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Biomedical subjects

P Kuusanmäki

Publications and source records attributed to P Kuusanmäki.

At least 19 recordsLinked to original sources
PubMed2001

Autotransplantation modulates ileal enteroendocrine cell expression in the pig.

BACKGROUND: Enteroendocrine cell-derived peptides modulate postresectional small bowel adaptation, which may be attenuated by transplantation. We investigated whether autotransplantation modulates the number and distribution of ileal enteroendocrine cells in pigs with proximal small bowel resection. MATERIALS AND METHODS: Fifteen pigs were assigned into either small intestinal transection or 75% proximal small intestinal resection with or without autotransplantation of the remaining ileum. After 14 weeks the number and subtype distribution of enteroendocrine cells, crypt cell proliferation, and mucosal histology were analyzed from the proximal and distal ends of the remaining ileum. RESULTS: When compared to resected controls, autotransplantation of the ileum decreased the absolute (P < 0.05 in proximal ileum) and proportional (P < 0.05 in distal ileum) crypt enteroendocrine cell number. In addition, autotransplantation reduced somatostatin and glicentin expressing cell counts and abolished the proximodistal gradient of the enteroendocrine cell number. When compared to transected controls, villus height, crypt depth, number of proliferating crypt cells, and crypt cell proliferation index increased after the proximal resection (P < 0.05 in all except in crypt depth and proliferation index of the distal ileum) but remained virtually unchanged after autotransplantation of the ileal remnant. CONCLUSIONS: Autotransplantation decreases the crypt enteroendocrine cell number and alters their proximodistal and subtype distribution in the remaining ileum in pigs with proximal small bowel resection. These alterations are associated with attenuated adaptive response of the autotransplanted ileum.

Anastomosis, Surgical↗
PubMed2001

Effects of extrinsic denervation with or without ischemia-reperfusion injury on constitutional mucosal characteristics in porcine jejunoileum.

We investigated the effects of jejunoileal denervation with or without ischemia-reperfusion on mucosal characteristics and small intestinal structure. Growing pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal denervation with or without in situ ischemia-reperfusion. Small intestinal morphology, crypt cell proliferation, enterocyte ultrastructure, and disaccharidase activities were analyzed from jejunum and ileum after eight weeks. Immunohistological analysis of the ileum showed no staining of catecholaminergic neurons after extrinsic denervation. Neural isolation of the jejunoileum with or without ischemia-reperfusion injury reduced weight gain and villous enterocyte density in the ileum, abolished the proximodistal gradient of sucrase activity, and increased mucosal thickness, villus height, and villus surface area in the ileum. However, gross jejunoileal morphology, crypt cell proliferation, and enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal denervation in growing pigs selectively modulates constitutional mucosal characteristics in the ileum, presumably due to altered enterocyte turnover, without a decrease in small intestinal absorptive surface area. These changes are independent of short ischemia and subsequent reperfusion.

Animals↗
PubMed1999

Synchronous ileal autotransplantation impairs adaptation of remaining gut in pigs with proximal small bowel resection.

This study investigates the effects of ileal autotransplantation on morphology, crypt cell proliferation, and brush border disaccharidases of the remaining jejunoileum and colon in growing pigs with 75% proximal small bowel resection. Resection was performed on 30 pigs, of which 15 underwent an autotransplantation of the remaining ileum. The autotransplanted pigs showed reduced weight gain and remnant ileal length when compared to the resected controls. In the autotransplanted pigs, small bowel diameter and weight, mucosal weight and protein content, villus height and surface area, crypt depth, and the number of proliferating crypt cells were reduced similarly both in the intact jejunum and in the autotransplanted ileal remnant. Autotransplantation also decreased the number of proliferative crypt cells of the colon. Specific activities of maltase and sucrase tended to increase in the autotransplanted ileal remnant, whereas the total enzyme activities decreased. These results suggest that ileal autotransplantation disturbs postresectional adaptation of the remaining gut.

Adaptation, Physiological↗
PubMed1998

Absorption, excretion, and distribution of plant sterols after proximal gut resection and autotransplantation of porcine ileum.

