Biomedical subjects

M Ehrich

Publications and source records attributed to M Ehrich.

At least 73 records · Page 4Linked to original sources

PubMed1989

Effect of beta-naphthoflavone on o-tolyl saligenin phosphate-induced delayed neuropathy in two lines of chickens.

The effect of the microsomal enzyme inducer beta-naphthoflavone (beta NF) on the development of organophosphorus-induced delayed neuropathy (OPIDN) was examined in two laboratories (VPI and MSU), utilizing two strains of White Leghorn hens. A single intraperitoneal injection of beta NF at 80 mg/kg body weight 48 h prior to administration of o-tolyl saligenin phosphate (TSP), the neuroactive metabolite of tri-o-tolyl phosphate (TOTP), caused a significant increase in hepatic microsomal cytochrome P-450 concentrations and aniline hydroxylase activities after 72 h in both strains. Hepatic carboxylesterase and cholinesterase activities were not affected by beta NF treatment in either strain. Administration of TSP in single subcutaneous doses of 20 and 25 mg/kg body weight (VPI) or 30 and 60 mg/kg body weight (MSU) caused significant inhibition of whole-brain neuropathy target esterase (NTE) activity 24 h postdosing, and hens subsequently developed clinical signs characteristics of OPIDN. beta NF had no significant effect on NTE inhibition or on initiation or severity of OPIDN clinical signs. However, OPIDN clinical signs were less severe in the strain of bird (MSU) with the higher intrinsic hepatic carboxylesterase activity and the higher beta NF-induced cytochrome P-450 concentration. The study indicates that microsomal enzyme induction, which has been shown to alleviate TOTP-induced delayed neuropathy, could not alleviate OPIDN resulting from exposure to TSP. This study also suggests that strain may affect susceptibility to TSP-induced delayed neuropathy.

Animals↗

PubMed1989

Differences in response of chickens from two genetic lines to diisopropyl phosphorofluoridate.

Neurotoxicity of diisopropyl phosphorofluoridate (DFP) was examined at 85 weeks of age in hens of two lines selected for high (HA) and low (LA) antibody response to sheep erythrocytes. DFP was administered by subcutaneous injection in doses of 0.25, 0.50 and 1.00 mg/kg and hens were observed for cholinergic signs at 30 min and for delayed neuropathy 8 to 14 days post-administration. Toxicity to DFP increased in severity with the dose and genetic differences were present because hens of line HA were more sensitive to DFP than were those of line LA. HA hens also had lower A-esterase activities and higher heterophil-to-lymphocyte ratios. No line x treatment interaction was evident, however, for activities of neurotoxic esterase or brain cholinesterase measured 24 hr after DFP administration.

Animals↗

PubMed1989

Myelinated nerve fiber regeneration following organophosphorus ester-induced delayed neuropathy.

Chickens which developed organophosphorus ester-induced delayed neuropathy (OPIDN) due to a single oral dose of 360 mg/kg tri-ortho-tolyl phosphate were followed for up to 64 days following toxicant administration. Neuropathy was well developed by day 14. Progressive, marked but incomplete clinical improvement was observed between that time and day 49, associated with regenerative process was initially noted on day 16 at a distal, non-terminal level of the tibial nerve branch to the lateral head of the gastrocnemius muscle. One or more axonal sprouts were seen in bands of Büngner, but only one regenerated fiber per band myelinated and grew. By day 64 the nerves from treated hens closely resembled those from the controls. Myelinated nerve fiber degeneration was noted in distal regions of long spinal cord white matter tracts, but no subsequent regeneration was observed in this region. These studies indicate that in OPIDN there is a transient period of neuronal injury, and that damaged cells having peripherally directed neurites are likely able to undertake axonal regeneration.

Animals↗

PubMed1988

Interactions of aflatoxin and the antioxidant butylated hydroxytoluene in two-week-old chicks.

Two-week dietary administration of 2500 ppb aflatoxin was sufficient to cause a decrease in bursal weights and a reduction in the number of splenic leukocytes in chicks. No significant effects on weight gain or feed efficiency were evident. The chicks also had elevated heterophil-to-lymphocyte ratios, suggesting a heightened reaction to stress. This effect could be blocked by dietary administration of the antioxidant butylated hydroxytoluene (BHT) at a concentration eight-fold over that normally present to preserve control feed. The BHT treatment increased the activities of the enzymes glutathione-S-transferase, aniline hydroxylase and O-demethylase, which metabolize aflatoxins in the liver.

Administration, Oral↗

PubMed1988

Types of adrenocorticoids and their effect on organophosphorus-induced delayed neuropathy in chickens.

