In milk-fed calves, the effects of sodium-butyrate (Na-butyrate) to replace flavomycin on growth performance and some mechanisms involved were studied. Pancreatic and intestinal morphology, digestive enzyme activities, plasma gut regulatory peptide concentrations, and expression of their receptors in the gastrointestinal tract were measured. Gastrointestinal tract defense systems were examined by measuring protein levels of 2 heat-shock proteins (HSP27 and HSP70). The calves were randomly allocated into 2 groups fed the same basic diet with flavomycin as an antimicrobial growth promoter or with Na-butyrate (3 g/kg of dry matter). Sodium-butyrate disappeared quickly in the upper gut and was not found in circulating blood. Supplementation with Na-butyrate enhanced growth rate and improved feed conversion into body weight gain compared with the flavomycin group. Supplementation with Na-butyrate was likely associated with an improvement in efficacy of the gastrointestinal tract digestive capacities expressed by enhanced production of digestive enzymes and increased absorptive capacities in the upper small intestine. The effects could have been controlled by insulin-like growth factor-1 but probably not by any of the cholecystokinin/gastrin peptide family. Concentrations of HSP27 and HSP70 were increased in stomach and colon of calves receiving Na-butyrate, thereby assuring protection of cells with intensive metabolism (chaperone function). In conclusion, beneficial effects of Na-butyrate on maturation of gastrointestinal functions were shown in milk-fed calves and may be applied to young mammals of other species.

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Spreading depression induces tolerance to ischemic injury, and ischemic tolerance has been associated with expression of heat shock proteins (Hsp). Here we examine Hsp27 expression after KCl-induced spreading depression. Twenty-minute cortical KCl application induced Hsp27 immunoreactivity in glial fibrillary acidic protein-positive astrocytes of the ipsilateral neocortex. Systemic administration of MK-801 (3 mg/kg) suppressed KCl-induced Hsp27 expression in the parietal cortex. Astrocytes in the posterior cingulate and retrosplenial cortex did not express Hsp27 after KCl application but did express Hsp27 after systemic administration of high dose MK-801 (9 mg/kg). Whereas Hsp27 was usually observed in all layers of the parietal cortex after 5-minute application of KCl, in 2 of 6 rats, Hsp27 was seen in clusters of astrocytes or in astrocytes in the superficial layers I to III of the parietal cortex. We conclude that (1) cortical application of KCl triggered Hsp27 astrocytic expression; (2) astrocytes in the cingulate and retrosplenial cortex responded differently compared with astrocytes of the parietal cortex; (3) Hsp27 expression progressed from small clusters of astrocytes throughout superficial layers of the cortex that joined and recruited astrocytes in deeper layers; (4) several mechanisms induced Hsp27 astrocytic expression. We propose that Hsp27 is involved in spreading depression-induced ischemic tolerance through protection of astrocyte function.

Heat shock proteins (HSP) play a central role in the protection of cells, tissues or organs subjected to various types of stressors. Different nutrients have been recently shown to exert their protection through the induction of HSP. Because these nutrients alleviate alterations of the intestine after weaning in pigs, this study was designed to obtain basic information on the expression of HSP 27, heat shock cognate 70 (HSC 70), HSP 70 and HSP 90 along the gastrointestinal tract (GIT) of young pigs and to study the effect of weaning on this expression. Pigs were weaned at 28 or 21 d and slaughtered at various times postweaning. All HSP were expressed in the GIT segments studied before and after weaning. However, the expression of HSP 27 and HSP 70 was transiently increased in the stomach and duodenum between 6 and 12 h postweaning and between 24 and 48 h in the mid-jejunum, ileum and colon. Their expressions were transiently decreased in the ileum. Expression of HSP 90 increased in the stomach and jejunum but decreased in the duodenum, ileum and colon. Similar results were obtained at both ages of weaning. We conclude that the HSP studied are present all along the gut of pigs and that their expression is modulated through weaning according to spatial-temporal patterns. The modulation by nutrients of HSP and their protective role on the GIT remain to be investigated in pigs.

Hypoxia at birth represents a very stressful event that can result in severe lifelong consequences in different tissues, including those of the heart. Heat shock and other associated stress proteins are involved in cellular protection, but their roles are not clearly defined at the time of birth. Newborn piglets were subjected to 5% oxygen and 95% nitrogen for either 1 or 4 hours. They were allowed to recover over periods of 1 to 68 hours. The relative levels of ␣B-crystallin, HspB8, Hsp20, Hsp27, Hsp60, and Hsp70 as well as nitric oxide synthases (NOS) (endothelial NOS, inducible NOS, neuronal NOS) were examined by Western blot analysis. Surprisingly, ␣B-crystallin expression was drastically increased in animals submitted to hypoxia. The hypoxia-associated factor HIFI␣ was also strongly and rapidly overexpressed. Heme oxygenase 1 was also increased. To a lesser extent, neuronal NOS was also increased in the left ventricle of animals submitted to hypoxia. This work clearly shows that the Hsp chaperone ␣B-crystallin is strongly overexpressed in the left ventricle of animals submitted to hypoxia. This observation dissociates the response to low oxygenation of ␣B-crystallin and other stress-associated proteins including Hsp27, and it indicates that heme oxygenase is not alone among HSPs in its oxygen-related gene expression.

The use of L-dopa in the treatment of Parkinsonism represents a great advance but we are becoming increasingly aware of the problems involved with its lo.ng-term use-side effects, abnormal involuntary movements, diurnal oscillations in performance ("on-off" effects), and loss of therapeutic efficiency after several years' treatment. Therefore, other substances are being sought to replace or to be used in conjunction with L-dopa. It is for these reasons that dopaminergic agonists have been synthesised: apomorphine, piribedil, lergotrile, N-propyl-aporphine and, more recently, bromocriptine (CB 154 Sandoz; Parlodel).First used for its inhibitory properties on prolactin secretion, bromocriptine also stimulates the postsynaptic (Corrodi et al., 1973) and presynaptic (Snider et al., 1976) central dopaminergic receptors which renders it suitable for the treatment of Parkinson's disease. Bromocriptine also seems to have a stimulating action on the serotoninergic receptors (Corrodi et al., 1975; Snider et al., 1976).Since the first clinical trials done by Calne and co-workers (1974a, b), bromocriptine has been the object of numerous studies. It improves the extrapyramidal symptoms (mainly tremor and rigidity) not only at low doses (20 to 30 mg) in conjunction Address for reprint requests: Professor A. Rascol,

Expression of the two closely related heat shock proteins (HSPs), αB-crystallin and Hsp27, was studied in various tissues of the developing pig. Expression of αB-crystallin was maximum in the lens while expression of Hsp27 was absent. In non-lenticular tissues, both proteins were strongly expressed in heart and muscle. Increases in αB-crystallin expression were observed in brain, liver and kidney while Hsp27 was increased in kidney at later stages. Relatively constant expression was found in heart while a decrease in both stress proteins was observed between 28 days and 6 months in skeletal muscle. In the different parts of the gastrointestinal tract, increased expression of αB-crystallin was seen following birth and weaning while increased expression of Hsp27 was restricted to weaning. These results are discussed in terms of the protective effects of HSPs during stressful events in the different tissues of the developing pig.