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Biomedical subjects

B W Karlsson

Publications and source records attributed to B W Karlsson.

At least 19 recordsLinked to original sources

The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin, secretin and cholecystokinin in growing pigs.

The effect of a potato fibre preparation on exocrine pancreatic secretions and on gastrointestinal hormone levels in plasma was studied in three 8 weeks old piglets that were surgically fitted with a jugular vein catheter for blood sampling, a pancreatic duct catheter and a T-shaped duodenal cannula for collection of pancreatic juice. The animals were fed for 2 weeks a control diet (experimental period 1), thereafter for 2 weeks the control diet supplemented with 2% potato fibre (experimental period 2) and for another 2 weeks the control diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions of the experimental diet, the control diet and potato fibre as well as i.v. infusions of a solution containing cholecystokinin (CCK) and secretin were administered. Potato fibre in the diet evoked in tendency an increase in the volume of secretion of pancreatic juice and a significant increase both in the mean values of the total protein content and total activities of lipase, trypsin and alpha-amylase when compared to the control diet. The i.d. infusion of the control diet, experimental diet and fibre infusate as well as the i.v. administration of the hormone infusate led to a spontaneous secretory response of the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other factors such as short chain fatty acids may be involved in the regulation of the exocrine pancreas.

Animals↗

The feeling of loneliness prior to coronary artery bypass grafting might be a predictor of short-and long-term postoperative mortality.

OBJECTIVES: To evaluate the effect of different aspects of quality of life (QL) upon mortality during short-and long-term follow-up after coronary artery bypass grafting (CABG). DESIGN: Prospective evaluation. MATERIALS: Consecutive patients from western Sweden who during 3 years underwent CABG. METHODS: They answered a questionnaire at the time of coronary angiography prior to CABG. Quality of life was measured with questions from the Nottingham Health Profile (NHP) part I. RESULTS: In all, 1290 patients were included in the analyses. When accounting for various preoperative factors known to be independently associated with morality the NHP question "I feel lonely" was found to be associated with mortality, both at 30 days (RR 2.61; 95% CI 1.15-5.95; p = 0.02) and at 5 years (RR 1.78; 95% CI 1.17-2.71; p = 0.007) after the operation. Thirteen per cent reported they felt lonely. At 5 years was, in addition, the statement "I have difficulty climbing stairs" also independently associated with mortality (RR 1.50; 95% CI 1.02-2.22; p = 0.04). CONCLUSION: Among the 38 statements in NHP as a judgment of QL prior to CABG, one of them, "I feel lonely" was independently associated with survival both at 30 days and 5 years after CABG.

Adult↗

Effects of systemic and local immunization on alveolar epithelial permeability to protein in the rat.

This study aimed to characterize the effect on alveolar epithelial permeability to protein as a result of immunization when animals were reexposed to antigen. Antigen (bovine serum albumin [BSA]) and a related bystander protein (human serum albumin [HSA]) were intratracheally instilled into lungs of immunized rats and their passages across the alveolar epithelium were measured as serum levels 16 h after instillation. Nonimmunized control rats showed similar passages of both BSA and HSA. In rats intradermally immunized against BSA, BSA was undetectable in serum, whereas serum levels of HSA were markedly increased compared with those in control rats. In rats immunized with BSA intratracheally, serum levels of both BSA and HSA were unchanged compared with those in control rats. Serum titers of specific IgG antibodies (anti-BSA) were measured and were higher in intradermally immunized animals than in intrapulmonary immunized animals, whereas no anti-BSA antibodies were detected in nonimmunized control rats. Anti-BSA antibodies were detected only in lavage fluid from intradermally immunized rats. These findings suggest that presence of specific antibodies locally in the lungs may increase alveolar epithelial permeability to protein. This finding may have clinical implications, e.g., for sensitive asthmatics, since increased nonspecific permeability caused by local immune-related inflammation may result in further allergies.

Animals↗

Mortality and morbidity among patients who undergo combined valve and coronary artery bypass surgery: early and late results.

