gastrins and Ostertagiasis

Nematode larvae developing within the glands cause local loss of parietal cells and mucous cell hyperplasia whereas reduced acid secretion, increased serum gastrin and pepsinogen concentrations and generalized histological changes are associated with parasites in the abomasal lumen. Parietal cells with dilated canaliculi and/or degenerative changes typical of necrosis are present soon after the transplantation of adult worms, and abomasal secretion is also affected. Anaerobic bacteria survive in greater numbers as the pH rises, with bacterial densities becoming similar to ruminal populations at an abomasal pH of 4 and above. Failure to lyse bacteria may affect adversely the nutrition of the host. The parasites may initiate the pathophysiology through the release of excretory/secretory (ES) products which either act directly on parietal cells or indirectly through enterochromaffin-like (ECL) cells by provoking inflammation or by disrupting the protective mucosal defence system. Parietal cell dysfunction is proposed as a key event which leads to loss of mature chief cells and mucous cell hyperplasia, as well as hypergastrinaemia. Inflammation increases circulating pepsinogen concentrations and may also contribute to increased gastrin secretion. Stimulation of mucosal proliferation and differentiation of parietal cells in the isthmus by the raised serum gastrin levels will be beneficial by generating a new population of active parietal cells and adequate acid secretion.

Topics: Abomasum; Animals; Anorexia; Bacteria, Anaerobic; Cattle; Cattle Diseases; Gastrins; Haemonchiasis; Haemonchus; Host-Parasite Interactions; Hydrogen-Ion Concentration; Intestinal Mucosa; Ostertagia; Ostertagiasis; Pepsinogens; Sheep; Sheep Diseases; Stomach Diseases

Ostertagia ostertagi and Cooperia oncophora are widely distributed and are the most important parasites affecting young bovine livestock. Therefore, there is a substantial need for sensitive and specific parameters in support of their diagnosis, especially for sub-clinical disease correlated to production loss. In this review, the value and the application as a diagnostic tool of pepsinogen, gastrin and antibody response are discussed. An increase in pepsinogen or gastrin reflects mucosal damage caused by an Ostertagia infection. Some controversy exists about the level of pepsinogen and gastrin, which may be considered indicative for the diagnosis of clinical and sub-clinical ostertagiasis. Pepsinogen levels between 3,000 tot 4,000 mU tyrosine are regarded indicative for subclinical disease, values in excess of 5,000 mU tyrosine are considered significant for diagnosing clinical disease. For gastrin, it is suggested that based on group means, values of 400 pg/ml are indicative for subclinical parasitic disease in calves with reduced daily weight gain, while threshold levels of > or = 1000 pg/ml gastrin are representative for clinical ostertagiasis. Antibody responses to Ostertagia and Cooperia can be assessed using the enzyme immunoassay (EIA). Until now, mainly crude worm extracts have been used as antigen source in the EIA. They are not species-specific as discussed experiments provide evidence of a close relationship between the onset of parasitic disease and the evolution of the group mean parameters. However, data demonstrate serious variations between animals, which impede a reliable individual diagnosis. For longitudinal epidemiological studies especially pepsinogen and gastrin have proven their value, exhibiting fast fluctuations induced by infection or as a result of treatment. Conversely antibody levels were found to be more stable and therefore are useful in large cross-sectional studies, enabling a rough assessment of the degree of infection.

Topics: Animals; Antibodies, Helminth; Cattle; Cattle Diseases; Enzyme-Linked Immunosorbent Assay; Gastrins; Ostertagia; Ostertagiasis; Pepsinogens; Radioimmunoassay

Ostertagia ostertagi is widely distributed and is one of the most important parasites affecting young bovine livestock. There is, therefore, a substantial need for sensitive and specific parameters in support of diagnosis of ostertagiasis, especially for subclinical disease related to production losses. In this review, the value and application of pepsinogen, gastrin and antibody response as diagnostic tools are discussed. These three parameters are useful and comparable for confirming clinical disease in calves during their first grazing season. However, their value for detecting subclinical parasitism is questionable. Differences in the course of gastrin and pepsinogen late in the grazing season can be correlated with larval inhibition and the possibility of ostertagiasis Type II. Relatively few serological methods have been developed for the immunodiagnosis of Ostertagia and until now the indirect antibody-detecting enzyme-linked immunosorbent assay (ELISA) has been the method of choice. Antibody measuring methods have several disadvantages, most notably a lack of sensitivity and specificity, which limits their use in longitudinal epidemiological studies. Considering the necessity of cost effectiveness and ease of use, it is anticipated that additional work will result in the enhancement and quality of current immunodiagnostic methods.

Topics: Animals; Antibodies, Helminth; Biomarkers; Cattle; Cattle Diseases; Clinical Enzyme Tests; Gastrins; Immunoglobulin G; Ostertagiasis; Pepsinogens

Pathophysiological changes in the ruminant abomasum caused by Ostertagia infections include changes in the activity and concentration of gastrointestinal enzymes and hormones. Under certain circumstances, increases in concentration also occur in the bloodstream and, as such, are detectable. Determination of serum pepsinogen levels is useful in evaluating the risk or presence of ostertagiasis Type I in a herd. It seems less reliable when used to diagnose (pre) ostertagiasis in individual animals. Measurement of the concentration of other zymogens is not useful. The variations in methodology to determine pepsinogen levels (e.g. biochemical and immunological measurements) are discussed. Serum gastrin levels are, generally, increased in animals with ostertagiasis. At present, gastrin is mainly determined by RIA assays using human gastrin antibodies, but few baseline data are available on normal levels in ruminants. The use of gastrin determination as a diagnostic tool in Ostertagia-infected ruminants is limited.