The present study examined the effects of a glucocorticoid and a mineralocorticoid on organophosphorus-induced delayed neuropathy (OPIDN) as previous investigations have indicated that an endogenous steroid with both properties could alter this syndrome in chickens. The glucocorticoid triamcinolone and the mineralocorticoid deoxycorticosterone were provided in the diet beginning 1 day before and continuing 10 days after triortho-tolyl phosphate (TOTP, 360 mg/kg po), phenyl saligenin phosphate (PSP, 2.5 mg/kg im), and diisopropyl phosphorofluoridate (DFP, 1 mg/kg sc). In a manner similar to that seen with corticosterone, a low concentration (0.1 ppm) of triamcinolone reduced and a high concentration (10 ppm) exacerbated clinical signs. Concentrations of deoxycorticosterone under 80 ppm also partially delayed or ameliorated ataxia induced by TOTP, PSP, and DFP, but a combination of 0.1 ppm triamcinolone and 80 ppm deoxycorticosterone was not more effective than triamcinolone alone. Peripheral nerve damage was noted in all chickens given organophosphorus compounds, whether or not they had been given corticoids. Both steroids induced hydroxylase activity, but effects on most other enzyme systems examined were unremarkable. High concentrations of triamcinolone (10 ppm) could, however, also reduce liver cytochrome P450 levels and liver cholinesterase activity. Exacerbation of OPIDN was most notable in chickens under highest stress, as indicated by elevated heterophil-to-lymphocyte ratios. The clinical, pathological, biochemical, and hematological indices of exposure to adrenocorticoids and agents inducing OPIDN in chickens were, therefore, similar for both a synthetic glucocorticoid and the endogenous steroid corticosterone.

Animals↗

PubMed1988

Assessment of organophosphorus-induced delayed neuropathy in chickens using needle electromyography.

The adult chicken provides the generally accepted animal model for organophosphorus-induced delayed neuropathy, exhibiting both clinical signs and histopathological damage after exposure. In this study, noninvasive electrodiagnostic methods were used for assessment of the development of neuropathy after administration of a single dose of protoxicant tri-ortho-tolyl phosphate (TOTP, 360 and 500 mg/kg po) and active congener phenyl saligen phosphate (PSP, 2.5 and 6 mg/kg im). Onset and severity of clinical signs were dose-related for both organophosphorus compounds. Extensive peripheral nerve lesions consistent with advanced stages of organophosphorus-induced delayed neuropathy were noted in selected chickens examined 19 d after TOTP administration. Needle electromyographic examinations of gastrocnemius, anterior tibialis, semitendinosus, and semimembranosus muscles were done before exposure and on d 8, 15, and 19 after exposure to TOTP and on d 8, 15 and 17 after exposure to PSP. Untreated chickens (negative controls) were also examined at each session. An untreated chicken with a transected sciatic nerve (positive control) was examined on d 13, 20, and 23 posttransection. Prolonged insertional activities were found in both treated and untreated chickens. Denervation potentials were found in only 2 of the 20 chickens administered organophosphates. Denervation potentials were, however, easily visible 13 d following transection of the sciatic nerve of a normal chicken. Needle electromyography could not evaluate organophosphorus-induced delayed neuropathy in chickens of this study.

Animals↗

PubMed1988

Chlortetracycline and aflatoxin interaction in two lines of chicks.

To determine if feed contaminants and feed additives interact, day-old chicks from lines bred for high and low antibody response to sheep erythrocytes were fed aflatoxin at a level of 3,000 ppb, chlortetracycline at a level of 550 ppm, or a combination of aflatoxin and chlortetracycline for a period of 6 wk. Weight gain in both lines of chicks was adversely affected by the aflatoxin treatment. There was a synergistic adverse effect in chicks of the low antibody response line when given chlortetracycline as well as aflatoxin, an effect not noted in chicks of the high antibody response line. Chlortetracycline alone had no effect on weight gain of low antibody response birds but increased the weight gain of chicks from the high antibody response line. Bursa to body weight ratios were adversely affected by aflatoxin in both lines of chicks, but chlortetracycline further adversely affected this parameter only in the low antibody response line. These results indicate that adverse effects of aflatoxin may be enhanced by addition of antibiotics to feed.

Aflatoxins↗

PubMed1988

The biventer cervicis nerve-muscle preparation of adult hens: effects of phenyl saligenin phosphate administration.