AIM: To describe mortality and morbidity early and late after combined valve surgery and coronary artery bypass grafting (CABG) as compared with CABG alone. PATIENTS AND METHODS: All patients from western Sweden in whom CABG in combination with valve surgery or CABG alone was carried out in 1988-1991. RESULTS: Among 2116 patients who underwent CABG, 35 (2%) had this combined with mitral valve surgery and 134 (6%) had this combined with aortic valve surgery, whereas the remaining 92% underwent CABG alone. Patients who underwent combined valve surgery and CABG were older, included more women and had a higher prevalence of previous congestive heart failure and renal dysfunction but on the other hand a less severe coronary artery disease. Among patients who underwent mitral valve surgery in combination with CABG the mortality over the subsequent 5 years was 45%). The corresponding figure for patients who underwent aortic valve surgery in combination with CABG was 24%. Both were higher than for CABG alone (14%; P < 0.0001 and P = 0.003, respectively). In a stepwise multiple regression model mitral valve surgery in combination with CABG was found to be an independent significant predictor for death but aortic valve surgery in combination with CABG was not. Among patients who underwent mitral valve surgery in combination with CABG and were discharged alive from hospital 77% were rehospitalized during the 2 years following the operation as compared with 48% among patients who underwent aortic valve surgery in combination with CABG and 43% among patients with CABG alone. Multiple regression identified mitral valve surgery in combination with CABG as a significant independent predictor for rehospitalization but not aortic valve plus CABG. CONCLUSION: Among patients who either underwent CABG in combination with mitral valve surgery or aortic valve surgery or CABG alone, mitral valve surgery in combination with CABG was independently associated with death and rehospitalization, but the combination of aortic valve surgery and CABG was not.

Aged↗

Bidirectional small intestinal permeability changes to different-sized molecules after HCl-induced injury in the rat.

A rat model was developed to assess bidirectional passage of macromolecules and low-molecular-weight markers across the intestinal barrier in intact and injured mucosa. Isolated in situ loops of distal small intestine were luminally perfused for 30 min with saline as control or HCI (pH 2.0) to induce an acute injury. The lumen-to-blood passage was followed during perfusion with bovine serum albumin, [14C]mannitol, and sodium fluorescein. Intravenously administered sodium fluorescein and endogenous serum albumin were used as blood-to-lumen markers. Acid exposure resulted in severe injury of the villi tips, with significantly increased lumen-to-blood passage of all markers compared with that of intact mucosa. Moreover, blood-to-lumen passage of rat serum albumin increased after the injury, while that of sodium fluorescein did not. The acid induced injury impaired the intestinal barrier function with an increased marker passage, where the macromolecules were more sensitive markers of the altered barrier function than low-molecular-weight markers.

Acute Disease↗

Pulmonary delivery of intratracheally instilled and aerosolized cyclosporine A to young and adult rats.

The delivery and pharmacokinetics of cyclosporine A (CyA) given locally to the airways or iv was evaluated in young and adult rats. After intratracheal (i.t.) instillation of saline suspended CyA to adult rats, the CyA plasma levels peaked at 30 min with a bioavailability of 78.1 +/- 6.9%. After the i.t. instillation of CyA with micelles forming surfactant, Cremophor EL, in adult and young rats, the plasma levels peaked at 5 min with a bioavailability of 77.5 +/- 7.2% and 66.3 +/- 4.5%, respectively. The bioavailability of aerosolized CyA was 80.1 +/- 4.1% in adults. Thus, CyA is absorbed by the lungs into the systemic circulation of the rat in high amounts, independent of age and type of delivery system. Long-term treatment with i.t. instillations did not affect body weight gain in young and adult rats, and no histopathological changes were found in the lungs. It is important to emphasize that CyA plasma clearance in young rats was lower and elimination half-life longer than in adults. The slow elimination of CyA in young rats indicated profound pharmacokinetic age differences for this species.

Aerosols↗

Influnce of oat saponins on intestinal permeability in vitro and in vivo in the rat.

