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Biomedical subjects

M Pakarinen

Publications and source records attributed to M Pakarinen.

At least 19 recordsLinked to original sources

Treatment with thiamine hydrochloride and astaxanthine for the prevention of yolk-sac mortality in Baltic salmon fry (M74 syndrome).

Two practical methods are reported for treating feral Baltic salmon with thiamine hydrochloride against M74 syndrome (abnormally high yolk-sac fry mortality of the Baltic salmon). Both bathing of the yolk-sac fry in thiamine hydrochloride (1000 mg l-1, 1 h) and a single intraperitoneal injection given to the female brood fish (100 mg kg-1 fish) during the summer 3 mo before stripping were shown to elevate the whole body total thiamine concentration in the fry. Both treatments were also shown to be effective in preventing mortality due to M74 syndrome. The effect of bathing the yolk-sac fry was shown to be dose-dependent. The results support the view that there is a causal relationship between the thiamine status of the yolk-sac fry and M74 mortality. An intraperitoneal injection of astaxanthine suspension administered to the female brood fish (11 mg kg-1 fish) in the summer 3 mo before stripping elevated the astaxanthine concentration in the eggs but did not affect mortality due to M74 syndrome. An interaction between astaxanthine and thiamine may occur in the developing embryo or yolk-sac fry, however. No association could be demonstrated between the various thiamine hydrochloride treatment practices and hepatic cytochrome P450 dependent 7-ethoxyresorufin-O-deethylase (EROD) activity in the yolk-sac fry. An injection of thiamine hydrochloride into the peritoneal cavity of wild Baltic salmon females could be used to raise thiamine concentrations in their offspring in the rivers. The effect on smolt production in Finnish Baltic salmon rivers needs to be investigated further, however.

Adjuvants, Immunologic↗

Nerve terminals containing neuropeptides decrease in number after massive proximal small bowel resection in the piglet.

The aim of this study was to evaluate possible changes in the neuropeptide innervation pattern of the remaining porcine ileum following 75% proximal resection of the small intestine. Three-month-old piglets were operated on and two months postoperatively full-thickness specimens of the proximal part of the distal ileum wall were taken. Age-matched 3- and 5-month-old unoperated piglets were used as controls. The number and intensity of VIP-, galanin-, enkephalin-, substance P-, and somatostatin-containing nerve fibers were estimated in sections processed for immunofluorescence microscopy and subjected to quantitative scoring. The VIP-, galanin-, and enkephalin-immunoreactive fibers of the circular muscle layer and villi were also quantitated by computer-assisted morphometry. The number and intensity of VIP-immunoreactive fibers in the mucosa and circular muscle layer markedly decreased after resection as compared to 3-month-old and 5-month-old controls (P < 0.05). The galanin immunoreactivity index decreased significantly after resection in the circular muscle layer as compared to both control groups (P < 0.05). The increase in the number of enkephalin-immunoreactive nerve fibers that normally occurred from 3 to 5 months of age was inhibited by the resection. We were not able to see any differences in somatostatin or substance P immunoreactivity between the groups. The results suggest that massive resection induces significant changes in the neuropeptide-containing innervation of the remaining small intestine. These findings are compatible with altered motor activity and mucosa function in the remain intestine.

Adaptation, Physiological↗

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↗

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↗

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↗

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↗

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↗

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↗

Gut failure in pediatric and adult patients. Candidates for small-bowel transplantation in southern Finland.

BACKGROUND: This study investigated the need for small-bowel transplantation (SBT) in southern Finland. In addition, we evaluated the effect of colon resection on the time required for intestinal adaptation in patients with gut failure. METHODS: Mortality, morbidity, intestinal adaptation time, and surgical management were evaluated retrospectively in 24 patients (12 adults and 12 children) with jejunoileal exculsion. Of the 24 patients 19 had undergone accompanying colon resection. RESULTS: Intestinal adaptation had occurred in 12 of 18 survivors (67%). Two unadapted survivors were considered to be currently suitable candidates for SBT. The length of the remaining colon was inversely correlated (correlation coefficient r = -0.789; p < 0.0001) with the duration of intestinal adaptation. CONCLUSIONS: Each year one to two patients per 1.27 million people could benefit from SBT in southern Finland. The length of the remaining colon is a major determinant of the duration of intestinal adaptation in patients with massive jejunoileal resection.

Adaptation, Physiological↗

Acute rejection of porcine small bowel allograft. An extended histological scoring system.

Using nonimmunosuppressed piglet small bowel grafts, we performed a detailed histological study on acute rejection and analyzed altogether 45 different histological parameters throughout the bowel wall, in 10 allografts and 6 autografts. Heterotopic grafts were followed by full-thickness biopsies every other day beginning on the 3rd day after transplantation. The parameters were scored from 0 to 3 according to the severity of the change and the values of every variable were compared statistically between the 2 groups. The earliest significant changes, beginning on days 3-5, were infiltration of inflammatory cells and pyroninophilia among these cells in lamina propria; edema, fibrosis, and inflammation in submucosa and muscularis; vacuolar degeneration of myocytes; and endothelial and intimal changes in vessels. Villous blunting and cuboidal epithelium were the other early markers. On day 7, the epithelial and vascular changes became most significant. We want to emphasize especially the vascular parameters: endothelial swelling and proliferation, intimal thickening, intramural inflammation, and obliteration of the lumen. The dilatation of lymph vessels and changes of Peyer's patches had no value in the estimation of rejection. All allografts became necrotic by day 11 after transplantation.

Acute Disease↗

C-reactive protein serum levels in patients with ocular disease.

Hepatocyte derived C-reactive protein (CRP) is a sensitive indicator for inflammatory or infectious processes in a variety of tissues. As several other plasma proteins it is regarded as part of the acute phase response to a variety of tissue damage. CRP is commonly used in general medicine as a tool for the follow-up of especially bacterial infections. However, it has not been widely used in ophthalmology. In the present study CRP values in serum samples from 51 patients with various acute ocular diseases were determined semiquantitatively. High CRP levels were found most frequently in patients with either preseptal cellulitis (83.3%) or endophthalmitis (25.8%) whereas in the serum of patients with keratitis and uveitis, CRP exceeded 20 mg/l in only 18.7% of the cases. In a control group of 10 patients with retinal detachment the mean CRP level was 2.3 mg/l (SD +/- 0.98 mg/ml). The clinical significance and the prognostic value of CRP determinations during ocular diseases are discussed.

C-Reactive Protein↗