Hormones, body composition and cardiovascular risk.
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Biomedical subjects
Publications and source records attributed to M Alpsten.
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The gastrointestinal transit and tablet erosion of felodipine extended release (ER) tablets 10 mg were studied by gamma scintigraphy in eight healthy young males after administration under fasting and nonfasting conditions. Plasma concentrations of felodipine were also measured. Gastric emptying after administration together with food (mean, 3.2 hr) was slower in all subjects compared to emptying under fasting conditions (mean, 0.6 hr). The mean small intestinal transit times for the two study conditions did not differ significantly (5.1 and 4.7 hr, respectively). Tablets did not leave the colon in any subject within 14 hr after administration. Felodipine was shown to be absorbed in the colon, although the major part of the dose was absorbed in the small intestine. The absorption rate of felodipine was related to erosion of the hydrophilic matrix tablet. Tablet erosion and hence drug absorption were slower in the more distal parts of the gastrointestinal tract. Administration together with food did not significantly affect tablet erosion.
Seven men with well-controlled, noninsulin-dependent (type 2) diabetes ingested on two different mornings, in random order, meals with or without a 5.0-g sodium alginate supplement (algae-isolate, 75% soluble fiber). The meals contained similar amounts of digestible carbohydrates, fat and protein. The gastric emptying rate of the meal containing sodium alginate, measured by detection of 51Cr mixed into the meals, was significantly slower than that of the fiber-free meal. Sodium alginate also induced significantly lower postprandial rises in blood glucose, serum insulin and plasma C-peptide. The diminished glucose response after the addition of sodium alginate could be correlated to the delayed gastric emptying rate induced by the fiber (rs = 0.92, P less than 0.01).
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A vitamin and trace element supplement containing recommended dietary amounts or "safe and adequate" levels was given to ten healthy subjects for 12 to 35 weeks. Plasma levels of selenium and zinc, activity of glutathione peroxidase in plasma and platelets, whole blood manganese, activity of superoxide dismutase in hemolysate, activity of alkaline phosphatase in serum, iron status indices and urinary excretion of zinc and selenium were measured. A small but significant change in plasma selenium from 1.01 +/- 0.14 mumol/L to 1.08 +/- 0.10 mumol/L was observed after two weeks. However, at the end of the supplementation plasma selenium levels did not differ from the initial levels. Plasma glutathione peroxidase levels showed a similar trend and changes in glutathione peroxidase activity in platelets were also transient. A small increase in serum zinc values was observed after 30 weeks of supplementation. No significant changes were observed in the other blood and urine parameters studied. In seven of the subjects absorption of zinc, manganese and selenium was measured after 30-31 weeks of supplementation by a radionuclide technique. The absorption of selenium and manganese after long term supplementation was 30-50% lower than observed previously in non-supplemented subjects. In conclusion, present available indices of trace element status are only to a limited extent affected by 30 weeks of a doubling of the normal dietary intake.
In this paper some radioanalytical methods will be described for assessing the contents of various elements in the human body. In vivo methods are necessary for this problem. Protein content can be estimated by means of in vivo measurements of nitrogen, bone minerals by means of the total body content of calcium. Fat contains a high concentration of carbon. Carbon in fat can be estimated and from this the total body fat can be calculated. Toxic elements such as lead, cadmium and mercury are assessed by in vivo measurements, both related to occupationally exposed workers and to members of the public.
Selenium level and activity of glutathione peroxidase in plasma were studied in seven patients with extensive short bowel resection due to Crohn's disease, before and during 27-54 weeks of intake of a vitamin and trace element supplement containing 50 micrograms of selenium as sodium selenite. Initial levels of selenium were normal in all except one of the patients. The supplementation had no or minor effects on plasma selenium levels and glutathione peroxidase activity. The absorption of zinc, manganese and selenium was measured with a radionuclide technique before and/or after the supplementation period in five of the patients. The absorption of zinc and manganese was similar to that observed earlier in healthy subjects, while the absorption of selenium was significantly lower. The results indicate that a higher selenium intake or a different form of selenium is needed in these patients to compensate for the impaired bowel function.
