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Biomedical subjects

P D Eckersall

Publications and source records attributed to P D Eckersall.

At least 19 recordsLinked to original sources

Changes in C-reactive protein and haptoglobin in dogs with lymphatic neoplasia.

Acute phase proteins (APP) are regarded as a useful diagnostic tool in humans with lymphomas, leukaemias and multiple myeloma. C-reactive protein (CRP) and haptoglobin concentrations were measured in dogs with malignant multicentric (high grade) lymphoma (n=16), acute lymphoblastic leukaemia (ALL) (n=11), chronic lymphocytic leukaemia (CLL) (n=7) and multiple myeloma (n=8). Twenty-five healthy dogs served as controls. Measurements of the CRP plasma concentration were performed using a commercial ELISA and haptoglobin was measured with an assay based on its haemoglobin binding capacity. Global group comparisons using Kruskal-Wallis-test revealed significant group differences for both APPs (P<0.0001). Median CRP concentrations were increased in all groups with neoplastic lymphatic disorders (lymphoma: 37.2mg/L, ALL: 47.8mg/L, CLL: 35.5mg/L, myeloma: 17.6mg/L) compared to controls (1.67mg/L; P<0.001). Compared to the healthy controls (median=0.59g/L), haptoglobin was especially increased in dogs with ALL (6.8g/L, P<0.0001) followed by dogs with malignant lymphoma (3.8g/L, P<0.0001), CLL (3.2g/L, P=0.0008), and multiple myeloma (3.0g/L, P=0.0163). For both APPs, a wide range of values was found in all patient groups. The results indicate that particularly severe and acute lymphatic neoplasia, such as high grade lymphoma and ALL, cause significant acute phase reactions in dogs and must be included in the differential diagnoses of increased blood levels of these APPs.

Animals↗

Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis.

The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M-SAA3 in mammary tissues was determined using immunocytochemistry. Increases of M-SAA3 and Hp in milk occurred within 12 h of Staphylococcus aureus infusion, with peak concentrations occurring 3 d after infusion of the bacteria. The increase of acute phase proteins in milk (15 h) preceded the increase in serum concentrations of both proteins (24 h). Expression of mRNA for M-SAA3 and Hp increased in both mammary and hepatic tissues 48 h after infusion of the mammary glands. In mammary tissue, the increase of M-SAA3 mRNA was greater than the increase in Hp mRNA expression, whereas in hepatic tissue, the increase in M-SAA3 mRNA was less than that for Hp mRNA. Immunocytochemistry demonstrated that M-SAA3 protein was present within secretory epithelial cells at significantly higher levels in infected mammary glands than in control tissues. These proteins, which have host defense and antibacterial activities, may play a significant role in the early response to invasion of mammary tissues by pathogenic bacteria.

Acute-Phase Proteins↗

Haptoglobin concentrations in dogs undergoing trilostane treatment for hyperadrenocorticism.

BACKGROUND: Increased concentrations of haptoglobin (Hp), a moderate acute phase protein, have been demonstrated in dogs with hyperadrenocorticism (HAC). Monitoring serum concentrations of Hp in hyperadrenocorticoid dogs before and after trilostane administration may provide valuable information on the response to therapy. OBJECTIVE: The aim of this study was to measure Hp concentrations in dogs with spontaneously occurring HAC at the time of diagnosis and after treatment with trilostane. METHODS: Serum Hp concentration was measured using an automatic biochemical assay based on Hp-hemoglobin binding and utilizing SB-7 reagent in 12 dogs with spontaneous HAC before and after treatment with trilostane (30 or 60 mg PO q 12-24 h). Post-treatment Hp concentrations were measured at the time the owner reported an improvement in clinical signs. Pretreatment and post-treatment Hp values were compared with reference values and with values from 4 healthy control dogs. RESULTS: Two dogs with HAC had pretreatment Hp values within the reference interval; 10 dogs had moderate (n = 8) or marked (n = 2) increases in Hp concentration. After treatment with trilostane, Hp concentration remained within the reference interval (n = 2), decreased to within the reference interval (n = 3), or remained moderately increased (n = 7; 3-10 g/L). Overall, a significant decrease was observed in Hp concentration after trilostane treatment compared with pretreatment values (P <.005). Both untreated and treated dogs with HAC had significantly higher Hp concentrations (P <.001) when compared with control dogs. CONCLUSIONS: Clinical control of HAC did not closely relate to serum Hp concentration. Further studies are required to assess whether this is because of inadequate control of disease or because a build-up of cortisol precursors or secondary effects of HAC affect Hp concentration.