A biventer cervicis nerve-muscle preparation was used to assess in vitro neuromuscular function in adult white leghorn hens with clinical signs of delayed neuropathy induced by phenyl saligenin phosphate (PSP). Denervation of fast-twitch muscle fibers 13-15 days after PSP was indicated by higher excitability thresholds and by discontinuities of the strength-duration curves. Nerve degeneration was also indicated by significantly elevated rheobase values for all three experimental groups (2, 6 and 10 mg/kg PSP, im) and by shorter chronaxie for preparations from hens receiving 6 and 10 mg/kg. Chronaxie values for preparations from hens given 2 mg/kg PSP were longer than controls, indicating only partial denervation. Biventer cervicis muscle from all PSP-treated hens was 100-1000x more sensitive to acetylcholine (ACh) than muscle from untreated hens, a response typical of denervated slow-tonic muscle. Tension development in response to ACh was 20-45x greater than control in muscle of PSP-treated hens. The greatest sensitivity and tension development in response to ACh was encountered in muscles from hens given 10 mg/kg PSP. Denervation was also indicated histologically by the extensive degeneration and loss of larger myelinated nerve fibers. This study indicates that alteration in neuromuscular function and morphology occurs in the neck region of chickens during OPIDN and that deficits in nerves innervating both fast-twitch and slow-tonic muscles can be differentiated by nerve stimulation and by denervation hypersensitivity to ACh.

Animals↗

PubMed1987

Comparative sensitivities of avian neural esterases to in vitro inhibition by organophosphorus compounds.

The inhibitory power of organophosphorus compounds in vitro was compared against neurotoxic esterase (also known as neuropathy target esterase, NTE), acetylcholinesterase and carboxylesterase activities in brains from chickens, turkeys, quail and rats. Brains from the species most susceptible to clinical signs of organophosphorus-induced delayed neuropathy (chicken, turkey) contained more NTE than did rat and quail. Higher concentrations of organophosphorus compounds were required to inhibit rat NTE and quail acetylcholinesterase than were necessary for inhibition of these enzymes in chicken and turkey brains. Total carboxylesterase and acetylcholinesterase activities were less in rats than in the avian species.

Animals↗

PubMed1987

Neuropathological effects of phenyl saligenin phosphate in chickens.

Cyclic phenyl saligenin phosphate (PSP) proved to be a potent delayed neurotoxin, eliciting clinical disease and lesions, and depressing neuropathy target esterase and plasma cholinesterase at much lower doses than the protoxicant tri-ortho-tolyl phosphate (TOTP). Using adult White Leghorn chickens, we noted qualitative similarities in clinical signs and peripheral nerve and spinal cord lesions elicited by PSP and the TOTP. Ataxia and weakness were prominent clinical effects. Lesions began as a distal axonopathy affecting larger myelinated fibers in spinal cord white matter and peripheral nerve. The latter were studied in detail. Major features of the lesion were intra-axonal collections of mitochondria, dense and lamellar bodies, and granular degeneration of neurofilaments. These led to Wallerian-like degeneration. Percentages of teased peripheral nerve fibers demonstrating such degeneration correlated with severity of clinical signs.

Animals↗

PubMed1986

Dose-related beneficial and adverse effects of dietary corticosterone on organophosphorus-induced delayed neuropathy in chickens.

Tri-ortho-tolyl phosphate (TOTP), 360 mg/kg, po, and 0,0'-diisopropyl phosphorofluoridate (DFP), 1 mg/kg sc, were administered to adult White Leghorn chickens 24 hr after they were placed on diets containing 0 to 300 ppm corticosterone. Supplemented diets were continued until clinical signs and lesions of delayed neuropathy appeared. Although low concentrations (less than or equal to 50 ppm) of corticosterone had beneficial effects on TOTP-induced neuropathy, greater than or equal to 200 ppm exacerbated clinical signs in chickens given either TOTP or DFP. Neurotoxic esterase activities 24 hr after TOTP or DFP were less than 20% of values measured in chickens not given organophosphorous compounds. Chickens given 200 ppm corticosterone without TOTP or DFP had significantly elevated activity of plasma cholinesterase and significantly inhibited activity of liver carboxylesterase. Degenerating myelinated fibers were also evident in distal levels of the peripheral nerves of chickens given TOTP or DFP.

Administration, Oral↗

PubMed1986

Effect of supplemental corticosterone and social stress on organophosphorus-induced delayed neuropathy in chickens.

Adult White Leghorn roosters maintained for 3 months in an environment of low social stress (LSS) were given triorthotolyl phosphate (TOTP), 180 mg/kg po, 24 h after initial exposure to either an environment of high social stress (HSS) or exogenously administered corticosterone (200 ppm in diet). The environment of HSS or the administration of corticosterone were continued for 10 days after TOTP administration. It was noted that the heterophil/lymphocyte ratio, a hematological indicator of stress, was similar in both groups and both had similar scores for clinical signs of delayed neuropathy. Both heterophil/lymphocyte ratios and clinical scores were significantly lower in chickens kept in the LSS environment and not fed corticosterone than in chickens kept in the HSS environment or fed corticosterone.

Administration, Oral↗

PubMed1986

Effect of neurotoxic organophosphorus compounds in turkeys.

