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Biomedical subjects

L M McLeay

Publications and source records attributed to L M McLeay.

At least 19 recordsLinked to original sources

Tremorgenic mycotoxins increase gastric smooth muscle activity of sheep reticulum and rumen in vitro.

Reticulum and rumen strips (consisting of both muscle layers and the myenteric plexus) were superfused with Tyrode Ringer and their contractions recorded isometrically. The strips were subjected to exogenous acetylcholine and electrical field stimulation (EFS) resulting in contractions that could be blocked by atropine. Responses to the tremorgenic mycotoxin penitrem A and others thought to be involved in ryegrass staggers, paxilline and lolitrem B (10(-10)-10(-6)M), were compared with those of control vehicle (0.1% DMSO). The tremorgens were without effect on quiescent preparations. Penitrem A and paxilline enhanced spontaneously active preparations and the amplitude of contractions in response to EFS. Responses to paxilline had a shorter latency than to penitrem A. Responses of spontaneously active preparations were resistant to atropine. Penitrem A, but not paxilline, increased responses to exogenous acetylcholine. Lolitrem B (10(-6)M) increased responses to EFS, but many responses were equivocal, possibly due to the lower solubility of lolitrem B in aqueous solutions compared to the other tremorgens. The results show that these mycotoxins have peripheral excitatory effects on the reticulorumen and it is suggested that such activity in vivo may reflexly affect centrally derived cyclical contractions.

Animals↗

Reticular groove contraction in dairy cattle following drenching with an anti-bloat solution or a combination of anti-bloat solution and NaCl.

AIM: To determine whether the inclusion of NaCl in an antibloat drench increased the incidence of contraction of the reticular (oesophageal) groove in cattle. METHODS: Non-lactating Friesian dairy cows aged 3-10 years (n=30) were subjected to a 13C-octanoic-acid breath test after being drenched with either an anti-bloat solution alone or a mixture of anti-bloat solution and NaCl, to determine the incidence of reticular groove contraction. RESULTS: Drenching with an anti-bloat solution alone did not result in detectable by-pass of the reticulorumen in 27/29 cows; minor by-pass occurred in 2/29 cows. The inclusion of NaCl in the anti-bloat solution increased the incidence of reticulorumen by-pass; minor by-pass occurred in 12/30 cows and substantial by-pass was detected in 5/30 cows. The incidence of by-pass did not vary significantly with cow age. CONCLUSIONS: Drenching with an anti-bloat solution alone did not result in significant by-pass of the reticulorumen. The inclusion of NaCl in the anti-bloat drench increased the incidence of reticulorumen by-pass. The proportion of anti-bloat/ NaCl fluid by-passed was considered to be of no practical significance to the protection from bloat afforded in the majority of animals, but may significantly decrease protection from bloat afforded by drenching in 10-15% of cows. The proportion of animals at risk within a herd may vary with their physiological state and the method and frequency (number of doses per drench) of drenching.

Journal Article↗

Tremorgenic mycotoxins paxilline, penitrem and lolitrem B, the non-tremorgenic 31-epilolitrem B and electromyographic activity of the reticulum and rumen of sheep.

The mycotoxic tremorgens penitrem, paxilline and lolitrem B had profound effects on electromyographic (EMG) activity of smooth muscle of the reticulorumen in conscious sheep, with a similar time course of action to their respective characteristic effects on the induction (1 to 2, 15 to 20 and 20 to 30 minutes) and the duration (1 to 2, 1 to 2 and 8 to 12 hours) of tremoring. Responses to penitrem revealed a greater sensitivity of smooth muscle than skeletal muscle. Effects included an inhibition of the vagally-dependent cyclical A and B sequences of contraction of the reticulorumen, an increase in their amplitude and an excitation of local intrinsic activity contributing to elevated baselines and the occurrence of chaotic activity of the reticulum. The excitatory local effects were partially blocked by atropine, indicating that stimulation of muscarinic cholinoceptors was involved. Increased local activity may mediate a reflex inhibition of cyclical contractions. A non-tremorgenic isomer of lolitrem B (31-epilolitrem B) had no effect on the reticulorumen. The intensity and duration of the effects of lolitrem B, up to 12 hours, indicate that severe disruption of digestion may occur in animals grazing endophyte-infected pasture.