The aim of the present study was to investigate whether oat saponins (avenacosides A and B) have any effect on the permeability of the rat intestine to actively and passively transported markers in vitro and in vivo. Intestinal segments were mounted in modified Ussing chambers, and the passage of the different marker compounds from the mucosal to the serosal side was measured for 120 min. Avenacosides (1 mg/ml) gave a significantly higher passage of the macromolecule ovalbumin and there was a tendency to increased passage of [14C]D-mannitol and [51Cr]EDTA. On the other hand, the saponins did not affect the active transport of [3H]methyl glucose. When rats were given saponins (40 mg/kg body weight) together with markers by gastric intubation, the passage of [51Cr]EDTA into blood and urine was somewhat reduced. For the macromolecule bovine serum albumin, no evident effect on the passage was observed in the presence of saponins. Thus, in contrast to the in vitro results, the in vivo marker passage seemed to be unaffected or even reduced in the presence of avenacosides. The study shows that saponins can affect the permeability of the rat intestine. However, this effect needs further investigation in vivo, especially regarding proteins.

3-O-Methylglucose↗

Alveolar epithelial clearance of protein.

Substantial progress has been made in understanding the rate, the pathways, and the mechanisms regulating alveolar protein removal from the uninjured lung. Whole animal studies and cellular studies have demonstrated that the majority of alveolar epithelial protein clearance occurs by passive nondegradative diffusional pathways. Some evidence, however, has been recently presented that alveolar epithelial cells express an albumin-binding receptor as well as a polymeric immunoglobulin receptor, both of which might be important for alveolar epithelial clearance of protein. However, the contribution of these receptors requires further studies. Little is known about alveolar clearance of protein during pathological conditions; further studies are required to determine the roles of the different cell types in the lung for removal of protein from the alveolar spaces of the lung. Alveolar macrophages are likely to play an important role in the degradation and removal of insoluble protein from the distal air spaces after acute lung injury. In conclusion, the present data suggest that most proteins and peptides deposited on the epithelial surfaces in the distal air spaces are cleared as intact molecules, predominantly via paracellular routes. The contribution of pinocytic processes appear to be of minor importance for translocation of bulk quantities of proteins or peptides across the alveolar epithelium.

Animals↗

Development and regulation of porcine pancreatic function.

A surgical and experimental procedure was developed to enable the collection of pure and inactivated pancreatic juice during the growth of the pig. Studies have shown that, during the suckling period, both the basal and the secretory responses to suckling are low, if present at all. After weaning, basal levels of the total exocrine secretion, total protein, amylase, and trypsin, respectively, increase slightly, while the postprandial levels of total protein, amylase, trypsin, lipase, colipase, and carboxylester lipase, respectively, increase markedly. The pancreatic juice enzyme composition changes qualitatively and the antibacterial activity of the pancreatic juice also significantly increases. Piglet age appeared to be of minor importance, since weaning at either 4 or 6 wk of age gave the same results. Secretin and CCK administered together in supraphysiological doses only significantly affect exocrine function from 3-4 wk of age. However, CCK may also affect the exocrine pancreas indirectly via reflexes initiated intraduodenally. Milk consumption in the suckling pig leads to a postprandial increase in glucose levels but not insulin. Milk appears to be able to regulate the exocrine pancreas to produce only the amount and type of enzymes required for digestion. Thus, milk components or digestive products may affect pancreas function regulation. Studies show that enterostatin, the procolipase activation peptide, may inhibit pancreatic secretion mediated indirectly through the GI tract. Pancreastatin, an endocrine peptide, inhibits both insulin secretion and protein and trypsin secretion to pancreatic juice. In hypoinsulinemic (alloxan+streptozotocin diabetes) pigs (15-20 kg), no postprandial pancreatic juice response is seen, although CCK 33 + secretin can stimulate pancreatic secretion. Hypoinsulinemic pigs have a reduced capacity for glucose tissue utilization, suggesting that tissue metabolism and exocrine pancreas secretion are related.

Animals↗

Enhanced intestinal absorption of oxytocin peptide analogues in the absence of pancreatic juice in pigs.

PURPOSE: The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. METHODS: In conscious chronically catheterized pigs (6-8 weeks of age) plasma concentration of the peptides, [Mpa, D-Tyr(Ethyl), Thr, Orn]-oxytocin (F314), [Mpa, D-Tyr(Ethyl), Val, D-Arg]-oxytocin (CAT), and [Mpa, D-Tyr(Ethyl), Thr, Orn, desGly, carba]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. RESULTS: All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. CONCLUSIONS: The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.

Animals↗

Stimulation of endocrine, but not exocrine, pancreatic secretion during 2-deoxy-D-glucose-induced neuroglycopenia in the conscious pig.

