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Biomedical subjects

M F Heath

Publications and source records attributed to M F Heath.

At least 19 recordsLinked to original sources
PubMed2005

Controlled clinical trial of the effect of a homoeopathic nosode on the somatic cell counts in the milk of clinically normal dairy cows.

Cows in a 250-cow Holstein-Friesian herd were allocated at random to be treated with either a homoeopathic nosode or a negative control, both treatments being applied by means of an aerosol spray to the vulval mucous membranes. A total of six treatments were given over a period of three days and milk samples were taken for the determination of somatic cell counts (SCC) on days -3, 3, 7, 9, 14, 21 and 28. Individuals applying the treatments or carrying out the SCC determination were unaware of which animals were receiving which treatment. Owing to the wide natural variations in SCC, the trial had only a 71 per cent possibility of detecting a 30 per cent difference in SCC between the two groups. There were no significant differences between the SCC of the two groups on any sample day, but there were significant variations between the SCC on different days (P=0.003) in both groups.

Animals↗
PubMed2004

Platelets enhance endotoxin-induced monocyte tissue factor (TF) activity in the horse.

Endotoxaemia is the leading cause of death in horses. Disseminated intravascular coagulation (DIG), stimulated by induced monocyte proteins, is a prominent feature. Monocyte-platelet cellular interactions are central to the vascular dysfunction produced by circulating endotoxin and are implicated in many thrombotic diseases in the horse. This study reports that endotoxin (0.01-10 microg ml(-1)) and blood platelets (2.5 x 10(7) - 1 x 10(8) ml(-1)) are potent inducers of expression and activity of monocyte tissue factor (TF), the primary activator of the blood coagulation protease cascade. The co-incubation of endotoxin-stimulated monocytes with platelets resulted in greater production of this protein. Cycloheximide (1 mM) inhibited part of the stimulatory effect of endotoxin and/or platelets, the uninhibited part indicating de-encryption of cell-surface TF. Hence, platelets are considered to be an important component of the endotoxin-stimulated response of equine monocytes. The role of platelets as potent stimulators of endotoxin-stimulated monocyte proteins and mediators in vitro is likely to be of significance in vivo in the clinical manifestations and management of endotoxaemia in the horse.

Animals↗
PubMed2002

Effects of a P2Y(12) receptor antagonist on the response of equine platelets to ADP. Comparison with human platelets.

Horses show susceptibility to platelet-related disorders. Equine platelets differ from human platelets in some of their responses, so information available about human platelets must be validated in the horse. Aggregation of platelets by ADP involves both P2Y(1) and P2Y(12) receptors on the platelet surface. We have compared the effect of the P2Y(12) antagonist, AR-C67085, on equine and human platelets in vitro using turbidimetric aggregometry to measure the rate and final extent of aggregation. Aggregation profiles, concentration-response curves and pA(2) values show that the rate of aggregation of equine platelets is much more susceptible to inhibition by AR-C67085 than that of human platelets. This species difference may reflect differences in the relative numbers of P2Y(1) and P2Y(12) receptors, or in intracellular signalling pathways, but will need to be considered by equine clinicians before using P2Y(12) antagonists in the treatment of thrombotic conditions.

Adenosine Diphosphate↗
PubMed2001

Agricultural intensification and the collapse of Europe's farmland bird populations.

The populations of farmland birds in Europe declined markedly during the last quarter of the 20th century, representing a severe threat to biodiversity. Here, we assess whether declines in the populations and ranges of farmland birds across Europe reflect differences in agricultural intensity, which arise largely through differences in political history. Population and range changes were modelled in terms of a number of indices of agricultural intensity. Population declines and range contractions were significantly greater in countries with more intensive agriculture, and significantly higher in the European Union (EU) than in former communist countries. Cereal yield alone explained over 30% of the variation in population trends. The results suggest that recent trends in agriculture have had deleterious and measurable effects on bird populations on a continental scale. We predict that the introduction of EU agricultural policies into former communist countries hoping to accede to the EU in the near future will result in significant declines in the important bird populations there.

Agriculture↗
PubMed1998

Identification of a P2X1 purinoceptor expressed on human platelets.

