In vitro and in vivo inhibition of chicken brain neurotoxic esterase by leptophos analogs

Inhibition of chicken brain neurotoxic esterase (NTE) by a series of O-halogenated-phenyl-O-alkyl phenylphosphonates was studied in vitro. The “apparent” activity was found to consist of “true” NTE (sensitive to mipafox) plus a minor mipafox-resistant component. The pI₅₀ of O-(2,6-dichlorophenyl) O-methyl phenylphosphonate for “true” NTE was 6.65, whereas it was about 3 for mipafox-resistant hydrolysis of phenyl valerate. This compound is suitable as an alternative to mipafox in the assay of “true” NTE, whereas the use of leptophos oxon gives a less accurate measure. The ethoxy analogs are about as potent in vitro as the corresponding methoxy compounds. Leptophosoxon and ethoxyleptophosoxon are more potent in vitro inhibitors than desbromoleptophosoxon. Within a like group of chlorinated phenylphosphonates, a reasonable correlation between in vitro neurotoxic esterase inhibition of the oxon and in vivo delayed neurotoxic potential by the corresponding phosphonothionate exists. In vivo inhibition of “apparent” NTE from chicken brain, studied 24 hr after an oral dose, is dose dependent for leptophos, ethoxyleptophos, and desbromoleptophos, the latter one being a very potent in vivo inhibitor. Ethoxyleptophos and leptophos have about equal in vivo esterase inhibitory properties. For desbromoleptophos and leptophos there is good agreement between the minimum dose causing delayed neurotoxicity and the dose leading to substantial inhibition of “apparent” NTE; ethoxyleptophos, on the other hand, inhibits the esterase at a dose much lower than the one which is neurotoxic. Several possible explanations for this discrepancy are considered.     

Viral infections of the respiratory tract of calves: Local immunity

Local immunity is the first defence mechanism against viral respiratory infections in young calves. The great variety of different viruses which may infect the very young animal makes it necessary to develop effective local defences early in life. The best approach appears to be to increase the subjects' defences by using immunoadjuvants and interferon inducers. With this end in view we should increase our knowledge of the immune system of the calf respiratory tract, particularly with respect to specific immunoglobulins, and cells which mediate the immune response.

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Kurzfassung Die örtliche Immunität ist der erste Abwehrmechanismus gegen virale Erkrankungen der Atemwege beim jungen Kalb. Da sich diese sehr jungen Tiere mit den unterschiedlichsten Viren infizieren können, ist ein frühzeitiger Aufbau einer wirksamen örtlichen Abwehr unerlässlich; dieses Problem liesse sich vielleicht durch eine Steigerung der Abwehrkräfte bei den Tieren mit Immunitatsadjuvanten und Induktoren von Interferonbildung bewältigen. Die bisher vorliegenden Angaben über das Immunsystem der Atemwege beim Kalb (spezifische Immunglobuline, Immunzellen) müssen zu diesem Zweck noch vertieft werden.

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Resume L'immunité locale est le premier mécanisme de défense contre les affections réspiratoires virales du jeune veau. La grande diversité des virus pouvant infecter ces sujets très jeunes rend indispensable l'établissement précoce de défenses locales éfficaces; l'augmentation des défenses des sujets par l'emploi d'adjuvants de l'immunite et d'inducteurs d'interféron semble être le moyen d'aborder ce problème. Les données que nous possédons sur le système immunitaire de l'appareil réspiratoire du veau (immunoglobulines specifiques, cellules effectrices de l'immunité) doivent, dans ce but, être approfondies.

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Riassunto L'immunita locale e il primo meccanismo di difesa del giovane vitello contro le affezioni virali delle vie respiratorie. La grande diversità dei virus in grado di infettare soggetti molto giovani rende necessaria l'instaurazione precoce di difese locali efficaci; la soluzione migliore dovrebbe consistere nel potenziamento delle difese dei soggetti mediante adiuvanti dell'immunità e induttori di interferon. A tal fine e necessario approfondire i dati in nostro possesso sul sistema immunitario dell'apparato respiratorio del vitello (Immunoglobuline specifiche, immunociti).

     

Les immunostimulants orientent la reponse locale au virus de l''I.B.R. vers la production d''Interferon

Immuno-adjuvants like MDP or levamisole inoculated in the calf through general route increase the respiratory mucosa response to the irradiation inactivated IBRV.

We have shown from the 2nd day of the inoculation an interferon activity in the nasal mucus. This interferon partially destroyed at pH2 and at 56°C, persists in the respiratory fluids for one week. It is never found in the sera of the animals.

This inactivated virus given through nasal route does not stimulate antibody production in the local system or in the serum.

The dose of levamisole administered is critical: 5 mg/kg are the minimal quantity required to give a favourable answer whereas the 2.5 mg/kg normally used are without effect.