The effects of autonomic nervous activation, initiated by 2-deoxy-D-glucose (2-DG)-induced neuroglycopenia, or endocrine and exocrine pancreatic secretion were investigated in the conscious pig. Pigs were surgically fitted with permanent pancreatic duct and duodenal reentrant cannulas, allowing long-term sampling of pancreatic juice, and a jugular vein catheter for blood sampling and infusion of 2-DG. 2-DG was administered as a 5-min intravenous infusion at three dose levels to conscious pigs. 2-DG (400 mg/kg) was found to elevate plasma glucagon and insulin levels (p < 0.01). In contrast, exocrine pancreatic secretion, measured as volume, total protein output, and output of trypsin activity was not affected by 2-DG at the dose levels of 75, 200, and 400 mg/kg. Secretin (440 pmol/kg/h), however, stimulated pancreatic exocrine output of fluid (p < 0.01), protein (p < 0.01), and trypsin (p < 0.05). It is concluded that autonomic nervous activation by 2-DG-induced neuroglycopenia, in the conscious pig under basal conditions, elevates the plasma levels of glucagon and insulin but does not affect exocrine pancreatic secretion. 2-DG-induced neuroglycopenia is, thus, a suitable model for studying autonomic neural influences on the porcine endocrine pancreas.

Animals↗

The pattern of the circadian rhythm of pancreatic secretion in fed pigs.

The pattern of the circadian rhythm of pancreatic secretion was studied in four 6- to 7-wk-old intact male pigs that were kept in metabolic cages under 12 h light:12 h dark cycles and fed three times a day at 0800, 1500, and 2200. Three 24-h collections of pancreatic juice and blood were begun at 0800 every 2nd day during 5 d. A biphasic pattern of the exocrine pancreas was detected. Secretions during the first phase (postprandial peak) contained large amounts of protein and enzymes, and secretions appeared immediately after feed ingestion. Secretions during the second phase (between meals) had lesser amounts (P < .001) of protein and enzymes, but were of longer duration (P < .001). The output of protein and trypsin activity were generally correlated (P < .001) with each other, but the correlation of either with the volume outflow were small. However, these variables were correlated (P < .01) with the volume outflow at night during the second phase. Plasma concentrations of insulin and glucose increased after each meal, but the increase was significant (P < .05) only for insulin. Insulin and glucose concentrations were correlated (P < .01) with each other after the meals at 0800 and 1500. The results indicated a biphasic pattern of the exocrine pancreas and a monophasic pattern of the endocrine pancreas in pigs. The regulation of these patterns seems to vary during the 24-h period. Furthermore, feed enhanced secretion, but it did not seem to be the only factor controlling the circadian pattern.

Analysis of Variance↗

Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat.

BACKGROUND: The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats. METHODS: The different-sized intestinal absorption markers 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged 51Cr-EDTA. RESULTS: In comparison with the sham-operated rats, septic rats had higher 51Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption. CONCLUSIONS: The results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit.

Animals↗

Induction of exocrine pancreas maturation at weaning in young developing pigs.

The influence of weaning, at either 4 or 6 weeks of age, on the maturation of the exocrine pancreas was studied in naturally reared Swedish Landrace pigs that had no access to solid food. The pigs were surgically fitted with chronic catheters at 3 weeks of age, permitting periodic sampling of pancreatic juice and blood in conscious animals < or = 4 weeks after weaning. During the suckling period, pancreatic fluid and enzyme secretion remained low, both before (preprandial) and after (postprandial) milk ingestion. After weaning at 4 or 6 weeks of age, juice secretion, output of total protein, and levels of different hydrolases (amylase, trypsin, lipase, and carboxylester lipase) and the cofactor colipase all increased markedly postprandially. Moreover, after weaning, the plasma insulin level increased postprandially. This did not happen before weaning, although blood glucose levels always rose after feeding. The data showed a relationship between the time of weaning and the induction of exocrine pancreatic maturation in pigs. This finding implies that postnatal development of pancreatic function is triggered by the dietary change from sow milk to dry solid food. In contrast, the age of the pig appears to be of minor importance, since weaning at either 4 or 6 weeks of age gave a similar result.

Animals↗

Lung to blood passage of albumin and a nonapeptide after intratracheal instillation in the young developing pig.