Contribution of different gut segments to plant sterol absorption, adaptation of plant sterol absorption after partial small bowel resection, and effects of gut transplantation (necessitates extrinsic autonomic denervation and lymphatic disruption) on plant sterol biodynamics are unclear. We studied the consequences of massive proximal small bowel resection and autotransplantation of the remaining ileum on the adaptive absorption and biodynamics of plant sterols. Dietary, fecal, biliary, hepatic and plasma plant sterols, fecal elimination and absorption of cholesterol, small bowel morphology, and intestinal transit were determined before (n = 5) and at 4, 8, and 14 wk after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) or transection (n = 5). Proximal gut resection significantly reduced cholesterol absorption efficiency; percentage absorption and biliary secretion of plant sterols; plasma, biliary and hepatic campesterol-to-cholesterol proportions; and sitosterol proportions in plasma and bile. Autotransplantation of the remaining ileum further significantly decreased cholesterol absorption efficiency; percentage absorption and biliary secretion of campesterol; campesterol proportions in plasma, bile and liver; and plasma proportions of sitosterol while increasing fecal excretion of neutral and acidic steroids. Plasma proportions of the two plant sterols, but absorption of just campesterol, were gradually improved with increasing cholesterol absorption and villus height after proximal gut resection; the same result was observed to a lesser degree after ileal autotransplantation. In addition, significant positive correlations were found between percentage cholesterol and campesterol absorption and the plasma plant sterol proportions in both proximal resection groups, between campesterol absorption and ileal villus height in the resection group, and between campesterol absorption and intestinal transit time in the autotransplantation group. In conclusion, plasma campesterol and sitosterol closely reflect absorption of cholesterol and plant sterols from intact and autotransplanted ileum during adaptation to proximal gut resection. A loss of proximal gut absorptive surface impairs cholesterol and campesterol absorption more than sitosterol absorption, the latter being apparently less dependent on available jejunal villus surface area.

Animals↗
PubMed1998

Intestinal adaptation after massive proximal small-bowel resection in the pig.

BACKGROUND: Small-intestinal adaptation to resection has been extensively studied in rats. The present study investigates morphology, crypt cell proliferation, and disaccharidase activities of the remaining small intestine and colon after 75% proximal resection of porcine small intestine. METHODS: Specimens were obtained from the proximal jejunum, middle and distal ileum, and proximal colon preoperatively (n = 5) and 14 weeks after small-bowel transection (n = 5) or resection (n = 5). Proliferation was analyzed immunohistochemically with the Ki-67 antigen MIB-1. Disaccharidase activities were determined in accordance with the method of Dahlqvist. RESULTS: In addition to macroscopic enlargement, resection markedly increased the villi and crypts of the remaining small bowel. Crypt cell proliferation decreased with advancing age after transection but remained at the preoperative level after resection. Specific, but not total, activities of maltase and sucrase in the mid-ileum decreased after resection. CONCLUSION: Small-intestinal adaptation in the pig involves macroscopic enlargement and a prompt increase in villus size, which is associated with high crypt cell proliferation.

Animals↗
PubMed1998

Increased plasma, biliary, and hepatic cholesterol precursors in pigs with ileal autotransplantation-induced malabsorption of cholesterol and bile acids.

BACKGROUND: Small-bowel transplantation impairs intestinal absorptive function for unknown reasons. METHODS: The proportions of plasma, biliary, and hepatic cholesterol precursors to cholesterol were determined by gas-liquid chromatography after resection of the proximal 75% of the porcine jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) and were related to in vivo absorption and fecal excretion of cholesterol. RESULTS: Ileal autotransplantation significantly decreased serum (18%; P < 0.05) and liver (7.6%; P < 0.05) cholesterol content, the esterification percentage of serum cholesterol (5.1%; P < 0.0001), and the total amount of cholesterol absorbed (48%; P < 0.05) and increased fecal excretion of bile acids (108%; P < 0.0001), net cholesterol elimination (53%; P < 0.001), and the proportions of plasma (207%; P < 0.0001), biliary (183%; P < 0.0001), and hepatic (114%; P < 0.0001) cholesterol precursors. The increases were most striking for the side-chain-saturated demethylated sterols, cholesterol and lathosterol, and monomethyl sterols, whose bile/liver and plasma/liver ratios were increased in the autotransplantation group. Plasma, biliary, and hepatic precursor proportions were positively related to each other and similarly correlated with fecal bile acids and the net elimination of cholesterol in feces. CONCLUSIONS: These findings suggest that ileal autotransplantation in pigs with proximal gut resection increased the levels of cholesterol precursor sterols in plasma, bile, and liver mainly due to a bile-acid-malabsorption-induced increase in hepatic synthesis of cholesterol. Enhanced secretion of cholesterol precursors from the liver into the plasma and bile may have contributed to their increased values during the increased rate of cholesterogenesis.

Animals↗
PubMed1997

Effect of ileal autotransplantation on cholesterol, bile acids, and biliary lipids in pigs with proximal small bowel resection.

