Veterinarians and food safety.

Since the early days of veterinary science, vets have played an important part in protecting public health through controls over the safety of food of animal origin. Traditionally, public health has been treated as a topic separate from the mainstream veterinary subjects of diagnosis and treatment of animal disease. However, there is now increasing awareness of the interconnection between animal and human health, and between the work of vets in production animal practice and those in food safety and other disciplines, as Kenneth Clarke explains.

A systematic review of animal based indicators of sheep welfare on farm, at market and during transport, and qualitative appraisal of their validity and feasibility for use in UK abattoirs.

In the UK, it has been suggested that abattoirs are ideal locations to assess the welfare of sheep as most are slaughtered at abattoirs either as finished lambs or cull ewes. Data from abattoirs could provide benchmarks for welfare indicators at a national level, as well as demonstrating how these change over time. Additionally, feedback could be provided to farmers and regulatory authorities to help improve welfare and identify high or low standards for quality assurance or risk-based inspections. A systematic review of the scientific literature was conducted, which identified 48 animal-based indicators of sheep welfare that were categorised by the Five Freedoms. Their validity as measures of welfare and feasibility for use in abattoirs were evaluated as potential measures of prior sheep welfare on the farm of origin, at market, or during transportation to the abattoir. A total of 19 indicators were considered valid, of which nine were considered theoretically feasible for assessing sheep welfare at abattoirs; these were body cleanliness, carcass bruising, diarrhoea, skin lesions, skin irritation, castration, ear notching, tail docking and animals recorded as 'obviously sick'. Further investigation of these indicators is required to test their reliability and repeatability in abattoirs. Novel welfare indicators are needed to assess short-term hunger and thirst, prior normal behaviour and long-term fear and distress.

Effect of baclofen on sensory transmission through the ventrobasal thalamic nucleus of the rat.

Previous work suggests that after administration of baclofen there is a reduction in excitatory cuneothalamic transmission, while preliminary experiments in this laboratory had shown that baclofen produces lowered level of cortical activity. Since much of the corticothalamic output is inhibitory, the consequences of possible reductions in excitatory corticopetal and inhibitory corticofugal flow into the ventrobasal thalamus required investigation. Baclofen produced increased latency and decreased probability of discharge of the short-latency discharge of single ventrobasal thalamic units to peripheral stimulation. It is suggested that these observations are compatible with a decreased excitatory cuneothalamic volley. Accompanying the decline in the early discharge was a development of later rhythmic discharges at 80-100 msec intervals, lasting up to 900 msec. This type of response is also seen in decorticate rats and has the same temporal pattern as the inhibition of the response to the second of a pair of peripheral stimuli shown in rats with an intact cerebral cortex. Since baclofen produced a decline in cortical activity (N1 wave of evoked potential, synchronisation of the ECoG), is suggested that this emergence of rhythmic activity is produced by a reduction of corticothalamic inhibition.

The effects of trimethadione on pentetrazol-induced discharges of primary muscle spindle afferents from the hind limb of the rat.

1 Recordings have been made from primary muscle spindle afferents in split dorsal root filaments of rats anaesthetized with urethane. 2 Injection of pentetrazol (PTZ, 10 mg/kg) produced elevated discharge in the afferents with intact efferents without any charge in tension or electrical activity of the muscle of origin. 3 This elevated discharge was found to contain elements of both gamma d and gamma s activation. 4 Trimethadione (100 mg/kg), itself produced a transient increase in discharge and effectively suppressed PTZ-induced discharges of the afferents for at least 2 h. 5 These results are discussed in the context of established effects on sensory and motor systems.

Motoneurone excitability after administration of a thyrotrophin releasing hormone analogue.

Recording have been made of motoneurone field potentials at vertebral level L1 to stimulation of the ventral root, in rats anaesthetized with urethane. Injection of thyrotrophin releasing hormone (TRH) analogue RX77368 (2 mg kg-1) produced an increase in the amplitude of the field potential within 1 min of injection, reaching peak amplitude of 51-69% above control values 6-12 min after injection; the duration of the elevation was 30-65 min. Arguments are presented which show that this effect is compatible with an RX77368-induced depolarization of the motoneurone, allowing the antidromic volley to invade more cell bodies.