Adrenocortical Hyperfunction↗

Pathophysiological and immune cell responses in calves prior to and following lung challenge with formalin-killed Pasteurella multocida biotype A:3 and protection studies involving subsequent homologous live challenge.

Pneumonic pasteurellosis is a common respiratory infection in cattle that has major economic and welfare implications world-wide and the incidence in the UK due to Pasteurella multocida, currently the same as that associated with Mannheimia haemolytica, is increasing. Whereas much is known regarding the pathogenesis of M. haemolytica infections little information is available on the pathogenic process of pasteurellosis initiated by P. multocida. In the present work calf systemic and innate immune responses to intratracheal challenge with formalin-killed P. multocida biotype A:3 and to subsequent experimental lung infection with live P. multocida were investigated. Eight-week-old calves were challenged intratracheally on day 0 with either 10(9) colony forming units (cfu) of formalin-killed P. multocida biotype A:3 in 300 ml saline (n = 10) or 300 ml saline alone (n = 10), followed, at day 21, by challenge with 10(9) cfu live P. multocida. Pathophysiological and lung phagocyte responses were assessed by clinical monitoring, sequential lung lavage and blood sampling. Results for samples obtained before, during and after challenge showed clinical and acute phase protein responses to both bacterial culture and saline control treatments, although higher responses were associated with bacterial challenge. Phagocytosis of P. multocida during 1h incubation periods with lavaged cells in vitro was unaffected by exposure in vivo to killed P. multocida and there was evidence that P. multocida was able to survive intracellularly during this assay. There was no indication that lung exposure to formalin-killed P. multocida conferred protection against subsequent homologous live challenge.

Animals↗

A comparison of acute phase protein measurements and meat inspection findings in cattle.

The acute phase proteins haptoglobin (Hp) and serum amyloid-A (SAA) are increased in the blood of cattle with infectious or inflammatory diseases. As it is important to identify such cattle at meat inspection, a study was undertaken to compare the levels of Hp and SAA in blood samples from cattle at abattoir with the post-mortem meat inspection findings. The serum concentrations of Hp and SAA were determined in healthy beef cattle (n = 16); healthy dairy cows with no pathological conditions (n = 22); and cows with pathologic conditions (n = 62). The last group was subdivided into cows with acute pathological conditions (n = 10) and those with non-acute pathological conditions (n = 52). The mean (+/-SD) Hp levels in plasma from beef cattle and cows without pathological conditions found were 0.11 +/- 0.08 mg/mL and 0.02 +/- 0.03 mg/mL, respectively, and the difference was statistically significant (p < 0.001). However, mean Hp level in cattle with pathological conditions was 0.27 +/- 0.40 mg/mL, significantly higher than the mean values of either group of healthy animals (p < 0.01 versus healthy dairy cows and p < 0.001 versus healthy beef cattle). The mean SAA concentration in plasma samples from 22 healthy dairy cows (with no pathological conditions found) was 51 +/- 38 microg/mL, significantly higher (p < 0.01) than the mean SAA value of 29 +/- 21 microg/mL calculated from 16 plasma samples from healthy beef cattle. In the group of 62 cows with pathological conditions, the mean SAA level was 94 +/- 115 microg/mL being significantly higher than the respective value in either groups of healthy animals (p < 0.01 versus healthy cows and p < 0.001 versus healthy beef cattle). Considerations of the acute phase proteins results obtained from the animals with pathological conditions did not reveal a clear association between acute phase proteins levels and respective specific pathological conditions, although there was a significant correlation between Hp and SAA concentrations at the individual animal level when all results were considered (R = 0.75, n = 100, p < 0.001). Nevertheless, when the dairy cows with pathological conditions were subdivided, some significant differences in mean values of acute phase proteins were observed enabling differentiation between animals with (broadly categorised) acute and non-acute pathological conditions. Significantly higher Hp (p < 0.05) and SAA (p < 0.05) concentrations were found in the acute pathology group than in the non-acute pathology group. Overall, the result of the present study indicated that the acute phase protein analysis could be an additional and useful tool enabling separation of "suspect" from "non-suspect" animals during ante mortem inspection within a modernised meat inspection system.