Our major aim was to investigate the consequences of ileal autotransplantation in pigs with proximal small intestinal resection on biliary lipids and metabolism of bile acids. Biliary lipid secretion rates and bile acid absorption were assessed by measuring dietary and biliary lipids, fractional cholesterol absorption, and fecal excretion of cholesterol and bile acids. In addition, serum bile acids and cholesterol, biliary and fecal bile acid species, and ileal villus height were determined after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum with systemic venous drainage (n = 15) or transection (n = 5). Autotransplantation further increased fecal excretion of neutral and acidic steroids and serum concentration of bile acids after proximal resection (P < .05 for all); autotransplantation significantly decreased serum cholesterol, ileal villus height, fractional bile acid and cholesterol absorption, and biliary molar percentage of total and primary bile acids, whereas biliary secretion of bile acids, enriched by secondary bile acids, and cholesterol remained unchanged. At 14 weeks, ileal villus height, fractional bile acid and cholesterol absorption, biliary molar percentage of bile acids, and proportion of secondary biliary bile acids were altered by transplantation from the respective postresection values of 864 +/- 22 microm, 97.9 +/- 0.6%, 26.9 +/- 3.9%, 91.8 +/- 1.2% and 9.2 +/- 1.3% to 428 +/- 21 microm, 91.1 +/- 1.5%, 9.5 +/- 1.1%, 83.9 +/- 1.4% and 52.5 +/- 3.5% (P < .005 for all). Posttransplantation biliary bile acid secretion correlated positively with fractional reabsorption (r = .70) and biliary molar percentage (r = .73) of bile acids and ileal villus height (r = .65; P < .01 for all). Decreased absorption efficiency and biliary molar percentage of bile acids, increased biliary secondary bile acids, and short ileal villi point to bacterial overgrowth-induced bile acid malabsorption, which with decreased absorptive area may contribute to malabsorption of other lipids after ileal autotransplantation. Compensatory increase in cholesterol synthesis in the pigs with autotransplanted ileum appeared sufficient for constant biliary secretion of cholesterol and bile acids.

Absorption↗
PubMed1997

Value of mucosal biopsies in the monitoring of acute small bowel rejection.

The value of mucosal biopsies in evaluating small bowel rejection is controversial. In this study, the value of mucosal biopsies was estimated in unmodified porcine small bowel rejection. Ten animals received the distal half of the small bowel as a heterotopic loop (Thiry-Vella loop). The allografts were followed by proximally and distally harvested full-thickness and mucosal biopsies every other day, starting from the 3rd day and continuing until the grafts became necrotic. The histological parameters in both types of biopsies were semiquantitatively scored from 0 to 3 and compared with each other. The difference in mean values on the subsequent days was not remarkable, the results favoring slightly higher values in full-thickness than in mucosal biopsies. Our results suggest that multiple mucosal biopsies are adequate in monitoring morphological changes of small bowel grafts during rejection and that the proximal and distal ileum are similarly affected by acute rejection.

Acute Disease↗
PubMed1997

Adaptive lipid metabolism after ileal autotransplantation in pigs with proximal gut resection.

BACKGROUND: Transplantation of the small intestine impairs intestinal absorptive function, but the adaptive response of a segmental graft is unknown. The aim of this study was to investigate the effects of ileal autotransplantation on the adaptive absorption and metabolism of lipids in pigs that had undergone proximal gut resection. METHODS: Serum lipids, plasma vitamins A and E, absorption and excretion of cholesterol, bile acids and fat, plasma cholesterol precursor and plant sterol proportions to cholesterol (respective markers of cholesterol synthesis and absorption), enteric structure, and transit were determined 4, 8, and 14 weeks after 75% proximal resection with (n = 15) or without (n = 15) autotransplantation of the remaining ileum. RESULTS: As compared with pigs that underwent proximal gut resection, the additional autotransplantation reduced the adaptive increase in total serum and high-density lipoprotein cholesterol, plasma plant sterol proportions and vitamin E concentrations, cholesterol and fat absorption efficiency, and villus height (p < 0.05 for all) during the 14 postoperative weeks and resulted in increases of up to 4.6, 2.7, 1.3, and 2.1 times the plasma cholesterol precursors (p < 0.005), fecal excretion of bile acids (p < 0.0005), neutral steroids (p < 0.005), and net elimination of cholesterol (p < 0.0005), respectively. Cholesterol and fat absorption and plasma plant sterols were significantly enhanced between 8 and 14 weeks after autotransplantation (p < 0.05, p < 0.005, and p < 0.05, respectively), whereas fecal elimination of cholesterol remained increased until the end of the follow-up. CONCLUSIONS: Autotransplantation of the ileum in pigs that have undergone proximal small bowel resection disturbs the adaptive absorption of cholesterol, bile acids, fat, and fat-soluble vitamins, resulting, through increased fecal elimination of cholesterol, in decreased serum cholesterol despite a marked compensatory increase in cholesterol synthesis.

