Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis

HistoryA 4‐year old, 500 kg Thoroughbred female horse diagnosed with bilateral forelimb laminitis and cellulitis on the left forelimb became severely painful and refractory to non‐steroidal anti‐inflammatory therapy (flunixin meglumine on days 1, 2, 3 and 4; and phenylbutazone on days 5, 6 and 7) alone or in combination with gabapentin (days 6 and 7).Physical examinationPain scores assessed independently by three individuals with a visual analog scale (VAS; 0 = no pain and 10 = worst possible pain) were 8.5 on day 6, and it increased to 9.5 on day 7. Non‐invasive blood pressure monitoring revealed severe hypertension.ManagementAs euthanasia was being considered for humane reasons, a decision was made to add an experimental new drug, trans‐4‐{4‐[3‐(4‐Trifluoromethoxy‐phenyl)‐ureido]‐cyclohexyloxy}‐benzoic acid (t‐TUCB), which is a soluble epoxide hydrolase (sEH) inhibitor, to the treatment protocol. Dose and frequency of administration were selected based on the drug potency against equine sEH to produce plasma concentrations within the range of 30 nmol L^?1 and 2.5 μmol L^?1. Pain scores decreased sharply and remarkably following t‐TUCB administration and blood pressure progressively decreased to physiologic normal values. Plasma concentrations of t‐TUCB, measured daily, were within the expected range, whereas phenylbutazone and gabapentin plasma levels were below the suggested efficacious concentrations.Follow upNo adverse effects were detected on clinical and laboratory examinations during and after t‐TUCB administration. No new episodes of laminitis have been noted up to the time of writing (120 days following treatment).ConclusionsInhibition of sEH with t‐TUCB was associated with a significant improvement in pain scores in one horse with laminitis whose pain was refractory to the standard of care therapy. No adverse effects were noticed. Future studies evaluating the analgesic and protective effects of these compounds in painful inflammatory diseases in animals are warranted.     

Effects of nutritional support on hospital outcome in dogs and cats

Objective – Investigate the effects of assisted nutritional support on hospital outcome in dogs and cats, and the relationship between hospital outcome and energy intake, body condition score (BCS), physical status score, and type of nutritional support used. Design – Retrospective analysis of hospitalized animals. Setting – Teaching Veterinary Hospital. Animals – Four hundred and sixty‐seven dogs and 55 cats. Interventions – Routine clinical nutritional support. Measurements and Main Results – The following variables were recorded for each animal: energy intake, body weight at admission and discharge, BCS, physical status score, and type of nutritional support used. Disease severity was negatively associated with hospital outcome and energy intake (P=0.009). Energy intake was positively associated with hospital discharge (P<0.001). Outcome may be related to BCS, with discharge rates of 73% for animals with low BCS, and 84.7% for those at an ideal BCS or overweight (P=0.04). Sixty‐four percent of animals showed voluntary food intake (92.9% were discharged), 19.0% received enteral support (71.8% were discharged), 7.0% were forced fed (75.0% were discharged), 6.0% received parenteral support (61.9% were discharged), and 4.0% did not receive calories (38.4% were discharged), suggesting a possible relationship between the type of nutritional support, energy intake, and outcome (P=0.009). Conclusions – Energy supply, even if modest and close to resting energy requirements appears to be positively associated with hospital discharge. However, disease severity was the main negative factor on outcome and also had a negative effect on energy intake, making it difficult to separate the effects of both factors when interpreting hospital discharge. Thin animals with low BCS had greater mortality.     

Insecticide selectivity and behavioral response of the earwig Doru luteipes

Insecticide lethal and sub-lethal effects on non-target species are a focus in pest management programs. However, such studies are usually centered in relatively few groups of natural enemies of insect pests. Earwigs, although insect pest predators of key importance in Neotropical maize fields, have received very little attention. The earwig Doru luteipes (Sccuder) (Dermaptera: Forficulidae) is one of the main predators of the fall armyworm Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). Both species were subjected to toxicity and selectivity studies with the insecticides chlorantraniliprole, chlorfenapyr, chlorpyrifos, λ-cyhalothrin, deltamethrin, etofenprox, methomyl and spinosad. The behavioral locomotory response of D. luteipes to these compounds was also assessed. Concentration-response bioassays indicated very low potency of chlorantraniliprole (>550,000× less toxic), followed by spinosad (>3,500× less toxic) and etofenprox (>1,100× less toxic) as compared to chlorpyrifos, the most toxic insecticide studied against this earwig species. These same three compounds exhibited the highest selectivity when comparing the earwig with its prey, the fall armyworm. Time-response bioassays using the insecticide label rates recommended against the fall armyworm confirmed the high selectivity of chlorantraniliprole and etofenprox, in addition to deltamethrin and methomyl. Again chlorpyrifos exhibited the lowest levels of selectivity. Exposure of the earwig to insecticide-treated surfaces indicated that spinosad reduced the locomotory activity of the adults probably increasing their insecticide exposure, while they avoided chlorfenapyr-, etofenprox-, and chlorpyrifos-treated surfaces. Chlorantraniliprole and etofenprox seem the most promising compounds for use against S. frugiperda whilst preserving populations of D. luteipes.     