Animals↗

Use of a breath test to determine the fate of swallowed fluids in cattle.

OBJECTIVE: To investigate a [13C]octanoic acid breath test as a means of detecting reticular groove contraction in cattle. ANIMALS: 19 adult dairy cows with fistulated rumen, 10 yearling bulls, and 6 yearling steers. PROCEDURE: Cows were given 200 mg of [13C]octanoic acid in the caudal portion of the rumen, reticulum, or omasum/abomasum through the reticulo-omasal orifice, or were given the same dose of label with a drench of water or sodium bicarbonate. Collected breath was analyzed for 13C in CO2 for up to 3 hours. Breath of yearlings was analyzed for 13C in CO2 over 20 minutes after drenching with 200 mg of [13C]octanoic acid with water or sodium chloride and after sucking 200 mg of [13C]octanoic acid with molasses and water. RESULTS: In cows, enrichment of 13C in breath CO2 peaked at 20 to 30 minutes after placement of [13C]octanoic acid through the orifice, compared with a lower peak at 60 and 90 minutes after placement in the reticulum and rumen, respectively. The maximal increase in enrichment after placement of [13C]octanoic acid in the reticulum did not overlap with the minimal increase when placed through the reticulo-omasal orifice. Enrichment values in cows after drenching were consistent with values obtained after direct placement of [13C]octanoic acid. In yearlings, the inclusion of sodium chloride in the drench greatly increased enrichment, compared with water, but enrichment was greatest after sucking of the molasses, water, and [13C]octanoic acid combination. CONCLUSIONS AND CLINICAL RELEVANCE: This breath test provides a simple, repeatable, nonradioactive, and noninvasive means of detecting the fate of swallowed fluids in cattle, thus revealing the route taken of orally administered therapeutic agents or nutrients.

Abomasum↗

Inhibitory effects of short intravascular infusions of propionate on reticulo-rumen motility in the sheep.

The effect of short infusions into the hepatic portal vein of propionate on reticulo-rumen motility was examined in conscious sheep. Infusions of 10 min duration of propionate at 1-6 mmol.min-1 into the portal vein reduced the frequency and amplitude of reticulum and rumen contractions, especially the amplitude of rumen contractions. Inhibitory effects were not confined to the portal route and were also obtained via the jugular vein, carotid artery, coeliac artery and anterior mesenteric artery. Butyrate was also effective, but acetate much less so and NaCl almost without effect. The inhibitory responses remained after section of nerves to the liver. It appears unlikely the effects reflexly originate from the liver or are derived centrally.

Acetates↗

Excitatory effects of volatile fatty acids on the in vitro motility of the rumen of sheep.

The effects of 1 to 100 mM volatile fatty acids (VFA) on the cranial dorsal rumen musculature of sheep were examined in vitro. Sodium acetate, sodium propionate and sodium butyrate, either singly or as a mixture, stimulated marked dose-dependent contractions of longitudinal muscle (LM) and internal oblique muscle (IOM). The threshold concentration was between 1 and 3 mM depending on the VFA and the muscle tissue and the responses were modified by the presence of the mucosal epithelium. The responses to VFA were significantly decreased by atropine (10(-6) M) and tetrodotoxin (10(-7) M) but were unaffected by hexamethonium (10(-3) M). Indomethacin (10(-6) M) modified the responses, suggesting that prostaglandins may also be involved. Acetic, propionic and butyric acids also stimulated dose-dependent contractions of LM and IOM. After having been stimulated with 100 mM acids the preparations became refractory to further stimulation by acetylcholine. It is concluded that in vitro the acid and salt forms of VFA excite contractions of the rumen by both cholinergic and non-cholinergic mechanisms.