Animals↗
PubMed1997

How to diagnose chronic rejection. A study in porcine intestinal allografts.

Porcine small bowel allografts were followed for 18 weeks during immunosuppression with cyclosporine-A (CyA), azatioprine and prednisone. The mucosal alterations noted at the 12th week were epithelial vacuolation and loss of Goblet cells. Moderate infiltration of inflammatory cells, mainly lymphocytes, was found in the lamina propria. In addition, a few grafts exhibited oedema and fibrosis. Vessels already showed endothelial swelling and intimal proliferation at the 12th week. In the submucosa, the infiltration of inflammatory cells was not present till the 18th week. Further changes in the mucosa at the 18th week were the blunting of villi, cuboidal epithelium, crypt abscesses and epithelial atrophy. The histological alterations of mucosa and lamina propria existing in the full thickness biopsies were mostly also detectable in mucosal biopsies, provided that multiple biopsies were taken. Thus these parameters analyzed from mucosal biopsy material are suitable for the diagnosis and monitoring of chronic small bowel rejection. In autopsy, the most prominent features were in the mesenterial arteries: intimal proliferation, vasculitis, proliferation of media and endothelial alterations. The activity of the mucosal disaccharidases maltase and sucrase remained near the initial level till the 12th week and had decreased markedly by the 18th week.

Abscess↗
PubMed1996

Ileal nutritional function after one-stage orthotopic ileum transplantation in the growing pig: reversal of lethal short bowel syndrome.

Intestinal isolation is associated with hypoplasia of defunctioned mucosa and reduction in the segmental absorption, whereas the presence of luminal nutrition is essential for the expression of the ileal adaptive response after proximal small bowel resection. On the other hand, intensive postoperative graft monitoring is obligatory because of the disastrous consequences of small bowel graft rejection. Thus, the authors sought to develop an experimental ileum transplantation model that provided immediate graft placement in bowel continuity, together with readily available graft monitoring connection through a proximal Roux-en-Y enterostomy. Four groups of pigs were prepared: RESTX (n = 9), proximal 50% small bowel resection with simultaneous orthotopic ileum autotransplantation; RES (n = 7), proximal 50% small bowel resection; NONRES (n = 6), transection; and SB (n = 5), short bowel. Early (1 to 4 weeks) and long-term (5 to 12 weeks) studies of animal growth, nutritional status, disaccharide absorption, water and electrolyte balances, and liver function were performed after ileum autotransplantation (IAT) in relation to small intestine of variable length with undivided mesentery (intact neural and lymphatic connections). The perioperative transplantation mortality rate remained at about 10%. Reasons not related to the transplantation procedure accounted for the late complication rate of 38%. In the ileum autotransplantation (RESTX) group, weight gain was recovered 2 to 3 weeks after transplantation, and the mean weight reached the preoperative level at 5 weeks. The SB pigs underwent progressive weight loss. The transection (NONRES) and proximal resection (RES) animals gained weight at similar rates. IAT had no effect on the plasma protein concentrations. Proximal resection, with or without IAT, was associated with depressed plasma cholesterol contents in the early period. Plasma cholesterol levels amended long-term, after both IAT and proximal resection. IAT resulted in deficient intraluminal processing of maltose, whereas isolated proximal resection tended to enhance disaccharide absorption early after the surgery. The short bowel pigs were not able to preserve sufficient nutritional status, and demonstrated a marked decline in the hemoglobin, protein, and cholesterol levels. No biochemical signs suggestive of potential liver damage caused by portocaval graft vascularization were recognized. These findings suggest that one-stage ileum autotransplantation provides sufficent absoprtive capacity to reverse otherwise lethal short bowel syndrome in the growing pig. However, transplantation disturbs the in vivo absorptive function of the nonrejecting ileum. Long-term impairment in disaccharide absorption may be partially related to an altered intestinal adaptive response secondary to proximal resection when combined with simultaneous transplantation. The authors developed this ileal small bowel transplantation model using rapidly growing pigs, wherein body weight gain represents an objective parameter of intestinal absorptive function. Only this type of animal model can yield clinically relevant data in the evaluation of a transplant's ability to provide sufficient nutritional function in a growing recipient.

