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Biomedical subjects

H C Sax

Publications and source records attributed to H C Sax.

At least 55 records · Page 3Linked to original sources
PubMedDate not supplied

Epidermal growth factor and neurotensin induce microvillus hypertrophy following massive enterectomy.

The compensatory hypertrophy that develops after massive enterectomy is rarely adequate to prevent the development of short bowel syndrome. Trophic hormones such as epidermal growth factor (EGF) and neurotensin (NT) may be useful in improving and accelerating this adaptive response. This study delineates the effects of NT and EGF on remnant small bowel at the microvillus cellular level, which is the prime determinant of surface area. New Zealand white rabbits (2 kg) underwent midgut transection (sham) or 70% jejunoileal resection. Alzet pumps containing saline solution (control), EGF (1.5 microg /kg/hr), or NT (900 microg/kg/day) were implanted in resected animals after which they underwent 1 week of infusion. A second group of EGF animals was killed 2 weeks after infusion completion to assess delayed effects (EGF-delayed). Proximal jejunum was fixed for light and electron microscopy; villus and microvillus parameters were read in a blinded fashion. EGF (2.17+/-0.05 microm), EGF-delayed (2.26+/-1.5 microm, and NT (1.96+/-0.02 microm) animals had significantly increased microvillus heights compared to the control group (1.49+/-0.04 microm). Calculated brush-border surface areas were increased in a similar fashion. EGF and NT failed to elicit increases in jejunal gross villus heights. EGF and NT induce enterocyte microvillus hypertrophy and increase absorptive surface area in remnant bowel after massive enterectomy. In addition, the trophic effects of EGF persist after cessation of infusion. These peptides may be useful in accelerating small bowel adaption and preventing the development of short gut syndrome.

Animals↗
PubMedDate not supplied

Glucocorticoids upregulate intestinal nutrient transport in a time-dependent and substrate-specific fashion.

Glucocorticoids mediate skeletal muscle proteolysis during critical illness to provide substrates for hepatic acute-phase protein synthesis and gluconeogenesis. The effects of hypercortisolemia on splanchnic substrate uptake are not well defined. This study characterizes intestinal nutrient transport in response to acute elevations of plasma glucocorticoid levels. New Zealand White rabbits were randomized to receive either dexamethasone (2 mg/kg intramuscularly) or vehicle and were killed 8, 16, or 24 hours after steroid treatment. Brush-border membrane vesicles were prepared from pooled small intestinal mucosa and the uptake of tritiated substrates was quantified. Serum insulin-like growth factor 1 (IGF-1) levels, mucosal DNA content, and mucosal morphology were determined. Glucocorticoids increased glucose and leucine uptake at 8 hours (80% and 24%, respectively) and 24 hours (147% and 50%, respectively). Glutanmine, alanine, and arginine transport increased by 42%, 96%, and 236%, respectively, at 24 hours. Sodium-independent transport (diffusion) of all substrates was increased by 240% by dexamethasone treatment at 24 hours. Mucosal DNA content increased by 32%, whereas microvillus heights decreased by 27% at 24 hours. No effects were noted on IGF-1 levels or gross villus heights. Glucocorticoids acutely accelerate intestinal nutrient transport in a time-related and substrate-specific fashion. Although the mechanism of glucocorticoid action remains unclear, both genomic and plasma membrane effects are implicated.

Alanine↗
PubMedDate not supplied

Growth factors regulation of rabbit sodium-dependent neutral amino acid transporter ATB0 and oligopeptide transporter 1 mRNAs expression after enteretomy.

BACKGROUND: Sucessful intestinal adaptation after massive enterectomy is dependent on increased efficiency of nutrient transport. However, midgut resection (MGR) in rabbits induces an initial decrease in sodium-dependent brush border neutral amino acid transport, whereas parenteral epidermal growth factor (EGF) and growth hormone (GH) reverse this downregulation. We investigated intestinal amino acid transporter B0 (ATB0) and oligopeptide transporter 1 (PEPT 1) mRNA expression after resection and in response to EGF and/or GH. METHODS: Rabbits underwent anesthesia alone (control) or proximal, midgut, and distal resections. Full-thickness intestine was harvested from all groups on postoperative day (POD) 7, and on POD 14 from control and MGR rabbits. A second group of MGR rabbits received EGF and/or GH for 7 days, beginning 7 days after resection. ATB0 and PEPT 1 mRNA levels were determined by Northern blot analysis. RESULTS: In control animals, ileal ATB0 mRNA abundance was three times higher than jejunal mRNA, whereas PEPT 1 mRNA expression was similar. By 7 and 14 days after MGR, jejunal ATB0 mRNA abundance was decreased by 50% vs control jejunum. A 50% decrease in jejunal PEPT 1 message was delayed until 14 days after MGR. Treatment with EGF plus GH did not alter ATB0 mRNA expression but doubled PEPT 1 mRNA in the jejunum. CONCLUSION: The site of resection, time postresection, and growth factors treatment differentially influence ATB0 and PEPT 1 mRNA expression. Enhanced sodium-dependent brush border neutral amino acid transport with GH plus EGF administration is independent of increased ATB0 mRNA expression in rabbit small intestine after enterectomy.

Adaptation, Physiological↗
PubMedDate not supplied

Hepatic complications of total parenteral nutrition.

Elevations in serum hepatic enzyme levels and alterations in hepatic morphology have been noted in patients on total parenteral nutrition, in some cases progressing to fatal hepatic failure. Various factors such as toxins, inappropriate substrates, overfeeding, deficiency states, and gut hormone alterations have been implicated. It would appear that the tailoring of nutritional support to meet patient needs and the maintenance of normal gut integrity will be of increasing importance in reducing the incidence of this potentially fatal complication.