Abattoirs↗

Serum concentrations of acute phase proteins in dogs with leishmaniasis.

The concentrations of haptoglobin, C-reactive protein and ceruloplasmin were measured in symptomatic and asymptomatic dogs naturally infected by Leishmania infantum, and in healthy uninfected dogs to determine the potential value of these proteins for the diagnosis and prognosis of leishmaniasis. The concentrations of the acute phase proteins were significantly higher in the dogs with leishmaniasis than in the control dogs, and the concentration of C-reactive protein was significantly higher in the symptomatic dogs than in the asymptomatic dogs. There were no correlations between the acute phase proteins and the gamma globulins, the albumin/globulin ratio or the titre of anti-leishmanial antibodies.

Acute-Phase Proteins↗

Experimental induction of pneumonic pasteurellosis in calves by intratracheal infection with Pasteurella multocida biotype A:3.

The study aimed to establish an experimental model to investigate the pathogenesis of lung infection by Pasteurella multocida, an important cause of bovine respiratory disease. An experimental model is required to assist the development of an effective vaccine. Sixteen 8-week-old calves were challenged intratracheally with 10(9) or 10(10) colony forming units of P. multocida in either 60 or 300 ml saline in a 2 x 2 factorial experiment. All animals became dull within 2-6h post-infection (p.i.) and two calves were killed humanely because of suspected endotoxic shock. Remaining animals showed increased respiratory rates by 15-20 h p.i. and, at 23 h p.i., calves given the high dose, high volume challenge showed higher (P < 0.05) rectal temperatures. From 24 to 36 h p.i., clinical signs decreased in a majority of animals. Plasma haptoglobin concentrations increased (P < 0.05) in calves given the high volume challenge irrespective of the number of bacteria. At post-mortem examination (4d p.i.), lung lesions, mainly in the apical lobes, were found in all calves. Histopathological examination showed areas of purulent pneumonia with a tendency to abscessation and inflamed interlobular septa characterised by accumulation of neutrophils and oedema. The clinical and pathological responses described were typical of bovine pneumonic pasteurellosis.

Animals↗

Development of a clinical syndrome resembling haemorrhagic septicaemia in the buffalo following intravenous inoculation of Pasteurella multocida serotype B:2 endotoxin and the role of tumour necrosis factor-alpha.

Clinical changes and acute phase responses, including tumour necrosis factor-alpha (tnfalpha), in six buffalo calves were examined following intravenous inoculation of a bolus of endotoxin (1 microg kg(-1) bodyweight in 10 ml of phosphate-buffered saline [ pbs ]) extracted from Pasteurella multocida serotype B:2, the bacterium responsible for haemorrhagic septicaemia (hs) in Asia. Endotoxin injection caused a rapid onset of clinical signs characterised by dullness, sternal recumbency, elevated rectal temperatures, excessive salivation and dyspnoea that lasted for up to 12 hours post-inoculation (p.i.). Serum concentrations of tnfalpha rose within 1 hour p.i. to reach peak values ranging between 8 and 140 ng ml(-1) at 1-2 hours p.i. and then declined rapidly to baseline levels 3-5 hours p.i. Endotoxin injection induced other acute phase changes, including a rapid leucopenia and reductions in the serum concentrations of iron and zinc and a delayed but prolonged increase in haptoglobin from 12 hours p.i. that reached a plateau from about 60 hours p.i. Three control calves injected with 10 ml pbs showed no clinical or blood compositional changes. By reproducing key signs of hs the work confirms a pivotal role of endotoxin in the pathogenesis of hs and emphasises the exquisite sensitivity of the buffalo to P multocida endotoxin.

