechanism; the neutral form of terbutryne molecules could be adsorbed by other mechanisms. Desorption of terbutryne is accompanied by a more marked hysteresis phenomenon in the case of neutral molecules, and, in an acid environment, calcium shows a weak capacity for displacement in relation lo the adsorbed herbicide.     

Trichoderma harzianum produces nonanoic acid, an inhibitor of spore germination and mycelial growth of two cacao pathogens

An isolate of Trichoderma harzianum Rifai from an infected cacao pod produces and secretes nonanoic (pelargonic) acid into a liquid culture medium. Nonanoic acid (NA) was very inhibitory to spore germination and mycelial growth of two cacao pathogens, Crinipellis perniciosa Stahel and Moniliophthora roreri Cif. H.C. Evans. It was highly active causing 75% inhibition of spore germination in an in vitro assay at a rate as low as 0.09 μM for M. roreri and 0.92 μM for C. perniciosa. Mycelial growth was comparatively less sensitive to inhibition, but still there was a 75% reduction in growth with 0.62 μM in M. roreri and 151 μM NA in C. perniciosa. In contrast, NA did not affect Trichoderma mycelial growth or spore germination at concentrations that were inhibitory to the pathogens. 6-pentyl-α-pyrone was also produced and secreted into the medium by T. harzianum, however; it was not antagonistic to the cacao pathogens. Although a number of metabolites produced by Trichoderma spp. have been identified in the past, this is the first report of NA production and secretion by any Trichoderma. The results suggest that NA may play a role in the successful use of some Trichoderma spp. isolates in the biocontrol of fungal diseases of plants.     

Long‐Term Totally Implantable Venous Access Ports in Dogs and Cats Receiving Chemotherapy

Introduction:  We evaluated the totally implantable subcutaneous vascular access port (VAP) in 16 cancer patients undergoing intermittent chemotherapy for more than 30 months.
Methods:  Ports were surgically placed (The CompanionPort, Norfolk Vet Products, Skokie, Illinois 60076) in the jugular vein of 12 dogs and 4 cats between 1/2002 and 7/2004. Body weight determined polyurethane catheter size (4, 5, 7 fr.). The polysulfone port, surrounded by titanium, was anchored to subcutaneous tissue in the dorsolateral neck and confirmed with C‐arm fluoroscopy. All blood samples were obtained via VAP. Nine anticancer agents, other medications, crystalloids/colloids, and whole blood were administered. Ports were flushed every 4–5 weeks with heparinized saline solution (100 IU/ml). Removed catheters were submitted for bacteriology.
Results:  Seven of 16 animals are still alive. VAP were used for 1.5 to more than 30 months with 4–60 injections/port. Catheter tips were visualized from the left atrium distally into the caudal vena cava. Adverse events included post‐operative subcutaneous bruising and/or hematoma (4/16), difficult aspiration (4/16), catheter malposition (1/16), positional flushing (1/16), and occlusion requiring replacement (1/16). No thrombus formation or extravasation was evident. Bacterial colonization without signs of septicemia was observed in 3/4 catheters.
Conclusions:  VAP are an effective way of achieving long‐term venous access in the dog and cat. Complications are typically minor and infrequent.     

The Blood-Vessel System of the Equine Periodontal Ligament: a Mesoscopic Study on Corrosion Casts

Several investigators have suggested that the blood-vessel system in the equine periodontal ligament does not only serve nutritional needs, but also specific functional needs, e.g. in terms of a shock absorbing system. In order to supplement the previous data, corrosion casts of the periodontal blood vessels were studied with special attention to the spatial arrangement and connections of the vessels. The heads of eight warm-blooded horses (age 2.5–23 years, seven female, one male), which had been killed for medical reasons, were dissected. The arteria alveolaris inferior and the a. infraorbitalis were perfused with 100 ml Heparin (20 000 IU) followed by 100 ml tap water. After storage at 4°C for 24–96 h, 10–200 ml methacrylate resin (Biodur^TM E20) were injected by use of a cartridge pistol for approx. 1 h. After polymerization for 24 h at 60°C, the jaws were frozen and cut with a steel band saw in a horizontal, sagittal or transversal plane to obtain segments that exposed the periodontal space. The specimens were macerated in detergent at 60°C until the soft tissues had vanished. Care was taken to keep the periodontal vessels complete and in topographical integrity. The vascular casts were mesoscopically examined by use of a dissection microscope (magnification 5.8×–40×). The blood vessels in the periodontal space connected with vessels in three other sites:

• (1)

  occlusal – with the blood vessels of the gingiva;

       

Growth performance, energy, and nitrogen balance of weanling pigs fed a cereal-based diet supplemented with Chinese rhubarb

Forty Swiss Large White piglets of 4 weeks of age were used to determine the effect of dietary Chinese rhubarb on growth performance, as well as on energy and nitrogen metabolism by means of indirect respiration calorimetry studies. A cereal-based diet, supplemented with four different dosages of Chinese rhubarb (0.0%, 0.25%, 0.5%, 1%), was offered ad libitum to the piglets. Gaseous exchange was measured, and urine, faeces, and blood samples were taken. The addition of 0.25% dietary rhubarb increased feed intake (+32%) and daily weight gain (+67%) compared to the diet containing the greatest amount of rhubarb (1%). The piglets fed diet supplemented with 0.25% rhubarb digested and metabolised more energy and nitrogen relative to the animals of treatment 1%. As a consequence, the same group (0.25%) converted more energy and nitrogen into body protein than piglets receiving diet supplemented with 1% rhubarb. However, compared to the control group, the addition of 0.25% rhubarb to the diet resulted in not significantly alter growth performance, energy, and nitrogen metabolism of the animals.Blood parameters were not affected by the rhubarb supplementation. The dose-responding effect of Chinese rhubarb was reflected by the dry matter content of faecal samples. According to the laxative effect of higher doses of rhubarb, the addition of 1% rhubarb to the diet reduced dry matter content of faeces. This effect was well visible in practice, although not relevant in statistical terms. The addition of 0.5% dietary rhubarb had no relevant effect on growth performance or on energy and nitrogen metabolism of treated animals.