The use of computer-generated electrostatic surface maps for the design of new ‘GABA-ergic’ insecticides

A computer model was constructed based on the observation that a number of structurally dissimilar compounds gave rise to similar biological activity. Mode of action work confirmed the link. The model was then used to prioritise targets for synthesis and successfully predicted many active series. The major limitation of the model was that it was unable to predict potency or spectrum. It is thought likely that the factors controlling these limitations are linked with LUMO energies, but this hypothesis has not been proven.     

Chlorpyrifos degradation in soil at termiticidal application rates

Chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate] is an organophosphorus insecticide applied to soil to control pests both in agricultural and in urban developments. Typical agricultural soil applications (0.56 to 5.6 kg ha^?1) result in initial soil surface residues of 0.3 to 32 μg g^?1. In contrast, termiticidal soil barrier treatments, a common urban use pattern, often result in initial soil residues of 1000 μg g^?1 or greater. The purpose of the present investigation was to understand better the degradation of chlorpyrifos in soil at termiticidal application rates and factors affecting its behaviour. Therefore, studies with [¹⁴C]chlorpyrifos were conducted under a variety of conditions in the laboratory. Initially, the degradation of chlorpyrifos at 1000 μg g^?1 initial concentration was examined in five different soils from termite-infested regions (Arizona, Florida, Hawaii, Texas) under standard conditions (25°C, field moisture capacity, darkness). Degradation half-lives in these soils ranged from 175 to 1576 days. The major metabolite formed in chlorpyrifos-treated soils was 3,5,6-trichloro-2-pyrid-inol, which represented up to 61% of applied radiocarbon after 13 months of incubation. Minor quantities of [¹⁴C]carbon dioxide (< 5%) and soil-bound residues (? 12%) were also present at that time. Subsequently, a factorial experiment examining chlorpyrifos degradation as affected by initial concentration (10, 100, 1000 μg g^?1), soil moisture (field moisture capacity, 1.5 MPa, air dry), and temperature 15, 25, 35°C) was conducted in the two soils which had displayed the most (Texas) and least (Florida) rapid rates of degradation. Chlorpyrifos degradation was significantly retarded at the 1000 μg g^?1 rate as compared to the 10 μg g^?1 rate. Temperature also had a dramatic effect on degradation rate, which approximately doubled with each 10°C increase in temperature. Results suggest that the extended (3–24 + years) termiticidal efficacy of chlorpyrifos observed in the field may be due both to the high initial concentrations employed (termite LC ₅₀ = 0.2– 2 μg g^?1) and the extended persistence which results from employment of these rates. The study also highlights the importance of investigating the behaviour of a pesticide under the diversity of agricultural and urban use scenarios in which it is employed.     

Effects of Carolina rinse solution, dimethyl sulfoxide, and the 21-aminosteroid, U-74389G, on microvascular permeability and morphology of the equine jejunum after low-flow ischemia and reperfusion

OBJECTIVE: To evaluate effects of Carolina rinse solution, dimethyl sulfoxide (DMSO), and 21-aminosteroid, U-74389G, on microvascular permeability and morphology of the equine jejunum after low-flow ischemia and reperfusion. ANIMALS: 20 healthy adult horses. PROCEDURE: Under anesthesia, full-thickness biopsy specimens of a distal portion of the jejunum were obtained for baseline measurements. In addition to a control segment, 2 jejunal segments were identified as sham-operated or experimental segments. Experimental segments underwent 60 minutes of low-flow ischemia and 3.5 hours of reperfusion. Treatments were as follows: U-74389G (3 mg/kg, IV; 6 horses), DMSO (20 mg/kg, IV; 6) diluted in 1 L of saline (0.9% NaCl) solution, local perfusion (via jejunal artery) of Carolina rinse solution (0.5 mL/kg; 4), and local perfusion of lactated Ringer's solution (0.5 mL/kg; 4). RESULTS: Jejunal microvascular permeability was significantly lower after treatment with Carolina rinse solution or DMSO, compared with U-74389G or lactated Ringer's solution treatments. After DMSO treatment, serosal- and submucosal-layer edema was significantly increased in experimental segments, compared with control or sham-operated segments; however, edema increases were significantly less than for lactated Ringer's solution or U-74389G treatments. Significant decreases in intestinal wet weight-to-dry weight ratio were found following Carolina rinse solution or DMSO treatments, compared with lactated Ringer's solution or U-74389G treatments. Edema formation and leukocyte infiltration in jejunal segments of horses treated with lactated Ringer's solution or U-74389G were increased, compared with Carolina rinse solution or DMSO treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Carolina rinse solution and DMSO may be protective against ischemia-reperfusion injury in the equine jejunum.     

