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Ghrelin has been shown to decrease firing of gastric vagal afferents at doses comparable with cir- culating levels in the fasted state. This raises the possibility that ghrelin may have a hormonal action on other vagal afferent populations. The aim of this study was to determine the effects of ghrelin on jej- unal afferent activity; including responses to disten- sion, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and cholecystokinin (CCK) in both naive and vago- tomized rats. Ghrelin significantly augmented the afferent response to distension. No effect was observed on baseline afferent discharge, or the response to 2-methyl-5-HT and CCK. The effect of ghrelin was more pronounced at lower ramp distending pressures (0-30 mmHg). Similarly, ghrelin augmented the jej- unal afferent responses to phasic distension at 10- 30 mmHg, but had no effect at higher pressures. Chronic subdiaphragmatic vagotomy and adminis- tration of the growth hormone secretagogue receptor (GHS-R) antagonist (D-Lys3)-GHRP-6 prevented the augmentation of the afferent responses to distension indicating ghrelin is acting through the GHS-R on vagal afferent fibres. Ghrelin augments the mechano- sensation of jejunal vagal afferents and hence may lead to increased perception of hunger contractions.

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.

The aim of the present study was to examine the sensitivity of mesenteric afferents supplying the rat small intestine to mu-opioid receptor ligands. Mesenteric afferent discharge was recorded electrophysiologically in response to [D-ALA2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO; 100 mug kg(-1) i.v.), before and after treatment with the mu-receptor antagonist alvimopan (1 mg kg(-1) i.v.). DAMGO markedly stimulated whole nerve mesenteric afferent discharge (P0.05), an effect completely blocked by alvimopan. The response of mesenteric afferents to 2-methyl-5-hydroxytryptamine (30 microg kg(-1) i.v.), bradykinin (0.1-1 microg kg(-1) i.a.) and both low- and high-threshold distension (0-60 mmHg) was unaffected by alvimopan. In chronically vagotomized animals, the low-threshold response to distension was attenuated while the remaining high-threshold response was unaffected by alvimopan. In conclusion, mesenteric afferent fibres are markedly stimulated by mu-opioid receptor agonists, an effect blocked by alvimopan, which may contribute to the gastrointestinal reflex and behavioural responses to opiate treatment or abuse. However, alvimopan did not influence the normal sensitivity of intestinal afferents to chemical and mechanical stimuli that activate different subpopulations of vagal and spinal afferents. Thus, alvimopan may be useful for the treatment of gastrointestinal sequelae following opiate treatment for postoperative or chronic pain.

Some cytotoxic drugs which are widely used to treat cancer are administered orally. Any hospital which has an emergency department (ED) must expect to admit patients who are taking oral chemotherapy drugs prescribed locally or elsewhere. The risks of repeat prescriptions of these medicines have long

Brook trout (Salvelinus fontinalis) adapt to chronic sublethal acid/Al stress. The accompanying acclimation confers greater resistance to short-term increases in Al and acidity. Adult trout were exposed in flowing soft water to eight combinations of pH (6.5, 5.2) × Ca2+(25, 400 μequiv/L) × Al (0, 75, 150 μg/L = 0, 2.8, 5.6 μmol/L). After 10 wk, blood sampling by caudal puncture revealed no significant variations in osmolality, plasma protein, or hemoglobin and only minor differences [Formula: see text] in plasma Na+and Cl−. Overall, most electrolytes were higher in fish exposed to higher water Al and/or Ca2+; only plasma Ca2+was directly depressed by low pH. Hematocrit was raised by both low pH and elevated Al. When trout naive to both acid and Al were challenged with pH = 4.8, Al = 333 μg/L under flow-through conditions, there were large negative whole-body Na+fluxes and marked depressions of plasma Na+and Cl−, hemoconcentration, and substantial mortality over 48 h. Prior exposure for 10 wk to pH = 5.2 plus either 75 or 150 μg Al/L prevented mortality and ameliorated or abolished these effects through a more rapid recovery of net Na+balance. Prior exposure to pH = 5.2 alone ameliorated these effects only slightly.

Adult brook trout (Salvelinus fontinalis) were exposed for up to 11 d to one of a matrix of 18 Al, low pH, and Ca2+ combinations, chosen as representive of acidified softwater environments in the wild. Reduction in water pH led to pH-dependent net losses of Na+ and Cl− exacerbated by the presence of Al in the water and reduced by elevating Ca2+. Any animal losing more than 4% of its total body Na+ over the first 24 h of Al exposure had a greater than 90% likelihood of eventual mortality. Na+ losses arose from inhibition of influx and stimulation of efflux. The inhibition was persistent and pH dependent. Addition of Al to acidified water had a slight further inhibitory effect on Na+ influx and a large stimulatory effect on efflux. The latter was dependent on Al concentration, was the main cause of initial ion losses and mortality, and declined with time in surviving animals. All Al-exposed fish accumulated Al on their gills, but this was apparently mainly surface or subsurface bound, since no internal Al (plasma or liver) could be detected. Nonsurviving fish had substantially higher gill Al levels than survivors.

Using scanning electron microscopy, a histological comparison was made between gills from unperfused, blood-perfused and saline-perfused trout heads. All gills examined appeared non-edematous, and no other morphological abnormalities were evident. The results are compared with those from a similar study using isolated eel holobranchs in which saline-perfusion resulted in severe and irreversible branchial edema.