Topics: Abomasum; Animals; Clinical Enzyme Tests; Gastrins; Ostertagiasis; Pepsinogens; Ruminants; Trichostrongyloidiasis

Twenty-five, castrated male Holstein-cross calves, between 4 and 5 months of age, weighing 156.5+/-12.2 kg and reared under conditions designed to minimise the risk of parasitic infection, were allocated to one of the five treatment groups on the basis of initial bodyweight. The groups were (1) ad libitum (ad lib) fed controls (ALC); (2) ad lib fed infected (INF) and treated with topical eprinomectin on Day 56; (3) controls pair-fed with the INF group (PFC); (4) ad lib fed controls treated with eprinomectin on Days 0 and 56 (E-ALC) and (5) ad lib fed, infected and treated with eprinomectin on Days 0 and 56 (E-INF). Infection comprised a trickle infection with the equivalent of 10,000 larvae of Ostertagia ostertagi per day from Day 0 to Day 56 and the study concluded on Day 77. Parameters measured throughout the study included: liveweight, feed intake, faecal egg counts; plasma pepsinogen, gastrin, ghrelin and leptin; plasma antibodies to adult O. ostertagi. No significant differences in feed intake or liveweight gain were observed between any of the different groups, a finding thought to result from the high quality of feed offered. Significant differences between the INF and control groups however were observed in faecal egg counts, plasma pepsinogen, gastrin and O. ostertagi antibodies, which were all elevated, and leptin, which was reduced. Values of these parameters for the E-INF group were intermediate between the INF and ALC groups. Plasma ghrelin showed no association with either feed intake or parasitism. Further studies are needed to fully elucidate the roles of various biochemical and neuroendocrine mediators for inappetence in ruminants with parasitic gastroenteritis.

Topics: Animals; Anthelmintics; Antibodies, Helminth; Cattle; Cattle Diseases; Feces; Feeding Behavior; Gastrins; Ghrelin; Ivermectin; Leptin; Male; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogen A; Time

Effects of Ostertagia ostertagi infection on secretion of insulin, pancreatic glucagon, cortisol, gastrin, and pepsinogen were studied in calves inoculated with 100,000 (group 1) or 10,000 (group 2) O ostertagi infective larvae weekly for 14 weeks. Plasma insulin concentrations in both inoculated groups were lower than those in a non-infected (group 3) control group. The differences between group 1 and group 3 were significant (P < 0.05) at 2 and 12 weeks after initial inoculation. Plasma pancreatic glucagon and cortisol concentrations of groups 1 and 2 did not differ significantly from those of the control group, although plasma pancreatic glucagon concentration was consistently lower in group-1 calves from 4 weeks to end of the study. Plasma pepsinogen and serum gastrin concentrations also increased significantly (P < 0.05) in both groups that received inoculations. We concluded that decreased plasma insulin concentrations are contributory to changes in postabsorptive protein metabolism, and that serum gastrin concentrations are more representative of the pathologic changes in the abomasum than are plasma pepsinogen concentrations.

Topics: Animals; Cattle; Cattle Diseases; Gastrins; Glucagon; Hormones; Hydrocortisone; Insulin; Male; Ostertagiasis; Pepsinogens

Heavy burdens of the abomasal nematode, Ostertagia (Telodorsagia) circumcincta, in growing lambs result in a reduction in liveweight gain due largely to a drop in voluntary feed intake. The present study investigated: (1) the role of subdiaphragmatic vagal and non-vagal visceral afferent nerves in mediating a reduction in voluntary feed intake, using subdiaphragmatic vagal deafferentation (vagotomy) either alone or in combination with coeliac-superior mesenteric ganglionectomy (vagotomy and sympathectomy); and (2) the association between appetite, abomasal pH, selected blood values (amidated gastrin (G-17-amide), glycine-extended gastrin (G-17-Gly), pepsinogen and leptin) and worm burden, in sheep experimentally infected with 100,000 O. circumcincta infective larvae per os. Neither vagotomy alone nor vagotomy and sympathectomy in combination adversely affected the establishment or course of development of the parasite burden, when compared with a control group subject to sham surgery. Furthermore, neither surgical procedure prevented the drop in appetite seen 5-10 days post-infection, although combined vagotomy and sympathectomy did reduce voluntary feed intake prior to the start of the study. Ostertagia infection resulted in a significant increase in abomasal pH in all three groups, which was accompanied by an increase in blood G-17-amide and in G-17-Gly, the latter reported for the first time in parasitized ruminants. There were no significant differences in blood leptin, also reported for the first time in parasitized sheep, either between groups or in comparison with pre-infection levels, though weak negative correlations were established between blood leptin and appetite from day 5 to the end of the study in all three groups and a positive correlation with blood G-17-amide in the control group over the same period. These data suggest that neither intact subdiaphragmatic vagal afferent nerves or coeliac-superior mesenteric ganglion fibres, nor changes in circulating gastrin and leptin concentrations play a major role in mediating the hypophagic effects of O. circumcincta in parasitized sheep.

Topics: Abomasum; Afferent Pathways; Animals; Anorexia; Energy Intake; Female; Gastrins; Hydrogen-Ion Concentration; Leptin; Male; Ostertagiasis; Random Allocation; Sheep; Sheep Diseases; Sympathectomy; Time Factors; Vagotomy; Weight Gain

Serum gastrin concentrations are typically elevated in parasitised sheep; however, in some animals serum gastrin concentrations may fall abruptly despite a very high abomasal pH. Although proliferating abomasal bacteria in culture generate a potent inhibitor of in vitro gastrin secretion, this inhibitor has not been detected in abomasal contents of unparasitised sheep. In sheep parasitised by O. circumcincta, all abomasal fluid samples of pH 5 and above were inhibitory to gastrin release in vitro. Inhibitory activity and abomasal pH were correlated in two separate experiments; the model best fitting the data being sigmoidal in each case, with zero activity at pH 3.6 and 4.6, respectively. There was no clear evidence that the presence of a gastrin inhibitor in the abomasal contents reduced the serum gastrin concentration in parasitised sheep. Serum gastrin was correlated with abomasal pH (log(10) serum gastrin concentrations conformed to log-linear sigmoidal models).