Survival and developmental impairment induced by the trypsin inhibitor bis-benzamidine in the velvetbean caterpillar (Anticarsia gemmatalis)

Proteinase inhibitors are potential insect control agents, but insect adaptation to these compounds is one of the main limitations for their potential use as such. The velvetbean caterpillar (Anticarsia gemmatalis Hübner) (Lepidoptera: Noctuidae) is a key soybean pest species well-adapted to its prevailing (serine-) proteinase inhibitors, particularly trypsin-like inhibitors. The recognition of proteinase inhibitors with insecticidal activity towards such pest species is therefore challenging and important as a basis for the development of mimetic peptides with potential use as biorational insecticides. Thus, bis-benzamidine was tested against the velvetbean caterpillar with the expectation of greater insecticidal activity of this more potent trypsin inhibitor than the negligible effects observed with other natural and synthetic trypsin inhibitors. Bis-benzamidine ingestion by the caterpillars led to higher survival time with increased doses up to 76 ppm, but drastically reduced survival time at higher doses (over 150 ppm). Insects exposed to bis-benzamidine doses of up to 76 ppm exhibited extended larval development and decreased pupa weight. Increased doses of this trypsin inhibitor led to increased diet consumption and protein digestibility during the larval phase, but drastically compromised the proteolytic activity in the caterpillar gut. These results indicate that, unlike benzamidine, another related synthetic trypsin inhibitor, bis-benzamidine exhibits insecticidal activity towards the velvetbean caterpillars at doses as low as 9.5 ppm in the insect diet due to suppression of gut proteinase activity despite the compensatory feeding. Such compensatory feeding may however increase insect damage in the field by more tolerant individuals and should be the object of further study.     

The metamorphosis of supernova SN 2008D/XRF 080109: a link between supernovae and GRBs/hypernovae

The only supernovae (SNe) to show gamma-ray bursts (GRBs) or early x-ray emission thus far are overenergetic, broad-lined type Ic SNe (hypernovae, HNe). Recently, SN 2008D has shown several unusual features: (i) weak x-ray flash (XRF), (ii) an early, narrow optical peak, (iii) disappearance of the broad lines typical of SN Ic HNe, and (iv) development of helium lines as in SNe Ib. Detailed analysis shows that SN 2008D was not a normal supernova: Its explosion energy (E approximately 6x10(51) erg) and ejected mass [ approximately 7 times the mass of the Sun (M(middle dot in circle))] are intermediate between normal SNe Ibc and HNe. We conclude that SN 2008D was originally a approximately 30 M(middle dot in circle) star. When it collapsed, a black hole formed and a weak, mildly relativistic jet was produced, which caused the XRF. SN 2008D is probably among the weakest explosions that produce relativistic jets. Inner engine activity appears to be present whenever massive stars collapse to black holes.     

The impact of animal age, bacterial coinfection, and isolate pathogenicity on the shedding of Porcine reproductive and respiratory syndrome virus in aerosols from experimentally infected pigs

The objective of this study was to evaluate the role of different variables (animal age, bacterial coinfection, and isolate pathogenicity) on the shedding of Porcine reproductive and respiratory syndrome virus (PRRSV) in aerosols. Animals were grouped according to age (2 versus 6 mo) and inoculated with a PRRSV isolate of either low (MN-30100) or high (MN-184) pathogenicity. Selected animals in each group were also inoculated with Mycoplasma hyopneumoniae. The pigs were anesthetized and aerosol samples (1000 breaths/sample) collected on alternating days from 1 to 21 after PRRSV inoculation. The results indicated that animal age (P = 0.09), M. hyopneumoniae coinfection (P = 0.09), and PRRSV isolate pathogenicity (P = 0.15) did not significantly influence the concentration of PRRSV in aerosols. However, inoculation with the PRRSV MN-184 isolate significantly increased the probability of aerosol shedding (P = 0.00005; odds ratio = 3.22). Therefore, the shedding of PRRSV in aerosols may be isolate-dependent.     

Haemonchus contortus protease inhibition by n-alkyl ferulates from Maprounea guianensis

This report describes the inhibition of the proteolytic activity of Haemonchus contortus lysate by a mixture of n-alkyl ferulates isolated from Maprounea guianensis. These compounds were evaluated in vitro for the ability to inhibit the H. contortus proteases using SDS-PAGE copolymerized with gelatine (zymography) and by assaying the hemoglobinolytic activity of these enzymes in solution. The ferulates abrogated the proteolysis compared to E-64, suggesting the activity is the result of a cysteine protease.