Branchial ionic transport processes were evaluated and compared in Ringer-perfused and blood-perfused heads of rainbow trout. Rates of Na+ and Cl- influx were similar to in vivo levels at the onset of perfusion. Na+ uptake deteriorated more rapidly over time during Ringer perfusion, whereas Cl- uptake was relatively stable regardless of the perfusate employed. Transepithelial potentials (TEP) were similar to values reported for intact freshwater teleosts and were unstable only during the initial period of blood perfusion. The TEP was extremely dependent on the external concentration of NaCl. Ammonia excretion (JNH4+net) was normal during both types of perfusion, although blood did have a stabilizing effect on JNH4+net over time of perfusion. JNH4+net was stimulated by the addition of carbonic anhydrase to Ringer, without a concomitant increase in Na+ uptake. Branchial net fluxes of Na+ and Cl- were stable but slightly negative and in this regard represented slightly stressed intact animals. Net acid flux (JH+net), however, was similar to in vivo rates. Na+ and Cl- uptake displayed Michaelis-Menten kinetics. The affinity constant (Km) for Na+ uptake was typical of intact fish during both Ringer and blood perfusion, whereas Km for Cl- uptake was abnormally high in both cases. The results are discussed with reference to the suitability of the perfused trout head preparation for studying gill ionic fluxes in vitro.

Branchial gas transfer, acid-base balance, and hemodynamics were critically evaluated and compared in Ringer-perfused and blood-perfused heads of rainbow trout. Blood perfusion stimulated O2 uptake and CO2 excretion across the gills to values more representative of intact fish. The stimulatory effect of blood on gas transfer was due to increased O2 carrying capacity (O2 uptake) and the presence of erythrocytic carbonic anhydrase (CO2 excretion). Adding carbonic anhydrase to Ringer enhanced CO2 excretion in a manner similar to blood. During Ringer perfusion, arteriovenous pH gradients were abnormal (arterial pH less than venous pH). Perfusion with blood or addition of carbonic anhydrase to Ringer reversed the pH gradients to typical in vivo levels. Branchial vascular resistance to flow was abnormally high in both Ringer- and blood-perfused preparations, primarily as a result of low dorsal aortic pressure. Input pressure increased during blood perfusion and was similar to ventral aortic pressure in vivo. Perfusion with Ringer may have caused irreversible deterioration of gill function as indicated by decreased arterial Po2 and O2 extraction effectiveness after a rapid switch from Ringer to blood perfusion. The results are discussed with reference to the suitability of perfused trout head preparations for studying gill gas transfer, acid-base balance, and hemodynamics. Comparisons are made between the perfused head preparation and intact fish as well as with other types of perfused gill preparations.

At the onset of moderate swimming activity,Callinectes sapidus rapidly increased branchial ventilation, heart rate, and oxygen uptake, reaching steady state values in 2–3 min, with a half-time of 30 sec. Although O2 extraction efficiency decreased slightly (50% to 43%) upon reaching steady state, O2 uptake was increased 2.6 fold over resting (routine) levels. HemolymphP O 2 did not change during sustained (30–60 min) exercise, but a marked decrease in pH (7.60 to 7.10), associated with a 14-fold increase in hemolymph lactate concentration, caused decreases in both pre-and postbranchial O2 content due to a large hemocyanin Bohr shift. The effect of the Bohr shift on O2 binding, however, was minimized by an increase in hemocyanin O2 affinity induced by lactate ions; the influence of lactate on hemocyaninP 50 was shown to be the same in vivo and in vitro. As a result of the interaction between the Bohr and lactate effects, only slight increases were observed in the a-v O2 difference (13%) and the quantitative role of hemocyanin in oxygen transport (11%) during exercise. The increase in O2 delivery was therefore attributed primarily to a 2.3 fold increase in cardiac output (Fick estimate), resulting from increases in both heart rate (1.61 X) and stroke volume (1.42X). During exercise hemocyanin remained 21% oxygenated upon leaving the tissues, thus maintaining a substantial ‘venous O2 reserve’ which could be utilized to fuel more strenuous levels of exercise at least partly by aerobic pathways. The high hemolymph lactate levels, however, indicate that anaerobic metabolism makes a significant contribution to energy production even during moderate exercise. These results are similar to the respiratory and circulatory responses reported for other decapod crustaceans and fish during mild exercise.C. sapidus, however, appears to be highly resistant to fatigue, which correlates with its welldeveloped locomotor capabilities.

Summary The survey indicates that seasonal variations in the proportion of failing samples is greater with the 1/2 hr. methylene blue than with the colony count test. The incidence of thermoduric organisms in the raw milk will no longer be important since such bacteria have little effect on the methylene blue test, but there will be a greater need for adequate cooling, efficient cold storage and avoidance of post-pasteurisation contamination. Plate count and coliform tests will, however, still be useful in the dairy laboratory. The methylene blue results for samples stored at atmospheric temperature or at 18° C. show good agreement. It is not known whether the agreement would be equally as good in very cold weather, as the results presented here do not cover such conditions. A small percentage of samples (1.7%) which by previous standards would have been regarded as highly satisfactory may fail the dye test; in addition, approximately 5.0% of samples showing high coliform contamination may satisfy the new standard.