A pharmacological study of the spontaneous convulsive activity induced by 1,2-dihydroxybenzene (catechol) in the anaesthetized mouse.

1. The convulsive activity induced by catechol has been examined in anaesthetized mice either by determining the CD50 for the convulsions in drug-treated and control animals, or by studying the effects of various drugs on the total whole body activity. 2. The results indicate that catecholamines play no part in the mechanism of action of catechol. Drugs which alter cerebral catecholamine levels had no effect on the convulsions, nor did the alpha- and beta-adrenoceptor blocking drugs. 3. 5-Hydroxytryptamine (5-HT) could possibly be important, though results with drugs which either change brain 5-HT levels, or block 5-HT receptors were inconsistent. 4. gamma-Aminobutyric acid also appears not to be involved in the mechanism of action of catechol. 5. The results strongly suggest that catechol primarily activates a central cholinergic system, in that muscarinic and nicotinic receptor blocking drugs inhibit, and anticholinesterases potentiate the convulsions.

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol.

The effect of fetal cortisol on the activity of the type 2 isoform of the enzyme, 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2), was examined in ovine placenta and fetal kidney by measuring tissue 11 beta-HSD2 activity during late gestation when endogenous fetal cortisol levels rise and after exogenous cortisol administration to immature fetuses before the prepartum cortisol surge. Placental 11 beta-HSD2 activity decreased between 128-132 days and term (approximately 145 days of gestation) in association with the normal prepartum increase in fetal plasma cortisol. Raising fetal cortisol levels to prepartum values in the immature fetus at 128--132 days of gestation reduced placental 11 beta-HSD2 activity to term values. In contrast, 11 beta-HSD2 activity in the fetal renal cortex was unaffected by gestational age or cortisol infusion. When all the data were combined, there was an inverse correlation between the log fetal plasma cortisol level at delivery and placental 11 beta-HSD2 activity, expressed both on a weight-specific basis and per mg placental protein. Fetal cortisol therefore appears to be a physiological regulator of placental, but not renal, 11 beta-HSD2 activity in fetal sheep during late gestation. These findings have important implications, not only for glucocorticoid exposure in utero, but also for the local actions of cortisol within the placental tissues that are involved in initiating parturition in the sheep.

TRH analogue affects information transfer through the ventrobasal thalamus.

Extracellular microelectrode recordings have been made from single ventrobasal thalamic neurones in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (2mg/kg), produced increases in spontaneous activity and decreases in the latency of response to peripheral stimulation, together with increased production of later, rhythmic discharges. These changes were maximal between 30 and 60 minutes after injection. Decreases in latency and increases in amplitude were also observed in the evoked potential recorded from the somatosensory cortex. These results are discussed in relation to previously observed effects of TRH. Since this system is important in the planning and execution of motor acts it is suggested that modification of information flow through this system could have effects on the production of motor activity.

Disturbance of spatiotemporal footfall contact patterns in the rat by TRH analogue CG3703.

Administration of TRH or its analogues to a rat changes the dynamics of locomotion resulting in shorter stance times and causes postural disturbances, including hunched back and pelvic girdle elevation. Locomotor disturbance, induced by a variety of methods, results in changes to the footfall patterns during the stance phase of locomotion. The present work investigated whether these postural and locomotor dynamic disturbances in the CG3703 treated rat were associated with changes to the pattern of paw/floor contact during locomotion. It was found that in treated animals the area of hindpaw contact increased while that of the forepaw decreased from control values. The pattern of contact changed, with hindpaw stance being shifted towards more distal elements while in the forepaw a reduction in the deployment of proximal elements without any compensating increase in distal contact was seen. These results are discussed in the context of the effects of TRH analogues on sensory and motor processing in the CNS.