Topics: Abomasum; Animals; Female; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Male; Ostertagia; Ostertagiasis; Regression Analysis; Sheep; Sheep Diseases; Stomach Diseases

It has been suggested that parasite excretory/secretory (ES) products may be capable of direct stimulation of gastrin secretion and of contributing to the hypergastrinaemia typical of abomasal parasitism. Ostertagia circumcincta ES products were tested on an ovine antral mucosal preparation which had been developed for a pharmacological study of gastrin secretion in the sheep. Its responsiveness to chemical stimulation was established by stimulation with amino acids and amines: tryptophan (0.1-5 mM) and phenylalanine (10-100 mM) stimulated gastrin release (151-160 and 117-129%, respectively), whereas glycine (0.1-100 mM) was without effect; ammonium sulphate, but not sodium sulphate, stimulated gastrin release in concentrations from 1mM (122%) to 50mM (148%). ES products were prepared by incubation of exsheathed third-stage larvae (L3) or parasites recovered on Day 8 p.i. (L4), Day 12 p.i. (10% L4, 90% immature adults), Day 21 p.i. (5% L4, 30% immature adults, 65% adults), Day 22 p.i. (20% immature adults, 80% adults), Day 30 p.i. (adults) and Day 35 p.i. (adults), or a mixed-age parasite population. Worms were recovered from agar and incubated in either distilled water or Hank's balanced salt solution (HBSS) adjusted to pH 2.5, 3.5, 4.5, 5.0 or 7.4. HBSS pH 7.4 was also prepared with antibiotics, without glucose, and with antibiotics but without glucose. Survival of Day 21 and 35 worms and exsheathed L3 in water or in a series of HBSS adjusted to pH 2.5, 3.5, 4.5, 5.0 or 7.4 was assessed from the percentage of motile parasites. L3 slowly became immotile over several days except in HBSS pH 2.5, in which survival was reduced, whereas adult worms did not tolerate incubation at 37 degrees C in water or HBSS at pH 2.5, retained motility for about 2 days at pH 3.5, but survived well at pH 4.5 and above. Incubates prepared from all stages of O. circumcincta, both in media favourable and unfavourable for parasite survival, failed to stimulate consistently the secretion of gastrin by tissue from both parasite-naive and previously exposed sheep, whereas a considerable number of incubates were significantly inhibitory. The inhibitor may not be produced by the nematodes, but by contaminating abomasal or environmental microflora, as inhibitory activity was predominantly generated by prolonged incubation, it was less potent when glucose was omitted and was not present in media containing antibiotics. This study did not find evidence for a gastrin stimulant in O. circu

Topics: Abomasum; Amino Acids; Animals; Anti-Bacterial Agents; Gastrins; Glucose; Hydrogen-Ion Concentration; In Vitro Techniques; Ostertagia; Ostertagiasis; Sheep; Time Factors

Infection with the bovine abomasal nematode, Ostertagia ostertagi, results in a loss of acid-secreting parietal cells and an increase in gastric pH. The effects of an experimental infection with Ostertagia and/or daily treatment with omeprazole (OMP) at 2mgkg(-1) bodyweight for four consecutive days (experiment days 24-27, inclusive) on voluntary feed intake, blood and tissue gastrin concentrations, abomasal G-cell numbers, gastric pH, and blood cholecystokinin (CCK) and pepsinogen concentrations were investigated in the calf. Ostertagia-infected calves demonstrated a significant drop in feed intake between days 24 and 27 post-infection (38%; P<0.001) and in G-cell numbers (42%; P<0.05) and significant increases in abomasal pH (P<0.001), fundic mucosal weight (99%; P<0.01), and blood gastrin (P<0.05) and pepsinogen (P<0.0001). OMP treatment of worm-free animals resulted in a significant drop in intake between days 24 and 27 (30%; P<0.001) and in G-cell numbers (17%; P<0.05) and significant increases in abomasal pH (P<0.01) and blood gastrin (P<0.001). OMP treatment of Ostertagia-infected animals with an existing hypergastrinaemia had no effect on feed intake, abomasal pH, blood gastrin or pepsinogen or abomasal G-cell numbers. Blood CCK concentrations were also unaffected by either Ostertagia infection or OMP treatment. These data suggest that: (a) the depression in feed intake associated with OMP in worm-free calves was not due to a side effect of drug treatment; (b) inappetance in Ostertagia-infected animals is closely associated with the parasite-induced hypergastrinaemia; and (c) the elevation in abomasal pH was a major factor responsible for the elevated blood gastrin concentrations seen in parasitised and OMP-treated animals.

Topics: Abomasum; Animals; Cattle; Cattle Diseases; Cholecystokinin; Eating; Enzyme Inhibitors; Feces; Female; Gastrins; Hydrogen-Ion Concentration; Immunohistochemistry; Omeprazole; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogen A

The acid secretory capacity of the abomasal mucosa was studied in sheep experimentally infected with Ostertagia leptospicularis. The acidity of the abomasal contents, permanently recorded by a pH probe located inside the abomasum, decreased markedly to mean levels between pH 5 and 6. Subcutaneous administration of histamine or carbachol successfully stimulated acid secretion (pH 3.4). The results indicate that the abomasal mucosa harboured a population of functional parietal cells which were also identified immunohistochemically (H(+)/K(+)-ATPase). Ultrastructural investigation before stimulation revealed that the majority of these cells was in a resting state. Despite high serum gastrin levels, the acid secretion was blocked either at the level of the parietal cell or the enterochromaffin-like cell by an unknown factor, possibly mediated by the parasites. This is the first report of a parietal cell dysfunction associated with a nematode infection in the abomasum. It is suggested that the parasites induce changes in their environment which favour their survival and/or increase their reproduction.