It has been proposed that platelets possess a P2X1-purinoceptor-like ligand-gated cation channel, through which Ca2+ enters platelets from the extracellular medium upon ADP or ATP stimulation. In this paper we describe the cloning of human P2X1-specific cDNA from human platelets, K562 and human erythroleukaemic cell lines. Sequence analyses of these cDNAs show 100% nucleotide sequence identity with that of human P2X1 cloned from urinary bladder. Western blotting of platelet lysates separated by SDS-PAGE and probed with anti-P2X1 IgG shows the expected protein with a molecular mass of 60 kDa and a second protein of 45 kDa. These data confirm that platelets possess at least two distinct purinoceptors: a P2T purinoceptor which mediates platelet aggregation, inhibition of adenylate cyclase, and release of intracellular Ca2+ stores and a platelet P2X1 purinoceptor which upon ATP and ADP stimulation mediates the rapid entry of extracellular Ca2+ into platelets.

Blood Platelets↗
PubMed1998

Dextran-70 inhibits equine platelet aggregation induced by PAF but not by other agonists.

Dextrans of mean molecular weight 70 kDa (dextran-70) have had clinical use as anti-thrombotics in man. A major part of the anti-thrombotic action is mediated via inhibition of platelet function. Greatorex (1975, 1977) treated thromboembolic colic in horses with infusions of dextran-70 and reported a 90% recovery rate, but this treatment is nonetheless rarely used. We have used an in vitro method to examine the effect of dextran-70 on equine platelet suspensions, in the hope that understanding the mechanism of action of dextran-70 might lead to the development of alternative therapeutic agents. The effects of dextran-70 on equine platelets occurred immediately in vitro with an initial activation and shape change. Subsequent assessment of aggregation revealed a dose-dependent specific inhibition of platelet-activating factor (PAF)-induced aggregation, significant in rate of aggregation at dextran-70 concentrations >40 g/l (P<0.05) and in extent of aggregation at dextran-70 concentrations >50 g/l (P<0.05). Pre-incubation with 60 g/l dextran-70 significantly inhibited the rate and extent of aggregation in response to PAF (1 nmol/l) (P<0.001 and P = 0.003, respectively) but this was not dependent on the duration of pre-incubation (from 0 to 150 min). No effects were seen when the agonist was adenosine 5'-diphosphate (200 nmol/l), collagen (10 mg/l), 5-hydroxytryptamine (100 micromol/l) or U44069 (600 nmol/l) (all P>0.1). Analysis of PAF concentration-aggregation curves after pre-incubation with 60 g/l dextran-70 indicated significant noncompetitive inhibition by dextran-70 (P<0.001 for rate and extent of aggregation). The ability of dextran-70 to inhibit responses of equine platelets to PAF is probably an important component of its beneficial effect as an anti-thrombotic in colic cases.

Adenosine Diphosphate↗
PubMed1996

The role of ADP in endotoxin-induced equine platelet activation.

We have shown previously that endotoxin induces platelet aggregation in equine heparinised whole blood in a platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) dependent manner. ADP is an agonist of platelets and is present in platelet dense granules with ATP in high concentrations. An investigation was carried out to establish whether endotoxin-induced platelet activation was associated with release of platelet ATP and ADP. ADP-scavenging enzyme systems significantly inhibited endotoxin-induced aggregation. Plasma levels of adenine nucleotides were measured using a luminometric assay following incubation of heparinised equine whole blood with endotoxin (300 ng/ml). After addition of endotoxin ATP and ADP were released from the platelets and then subsequently degraded to AMP. WEB2086 (4-[3-[4-(o-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-s-triazolo[4,3-a][1, 4] diazepin-2-yl]proprionyl]-morpholine) (100 nM), a competitive PAF receptor antagonist, inhibited endotoxin-induced aggregation and also inhibited the release of adenine nucleotides from the platelets. It is concluded that endotoxin-induced aggregation is dependent upon ADP released from platelet dense granules.

Adenosine Diphosphate↗
PubMed1995

The effects of tyrphostins B42 and B46 on equine platelet function and protein tyrosine phosphorylation.

The effects of the protein tyrosine kinase inhibitors tyrphostins B42 and B46 on equine platelet function and protein tyrosine phosphorylation (PTP) were assessed. Tyrphostins B42 and B46 (both at 100 microM concentration) produced significant inhibition of thrombin-stimulated equine platelet aggregation. The effect of tyrphostin B46 was also time-dependent. The same concentration of these inhibitors produced very little or no inhibition of platelet-activating factor (PAF)-induced aggregation. The effects of tyrphostins B42 and B46 on thrombin- and PAF-stimulated PTP were generally similar, although some bands were more strongly inhibited when thrombin was the agonist. Therefore, although thrombin and PAF both act via G-protein coupled receptors, PAF may be capable of utilising an alternative signal transduction pathway to that used by thrombin.