Acetylcholine↗

Fly ash, basic slag and Glenbrook slag toxicity in cattle.

In case studies of two herds of dairy cattle, a herd of 270 Friesian cows and heifers and a herd of 256 Jersey cows and heifers experienced high death rates and a protracted course of illness when fly ash was broadcast as a fertiliser over the farms at a rate of about 1 tonne per hectare. The onset of weakness, lassitude and diarrhoea in the cattle first appeared within 4-5 days and both fertility and milk fat production fell off dramatically. In the following 7 months, 51 animals died in the Friesian herd and a similar death rate and performance losses occurred in the Jersey herd. Emaciation and hepatic fibrosis were consistently reported from autopsies. Heavy metal poisoning was eliminated from the possible diagnosis. The slags and fly ash used as fertiliser had several features in common. They contained 29-40% calcium as calcium oxide, 15-35 grams of iron per kg, they were all extremely alkaline and concentrations of lead and arsenic were low. The effect of adding fly ash to rumen contents in vitro was to raise the pH to greater than 7.2, at which point fermentation was markedly-reduced.

Journal Article↗

Adrenal cortex response to adrenocorticotropic hormone in dairy cattle.

Adult dairy cows were treated with a range of doses (0.0125mg to 0.4mg) of synthetic ACTH1-24 and the plasma cortisol response was measured. Peak response was independent of dose. Higher doses of ACTH had a more prolonged effect such that the integrated response was dose dependent. Dose response curves were examined by regression analyses. Individual cows had a significant effect on y-axis intercept but not on the slope of the regression lines examined. A dose rate of 0.05mg ACTH iv was identified as a suitable dose rate for use in clinical assessment of adrenal cortex function, with 0, 50 and 120 min following ACTH being critical sampling times to identify the response.

Adrenal Cortex↗

Effects of epidermal growth factor on gastrointestinal electromyographic activity of conscious sheep.

Adult sheep were infused with depilating doses of epidermal growth factor (EGF) at 4 micrograms/kg per h for 24 h. Food was available ad libitum during recording of integrated electromyographic (EMG) activity of the gastrointestinal tract. In comparison with control sheep infused with saline, EGF reduced the frequency of A and B sequences of contraction of the reticulum and rumen over the 24-h period, an effect attributable to the consumption of less food. During the 24-h infusion, EGF stimulated phase III migrating myoelectric complex (MMC)-like activity of the duodenum with an associated decline in the EMG of the abomasal antrum. Infusion of EGF for 1 h at 2.5 and 5.0 micrograms/kg per h in fasted animals produced inhibitory effects on the frequency of A sequences of contraction of the reticulum and rumen during the infusion, and on the amplitude of the ruminal EMG during, and in the hour following, infusion. Phase III MMC-like activity of the duodenum was stimulated by EGF in fasted animals. It is concluded that in fed sheep, depilating doses of EGF have inhibitory effects on the EMG activity of the reticulum and rumen through reductions in food consumption and by other undefined mechanisms. Additional effects of EGF on the gastrointestinal tract of sheep include stimulation of duodenal phase III MMC-like activity.

Abomasum↗

Excitatory and inhibitory effects of gastrin peptides on gastric motility in sheep.

In conscious sheep, tetragastrin, pentagastrin, and synthetic human gastrin I, injected either subcutaneously or intravenously in doses of 156-5,200 pmol/kg body wt, inhibited the vagally dependent cyclical motility of the reticulum and rumen, whereas in vitro pentagastrin (10(-12) to 10(-6) M) had no demonstrable inhibitory or excitatory effects on intrinsically active or quiescent muscle of the reticulum, rumen, and omasal leaves. In vitro pentagastrin (10(-18) to 10(-4) M) stimulated quiescent and intrinsically active longitudinal and circular muscles of the body of the omasum and the body and antrum of the abomasum and potentiated contractile responses of antral muscle to electrical stimulation of intramural cholinergic nerves. Responses in the presence of hexamethonium, atropine, and tetrodotoxin indicated that the excitatory effects on mixed nerve-muscle preparations of omasal and abomasal tissue were mediated both through stimulation of cholinergic neurones and by direct actions on the muscle. In vitro the ovine stomach shows marked regional differences in both its response and sensitivity to gastrin peptides, and their inhibitory effects on reticuloruminal motility in vivo appear to be other than direct.