The interferon presence in the respiratory fluids gives a satisfactory interpretation of the good resistance to respiratory infection obtained in 500 calves with this treatment: inactivated virus by nasal route and immuno-adjuvant by intradermic or intramuscular route.     

EXPERIMENTAL ARACHNOID FIBROSIS PRODUCED BY METRIZAMIDE IN THE DOG*

The short-term neurologic and long-term leptomeningeal effects of repeated subarachnoid administration of metrizamide at concentrations of 170 mg I/ml and 300 mg I/ml were investigated in dogs. After two months, arachnoid fibrosis of varying degrees was present in all dogs that had received metrizamide at the higher concentration. The higher concentration of met-rizamide was more epileptogenic than the concentration of 170 mg I/ml. The presence of subarachnoid hemorrhage was not considered to play a role in the development of the arachnoid fibrosis. Veterinary Radiology Vol. 21, No. 2, 1980; pp 78–81.     

Conduciveness of different soilless growing media to <Emphasis Type="Italic">Pythium</Emphasis> root and crown rot of cucumber under near-commercial conditions

Substrates made from rockwool, coir dust, pumice and perlite were compared for conduciveness to Pythium root and crown rot in cucumber under near-commercial conditions. Rockwool slabs of 7 cm height were more conducive to the Pythium disease than coir dust slabs, pumice or perlite under these conditions. Temperature, oxygen concentration and water content were determined in the substrates to explain differences in conduciveness between the inorganic substrates rockwool, pumice and perlite by differences in the physical conditions. Temperature and oxygen concentration could not explain the differences but the higher disease level on rockwool was associated with a much higher water content of this substrate as compared to coir dust, pumice and perlite. Increasing the height of the substrate from 7 to 14 cm greatly decreased the percentage of diseased plants due to the Pythium disease on rockwool but had no effect on the level of disease on perlite when the substrate had been infested 4 cm below the planting hole. This difference in response in substrate height between rockwool and perlite could be explained by a much larger decrease in water content with substrate height in the rockwool than in the perlite substrate. Temperature in the substrates were above 30 °C for more than 6 h on sunny days in June and reached maximum values of 35 °C or more. These temperatures are highly favourable for the pathogen P. aphanidermatum but will have adverse effects on most biocontrol strains.     

Germination of <Emphasis Type="Italic">Plasmodiophora brassicae</Emphasis> resting spores stimulated by a non-host plant

Plant-induced germination of Plasmodiophora brassicae resting spores was studied in a laboratory experiment. Spore reaction was analysed in nutrient solution with exudates from growing roots of different plant species – one host plant (Brassica rapa var. pekinensis) and four non-host plants (Lolium perenne, Allium porrum, Secale cereale and Trifolium pratense) – and in controls with distilled water and nutrient solution. It was found that root exudates from L. perenne stimulated spore germination more than exudates from the other plants, including those from the host plant. The effect could not be explained by differences in the nutritional composition of the solutions due to differential uptake of the plant species, or by differences in root activity, measured as exudation of soluble sugars. This is the first time such a separation of factors has been done in analysing the influence of plants on P. brassicae germination. Although stimulation of P. brassicae resting spore germination is not restricted to the presence of host plants, it seems to vary depending on the plant species.     

Cardiovascular and respiratory effects of ketamine infusions in isoflurane-anesthetized dogs before and during noxious stimulation

OBJECTIVE: To characterize the effects of ketamine administration on the cardiovascular and respiratory systems and on acid-base balance and to record adverse effects of ketamine in isoflurane-anesthetized dogs. ANIMALS: 6 healthy adult mongrel dogs. PROCEDURE: Dogs were anesthetized with isoflurane (1.25 times the individual minimum alveolar concentration) in oxygen, and ketamine was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, 8, and 11 microg/mL. Isoflurane concentration was reduced to an equipotent concentration. Cardiovascular, respiratory, and acid-base variables; body temperature; urine production; and adverse effects were recorded before and during noxious stimulation. Cardiac index, stroke index, rate-pressure product, systemic vascular resistance index, pulmonary vascular resistance index, left ventricular stroke work index, right ventricular stroke work index, arterial oxygen concentration, mixed-venous oxygen concentration, oxygen delivery, oxygen consumption, oxygen extraction ratio, alveolar-arterial oxygen partial pressure gradient, and venous admixture were calculated. Plasma ketamine and norketamine concentrations were measured. RESULTS: Overall, ketamine administration improved ventilation, oxygenation, hemodynamics, and oxygen delivery in isoflurane-anesthetized dogs in a dosedependent manner. With the addition of ketamine, core body temperature was maintained or increased and urine production was maintained at an acceptable amount. However, at the higher plasma ketamine concentrations, adverse effects such as spontaneous movement and profuse salivation were observed. Myoclonus and dysphoria were observed during recovery in most dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of ketamine appears to be a suitable technique for balanced anesthesia with isoflurane in dogs. Plasma ketamine concentrations between 2 to 3 microg/mL elicited the most benefits with minimal adverse effects.