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Biomedical subjects

J Egerton

Publications and source records attributed to J Egerton.

14 recordsLinked to original sources
PubMed2003

Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency.

BACKGROUND: Faecal urgency and incontinence with rectal hypersensitivity is a distressing, unexplained disorder that is inadequately treated. We aimed to determine whether expression of the heat and capsaicin receptor vanilloid receptor 1 (TRPV1 or VR1) was changed in rectal sensory fibres, and to correlate nerve fibre density with sensory abnormalities. METHODS: We compared full-thickness rectal biopsy samples from nine patients with physiologically characterised rectal hypersensitivity with tissue samples from 12 controls. Sensory thresholds to rectal balloon distension and heating the rectal mucosa were measured before biopsy. We assessed specimens with immunohistochemistry and image analysis using specific antibodies to TRPV1; nerve growth factor (NGF) receptor tyrosine kinase A; glial cell line-derived neurotrophic factor (GDNF); neuropeptides calcitonin gene-related peptide (CGRP) and substance P; the related vanilloid receptor-like protein (VRL) 2; glial markers S-100 and glial fibrillary acid protein (GFAP); and the nerve structural marker peripherin. FINDINGS: In rectal hypersensitivity, nerve fibres immunoreactive to TRPV1 were increased in muscle, submucosal, and mucosal layers: in the mucosal layer, the median% area positive was 0.44 (range 0.30-0.59) in patients who were hypersensitive and 0.11 (0.00-0.21) in controls (p=0.0005). The numbers of peripherin-positive fibres also increased in the mucosal layer (hypersensitive 3.00 [1.80-6.50], controls 1.20 [0.39-2.10]: (p=0.0002). The increase in TRVP1 correlated significantly with the decrease in rectal heat (p=0.03) and the distension (p=0.02) sensory thresholds. The thresholds for heat and distension were also significantly correlated (p=0.0028). Expression of nerve fibres positive for GDNF (p=0.001) and tyrosine kinase A (p=0.002) was also increased, as were cell bodies of the submucosal ganglia immunoreactive to CGRP (p=0.0009). INTERPRETATION: Faecal urgency and rectal hypersensitivity could result from increased numbers of polymodal sensory nerve fibres expressing TRPV1. The triggering factor or factors remain uncertain, but drugs that target nerve terminals that express this receptor, such as topical resiniferatoxin, deserve consideration.

Adult↗
PubMed2002

TRPV3 is a temperature-sensitive vanilloid receptor-like protein.

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.

Amino Acid Sequence↗
PubMed2001

Titration of subcutaneously administered eprinomectin against mature and immature nematodes in cattle.

Eprinomectin has been approved for use as a topically applied endectocide for beef and dairy cattle. To determine if eprinomectin has utility as an injectable anthelmintic, it was titrated at 0.05, 0.1, and 0.2 mg/kg s.c. against adult (Trial 1) and at 0.05, 0.1, 0.14, and 0.2 mg/kg s.c. against immature (Trial 2) stages of lung and gastrointestinal nematodes in cattle. In Trial 1, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, T colubriformis, Cooperia punctata, Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus. Adult C. oncophora was the only exception. However, even against this species, the lowest dose of 0.05 mg/kg showed 93% efficacy, and the efficacious dose necessary to kill 95% (ED95) of adults was 0.056 mg/kg. In Trial 2, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against the immature stages of all of the above species of endoparasites. As a result, ED95 values could not be calculated. Consequently, the exquisite potency against endoparasites through parenteral administration suggests that eprinomectin may also have potential utility as an injectable product for cattle.

Age Factors↗
PubMed1992

Antipyrine, erythromycin and oxytetracycline disposition in experimental fasciolosis.

The effects of fasciolosis on drug disposition were studied by administration of antipyrine, erythromycin and oxytetracycline to sheep and cattle. Fasciolosis was produced by administration of 200 or 400 metacercariae (MC) of Fasciola hepatica to sheep and 500 MC to cattle. The disease was subsequently confirmed by determination of plasma glutamate dehydrogenase and gamma-glutamyl transferase and identification and quantitation of mature flukes in the liver at necropsy. Acute or subacute fasciolosis in sheep was accompanied by a significant decrease in the elimination rate constant (beta) and increase in the elimination half-time (t 1/2) for antipyrine and erythromycin when compared with controls or infected sheep which had been treated with the anthelmintic luxabendazole. An increase in apparent volume of distribution (Vd) was seen only for erythromycin in sheep given 400 MC. There were no changes in the disposition of oxytetracycline in sheep with either acute or subacute infection and no effects on disposition of the three test drugs in chronically infected sheep. With early chronic disease in calves, only the disposition of oxytetracycline was affected; not that of antipyrine or erythromycin.

Animals↗