The passage via the lower respiratory tract of the macromolecule, bovine serum albumin (BSA, mol. wt = 67000) and the nonapeptide, 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, mol. wt = 1067), was assessed for 240 h after intratracheal instillation in young, developing pigs. The plasma levels of immunoreactive BSA increased with time, reaching a maximum between 36-86 h after instillation, and the main portion of BSA in plasma appeared intact, as assessed by crossed immunoelectrophoresis. The dDAVP levels reached a maximum after 1-3 h. The time to reach maximal plasma levels increased with the age of the pig for BSA, while no such effect was observed for dDAVP. The total lung passage, as calculated by dividing the area under the plasma level-time curve obtained after intratracheal instillation with that obtained after intravenous administration (elimination curve), showed no significant differences with age for BSA (21.8 +/- 9.0% in the newborn, 15.1 +/- 8.0% in the 2-day-old and 16.1 +/- 4.2% in the 70-day-old pigs). For dDAVP, a significant decrease in the total passage was obtained with age, from 74.6 +/- 9.4% in the newborn pigs to 44.1 +/- 13.3%, in the 2-day-old pigs (P < 0.001), and to 23.6 +/- 7.1% (P < 0.01) in the 70-day-old pigs. The study showed that the marker molecules, BSA and dDAVP, passed over the porcine lung into the blood circulation in high amounts, apparently inversely related to their molecular size. The total lung passage of dDAVP, but not that of BSA, was affected by changes with age, indicating that these two markers might traverse the lung epithelium via different routes that are differently affected during postnatal development.

Animals↗

Lung to blood passage of different-sized molecules during lung inflammation in the rat.

The passage of different-sized marker molecules over the lower respiratory tract into the blood circulation during pulmonary inflammation induced by dextran, endotoxin [i.e., lipopolysaccharide from Escherichia coli (LPS)], or ferritin was assessed in the rat. Bovine immunoglobulin G (BIgG, mol wt = 150,000 Da), bovine serum albumin (BSA, mol wt = 67,000 Da), and the nonapeptide 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, mol wt = 1,067 Da) were used as permeability markers after intratracheal instillation. The pathophysiological indexes of a proceeding lung inflammation were increased total cell number, changed leukocyte proportions and increased total protein content obtained in bronchoalveolar lavage, and lung edema formation shown as an increased lung wet-dry weight difference. Intratracheal instillation of dextran induced a moderate neutrophil invasion into the lungs but had no effect on the passage of the different markers over the lungs (BIgG 1.8 +/- 0.6%, BSA 3.5 +/- 1.2%, dDAVP 26.1 +/- 20.7%) compared with control rats instilled with the markers alone (1.8 +/- 0.4%, 4.1 +/- 1.3%, 20.0 +/- 3.8%, respectively). Endotoxin administration resulted in markedly higher lavage cell counts and lung edema concomitantly with an increased lung passage of the markers (3.2 +/- 0.9%, 22.0 +/- 6.1%, 33.3 +/- 12.0%, respectively; P less than 0.01-P less than 0.001). The highest marker passage was obtained when the inflammation was most severe, i.e., after ferritin administration (17.6 +/- 2.3%, 60.0 +/- 6.7%, 41.6 +/- 6.9%, respectively; P less than 0.001), which resulted in markedly elevated lavage cell numbers and protein content as well as edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Blood serum characteristics of newborn pigs: comparison of unaffected pigs with pigs belonging to five mortality groups.

The blood serum levels of glucose, hemoglobin, insulin, cortisol, albumin, alpha-fetoprotein, alpha 2-macroglobulin f and s, alpha 2-antitrypsin inhibitor and alpha 1-protease inhibitor were determined at birth in 5 clinically and morphologically identified mortality groups of pigs. These were compared with the levels observed in unaffected, apparently normal newborn unsuckled pigs. The blood serum profile of the pigs in the stillborn intra partum, weak, splayleg and trauma groups, respectively, as well as that of clinically normal splayleg littermates, differed significantly from that of the unaffected pigs. This was especially true for the levels of hemoglobin and the two macroglobulins. The importance of placental insufficiency causing chronic episodes of hypoxia which ultimately lead to a disturbance in organ development in the etiology of the mortality groups is discussed.

Animals↗