Animals↗

Acute phase proteins in serum and milk from dairy cows with clinical mastitis.

The serum concentrations of haptoglobin, serum amyloid A and alpha1 acid glycoprotein were determined in serum collected from healthy dairy cows and cows with clinical mastitis, graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s) to assess their relative diagnostic value in detecting the disease. The concentrations of haptoglobin and serum amyloid A were also measured in milk collected from infected and uninfected quarters. The concentrations of haptoglobin and serum amyloid A were higher in the serum and milk from the cows with mild or moderate mastitis. The diagnostic value of haptoglobin in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 82 per cent and 94 per cent respectively with serum and 86 per cent and 100 per cent with milk. The diagnostic value of serum amyloid A in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 83 per cent and 90 per cent with serum and 93 per cent and 100 per cent with milk. The diagnostic value of serum alpha1 acid glycoprotein in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 62 per cent and 91 per cent.

Acute Disease↗

Role of endotoxin in the pathogenesis of haemorrhagic septicaemia in the buffalo.

The pathogenesis of haemorrhagic septicaemia in buffalo infected with Pasteurella multocida is poorly understood. However, the characteristic of sudden onset leading to the rapid death of infected animals is similar to that seen in other clinical conditions known to involve endotoxic shock. The objectives of the work were to assess the contribution of endotoxaemia to the disease's pathogenesis and to characterize the pathophysiological reaction, including the acute phase response, of buffalo to experimental infection with P. multocida serotype B:2, the bacterium responsible for the disease in Asia. After intranasal infection of eight buffaloes with a culture of a field isolate of P. multocida serotype B:2, three animals succumbed to the disease at 26-30 h post-infection (p.i.) and five survived. Rectal temperatures of infected animals rose to a peak at about 10 h p.i. and surviving animals showed a second peak in rectal temperature at 36 h p.i. Endotoxin was present only in serum of non-surviving animals 3-5 h before death or killing during which time concentrations increased rapidly, correlating with the development of overt clinical signs and reductions in rectal temperature, concentrations of white blood cells, serum thyroxine, iron, copper and zinc, an increase in serum haptoglobin and cortisol and the detection of a low-grade bacteraemia. A strong acute phase response was maintained in surviving animals with a progressive rise in serum haptoglobin over 96 h p.ia slow rise in the serum copper concentration from 24 h p.i. and an increase, from about 65 h p.iin serum alpha(1)-acid glycoprotein. The findings demonstrate that a progressive endotoxaemia and associated sequelae correlates with the development of overt haemorrhagic septicaemia disease and sudden death in buffalo.

Acute-Phase Proteins↗

Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice.

Stimulation of the acute phase response during infection of mice with Trypanosoma brucei brucei (T. b. brucei) was investigated in an experimental model of the post-treatment reactive encephalopathy (PTRE), a common side-effect of anti-trypanosome therapy. Plasma levels of the acute phase proteins (APP), haptoglobin (Hp) and serum amyloid P (SAP) increased by day 7 post-infection, but by day 20 had fallen to an intermediate level. This was accompanied by induction of the cytokines, interleukin (IL)-6 and tumour necrosis factor-alpha (TNFalpha) in both liver and brain. Treatment of mice on day 21 with a subcurative dose of diminazene aceturate (Berenil), a procedure known to induce a mild PTRE, cleared the parasite from the circulation with plasma APP and liver expression of mRNA for IL-6 and TNFalpha returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFalpha was detected in the brains of animals with developing PTRE although TNFalpha was not significantly greater than in the control group. A further subcurative dose of Berenil, leading to a more severe PTRE, was associated with elevated serum concentrations of Hp and SAP, increased TNFalpha mRNA in the liver and detectable IL-6 and TNFalpha mRNA in the brain. mRNA for IL-1alpha was expressed in brain and liver samples from all animals. A severe PTRE caused a systemic acute phase response which was not apparent with a mild PTRE. The pattern of cytokine mRNA induction was similar following both drug treatments. However, the difference in APP production could be caused by a breakdown in the blood-brain barrier during severe PTRE allowing cytokine synthesised in the brain to enter the circulation and maintain a systemic response.