Insertion sequence profiling of UK Mycoplasma bovis field isolates

Mycoplasma equigenitalium and Mycoplasma subdolum have been associated with infertility, endometritis, vulvitis and abortions in mares, and with reduced fertility and balanoposthitis in stallions. Despite their role in equine genital disorder, determinants of virulence and pathogenesis as well as factors provoking specific host immune responses have not been identified, so far. To establish the major immunogenic components of Mycoplasma (M.) equigenitalium and M. subdolum, antigen profiles of their type strains as well as 30 clinical isolates were compared by SDS-PAGE and immunoblot analysis using hyperimmune rabbit sera and equine sera from clinical cases. To define the major protein antigens of both mycoplasma species, detergent-phase fractionation with Triton X-114 was performed. Western blot analysis of 30 clinical isolates revealed a high similarity of their overall antigen profile with only slight differences. In contrast, monospecific polyclonal antibodies raised against detergent-phase proteins of the two mycoplasma species identified three prominent proteins (pST17, pST42, and pET45) undergoing variation in expression and size among clinical and clonal isolates.     

Biochemical characterisation of some non fermenting, non arginine hydrolysing mycoplasmas of ruminants

The pattern and kinetics of substrate oxidation by type and recent field strains of Mycoplasma agalactiae, Mycoplasma bovis, Mycoplasma bovigenitalium and Mycoplasma ovine/caprine serogroup 11 were investigated by measurement of oxygen uptake. Metabolism of a range of organic acids, sugars and alcohols was detected. All the test strains were unable to oxidise sugars, glycerol and the organic acids, fumarate, malate and alpha-ketoglutarate (1 mM). All strains oxidised organic acid l-lactate, 2-oxobutyrate and pyruvate and demonstrated the ability to oxidise alcohols, particularly isopropanol, which was oxidised at a high rate and high affinity (0.5 mol/mol isopropanol). Its oxidation was consistent with acetone formation, which may be of important in relation to pathogenicity. All strains oxidised similar substrates, however differences were observed between strains in terms of the relative rates and kinetic values for some substrates.     

Variation in response to neonicotinoid insecticides in peach-potato aphids,Myzus persicae (Hemiptera: Aphididae)

Laboratory bioassays applying the neonicotinoid insecticides imidacloprid, acetamiprid and nitenpyram against clones of the peach-potato aphid Myzus persicae (Sulzer) demonstrated that these compounds effectively circumvent the known carboxylesterase, modified acetylcholinesterase (MACE) and knock-down (kdr) insecticide resistance mechanisms in this species. However, some clones showed cross-tolerance (up to 18-fold) of these compounds relative to susceptible standards. A survey assessing the frequency of neonicotinoid tolerance in M persicae in the UK, based on samples collected from the field and glasshouses between 1997 and 2000, showed that such tolerance is still rare. Experiments on neonicotinoid-susceptible and -tolerant populations of M persicae under simulated field conditions in the laboratory showed that, although the latter were well controlled by imidacloprid applied at recommended application rates, they were more likely to survive and reproduce when this compound was applied at lower concentrations. Such conditions are probably periodically present in imidacloprid-treated field and glasshouse crops. Selection favouring tolerant forms of M persicae could lead to increases in their frequency and the evolution of more potent resistance to neonicotinoids.     

Umbilical herniorrhaphy in a juvenile Asian elephant (Elephas maximus).

An umbilical hernia was diagnosed in a 2-wk-old Asian elephant (Elephas maximus) by physical and ultrasonographic examinations. Umbilical herniorrhaphy was elected because the defect was large (approximately 7 cm long and 10 cm deep) and could potentially lead to incarceration of an intestinal loop. General anesthesia was induced with a combination of ketamine, xylazine, and diazepam and maintained with isoflurane in oxygen. The hernial sac was explored and contained fibrous tissue, fat, and an intestinal loop but no adhesions. The hernial sac was resected and the body wall closed using the technique of simple apposition. Following a superficial wound infection, the surgical site healed with no further complications.     

The effects of phytochemical pesticides on the growth of cultured invertebrate and vertebrate cells

A range of cultured cells of invertebrate and vertebrate origin was grown in the presence of a number of phytochemical pesticides to test the effect of the latter on cell proliferation. The main observation was that azadirachtin was a potent inhibitor of insect cell replication, with an EC50 of 1.5 x 10(10) M against Spodoptera cells and of 6.3 x 10(9) M against Aedes albopictus cells, whilst affecting mammalian cells only at high concentrations (> 10(-4) M). As expected, the other phytochemical pesticides, except for rotenone, had little effect on the growth of the cultured cells. Rotenone was highly effective in inhibiting the growth of insect cells (EC50:10(-8) M) but slightly less toxic towards mammalian cells (EC50:2 x 10(-7) M). Neem terpenoids other than azadirachtin and those very similar in structure significantly inhibited growth of the cell cultures, but to a lesser degree. The major neem seed terpenoids, nimbin and salannin, for example, inhibited insect cell growth by 23% and 15%, respectively.     

Cubitus-curvus chez une chienne

Cubitus-curvus in a bitch