Chemical and Drug Induced Liver Injury↗
PubMedDate not supplied

Practicalities of lipids: ICU patient, autoimmune disease, and vascular disease.

Although the use of lipids should be individualized, certain generalizations are appropriate. 1. Lipid infusion should be limited in the fulminately septic patient to 10% of total calories in an effort to reduce immunosuppression. 2. The stressed, nonseptic patient with difficulties in ventilator weaning or TPN-induced hepatic dysfunction may reap benefit from a reduction in dextrose calories and the provision of daily lipids. 3. Patients with severe autoimmune disease have had mild amelioration of symptoms with PUFA supplementation. The relative benefits of omega-6 vs omega-3 continue to be examined. 4. Dietary immunomodulation in transplant and burns remains an area of active investigation. 5. Patients with fat-free TPN show transient declines in serum lipids. The development of a "fat-solubilizer" remains in the experimental realm. 6. The provision of fish oil, high in W-3 EPA, has shown promise in atherosclerosis and immunomodulation. The changes in the relative amounts of each prostaglandin class depend on precursor prevalence.

Autoimmune Diseases↗
PubMedDate not supplied

Comparison of weighted vs unweighted enteral feeding tubes for efficacy of transpyloric intubation.

Routine transpyloric placement of feeding tubes reduces aspiration in intensive care unit patients. Spontaneous passage eliminates the need for radiologic or endoscopic intervention. It is unclear whether the addition of a weight to the end of the tube or the use of the prokinetic agent metoclopramide in the conventional dose (10 mg) improves spontaneous transpyloric placement. In a randomized, prospective trial, 39 intensive care unit patients (age > 2 years) had a total of 50 nasoenteral tubes placed after intravenous metoclopramide (20 mg in adults, 0.2 mg/kg in children). The tubes were 8 French in diameter with either a weighted end or an unweighted bullet tip. Tip position was confirmed radiographically within 4 hours after blinded placement and at 1 and 2 days if spontaneous passage had not occurred. At 4 hours, 36% of the weighted tubes and 84% of the unweighted tubes (p < .002) had passed through the pylorus. At 1 day, 48% of the weighted tubes and 86% of the unweighted tubes (p < .007) had achieved transpyloric position. At 2 days, 56% and 92% of the weighted and unweighted tubes, respectively, had passed through the pylorus (p < .009, chi 2). The occurrence of transpyloric passage and the rapidity at which it occurred was significantly greater for the unweighted tube during all time periods. A poststudy trial was conducted to evaluate the effect of the normal dose of metoclopramide (10 mg in adults and 0.1 mg/kg in children) and the transpyloric passage of the unweighted feeding tube. Twenty-five patients received 10 mg of metoclopramide before the insertion of the unweighted tube.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Epidermal growth factor and human growth hormone induce two sodium-dependent arginine transport systems after massive enterectomy.

BACKGROUND: A combination of epidermal growth factor (EGF) and human growth hormone (hGH) after massive enterectomy induces a 400% increase in arginine transport in the remnant distal small intestine. The kinetic mechanism(s) responsible for enhanced arginine transport under these conditions is unknown. METHODS: New Zealand White rabbits underwent 70% midjejunoileal resection. After a 1-week recovery period, animals received hGH (0.2 mg/kg/d IM), EGF (1.5 microg/kg/h SC), hGH + EGF, or vehicle (equal volume) for 7 days. Transport of tritiated arginine into brush border membrane vesicles prepared from distal remnant small intestinal mucosa was quantified in the presence and absence of a sodium gradient over a range of arginine concentrations (25 to 5000 micromol/L). RESULTS: Eadie-Hofstee transformation of the kinetic data demonstrates two sodium-dependent arginine transport systems, comprising a high-capacity, low-affinity system and a low-capacity, high-affinity system. A combination of EGF and hGH significantly upregulates both the high-capacity (685%) and low-capacity (350%) maximum transport velocity (Vmax). Additionally, EGF alone significantly upregulates Vmax by 200% in the low-capacity system. There were no significant changes in transport affinity (Km) in either system. CONCLUSIONS: There are two quiescent sodium-dependent arginine transport systems in the distal small intestine. A combination of EGF and hGH after massive enterectomy increase arginine transport by Vmax upregulation in both the high-capacity/low-affinity and low-capacity/high-affinity systems.

Animals↗
PubMedDate not supplied

Enterocyte nutrient transport is preserved in a rabbit model of acute intestinal ischemia.

BACKGROUND: The use of enteral nutrition in patients with nonocclusive splanchnic hypoperfusion is controversial. This study aims to quantitate enterocyte nutrient transport and correlate function with morphology during intestinal ischemia. METHODS: New Zealand White rabbits were randomized to control (celiotomy only) 60-minute infrarenal aortic clamp (IRC) or 60-minute supraceliac aortic clamp (SCC). Small intestinal brush border membrane vesicles (BBMVs) were prepared by magnesium precipitation and serial differential centrifugation. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into BBMVs was quantitated by rapid mixing and filtration. Histologic examination of the intestine was performed by a pathologist blinded to groups. Data are reported as mean values+/-SEM, with significance determined by analysis of variance at p < .05. RESULTS: Villus heights in the IRC and SCC groups were 20% and 48% less than control, respectively. SCC histology was characterized by extensive epithelial denudation and necrosis, whereas IRC had mild focal villus edema only. Sodium-dependent glucose and leucine transport each exhibited nonsignificant increases of 20% to 25% in the IRC group and 30% to 55% in the SCC group. No changes were noted in sodium-dependent glutamine, alanine, and arginine uptake or sodium-independent transport. CONCLUSIONS: Enteral nutrient transport does not correlate with mucosal architecture, is maintained during splanchnic hypoperfusion states, and likely occurs via intact crypt cells.

Acute Disease↗