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Biomedical subjects

M McFadyen

Publications and source records attributed to M McFadyen.

10 recordsLinked to original sources

Characterization and autoradiographic localization of the epidermal growth factor receptor in the jejunum of neonatal and weaned pigs.

Receptors for epidermal growth factor (EGF) were characterized on the intestinal membranes of newborn, sucking and weaned pigs. 125I-labelled EGF (125I-EGF) binding to membrane homogenates was time-dependent, saturable, linearly correlated to membrane protein and reversible. Analysis of saturation curve data revealed a single class of 125I-EGF binding sites in both newborn and weaned pigs. Receptor levels tended to be higher in weaned than in newborn pigs; the converse was true for the receptor affinity. In contrast, virtually no binding sites were found on the intestinal membranes of sucking pigs. Autoradiography in vitro of jejunal sections of newborn and weaned pigs demonstrated 125I-EGF receptors on both microvillar and basolateral surfaces of enterocytes, suggesting that luminal EGF could influence developmental processes in the intestine either directly or indirectly following transcytosis of the ligand.

Animals

Polyamide profiles of porcine milk and of intestinal tissue of pigs during suckling.

Previous studies have suggested that luminal polyamines can directly influence intestinal differentiation of neonatal rats. The present investigation has demonstrated the presence of high levels of polyamines in porcine milk and in the intestinal tissues of suckling pigs. The quantities of polyamines in sow's milk sampled between wk 1 and 8 of lactation were determined using high performance liquid chromatography (HPLC). The concentration of milk spermidine (SPD) remained constant over the first 3 to 4 wk of lactation but increased 4-fold between wk 4 and 7. Neither putrescine nor spermine (SPN) were detected in any of the milk samples. During intestinal development the mucosal SPD/SPN ratio was elevated between wk 1 and 3 and wk 5 and 7. The latter period of increase corresponded with the surge in milk SPD concentration. It is suggested that milk SPD is taken up from the intestinal lumen and is involved in potentiating intestinal differentiation during the latter part of the suckling period.

Animals

Effect of lactation on the decline of brush border lactase activity in neonatal pigs.

It has been shown that during the early phase of lactation porcine milk contains high concentrations of hormones and growth factors. The aim of the present investigation was to examine the hypothesis that the temporal coordination of intestinal maturation in piglets can be extrinsically regulated through changes in the composition of milk during the suckling period. Gut morphology and the ontogeny of brush border lactase activity were investigated in piglets reared on two suckling regimens designed to expose the animals to compositionally distinct milk. The first group of animals were cross-fostered onto postcolostrum sows and thereafter suckled normally for up to eight weeks. These normally suckled (N) animals consequently received both early and late lactation products. The second group of piglets were cross-fostered each week, for up to eight weeks, onto newly farrowed sows which were postcolostrum. As a result of this repeated cross-fostering (CF) these animals received only early lactation products. Animals were sacrificed at one, three, five, seven, and eight weeks postpartum. Biochemically active lactase decreased significantly (p less than 0.001) in both groups over eight weeks, but the rate of loss of activity was greater in the CF animals than in the N pigs by approximately 50% at week 3 and 25% at week 8. Quantitative histochemical analysis of lactase activity corroborated the biochemical data. At three weeks maximal enzyme activity was observed approximately 400 microns from the villus/crypt junction. Histochemically detected lactase decreased throughout the suckling period, but the intensity of reaction product was consistently weaker over the entire villus surface in the CF animals. Immunocytochemically detectable lactase was identified at the same sites as the histochemical reaction products. In addition, immunofluorescence microscopy showed the presence of histochemically undetectable enzyme on the basolateral and brush border membranes of both villus and crypt cells. Villus/crypt ratios were significantly lower (p<0.001) in the CF animals than in the N pigs between weeks 3 and 5. The results of this study suggest that lactation products can accelerate the loss of brush border lactase activity. The observed decline in biochemically and histochemically detected lactase was considered to be a consequence of reduced enterocyte lifespan, decreased synthesis of enzyme protein, or altered post-translational modification of enzyme protein, or a combination of there.

Animals

Intermittent alexia.