Age Factors↗
PubMed1996

Cholesterol absorption and synthesis after autotransplantation of porcine ileum.

BACKGROUND: Cholesterol, long-chain fatty acids, and fat-soluble vitamins are absorbed mainly in the upper small intestine and bile acids in the terminal ileum. This study determined the consequences of ileal autotransplantation on cholesterol metabolism, plasma fatty acids, and vitamin A absorption. METHODS: Plasma lipids, cholesterol precursors, plant sterols, cholestanol, fatty acids, vitamin A absorption, and animal growth were studied for 3 months after transection (n = 5), jejunal (50%) resection (n = 7), jejunal (50%) resection combined with orthotopic ileal autotransplantation (n = 7), and enterectomy (n = 7). RESULTS: Cholesterol precursor to cholesterol proportions in plasma (reflect cholesterol synthesis) remained unchanged after transection and jejunal resection. The plasma plant sterol proportions (reflect cholesterol absorption) and retinol absorption increased after transection and less significantly after jejunal resection, whereas plasma fatty acid compositions were virtually unchanged. Transplantation of ileum and enterectomy amended up to sixfold the precursor proportions (p < 0.05 versus transection or jejunal resection) and impaired body weight gain. The plant sterol proportions, vitamin A absorption, and plasma cholesterol levels, respectively, were significantly (p < 0.05) decreased after transplantation when compared with those of the transected control group but remained markedly higher than those in the enterectomized group. Linoleic acid was significantly (p < 0.05 versus transection) decreased, whereas monoenoic fatty acids and eicosatrienoic acid were increased (p < 0.05 versus jejunal resection) in plasma lipids. CONCLUSIONS: These results indicate that autotransplantation of ileum in pigs that have undergone jejunectomy impairs sterol, essential fatty acid, and vitamin A absorption so that plasma cholesterol levels decrease despite markedly increased cholesterol synthesis and that these changes clearly exceed those found after jejunal resection alone.

Animals↗
PubMed1996

Brush border enzymes in evaluation of acute small bowel rejection.

The change in activity of three disaccharidase enzymes (maltase, sucrase and lactase) was determined according to the method of Dahlqvist during acute rejection in non-immunosuppressed piglet small bowel grafts. In addition, two brush border enzymes, lactase and aminopeptidase, were stained with monoclonal antibodies. Diminishing disaccharidase activity was an early event during rejection. Diminution began 2 days before distinct morphological changes were seen in the mucosal biopsies. Evaluation of disaccharidase activity can thus be used as a confirmatory method in detecting rejection. Reduction in immunohistological staining of lactase and aminopeptidase with monoclonal antibodies and changes in mucosal morphology were observed to progress simultaneously.

Animals↗
PubMed1996

Adaptation of cholesterol absorption after proximal resection of porcine small intestine.

Cholesterol absorption occurs primarily in the upper small intestine. Our aim was to assess absorption of cholesterol during ileal adaptation after proximal small intestinal resection. In vivo absorption and elimination of cholesterol, plasma cholesterol, cholesterol precursors, and plant sterols were related to intestinal morphology and transit 4 (n = 5), 8 (n = 5), and 14 (n = 5) weeks after a 75% proximal resection of porcine small intestine, and compared to preoperative (n = 5) and transected (n = 5) control animals. Fractional cholesterol absorption, the daily amount of cholesterol absorbed, plasma cholesterol, and plant sterol to cholesterol proportions were significantly (P < 0.05 or less) decreased, whereas fecal loss of cholesterol as neutral steroids, less so as bile acids, plasma cholesterol precursor proportions, and ileal mass and villus height were significantly increased (P < 0.05 or less) after 8 weeks of the resection. Cholesterol absorption efficiency, decreased by the resection, was gradually increased from 5.4 +/- 2.2 to 26.9 +/- 3.9% during the 14 postoperative weeks (P < 0.0001) simultaneously with a 46% increase in villus height compared with transection (P < 0.0001), but absorption remained still below control levels (80.4 +/- 2.5%, P < 0.0001). In resected and control animals, villus height correlated positively with cholesterol absorption efficiency (r = 0.85, P < 0.0001; r = 0.76, P = 0.01) and plasma plant sterol proportions (r = 0.94-0.95, P < 0.0001; r = 0.78-0.85, P < 0.008), respectively. In conclusion, after massive proximal small bowel resection, adaptation of intestinal cholesterol absorption efficiency occurs in the distal ileum closely parlleling villus hypertrophy.

Adaptation, Physiological↗