TRH analogue antagonizes anaesthetic induced depression of information transfer through the ventrobasal thalamus of the rat.

Previous studies have indicated an anti-narcotic action of TRH and its analogues. A major site of anaesthetic action is in the ventrobasal thalamus (VBT). The present experiments were performed to determine whether there was antagonism between anaesthetics and a TRH analogue on VBT transmission. It was found that the TRH analogue CG3703 reversed the depressant actions of the anaesthetics urethane, sodium pentobarbitone and sodium brietal on ventrobasal transmission. These actions were also observed at the cortical level but cuneate transmission was unaffected. These results are discussed in the context of modulation of information flow through VBT. In particular it is suggested that TRHergic input from the thalamic reticular nucleus may be an important regulator of VBT transmission.

Stimulation of locomotion in neonate rats by TRH analogue CG3703.

Thyrotropin releasing hormone (TRH) and its analogues have been shown to depolarise motoneurons and stimulate cyclical motor activities such as respiration and locomotion. It has been suggested that one of its roles might be modulation of neuronal membrane excitability to release intrinsic rhythmicity. The present experiments were designed to determine whether it would initiate locomotion in the neonate rat prior to the development of spontaneous walking. It was found that the TRH analogue CG3703 did activate locomotion in 3-day-old rat pups. Quantification of various gait parameters and study of spatiotemporal footfall patterns showed the gait to be indistinguishable from the spontaneous locomotion of older pups. Possible loci of action are discussed.

Further studies on the effects of a thyrotropin releasing hormone analogue on locomotor activity in the rat.

In these experiments, the relationship between two of the variables of locomotion, stepping frequency and velocity, after injection of the TRH analogue RX77368 (10 mg/Kg i.p.), has been studied. A shift towards higher stepping frequencies was observed, confirming previous observations. However, there was no difference between the velocities of locomotion produced by treated and control rats. In the treated rats the relationship between stepping frequency and velocity was disturbed, such that a higher stepping frequency was employed to attain any particular velocity. This was accompanied by a reduction in stride length. Possible reasons for this disturbance are discussed in terms of changes in muscle stiffness and proprioceptive reflexes.

Interactions between adrenergic systems, anaesthetic and TRH analogue induced analeptic effects on VBT transmission.

Previous behavioural and electrophysiological studies have indicated an antinarcotic action of thyrotropin-releasing hormone (TRH) and its analogues in antagonizing the action of CNS depressant drugs, including baclofen and a variety of anesthetics. While beta-adrenergic receptors are implicated in the level of anaesthesia/arousal, whether the analeptic action of TRH involves adrenergic systems for its expression is uncertain. The object of the present experiments, therefore, was to examine interactions between adrenergic systems and the anti-anaesthetic effects of TRH analogue CG3703. It was found that pretreatment with the beta-block (+/-)propranolol did not abolish or reduce the ability of CG3703 to antagonize urethane-induced depression of VBT transmission. These results suggest therefore, that beta-adrenergic systems are unlikely to be involved in the anti-anaesthetic effect of the tripeptide.

Effects of a thyrotropin releasing hormone analogue on locomotor and other motor activity in the rat.

In the present experiments, locomotion has been studied in rats after injection of TRH analogue RX77368 (10 mg/kg i.p.). The measure used was the frequency of the cyclic shifts of weight from side to side (WTF) which accompany the progress of locomotion. It therefore provides an indirect measure of stepping frequency. After injection of RX77368 there was a shift in WTFs towards higher frequencies, i.e. when the rat walked it was taking more steps per second. These results suggest that RX77368 stimulates basic motor patterns associated with locomotion. The results obtained in these experiments are compared with those obtained using different quantification methods for locomotion and there is speculation concerning the possible modes of action of RX77368 including interactions with other neurotransmitter systems.

Antagonism of baclofen induced reduction in ventrobasal thalamic transmission by a TRH analogue.