A case of intermittent alexia, sometimes accompanied by severe dysgraphia and sometimes by mild dysgraphia, which had a probable migrainous origin, is described. On some occasions the patient could write to dictation, although with many errors, while unable to read words or letters. On other occasions the patient's writing to dictation was seriously disordered in terms of content and the letters were produced clumsily. Reading of numbers, colour vision and colour naming were normal although impairments on right-left orientation and visual short term memory were present and a mild finger agnosia was apparent. Blood flow scans (SPECT) taken under normal and alexic conditions support the view that the disturbance had a vascular origin.

Adolescent

Pattern of gastric emptying in the pig: relation to feeding.

The aims of the present study were to compare the gastric emptying of dry matter (DM) and liquids during the feeding period with that following meal consumption, to clarify the relationship between feeding and gastric emptying, and to investigate how gastric emptying changes in growing animals. The studies were performed in pigs fitted with a gastric cannula and fed on a normal finely ground solid diet mixed with water containing CrEDTA as liquid marker. Gastric emptying was measured using a gastric evacuation technique. It was observed that between 0.75 and 6 h after feeding the total amounts emptied increased, but the proportion of the meal emptied fell, with increase in meal size; emptying of both DM and liquids with large and small meals followed an exponential pattern. In contrast, while the animals were feeding, there was linear and rapid emptying of both DM and liquids following a very short (approximately 2 min) lag phase before emptying began. The rate of emptying increased linearly with body-weight (by 0.055 g DM/min and by 0.24 ml/min per kg body-weight over the range 58-200 kg) such that the emptying of digestible energy per kg metabolic body-weight (W0.75) was roughly maintained (between 2.9 and 3.2 kJ/min per kg W0.75). This suggests that the rate of emptying may be linked in some way with the metabolic requirements of the body. The biphasic pattern of gastric emptying observed is probably the intrinsic pattern of emptying of a meal which does not require breakdown of particles before emptying can occur.

Animal Feed

Duodenal infusion of fat, cholecystokinin secretion and satiety in the pig.

The influence of the cholecystokinin (CCK) antagonist L-364,718 (0.1 mg/kg) on short-term control of food intake was studied in 6 pigs. Arterial injection of L-364,718 abolished the inhibition of intake to CCK octapeptide infusion (4 micrograms/kg/hr; from 42% p less than 0.001, to 97% of control intake), but did not alter control intake (99%). Injection of L-364,718 also abolished the inhibition of intake to duodenal infusion of emulsified fat (12 g/hr; from 76% p less than 0.001 to 105%) and of monoglyceride (24 g/hr; from 64% p less than 0.001 to 101%), but did not alter the inhibition to oleic acid (60 g/hr; 48% p less than 0.01 and 61% p less than 0.02), to glycerol (127 g/hr; 84% p less than 0.05 and 89%) or to glucose (144 g/hr; 78% p less than 0.02 and 69% p less than 0.001). These results suggest that monoglyceride-induced CCK secretion is mainly responsible for the satiety to duodenal fat in the pig, but that there is also a CCK-independent effect via the fatty acid. The results further indicate that intake of a normal barley-based diet (2% fat) is controlled via CCK-independent mechanisms.

Animals

Relation between gastric emptying and short-term regulation of food intake in the pig.

The relation between gastric emptying (GE), measured by gastric evacuation, and food intake (FI) was studied in pigs fed two meals to appetite per day. Duodenal infusion of emulsified fat (Intralipid; KabiVitrum) inhibited both FI and GE of digestible energy by more than the energy infused, but the gastric volume at satiety was more than 20% below the control. Duodenal infusions of glucose inhibited FI calorically, and generally inhibited GE calorically; but gastric volume at satiety was always equal to control volume. Thus GE (via gastric distension) may regulate FI to duodenal infusion of glucose but not to Intralipid. In pigs given no infusions, removal of the gastric contents immediately prior to the p.m. meal increased intake by 10%, However, when the contents were retained the pigs ate two equal-sized meals in the day, even though the gastric volume after the p.m. meal was 24% greater than after the a.m. meal. Therefore, although gastric volume may influence intake it cannot be the only factor determining satiety on this diet.