Topics: Abomasum; Animals; Feces; Gastric Acid; Gastrins; Gastroscopy; Hydrogen-Ion Concentration; Immunohistochemistry; Microscopy, Electron; Ostertagia; Ostertagiasis; Parietal Cells, Gastric; Pepsinogen A; Sheep; Sheep Diseases

Nine lambs, approximately 9 months of age were allocated to three groups (A, B, C), with three animals in each. Sheep in Groups A and B were trickle-infected with doses of 1000 third-stage larvae (L3) of Ostertagia leptospicularis (five times per week) over periods of 7.5 and 10.5 weeks, respectively, and were subsequently treated with fenbendazole (7.5 mg/kg). Approximately 3 weeks after anthelmintic treatment, all sheep were challenged with a single dose of 100,000 L3, whereas sheep of Group C received the same dose as a primary infection. Sheep of Groups A and B were almost completely refractory against the challenge infection, as indicated by negative faecal egg counts and adult worm burdens. A relatively high infection level was present in the sheep of Group C. The results indicate that a comparatively short immunization period of 7.5 weeks is sufficient to protect lambs against subsequent larval challenge. During immunization, the pepsinogen-, gastrin- and IgA-responses were similar in the individual sheep. In contrast to parasite-specific IgG1 and IgG2 levels, IgA decreased rapidly after cessation of trickle infection and parallel anthelmintic treatment, and may therefore indicate current exposure to parasite antigen. After challenge, the majority of the immunized sheep exhibited immediate and short-term responses of pepsinogen, gastrin and IgA in the serum. The time course and the level of each of these responses were very similar in the individual sheep, suggesting that the release of pepsinogen, gastrin and IgA into the circulation was influenced by related mechanisms.

Topics: Animals; Antibodies, Helminth; Antinematodal Agents; Feces; Female; Fenbendazole; Gastrins; Immunization; Larva; Male; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogen A; Sheep; Sheep Diseases; Time Factors

Serum gastrin and pepsinogen concentrations, food intake, abomasal pH and abomasal aerotolerant and anaerobic bacterial populations were measured in sheep infected with Ostertagia circumcincta to search for links between hypergastrinaemia, food intake and changes in the abomasal environment. Abomasal pH and serum gastrin and pepsinogen concentrations were elevated in each of five sheep infected via abomasal cannulae with 150000 exsheathed larval stage three, followed 11 days later by 100000 sheathed larvae given intraruminally. Unparasitised abomasa contained aerotolerant bacterial population densities of between 10(3) and 10(6) cells ml(-1) and these did not change significantly following parasitism. In contrast, anaerobic bacterial population densities increased markedly by about 10(4)-fold following parasitism. Anaerobic numbers changed rapidly when abomasal pH increased from 2.5 to 3.5. At pH 4 and above, anaerobic bacterial numbers approached levels expected in rumen contents but parameters other than pH did not relate to bacterial numbers. Brief periods when serum gastrin was lower than expected, coinciding with raised abomasal pH, were not explicable by increased bacterial numbers. Food intake, which decreased for a variable period from around Day 5 p.i., correlated poorly with serum gastrin concentration, suggesting hypergastrinaemia is not the sole cause of anorexia in parasitised animals. The survival of substantial numbers of rumen bacteria in the abomasum at only slightly raised pH may significantly lower the bacterial protein available to the sheep.

Topics: Abomasum; Animals; Bacteria; Bacteria, Anaerobic; Colony Count, Microbial; Feces; Gastrins; Hydrogen-Ion Concentration; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogen A; Sheep; Sheep Diseases; Stomach Diseases

Gastric endocrine cell populations and serum and tissue gastrin have been examined in sheep which were infected either intraruminally by tube with 150,000 Ostertagia circumcincta larvae followed by a trickle infection of 10,000 larvae thrice weekly for 8 weeks or by the transfer of 15,000 adult worms directly into the abomasum and killed 8 days later. Depletion of both antral gastrin and somatostatin was evident in both groups: tissue gastrin concentrations were reduced by 85% in the trickle infection and both G cells (gastrin-containing) and D cells (somatostatin-containing) were pale and fewer after adult worm transfer. The concurrent depletion of antral gastrin and somatostatin supports the contention that the hypergastrinaemia in parasitised sheep is largely secondary to the increase in abomasal pH. Although there was no change in the proportions of G34 and G17 in the tissues, there was an increase in the longer form of gastrin in the circulation of the larval-infected sheep, suggesting that there may be differential secretion of G17 and G34 which may be exaggerated as the rate of secretion increases. Although the fundic mucosa was thicker following trickle infection, there was no evidence of enterochromaffin-like cell hyperplasia in either infected group. It is suggested that hyper-gastrinaemia may be beneficial to the host, as it may allow the abomasum to regain the ability to acidify its contents during continued exposure to the parasites.