Abomasum↗

In vitro spontaneous motility of gastric smooth muscles of the sheep.

Whole strips of muscle wall cut parallel to their corresponding longitudinal, circular or internal oblique orientations in the reticulum, rumen, omasal body, abomasal body and antrum and to the muscularis mucosae of the omasal leaves were mounted along a vertical axis and their mechanical activities recorded isometrically. The strips were perfused with Tyrode-Ringer solution at 37 degrees C bubbled with 100% O2 or a mixture of 95% O2 + 5% CO2. Spontaneous activity was observed in muscle strips from all regions but not all muscle strips were spontaneously active: markedly greater spontaneous activity and a greater sensitivity to stimulatory agents occurred with 100% O2. Spontaneous activity was unaffected by the ganglionic blocking agent hexamethonium (10(-5) M) whereas atropine (10(-6) M) had no effect, or reduced and in some cases with rumen only, abolished activity. Acetylcholine (10(-6)-10(-7) M) caused contraction of all muscle except muscularis mucosae from omasal leaves. Electrical stimulation evoked responses which included atropine-sensitive contractions, relaxations and rebound contraction especially following atropine. The experiments showed that both major muscle layers of the reticulum, rumen, omasum and abomasum in mixed-layer preparations exhibited spontaneous activity when removed from the influence of their cholinergic innervation and this included atropine-resistant diphasic contractions of the internal oblique muscle of the reticulum. The muscularis mucosae of the omasal leaves exhibited spontaneous contractile activity unaffected by cholinergic agonists and antagonists.

Acetylcholine↗

Motility of the reticulum and rumen of sheep given juice-extracted pasture.

1. Sheep were fed on different diets of juice-extracted herbage to determine what effect juice-extraction had on reticulo-rumen motility. 2. The frequency of A and B sequences of contraction of the reticulo-rumen were recorded during eating, rumination and inactivity for continuous periods of 24-72 h by using integrated electromyograms obtained from electrodes implanted in the musculature of the reticulum and cranial dorsal rumen. 3. Animals were fed on herbage in which approximately 200 g/kg drug matter had been removed in juice extracted from ryegrass (Lolium perenne), white clover (Trifolium repens), mixed ryegrass-white clover and lucerne (Medicago sativa). 4. Over all the frequency of A sequences of contraction did not differ in animals fed on pressed herbage or the unpressed material from which it was derived, although it was slower during rumination on some of the pressed material. In contrast, the frequency of B sequences was higher on the pressed material. The frequencies of contraction of A and B sequences in animals fed on pressed herbage was related to the activity of the animals in the order eating greater than rumination greater than inactivity. 5. Changes in reticulo-rumen motility due to juice extraction were small and the frequencies of A and B sequences of contraction in sheep fed on pressed herbage were in the range encountered in ruminants consuming more conventional foods.

Animal Feed↗

Inhibition of ovine gastric acid secretion by intraduodenal long-chain fatty acids.

Effects on ovine gastric function of procedures that increase intestinal unsaturated fatty acid content are unknown, and the present aim was to compare the effects of duodenal unsaturated and saturated fatty acids on gastric secretion in conscious sheep. During the maximal gastric secretory response to a meal, 10 ml gallbladder bile alone or with myristic, palmitic, and stearic acids and oleic, linoleic, and linolenic acids were infused into the duodenum at a rate of 5 g fatty acid . h-1 for 1 h. Compared with control 154 mM NaCl (100%), acid output was reduced to 4-7% of control with infusion of oleic, linoleic, and linolenic acids and myristic acids plus bile. Reductions in acid secretion persisted for up to 5 h from the end of infusion. In contrast, the infusion of palmitic and stearic acids with bile caused mean maximal reductions in acid output, respectively, to only 64 and 55% of control, and levels returned to control within 1 h of the end of infusion. Bile infusion alone caused no reduction in acid secretion. Under the conditions used, C18 unsaturated fatty acids and myristic acid were potent inhibitors of ovine gastric acid secretion. The lesser effects of palmitic and stearic acids were probably related to their reduced solubility and absorption.

