Mandy M. Lam

Impairment of nutrient uptake in a rabbit model of gastroschisis

Infants with gastroschisis (GS) commonly require total parenteral nutrition and prolonged hospitalization because of intestinal dysfunction resulting from dysmotility and/or malabsorption. To investigate prepartum small intestinal (SI) nutrient absorption in GS, a fetal rabbit model was surgically created on gestational day 24 (term, 31 to 33 days) in 11 time-mated New Zealand White does in each left ovarian-end fetus. Each right ovarian-end fetus served as a control (C) and was manipulated only. All does, 10 of 11 GS fetuses (91%), and 8 of 11 C fetuses (73%) survived to gestational day 30. GS fetuses had significantly reduced total body weights, SI weights, and SI lengths compared with C fetuses. Using the everted mucosal sleeve technique, the uptakes of an amino acid (proline) and a sugar (glucose) were determined. The uptakes of proline per milligram SI, proline per centimeter SI, and glucose per milligram SI were significantly impaired in GS fetuses compared with C fetuses (P < .04 by Students paired t test). The uptake of glucose per centimeter SI was also reduced in GS fetuses, but not significantly. Uptake capacities (a measure of the entire SIs ability to absorb a given nutrient) were significantly reduced in GS fetuses compared with C fetuses (proline, 2,670 +/- 612 nmol/min/entire SI v 6,842 +/- 399 nmol/min/entire SI, P < .008 by Students paired t test; glucose, 402 +/- 69 nmol/min/entire SI v 950 +/- 103, P < .008 by Students paired t test).

Upregulation of nutrient transport in fetal rabbit intestine by transamniotic substrate administration

Delivery of nutrients to the developing fetal gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. To examine the effect of intrauterine nutrient administration on the uptake capacity of the intestine, 16 maternal rabbits underwent bilateral ovarian-end transamniotic catheter placement on gestational Day 24. Study fetuses received a galactose solution; the contralateral controls received mannitol, a physiologically inert carbohydrate. Infusions were continued until Day 30 when an everted sleeve technique was used to measure radiolabeled uptake of both galactose and glucose in the proximal, middle, and distal small intestine. Mucosal scrapes were obtained, weighed, and the percentage of weight was calculated. Results were analyzed by ANOVA and Students t test with P less than 0.05 being considered significant. There were 2 maternal deaths with 11 fetal pairs surviving (79%). There was increased uptake of galactose in the study fetuses compared to controls reaching significance in the middle and distal segments. Similarly, glucose uptake was significantly increased in the proximal and distal segments. Mucosal weight was increased in all regions, reaching significance in the proximal segment. Total intestinal uptake of galactose and glucose was significantly increased in the study fetuses compared to controls. Intraamniotic galactose infusion caused not only upregulation of its own mucosal transport but also that of glucose, along the entire fetal small intestine, achieving statistical significance particularly in distal segments. Fetal implications for transamniotic feeding are under investigation.

Loads, capacities and safety factors of maltase and the glucose transporter SGLT1 in mouse intestinal brush border

Safety factors are defined as ratios of biological capacities to prevailing natural loads. We measured the safety factor of the mouse intestinal brush‐border hydrolase maltase in series with the glucose transporter SGLT1, for comparison with previous studies of sucrase and lactase. Dietary maltose loads increased 4‐fold from virgin to lactating mice. As in previous studies of intestinal adaptive regulation, that increase in load without change in dietary composition resulted in an increase in maltase and SGLT1 capacities mediated non‐specifically by an increase in intestinal mass, without change in maltase or SGLT1 activities per milligram of tissue. Maltase and SGLT1 capacities increased only sublinearly with load during lactation, such that safety factors decreased with load: from 6.5 to 2.4 for maltase, and from 1.1 to 0.5 for SGLT1. The apparently high safety factor for maltase may be related to the multiple natural substrates hydrolysed by the multiple sites of maltase activity. The apparently low safety factor for SGLT1 is made possible by the contribution of hindgut fermentation to carbohydrate digestion. SGLT1 activity is paradoxically higher for mice consuming sucrose than for mice consuming maltose, despite maltose hydrolysis yielding double the glucose load yielded by sucrose hydrolysis, and despite glucose constituting the load upon SGLT1.

Quantitative evolutionary design of nutrient processing: Glucose

Quantitative evolutionary design involves the numerical relationships, evolved through natural selection, of biological capacities to each other and to natural loads. Here we study the relation of nutrient-processing capacities of the intestine and of organs beyond it (such as liver and kidneys) to each other and to natural loads of nutrients normally consumed. To control experimentally the rate of nutrient delivery to organs beyond the intestine, we administered nutrients directly into the veins of rats by the method of total parenteral nutrition (TPN). Control rats consuming the TPN solution by mouth ingested glucose at 42 mmol/day and processed it completely, as gauged by negligible appearance of glucose in urine and feces. Experimental rats receiving TPN were able to process infused glucose completely at rates up to 92 mmol/day. At higher infusion rates, they were unable to process further glucose, as gauged by rises in serum and urinary glucose levels and serum osmolality. At the highest infusion rates, they exhibited diuresis, dehydration, and both decreased weight gain and survival. These symptoms closely resemble the human diabetic condition known as nonketotic hypertonicity. Thus, a rats body has a safety factor of 2.2 (=92/42) for glucose processing: it can process glucose at a rate 2.2 times its voluntary intake. This safety factor represents apparent excess capacity that may have evolved to process other nutrients converted into glucose, to minimize the risk of loads swamping capacities, to handle suddenly increased nutrient requirements, or to effect rapid mobilization of glucose.

Glucose uptake in dilated small intestine

BACKGROUND/PURPOSE The development of dilated small intestine in patients with short bowel syndrome results in increased mucosal surface area. This study examines whether the incremental increase in surface area leads to a proportional increase in absorptive function of the small intestine. METHODS Partial obstruction of the small intestine was created in rats by placing an intussusception valve in the proximal jejunum. Rats that underwent sham operations served as controls. One week postoperatively, the small intestine proximal and distal to the valve was removed. The intestinal diameter proximal and distal to the obstruction was measured. The rate of glucose uptake was measured by the everted sleeve technique. The results were analyzed by analysis of variance (ANOVA). RESULTS The intestine proximal to the valve was significantly dilated and thickened when compared with the intestine distal to the valve. The wet mass per centimeter of the dilated segment was 2.5 times that of the control group (P<.001). The glucose uptake capacity of the dilated segment was slightly higher than that of the control group (540 v 420 nmol/min/cm, P<.05). However, the specific glucose uptake rate was reduced significantly in the intestine proximal to the valve (247 v 335 nmol/min/cm2, P<.01). CONCLUSIONS Although the partial obstruction of small intestine resulted in a substantial increase in the intestinal surface area, the absorptive capacity of the dilated intestine per unit surface area was decreased significantly. This translated ultimately into a slight increase in the overall functional absorptive capacity of glucose in the small intestine. These results suggest that dilated small intestine may not enhance mucosal absorption.

Magnetically Actuable Scaffolds for Tissue Regeneration

Presented here are methods to fabricate magnetically modified biocompatible polymer scaffolds, which can be actuated by remotely applied magnetic fields. The magnitude of the actuation is shown to be biologically useful by simple tests in known magnetic fields and magnetic field gradients. Methods of processing the functionalized polymers into three-dimensional scaffolds have been demonstrated, suggesting wide applicability in tissue engineering.Copyright