Topics: Abomasum; Animals; Enteroendocrine Cells; Gastric Fundus; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Hydrogen-Ion Concentration; Larva; Ostertagia; Ostertagiasis; Sheep; Sheep Diseases; Somatostatin; Somatostatin-Secreting Cells; Stomach Diseases

The infection of parasite-naive sheep with approximately 15,000 adult Ostertagia circumcincta via abomasal cannulae resulted in marked changes in the structure and function of the abomasum. The functional changes, which have been characterised previously, included elevated abomasal pH and increased serum concentrations of pepsinogen and gastrin. Eight days after the transplant of adult worms, the abomasa of recipient animals were significantly heavier than those of controls (P < 0.001), the thickness of the fundic mucosa was greater (P < 0.01), there were fewer parietal cells (P < 0.01) and increases in the numbers of mitotic figures and mucus-producing cells. Mucous cell hyperplasia was also evident in the fundic mucosae of sheep receiving a trickle infection of infective, third-stage O. circumcincta larvae and was prominent within nodules associated with larval development. In non-nodular mucosa, there was hyperplasia of mucous cells and changes in the distribution of parietal cells. Decreases in the number of parietal cells at the gland base were offset by increases at a mid-gland level, probably due to chronic hypergastrinaemia, so that, overall, total parietal cell number was unaffected. Mucous cell hyperplasia and the diminution of parietal cell number are seen in a diverse range of disease states and may be mediated by host growth factors such as Transforming growth factor-alpha. Alternatively, the cellular and/or the secretory changes in response to the presence of adult worms are mediated by chemicals that are cytotoxic/inhibitory for parietal cells, and released by the parasites themselves.

Topics: Abomasum; Age Factors; Animals; Gastric Fundus; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Hyperplasia; Larva; Organ Size; Ostertagia; Ostertagiasis; Parietal Cells, Gastric; Pepsinogen A; Pylorus; Sheep; Sheep Diseases; Specific Pathogen-Free Organisms; Stomach Diseases

1. Infection with the bovine abomasal nematode Ostertagia ostertagi results in a loss of acid-secreting parietal cells and an increase in gastric pH. The effects of an experimental infection on gastrin mRNA expression, blood and tissue gastrin concentrations, the different molecular forms of gastrin in each, and pyloric mucosal chromogranin A-derived peptides were investigated in the calf. 2. An increase in blood gastrin concentrations in the infected group reached a peak by day 28 postinfection (635 pg ml-1; P < 0.01). Gel chromatography analysis of blood samples revealed that the hypergastrinaemia comprised largely gastrin-34 (G-34) in parasitized calves while gastrin-17 (G-17) predominated in control animals. 3. An 11-fold increase in gastrin mRNA expression was recorded in the parasitized animals which was accompanied by a 23.8% reduction in pyloric mucosal gastrin content and an apparent drop of 24.7% in the number of gastrin-producing G cells detected. There was no major change in the relative abundance of G-17 and G-34 in the pyloric mucosa of infected calves. No significant differences in the concentration of pyloric mucosal chromogranin A-derived peptides were recorded between infected and control groups. 4. These data suggest that the hypergastrinaemia seen in parasitized calves results largely from an increase in gastrin synthesis and that depletion of previously stored peptide makes virtually no contribution to elevated blood gastrin concentrations.

Topics: Animals; Cattle; Cattle Diseases; Chromatography, Gel; Chromogranin A; Chromogranins; Gastric Mucosa; Gastrins; Gene Expression Regulation; Immunohistochemistry; Ostertagia; Ostertagiasis; Pancreatic Hormones; Pepsinogens; Radioimmunoassay; RNA, Messenger

Infection of sheep with adult or larval O. circumcincta increased serum pepsinogen and gastrin and abomasal pH. The upper limits of the normal range, calculated from over 1000 samples collected from parasite-naive sheep, were set at 2 standard deviations above the mean; these were for serum pepsinogen, 454 mU tyrosine l-1; serum gastrin, 64 pM and abomasal pH, 3.26. Five infection regimes were used: sheep previously exposed to field parasitism were infected with 30,000 larvae intraruminally (Group A), while parasite-naive sheep were administered either 50,000 larvae intraruminally (Group B), 150,000 larvae intraruminally followed by a trickle infection of 10,000 larvae thrice weekly from days 21 to 45 (Group C), 150,000 exsheathed larvae via an abomasal cannula (Group D) or 15,000 adult worms via an abomasal cannula (Group E). Whereas the presence of adult worms rapidly increased serum pepsinogen (after 8 h) and abomasal pH and serum gastrin (after about 19 h), the early infective larval stages, regardless of the infection regime, had minimal effects until the abrupt rise in all parameters 5-6 days after infection. Abomasal pH returned to near normal levels when the infections became patent and was not re-elevated by a subsequent trickle infection, whereas serum gastrin and pepsinogen remained high. The initial hypergastrinaemia was coincident with the increased abomasal pH, but was preceded by the increase in serum pepsinogen. In several sheep, serum pepsinogen increased very little during the parasitism, although there were typical effects on abomasal pH and serum gastrin. Serum gastrin was depressed when the abomasal pH exceeded about 5.5. It is suggested that an inhibitor of gastrin release is generated by proliferating abomasal microbes under these conditions and that this is a limitation to the use of elevated serum gastrin in the diagnosis of parasitism in individual sheep.

Topics: Abomasum; Animals; Eating; Feces; Female; Gastrins; Hydrogen-Ion Concentration; Larva; Male; Ostertagia; Ostertagiasis; Pepsinogens; Reference Values; Sheep; Sheep Diseases

Four groups of three lambs were used to investigate the pathophysiological changes during the development of a protective immunity against Ostertagia leptospicularis induced by a trickle infection. Three groups (A, B and C) were infected daily with 1000 third-stage larvae (L3) for a period of 26 weeks; group D remained uninfected until challenged. Egg excretion ceased after about 10 weeks in groups A, B and C and at the end of the trickle infection no parasites were found in group A sheep after slaughter. The sheep of groups B and C were highly refractory to two challenge infections, with 100,000 and 200,000 L3, given four and 17 weeks after the end of the trickle infection. Both challenge infections were followed by short term increases in the concentrations of gastrin and pepsinogen in the serum. Group C sheep were immunosuppressed with flumethasone during the second larval challenge and had higher pepsinogen concentrations but similar gastrin concentrations to the untreated sheep of group B.