Acute-Phase Proteins↗

Fructosamine concentration and resistance to natural, predominantly Teladorsagia circumcincta infection.

Fructosamine concentrations reflect protein status and because infection with Teladorsagia circumcincta can induce a relative protein deficiency, we examined the usefulness of fructosamine concentrations as markers of the intensity of infection in naturally infected lambs. Fructosamine concentration was a heritable trait and variation in fructosamine concerntrations was associated with differences in body weight, and a variety of parasitological variables; animals with increased fructosamine concentrations grew more quickly, had increased faecal egg counts in one of the three study years, had decreased pepsinogen concentrations and decreased IgA activity against 4th-stage larvae of T. circumcincta. Fructosamine concentrations were also associated with variation in the subsequent acquisition of nematodes and in the length of adult female T. circumcincta; lambs with increased fructosamine concentrations had fewer nematodes but the mean length of adult female T. circumcincta was longer. Therefore fructosamine concentrations are potentially useful indicators of the severity of nematode infection and may predict magnitude of subsequent infection.

Abomasum↗

The influence of relative resistance and urea-supplementation on deliberate infection with Teladorsagia circumcincta during winter.

The consequences for lambs of infection over the winter with Teladorsagia circumcincta were quantified by deliberate, trickle infection of selected animals at 7 months of age. Infected and control uninfected animals were each allocated into four groups, relatively resistant animals on a normal diet, relatively resistant animals on an isocaloric diet supplemented with urea, and relatively susceptible animals on the same two diets. Resistance and susceptibility was assessed by faecal egg counts following natural infection during the summer preceding the deliberate infection. During the deliberate infection egg counts remained low and most parasites recovered at necropsy were inhibited larvae. Nonetheless, infection reduced weight gain, decreased albumin and fructosamine concentrations and provoked a noticeable pepsinogen and eosinophil response. As most larvae were inhibited these responses may have been largely a consequence of immuno-inflammatory responses in the host rather than the direct action of parasites themselves. Relatively resistant animals on the supplemented diet allowed fewer larvae to establish and had higher fructosamine concentrations, higher albumin concentrations and decreased pepsinogen responses. Therefore, a combination of relatively resistant sheep and nutritional supplementation appears most efficient at controlling infection.

3-Hydroxybutyric Acid↗

Acute phase proteins in cattle: discrimination between acute and chronic inflammation.

Acute phase proteins such as serum amyloid A, haptoglobin, and alpha 1-acid glycoprotein have been identified as markers of inflammation in cattle because they are produced by the liver in response to pro-inflammatory cytokines. This study was designed to assess whether they could be used to discriminate between acute and chronic inflammation. Their concentrations were measured in serum samples from 81 cattle in which inflammation was classified by thorough clinical examination, supported by postmortem findings, as being acute in severity in 31 and chronic in 50. The classical haematological markers of inflammation were also determined in blood from the animals. Serum amyloid A had a maximum (100 per cent) clinical sensitivity in discriminating between the acute and chronic cases, and haptoglobin had the highest clinical specificity of 76 per cent; counts of neutrophils and band neutrophils had sensitivities of 71 per cent and 42 per cent and specificities of 30 per cent and 72 per cent, respectively. It was concluded that serum amyloid A and haptoglobin may be used to discriminate between acute and chronic inflammatory conditions.

Acute Disease↗