To determine the neurotoxic effects of organophosphorus compounds in turkeys, adult birds were given a single oral dose of 125, 250, 500 mg/kg triorthotolyl phosphate (TOTP) or a single subcutaneous dose of 0.4 mg/kg O,O'-diisopropyl phosphorofluoridate (DFP). At 24 h after dosing with TOTP, neurotoxic esterase activity was found to be inhibited in a dose-related manner, as were the activities of blood cholinesterase and liver cholinesterase. Clinical signs of neuropathy appeared within 2 wk in TOTP-treated groups of birds with neurotoxic esterase activities at 59 +/- 3% (125 mg/kg), 47 +/- 7% (250 mg/kg) and 33 +/- 3% (500 mg/kg) of control values (mean +/- SEM, n = 5) at 24 h after dosing. Signs appeared earlier in turkeys given DFP. Histological examination revealed only mild lesions of delayed neurotoxicity in birds given either TOTP or DFP.

Administration, Oral↗

PubMed1986

Effects of prolonged tremor due to penitrem A in mice.

Adult mice were given subcutaneous injections of purified penitrem A (10 mg/kg) dissolved in corn oil. The mycotoxin was prepared by ether extraction and absorption chromatography; identity was established by absorption and mass spectra. Tremors were sustained for 72 hr following a single dose; readministration every 3 days was used to provide continuous trembling for 18 days. No lesions specifically attributed to penitrem A could be detected by histological examination of brains even after 18 days of trembling. Pharmacological agents affecting central nervous system neurotransmitters had some capacity to modify the effects of penitrem A. The results of those studies were such that a definitive conclusion regarding mechanisms of action of the toxin could not be determined.

Animals↗

PubMed1986

Neurotoxicity of triorthotolyl phosphate in chickens of different genotypes in the presence and absence of deoxycorticosterone.

Indices of acute and delayed toxicity following administration of triorthotolyl phosphate (TOTP) were measured in roosters from lines of chickens originating from the Cornell randombred population. Matings were designed to produce individuals that had presence or absence of allele 21 of the B blood system. Non-B21 individuals had allele 13 or 31. Acute inhibition of esterases (neurotoxic esterase, liver cholinesterase, plasma cholinesterases, and plasma carboxylesterases) occurred in all birds within 24 hr of a single oral dose of 360 mg/kg TOTP. Clinical signs of delayed neuropathy were evident within 12 days of TOTP administration, with no significant difference between genotypes. Dietary deoxycorticosterone (40 to 200 ppm) appeared incapable of statistically significant modification of the strong effects of TOTP. Activities of blood esterases were different between roosters having B21/B21 and those with B13 and/or B31.

Acetylcholinesterase↗

PubMed1985

An expert system for information on pharmacology and drug interactions.

Pharmacological information has been organized and encoded in rules and frames for systematic retrieval. This includes: delineation, definition, and hierarchical subdivision of mechanisms responsible for drug interactions; division of pharmacological agents into a hierarchy of subclasses to allow for defining interacting drugs by classes as well as by specific agents; correlation of drug classes and specific drugs with mechanisms by which they may be involved in drug interactions. This information, accessible through a natural language-like and menu driven interface, allows clinicians to know what may happen when two drugs are used together, why, what can be done to alleviate detrimental interactions, and what related drugs may also be involved in similar interactions.

Drug Information Services↗

PubMed1985

Aflatoxin effects in white Leghorn chickens selected for response to sheep erythrocyte antigen. 2. Serological and organ characteristics.

Aflatoxin was fed to chickens from lines selected for high and low antibody response to sheep erythrocyte (SRBC) antigen and reciprocal crosses between the two lines. Differences were found among populations for liver, bursa, and thymus weight and antibody production to SRBC but not for spleen weight or heterophil: lymphocyte ratios. Dietary aflatoxin depressed absolute and relative weights of bursae and thymi and absolute weights of livers and spleens. Relative to body weight, however, liver and spleen weights increased. There was a large decrease in liver metabolism and a dramatic increase in heterophil: lymphocyte ratios when 5700 ppb of aflatoxin was fed, but no alteration in antibody production to SRBC antigen was detected. Population by response to aflatoxin interactions were not significant for any of the traits measured except bursa and spleen weights, suggesting a general response to this mycotoxin among lines of chickens known to be immunologically different.

Aflatoxins↗

PubMed1985

Aflatoxin-antioxidant effects on growth of young chicks.

Butylated hydroxytoluene (BHT), an antioxidant, was provided to chicks at 8 X, 30 X and 80 X the normal concentrations in their feed beginning at 1 day of age and continuing for the next 6 weeks. The ability of these birds to resist the adverse effects of dietary aflatoxin (3000 ppb, beginning Day 8) was measured by weight gain and feed efficiency over the 6-week period of study. Birds on aflatoxin-contaminated feed did not gain weight as rapidly or as efficiently as birds on uncontaminated feed. Depression of growth caused by aflatoxin was significantly less in birds given BHT than in those fed the diet not containing antioxidant.

Aflatoxins↗