Topics: Animals; Antibodies, Helminth; Enzyme-Linked Immunosorbent Assay; Feces; Female; Gastrins; Male; Ostertagiasis; Pepsinogens; Sheep; Sheep Diseases

Effects of strategic anthelmintic treatment on pathophysiologic and immunomologic changes induced by infection with Ostertagia ostertagi and Cooperia oncophora were studied in 2 groups, of 12 calves each: an infected group, inoculated with 200,000 mixed O ostertagi and C oncophora third-stage larvae (L3) on day 1; and an infected-treated group, similarly inoculated, but treated with ivermectin at 9 and 33 days. All calves were also inoculated at 12 weeks with Brucella abortus vaccine, at 13 weeks with bovine rhinotracheitis vaccine (bovine herpesvirus 1), and at 14 weeks with a soluble O ostertagi L3 extract, then were allowed to graze on a contaminated pasture. Four calves from each group were slaughtered at 7, 11, and 19 weeks of the study. Calves of the infected group had significantly (P < 0.05) lower weight gain than did those in the infected-treated group (60.90 kg vs 75.86 kg). They also had high plasma pepsinogen and serum gastrin values, and low serum albumin concentration from 2 or 4 weeks. Calves in the infected-treated group had steady weight gain and no significant changes in albumin and gastrin values. They also had less severe abomasal lesions and higher carcass yield. Compared with calves of the infected-treated group, those of the infected group had significantly (P < 0.05) lower blood lymphocyte reactivity to phytohemagglutinin at 14 and 16 weeks, to concanavalin A at 10 weeks, to pokeweed mitogen at 14 weeks, and to soluble O ostertagi L3 extract at 2, 4, and 14 weeks. (ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anthelmintics; Body Weight; Brucella abortus; Brucella Vaccine; Cattle; Cattle Diseases; Gastrins; Gastrointestinal Diseases; Herpesvirus 1, Bovine; Lymphocyte Activation; Lymphocytes; Male; Nematoda; Nematode Infections; Orchiectomy; Ostertagiasis; Parasite Egg Count; Pepsinogens; Time Factors; Viral Vaccines; Weight Gain

The influence of different levels of infection with Ostertagia ostertagi on the development of a protective immune response in calves was investigated. Four groups of calves were infected with either 5000 (Group A), 10,000 (Group B), 20,000 (Group C) or 40,000 (Group D) infective larvae (O. ostertagi L3) weekly until treatment began. Group E functioned as controls. All animals were treated with oxfendazole (9 mg ml-1) at Week 17 (Groups A, B and E) or Week 18 (Groups C and D). Sixteen days post-treatment all calves received a challenge infection of 150,000 O. ostertagi L3 spread over 10 consecutive days. Faeces and blood were collected weekly for egg counts and to assess levels of pepsinogen, gastrin and IgG1 and IgG2 Ostertagia antibodies. All calves were necropsied 31 days post-challenge for worm counts. Egg counts and pepsinogen levels were proportional to the infection level during the first few weeks of the experiment. Only in the high-dosed Group D was a gastrin response evoked. Ostertagia IgG1 antibodies increased between Day 25 and Day 95, and in the non-infected control group an antibody rise was observed from Day 67 onwards. All measured parameters except Ostertagia antibodies showed a gradual decrease from Day 70 until the day of treatment. At necropsy there was no significant difference between the groups in the total worm populations. Only the composition of the worm populations differed, with 35% early L4 (EL4) larvae in the previously infected Groups A, B, C and D and only 5% in the control Group E. The results indicate a slow immune response against O. ostertagi in cattle and question the possible role of the EL4 stage in developing immunity.

Topics: Animals; Antibodies, Helminth; Antinematodal Agents; Benzimidazoles; Cattle; Cattle Diseases; Dose-Response Relationship, Immunologic; Feces; Female; Gastrins; Immunoglobulin G; Larva; Male; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogens; Time Factors

The effects of a single challenge with 60,000 infective Ostertagia ostertagi larvae on blood and gastrointestinal mucosal gastrin concentrations, gastrin-producing G-cell numbers in the pyloric mucosa and growth of different parts of the gut were investigated in 16, two-and-a-half-month-old calves. Infected calves exhibited a rise in abomasal pH which was accompanied by a 145 per cent increase in wet weight of the fundic mucosa (P < 0.05) and a significant rise in blood total gastrin concentrations (P < 0.01). Circulating little gastrin (G-17) was unaffected. Pyloric mucosal total gastrin concentrations remained unaltered in the infected calves until day 28 when levels fell to 36.9 per cent of control group values (P < 0.01). Pyloric mucosal G-cell numbers declined during the experiment in the infected group. It is suggested that release of previously stored tissue gastrin and not a change in G-cell numbers contributes to the hypergastrinaemia associated with ostertagia infection in the calf.

Topics: Animals; Cattle; Cattle Diseases; Gastric Mucosa; Gastrins; Immunoenzyme Techniques; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogens; Radioimmunoassay; Reference Values

Gastrin values were evaluated in 130 parasite naive calves, in 61 first season grazing calves during six field trials and in 8 experimentally infected adult immune cows. The gastrin values were linked to pepsinogen levels and daily weight gain. Also the influence of an anthelmintic treatment on pepsinogen and gastrin values was assessed during a clinical outbreak of ostertagiosis in a group of first season grazing calves. Mean gastrin levels in parasite naive calves were 106 pg/ml. Results show that a group mean of 400 pg/ml gastrin in first season grazing calves indicates a reduced daily weight gain but with no obvious clinical signs. During clinical outbreaks mean gastrin levels frequently reached 1,000 pg/ml with a severe weight loss and a mean pepsinogen level of 5,000 mU tyr. The serum gastrin concentration was strongly reduced 4 days post treatment. No gastrin response was noted following an Ostertagia challenge in adult immune cows. The value of gastrin as a diagnostic aid for ostertagiosis is discussed in relation to pepsinogen, the adult worm burden, larval inhibition and the technique involved in assessing gastrin.