Animals↗
PubMed1995

Protein tyrosine phosphorylation in equine platelets: the effect of stimulation by thrombin and platelet-activating factor (PAF)

Protein tyrosine phosphorylation (PTP) in thrombin- and platelet-activating factor (PAF)-stimulated equine platelet activation was investigated in the absence and presence of 2 protein tyrosine kinase inhibitors (PTKIs), methyl 2,5-dihydroxycinnamate (MDHC) and genistein. Washed equine platelets aggregated irreversibly in response to thrombin or PAF in an agonist concentration dependent fashion. MDHC produced an MDHC concentration and time dependent inhibitory effect on rate and extent of thrombin- and PAF-induced aggregations, whereas the effect of genistein on the same parameters was only genistein concentration dependent. Western blotting demonstrated tyrosine phosphorylated proteins in resting platelets. Changes in the PTP pattern occurred both when platelets were stimulated with varying concentrations of thrombin or PAF for a standard time (3 min) or with a standard agonist concentration (0.17 u/ml thrombin or 10(-10) mol/l PAF) for varying times. Different patterns of PTP were produced by thrombin and PAF. 500 mumol/l MDHC and 300 mumol/l genistein each affected the PTP patterns produced in response to thrombin or PAF, but in different ways. PTP results with thrombin and PAF in the presence of 500 mumol/l MDHC were similar, as were those in the presence of 300 mumol/l genistein. However, there were many differences in the PTP results between thrombin (or PAF) in the presence of MDHC and between thrombin (or PAF) in the presence of genistein. Therefore, although both inhibitors are PTKIs, they have different effects on the PTP induced by either agonist. Our work has produced the first evidence of PTP in equine platelets. It is probable that the changes in PTP are related to events in the signal transduction pathway.

Animals↗
PubMed1994

The effects of aspirin and paracetamol on the aggregation of equine blood platelets.

The responses of equine blood platelets in citrated platelet-rich plasma to arachidonic acid, U44069 (prostaglandin endoperoxide analogue), adenosine 5'-diphosphate, platelet-activating factor or collagen were investigated by turbidimetric aggregometry. Pre-treatment of the platelets with aspirin (1 mmol/l) or paracetamol (1.3 mmol/l) abolished shape change and aggregation in response to arachidonic acid; decreased the rate of aggregation in response to collagen, with no separate effect on shape change; had no marked effect on aggregation caused by the other agonists; but in no case transformed irreversible aggregation to reversible aggregation. We conclude that thromboxane A2 generation is of minor importance in the aggregation of equine platelets, and in particular that thromboxane A2 is not a significant mediator of irreversible aggregation.

Acetaminophen↗
PubMed1994

Changes in fetal thyroid hormone levels in adrenalectomized fetal sheep following continuous cortisol infusion 72 h before delivery.

Continuous infusion of cortisol into adrenalectomized fetal sheep during the last 72 h of gestation (term = 145 +/- 2 days) produced a significant (P < 0.05) rise in fetal serum tri-iodothyronine (T3) mean +/- S.E.M. concentrations from 398 +/- 65 to 1340 +/- 238 ng/l. A concurrent decrease in plasma thyroxine (T4) levels was observed in three out of four animals. No significant changes in the concentrations of either hormone were noted prior to the start of cortisol infusion. The plasma concentrations of cortisol, T3 and T4 at term were similar to those in untreated full-term lambs. Adrenalectomized fetuses not given cortisol infusions still had low levels of T3 at term, with no increase being observed. The results suggest that cortisol plays an important role in the increase of fetal plasma T3 observed towards the end of gestation. This is probably achieved by the stimulation of the monodeiodination of T4 to T3 in the peripheral tissues.

Adrenalectomy↗
PubMed1993

ADP induces desensitisation of equine platelet aggregation responses: studies using ADP beta S, a stable analogue of ADP.