Animals↗

Location and secretion of gastric intrinsic factor in the sheep.

The site of production and secretion of intrinsic factor (IF) in the sheep has been studied using a human auto-antibody directed against IF. Immunofluorescent studies indicated the abomasal parietal cell was the source of IF in the sheep. Concentrations of IF in pure gastric secretion of sheep were relatively stable at 3 to 4 iu/ml and it was estimated that the total abomasal output of IF was 10,000 to 23,500 iu per 24 hours.

Abomasum↗

The effect of duodenal infusion of milk, casein, lactose and fat on gastric emptying and acid secretion in the milk-fed calf.

1. The effect of infusion of the duodenum with milk, casein, lactose and fat on gastric acid secretion and abnormal emptying of a saline meal was studied in milk-fed calves. 2. Compared with sodium bicarbonate, infusion with casein or lactose, alone or together, caused a small but statistically significant slowing of gastric emptying but did not effect gastric acid secretion. 3. Infection of the duodenum with cows' milk replacer or bovine milk fat slowed gastric emptying markedly and reduced gastric acid secretion significantly below levels obtained with sodium bicarbonate infusion. 4. The experiments provide evidence for the existence of mechanisms which prevent the passage of substantial amounts of whole milk into the duodenum before it has been subjected to gastric digestion.

Animals↗

Acid and pepsin secretion of separated gastric pouches during perfusion of antral pouches with cholinergic stimulating and blocking agents and lignocaine.

1. Secretion of HCl and pepsin from abomasal fundic pouches was studied in sheep during perfusion of antral pouches with cholinergic blocking and stimulating agents and lignocaine. 2. Resting secretion was reduced to about 50% of control levels and secretory responses to feeding were largely or completely blocked during antral pouch perfusions with atropine (0-01-0-16%) and hexamethonium (1%). 3. Antral pouch perfusions with lignocaine (2%) reduced fundic pouch resting secretion to about 60% of control values but did not block secretory responses to feeding. 4. Perfusions of acetylcholine (0-1%) and carbachol (0-0037 and 0-005%) through antral pouches characteristically stimulated increases in the concentration of acid, outputs of acid and pepsin, but not concentration of pepsin. 5. The mechanisms involved in the release of gastrin in the sheep are discussed. 6. It is concluded that antral secretion of gastrin contributes both to the maintenance of resting secretion of acid and the secretory responses of fundic pouches of sheep when they eat freshly provided food.

Abomasum↗

Inhibition of hydrochloric acid and pepsin secretion from gastric pouches by antral pouch acidification in sheep.

1. Secretion of acid and pepsin from separated pouches of the body of the abomasum was studied in sheep during perfusion of antral pouches with acid solutions. 2. Resting secretion of acid and pepsin was reduced by acidification of antral pouches to pH 2.7 or less. 3. Increases in the secretion of HCl and pepsin normally obtained on feeding were reduced or abolished by perfusion of antral pouches with solutions at pH 1.3--2.0. 4. Perfusion of antral pouches with acetylcholine at pH 2.5 failed to stimulate acid secretion as it did at a higher pH. 5. Pentagastrin stimulated acid and pepsin secretion during the inhibition of secretion produced by antral pouch acidification. 6. Increases in reticular motility occurred on antral pouch acidification with solutions of pH 1.1--1.3. 7. The contribution of antral pH in regulating abomasal acid secretion is discussed.

Abomasum↗