Topics: Animals; Cattle; Cattle Diseases; Gastrins; Ostertagiasis

Pathophysiologic effects of Ostertagia ostertagi infection and their prevention by strategic anthelmintic treatments were studied in 3 groups each of 6 steer calves. Group-1 calves were noninfected controls. Group-2 calves were inoculated with 100,000 third-stage larvae on the 1st and 28th days of the experiment and grazed on pasture initially free of contamination. Group-3 calves were on a similar regimen as those in group 2, but were also treated with ivermectin 9 days after each larval inoculation. Group-2 calves had increased plasma pepsinogen and gastrin values and decreased weight gains, and total serum protein and albumin concentrations from the 2nd week of infection onward. They were anemic at 10 to 12 weeks and had lower carcass and meat quality at slaughter. Strategic anthelmintic treatments were effective in preventing these effects and calves in groups 1 and 3 had similar performances. On the basis of our findings, high pepsinogen values were related to worm burdens, whereas high gastrin concentrations were related to gastric lesions.

Topics: Abomasum; Animals; Blood Proteins; Blood Urea Nitrogen; Cattle; Cattle Diseases; Feces; Gastrins; Hematocrit; Ivermectin; Male; Meat; Nutritional Status; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogens; Random Allocation; Serum Albumin, Bovine; Weight Gain

Daily changes in serum gastrin and pepsinogen concentration have been studied during two types of infection with Ostertagia ostertagi in calves. In a first experiment two calves were trickle infected (10 times 10,000 L3 Ostertagia) and two animals received a single infection of 100,000 L3 Ostertagia. Gastrin and pepsinogen changes are discussed in relation to adult wormburdens. The second experiment involved 8 calves and was designed to investigate pepsinogen and gastrin changes following a challenge infection in previously sensitized calves. The high dosed group was infected with 5,000 L3 O. ostertagi during 30 days, the low dosed group received 500 L3 O. ostertagi and group 3 served as uninfected control. At day 41 post infection all animals were treated with oxfendazole and on day 61 challenged with 100,000 L3 O. ostertagi. Only in the high dosed group a distinct pepsinogen and gastrin reaction was noticed. Both parameters dropped to almost preinfection levels after treatment. Two days post challenge a moderate rise (+/- 1,000 mU tyr) of the pepsinogen concentration was observed in the previously infected animals and gastrin showed a temporary slight increase in several animals 8 to 10 days post challenge. The effect of treatment and challenge infection is discussed in relation to gastrin and pepsinogen changes and immunity.

Topics: Animals; Cattle; Cattle Diseases; Feces; Gastrins; Ostertagiasis; Parasite Egg Count; Pepsinogens

This study was conducted to evaluate the effects of tactical treatments with ivermectin against trichostrongyles in first-season grazing heifer calves in the Danish marshland. A group of Black-Pied Friesian calves was turned out in early May on a permanent pasture naturally infected with trichostrongyle larvae. In late July, when high herbage infectivity started to appear, the pasture was divided into two plots of equal size, which from then and until housing in late October were each grazed by half of the original group of calves. One of these groups was given three anthelmintic treatments with ivermectin at 4-week intervals starting in late July. The other group served as non-treated controls. Ostertagia ostertagi and Cooperia oncophora were the predominant trichostrongyles. Nematodirus helvetianus was observed on few occasions. Although the animals were exposed to a high herbage infectivity from July onwards, the anthelmintic treatments conferred a significant reduction in trichostrongyle loads, as evidenced by an almost complete cessation of egg excretion and a significant lowering of pepsinogen and gastrin levels in the blood. This was reflected in higher weight gains.

Topics: Animals; Cattle; Cattle Diseases; Feces; Female; Gastrins; Intestinal Diseases, Parasitic; Ivermectin; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogens; Seasons; Serum Albumin, Bovine; Trichostrongyloidea; Trichostrongyloidiasis; Weight Gain

Blood gastrin and pepsinogen responses to a single infection with 100,000 Ostertagia ostertagi infective larvae in lactating dairy cows were investigated. None of the infected cows showed signs of clinical ostertagiasis, nor was there any difference in live weight gain, milk yield or faecal egg count between groups. Pepsinogen levels of the infected group were significantly elevated between days 3 and 24 after infection (peak 1041 mU tyrosine; day 14). In contrast, there was no significant difference in blood gastrin levels between infected and control animals suggesting that few adult worms had become established in the former group. These data are compared with the increases in both gastrin and pepsinogen levels recorded in susceptible calves exposed to the same level, pattern and strain of ostertagia infection in a previous experiment. It is suggested that gastrin assay may be of value in adult cattle for indicating when elevated pepsinogen levels are merely associated with a rise in larval intake and not with the establishment of large adult worm burdens.

Topics: Animals; Cattle; Cattle Diseases; Female; Gastrins; Lactation; Ostertagiasis; Pepsinogens; Pregnancy; Trichostrongyloidiasis

Parasite-free, 4-month-old-calves were inoculated with Ostertagia ostertagi and/or Trichostrongylus axei, followed 6 weeks later by inoculation with increasing doses of O ostertagi for 8 weeks in the 2 groups (n = 4) of calves that had been given O ostertagi. Gastrin immunoreactivity concentration in serum was measured before and after infection and was correlated with changes in mucosal thickness. Gastrin immunoreactivity concentration in preinoculation control sera ranged from 95.2 to 287.1 pg/ml, and increased values were measured in all parasitized calves after 15 weeks. Significantly (P less than 0.05) increased serum gastrin immunoreactivity concentration compared with the preinfection value, was found in calves infected with O ostertagi or T axei, and highly significant (P less than 0.01) values were observed in calves infected with both parasites. Abomasal mucosal hyperplasia was observed in all parasitized calves; increased mucosal thickness and mucosal cross-sectional area were most prominent in calves infected with O ostertagi and T axei.