It has been shown previously that baclofen, the GABB beta receptor agonist, reduces the excitability of ventrobasal thalamic relay neurons measured by increases in latency and decreased discharge probability, while thyrotropin releasing hormone (TRH) analogues have the opposite effects. The present experiments have shown that the excitability reducing effects of baclofen on ventrobasal transmission are antagonised by the administration of TRH analogue CG3703. These results are discussed in the context of possible GABAergic and TRHergic modulation of VBT transmission from the thalamic reticular nucleus.

Abnormal locomotion in the rat after administration of a TRH analogue.

Previous studies have indicated that the TRH analogue CG3703 induces changes in gross measures of motor activity. The purpose of the present study was to determine whether it affected the underlying components of the locomotor cycle, stance and swing times. It has been found that while total stride time was unaffected there was an alteration in the balance between swing and dual stance times such that treated rats used longer swing times and shorter dual stance times. For both control and treated animals dual stance time increased with stride time. However, for any particular stride time, treated animals deployed longer swing times and shorter dual stance times. Possible mechanisms for these observations are discussed.

Motoneurone excitability during antidromically evoked inhibition after administration of a thyrotrophin releasing hormone (TRH) analogue.

Acute experiments have been performed in urethane anaesthetised rats to determine the effect of a TRH analogue (RX77368) on the excitability of motoneurone pools in the lumbar region of the spinal cord to paired antidromic stimuli ( interval 10ms) delivered to the ventral root, by measuring the field potentials produced. Following the response (CR) to the first stimulus (conditioning stimulus), the response (TR) to the second stimulus (test stimulus) is reduced in size. In control experiments, the greater the amplitude of CR, the smaller TR becomes. After RX77368 injection, CR progressively increases over the initial post injection period. It would be expected therefore that during this time there would be a progressive decline in TR relative to CR. It has been shown however, that over this period there is no decline of TR relative to CR. There is speculation on a possible role of putative neuromodulators such as TRH in the maintenance of control parameters during motoneurone recruitment and/or increases in discharge frequency.

Potentiation of motoneurone excitability by combined administration of 5-HT agonist and TRH analogue.

Motoneurone field potentials have been recorded from the lumbar region of the spinal cord, to antidromic stimulation of a ventral root, in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (1mg/kg) plus the 5-hydroxytryptamine (5-HT) receptor agonist 5-methoxy-N, N-dimethyl-tryptamine (5MeODMT 0.4mg/kg) resulted in a potentiation of the increase in amplitude and duration of response, compared to when the drugs were given singly. These results are discussed in the context of possible interactions between 5-HT and TRH systems.

Locomotion in the rat after 5-hydroxy-L-tryptophan.

Previous work has shown that administration of 5HTP in amounts substantially less than those required to elicit 'serotonin syndrome' to rats pretreated witha peripheral decarboxylase inhibitor, produced increases in locomotion, measured by whole body movements. The purpose of the present work was to study the cyclic shifts of weights from side to side which underly the progress of locomotion and to see whether these change after 5HTP. From the reciprocal of the interval for one complete cycle was calculated the weight transferral frequency (WTF). The modal WTF for control and treated rats were in the ranges 1-1.49 and 2-2.49 Hz respectively, while the medians were in the ranges 2-2.49 and 2.5-2.99 Hz respectively. Testing of goodness of fit between the frequency distribution curves in control and treated animals showed significant differences. It is concluded that after 5HTP treatment, basic locomotor patterns are shifted towards higher frequencies.

Swing time changes contribute to stride time adjustment in the walking rat.

Locomotor analysis is a useful tool for assessing normal and disturbed brain function. Previous studies have indicated that, during locomotion at walking velocities, the rat adjusts its velocity by changes to stride time and length. The present work has shown that, in the Sheffield strain rat, changes in stride time are achieved by a differential deployment of its two components, stance time and swing times. During slow walking, swing time changes provide minimal contribution to stride time reductions. At above average stride frequencies, however, swing time changes become significant, providing for more than half the reduction over parts of the range.