Animals

Control of gastric emptying in the pig: influence of duodenal infusions of glucose and emulsified fat.

The influence of duodenal infusions of emulsified fat (20% Intralipid) and glucose (40%, w/v) on gastric emptying during the feeding period was studied in five pigs. Gastric emptying was measured by evacuation of gastric contents immediately the pigs had finished feeding in animals fitted with a gastric cannula and a duodenal catheter and fed a solid meal mixed with water. Infusions at various rates of Intralipid and glucose given either from the start of feeding or up to 30 min prior to feeding until the pigs had finished feeding inhibited gastric emptying of dry matter (DM) and liquids in a qualitatively similar but quantitatively different manner. With both infusions the rates of gastric emptying of DM and liquids were progressively reduced with pre-infusions of 0, 10, 20 and 30 min. Slow infusions of Intralipid (2.3 and 4.6 ml/min) inhibited gastric emptying of DM and liquids to a greater extent than equicaloric infusions of glucose (3 and 6 ml/min), but faster infusions of Intralipid (6 ml/min) inhibited emptying less than equicaloric infusions of glucose (8 ml/min). When the DM emptied was converted into digestible energy (DE) there was no evidence that Intralipid inhibited gastric emptying calorically. In contrast the results showed that there was caloric regulation of gastric emptying with infusions of glucose begun at the start of feeding. There was a linear reduction in the rate of DM emptied with increase in the rate of glucose infusion (2-8 ml/min) of 64.5 +/- 4.8 g DM per MJ/min glucose infused, i.e. equivalent to a reduction of 0.98 +/- 0.07 kJ/min DE emptied for each kJ/min glucose infused. These changes in gastric emptying with duodenal infusions of glucose and Intralipid mirror the changes previously observed in food intake following similar infusions, and the results are therefore compatible with control of gastric emptying being an important site of short-term regulation of food intake in the pig.

Animals

Brain imaging and treatment response in spasmodic torticollis.

A patient with spasms of the neck, occurring when he turned his head to the left, responded to treatment with benzhexol. Cerebral blood flow imaging demonstrated reduced uptake in the right corpus striatum compared with the left. The study demonstrates the presence of an abnormality in the basal ganglia; it also illustrates response to drug treatment. Cerebral blood flow imaging may be useful in the detection of basal ganglia abnormalities in spasmodic torticollis and assist in the selection of cases which should be targeted for treatment with drugs.

Adult

The influence of gastrointestinal infusions of glucose on regulation of food intake in pigs.

The influence of gastrointestinal infusions of glucose on short-term and 24 h control of food intake was studied in sixteen pigs fed twice per day and nine fed three times per day. The pigs were fitted with up to four catheters each, placed in the stomach, the duodenum and at 2 and 8 m from the ligament of Treitz (l.t.). Infusions were given into the catheters, beginning 30 min before the first meal (two feeds) or second meal (three feeds) of the day, and continuing until the pigs stopped eating. The effects of the infusions on both short-term and 24 h intakes were the same whether the pigs were given two or three feeds per day. Infusions of glucose (400 g/l) into the stomach or small intestine altered short-term (meal) intake, but had no effect on intake at the following meal. With glucose infusion at rates above a threshold level (4 ml/min) to the stomach, duodenum or ileum (8 m from l.t.) food intake at that meal was suppressed such as to compensate for the amount of energy infused. Glucose infusions to the jejunum (2 m from l.t.) caused greater inhibition of short-term intake than infusions elsewhere, and 6 ml/min glucose inhibited intake by more than the amount of energy infused. Duodenal injection of the local anaesthetic lignocaine markedly suppressed the inhibition of intake caused by gastric infusion of glucose. The reductions in intake with glucose infusions at various rates into the stomach or duodenum were nearly identical to those with the same rates of infusion of NaCl at the same high osmolarity. It is concluded that glucose activation of receptors over a large part of the small intestine participates in the short-term control of energy intake in the pig, and that the receptors are activated equally by glucose in terms of an osmotic or caloric stimulus. It is suggested that activation of these receptors is involved in the caloric regulation of gastric emptying leading to gastric distension and inhibition of further intake.

Animals