Topics: Abomasum; Animals; Cattle; Cattle Diseases; Gastric Mucosa; Gastrins; Hyperplasia; Ostertagiasis; Trichostrongyloidiasis; Trichostrongylosis

Topics: Abomasum; Animals; Gastric Mucosa; Gastrins; Hyperplasia; Organ Size; Ostertagiasis; Sheep; Sheep Diseases; Trichostrongyloidiasis

Topics: Abomasum; Animals; Cattle; Cattle Diseases; Diet; Gastrins; Hydrogen-Ion Concentration; Ostertagia; Ostertagiasis; Poaceae; Trichostrongyloidiasis

Calves infected by surgical transplantation of adult Ostertagia ostertagi had raised levels of plasma pepsinogen and those in which the largest number of worms established also had elevated plasma gastrin concentrations. Despite the elevated plasma pepsinogen values, the abomasal pH of the animals did not change significantly, and there was no significant difference in the percentage establishment of adult parasites in calves previously infected with O ostertagi third stage larvae and those which had been maintained parasite-naive before transplant.

Topics: Abomasum; Animals; Cattle; Cattle Diseases; Gastrins; Hydrogen-Ion Concentration; Ostertagiasis; Pepsinogens; Trichostrongyloidiasis

The sequential development of Type I and Type II ostertagiasis over a 2-year period in the same naturally infected cattle is described for the first time. Particular reference is made to biochemical and serological changes. Positive relationships were demonstrated between the clinical signs of both Type I and Type II disease, and marked increases in the levels of plasma pepsinogen, plasma gastrin and antibody titres to adult Ostertagia antigen. At necropsy, there were significant relationships between the combined total of adult and developing 5th stage larvae of Ostertagia spp. and the levels of both plasma pepsinogen and gastrin. By the end of the second grazing season the cattle had acquired an immunity to infection with Ostertagia spp. and had very low burdens of this parasite at necropsy. However some of these cattle maintained elevated plasma pepsinogen levels when under natural challenge by Ostertagia spp. larvae and the aetiology of these changes and the problems of diagnosis using this parameter are discussed. Similar trends of infection were observed for Cooperia oncophora, although resistance to the parasite developed more rapidly.

Topics: Abomasum; Animals; Antibodies; Antigens, Helminth; Cattle; Cattle Diseases; Feces; Gastrins; Hydrogen-Ion Concentration; Intestinal Diseases, Parasitic; Larva; Male; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogens; Seasons; Trichostrongyloidiasis

Topics: Abomasum; Animals; Feces; Female; Gastrins; Larva; Ostertagiasis; Pancreatic Polypeptide; Parasite Egg Count; Pepsinogens; Sheep; Sheep Diseases; Trichostrongyloidea

Radio-immunoassay of plasma gastrin showed that hypergastrinaemia developed in sheep during experimental infections with Ostertagia circumcincta. Elevations of plasma gastrin occurred within 8 days of the first dose of infective larvae, with the most marked increase being after 11-20 days when adult worms would be expected to be present in the abomasum. Increases of plasma gastrin levels from 69.0 +/- 7.6, 28.7 +/- 5.3, 48.7 +/- 5.9 and 60.6 +/- 9.4 pg/ml before infection to maxima of 650, 230, 900 and 750 pg/ml respectively were recorded in 4 sheep infected for the first time. In 2 others which had been previously infected and then treated with anthelmintic, plasma gastrin rose from 16.0 +/- 4.0 and 377 +/- 87 pg/ml to maxima of 260 and 900 pg/ml at 24 and 29 days after re-infection, respectively. The cause of hypergastrinaemia has not been established. The elevation of abomasal pH which occurs in ostertagiasis may result in increased gastrin levels but is thought not to be the only cause since plasma gastrin increased before the abomasal pH rose and developed in sheep infected for a second time although their abomasal contents remained at pH 4.0 or lower. The presence of the parasite is critical for development of hypergastrinaemia as shown by return of the gastrin level to normal following therapy with an anthelmintic. It was shown that the parasites do not depend on the hypergastrinaemia since O. circumcincta became established in antrectomized sheep in which hypergastrinaemia did not develop.

Topics: Animals; Female; Gastric Acid; Gastrins; Hydrogen-Ion Concentration; Ostertagiasis; Sheep; Sheep Diseases; Stomach; Trichostrongyloidea; Trichostrongyloidiasis

Topics: Abomasum; Animals; Duodenum; Gastrins; Ostertagiasis; Sheep; Sheep Diseases; Trichostrongyloidiasis

Sheep and calves prepared with separated, innervated pouches made from the acid secreting region of the abomasum were given single or multiple infections of Ostertagia spp and comparisons were made of the secretory changes of parasitised and non-parasitised mucosa by means of cannulas placed in the abomasum and pouch. Contrary reactions of the parasite-free pouches and infected main part of the abomasum are described and explained in terms of a two-part hypothesis. The inhibitory effect on acid secretion of the abomasum (resulting in its contents being pH 5 to 7) was postulated to be due to the direct suppressive effects of substances released locally by parasites or injured host tissues, whereas increased secretion of the hormone, gastrin, was thought to account for the stimulatory effects of infection on acid secretion from the pouches. In sheep treated with anthelmintic and then reinfected the inhibitory effects on abomasal pH were not obtained. The hypersecretion from the pouches still persisted.

Topics: Abomasum; Animals; Cattle; Gastric Juice; Gastrins; Gastritis; Ostertagiasis; Sheep; Sheep Diseases; Trichostrongyloidiasis

Topics: Animals; Gastrins; Gastritis; Ostertagiasis; Sheep; Sheep Diseases; Trichostrongyloidiasis