Pre-incubation of equine platelets in platelet-rich plasma with adenosine 5'-diphosphate (ADP) induced a reduction in aggregation responsiveness to subsequent additions of ADP. The desensitisation was shown to be homologous since the responsiveness to platelet-activating factor, thrombin, collagen, 5-hydroxytryptamine or ionomycin remained unchanged. Adenosine 5'-(beta-thio)-diphosphate (ADP beta S), a non-hydrolysable analogue of ADP, was shown to act as an agonist inducing aggregation by interaction with the ADP receptor. ADP beta S was then used in the desensitisation studies in which residual ADP was degraded by the addition of apyrase. The desensitisation to ADP beta S fully recovered by one hour after pre-treatment with ADP and was not induced by an extracellular mediator. The mechanism of desensitisation is therefore likely to involve the ADP receptor or proximal intermediates in the signal transduction pathway for ADP.

Adenosine Diphosphate↗
PubMed1993

A method for loading equine platelets with the fluorescent calcium indicator Fura-2: ADP induces a rise in the cytosolic free calcium ion concentration.

Equine platelets in platelet-rich plasma were incubated with the fluorescent indicator dye, Fura-2-AM (Fura-2-acetoxymethyl ester) and the degree of loading of the cells with the dye and the extent of hydrolysis of the ester was assessed by quantitative fluorimetry and by thin-layer chromatography respectively. Under these conditions the cells loaded poorly with Fura-2 to a concentration of 4 microM. The technique was validated by demonstrating adequate loading of human platelets with Fura-2, to a concentration of 250-300 microM, using the same method. The removal of plasma from the extracellular medium was important for successful loading of the cells with the dye since washed cells resuspended in a physiological salt solution loaded adequately with Fura-2 to a concentration of 190 microM. Cells loaded as such showed a resting [Ca2+]i of 129 nM and a concentration-dependent rise in [Ca2+]i to a transient maximum of 350 nM when stimulated by the pro-aggregatory agonist adenosine 5'-diphosphate (ADP).

Adenosine Diphosphate↗
PubMed1992

A modified helium dilution technique for measuring small lung gas volumes.

The present study was undertaken to devise an accurate method for measuring functional residual capacity, FRC, in small and lively newborn animals such as lambs and piglets under flexible laboratory conditions using relatively simple equipment. This was achieved by adapting the standard helium dilution method so that FRC could be calculated from the helium equilibration concentration reached when the subject, having breathed a gas mixture with a high helium concentration, rebreathed from an air-filled spirometer. Using this technique, typical results for test volumes of 10, 20, 30 and 40 ml were measured as 10.7 +/- 0.34, 20.2 +/- 0.19, 30.5 +/- 0.40 and 40.6 +/- 0.75 ml respectively with corresponding coefficients of variation of 6.4%, 1.9%, 2.6% and 3.7%. Repeat measurements made on each of 3 urethane anaesthetised rabbits gave values for FRC of 45.64 +/- 0.9 ml (5 measurements), 37.22 +/- 0.8 ml (8 measurements) and 48.95 +/- 0.99 ml (8 measurements) confirming the reproducibility of results from animal preparations. The FRC of newborn lambs (12 animals) was 81.4 +/- 9.2 ml. The technique also allowed clear recordings of respiratory pattern essential to the analysis of variations in FRC.

Animals↗
PubMed1991

Interaction of Ostertagia and Nematodirus species in sheep and the potential of serum fructosamine determination in monitoring gastrointestinal parasitism.

Serum fructosamine concentration falls with an increase in plasma protein turnover. Since this increase is a feature of gastrointestinal parasite infection at all sites, a falling serum fructosamine level may be of general application in the interpretation of parasite-related events. The circulating fructosamine level was investigated in the lamb as an indicator of protein-losing gastroenteropathy associated with two parasites at different sites, Ostertagia circumcincta (abomasum) and Nematodirus spathiger (small intestine). Infection with 10,000 N spathiger infective larvae daily for seven weeks produced only slight clinical signs, and only a small change in serum fructosamine levels. 2500 O circumcincta L3 daily gave no clinical signs in most animals, but serum fructosamine was more strongly affected in this group. Concurrent infection with both organisms caused some degree of diarrhoea in all lambs, and a sustained fall in serum fructosamine, more accentuated than that observed in either of the single infection groups, supporting the value of serum fructosamine determination in monitoring gastrointestinal parasitism.

Abomasum↗