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Two meals of mashed-bean or potato flakes and meat were served in random order to six healthy male subjects to determine effects on gastric emptying and glycemic reactions. The meals had comparable physical appearance and contained similar amounts of digestible carbohydrate, fat, and protein. No difference in gastric emptying, recorded by gamma camera after mixing 51Cr with the meals, was found between the meals. The bean-flakes meal gave significantly lower blood glucose (p less than 0.01) and serum insulin (p less than 0.05) concentrations than did the potato-flakes meal. The overall blood glucose response, calculated as incremental area under the curves for 2 h, also differed between the meals (p less than 0.05) whereas the overall insulin response did not differ significantly. The low glycemic response after bean flakes could not be explained by the gastric emptying rate, which provides additional evidence for the slow digestion of bean starch in the small intestine.
Meals (425 kcal) containing various doses of guar gum (0, 2.5, 7.5 or 12.5 g) were ingested by nine healthy male subjects after a 12-h fast. The rise in blood glucose was higher after the control meal without guar gum than after the guar gum-containing meals, which all gave a similar rise in glucose. In contrast, increased doses of guar gum led to a greater reduction in the postprandial rise in insulin. The postprandial increase in serum hydroxyproline, an amino acid added to all meals, was decreased in a similar manner by all of the guar gum doses. Gastric emptying was measured after the control meal without guar gum and the meal containing 12.5 g of guar gum by monitoring 51Cr, which was added to the meals. Guar gum was found to reduce the variation between individuals, as well as the initial rate of gastric emptying, which correlated with changes in both serum hydroxyproline (rs = 0.93, P less than 0.01) and blood glucose (rs = 0.83, P less than 0.01). The effectiveness of guar gum in reducing postprandial response was lost after heating and homogenization for canning. A threshold in the reduction in rise of glucose or hydroxyproline was reached with the lowest dose (2.5 g) of viscous guar gum; larger doses had no additional effects. The reduced absorption seems to be an effect of a slower gastric emptying rate.
The whole body retention of 75Se, 65Zn, and 54Mn after intake of a labelled vitamin and mineral supplement was followed in 12 healthy volunteers. The supplement had a vitamin and mineral content according to recommended dietary allowances or the so-called "safe and adequate levels" for trace elements, including 15 mg of zinc as zinc citrate, 50 micrograms of selenium as sodium selenite and 2.5 mg of manganese as manganese sulphate. The supplement was taken either in the fasting state or together with a light meal. Retention day 14 was 48 +/- 6%, 33 +/- 6% and 5 +/- 2% (mean +/- SD) for selenium, zinc and manganese, respectively, when the supplement was taken fasting and 45 +/- 3%, 8 +/- 1% and 1.0 +/- 0.2% when it was taken with food. During day 1-14, 27%, 1% and less than 0.01% of the administered selenium, zinc and manganese radionuclides, respectively, were excreted in the urine. Based on the rate of turnover of the radionuclides and the urinary losses of 75Se, the absorption of selenium, zinc and manganese from the supplement was estimated to be 89 +/- 5%, 38 +/- 7%, 9 +/- 3% (mean +/- SD) in the fasting state and 87 +/- 4%, 10 +/- 2% and 2 +/- 1% with food. These results indicate that when a supplement is taken with food the minerals are absorbed and metabolized in the same way as are native minerals in food. When the supplement is taken in the fasting state, the absorption of zinc and manganese can be substantially higher.
Composite meals with mashed potatoes, polished rice or mashed white beans were administered to eleven diabetic subjects (seven Type II and four Type I). As earlier reported in non-diabetic subjects (Torsdottir et al., 1984) the difference in gastric emptying, measured by 51Cr-technique, correlated with the difference in blood glucose response when comparing the meals including mashed potatoes and polished rice, rs = 0.93 (P less than 0.01), but no such correlation was found after the meal with white beans.
Gastric emptying of a 51Cr labelled solid meal was studied before and at least 6 months after operation for pyloric-prepyloric ulcer disease. All patients underwent an antrectomy, selective gastric vagotomy but 10 were randomized to a gastroduodenostomy and 12 to a Roux-en-Y gastrojejunostomy. There was no significant difference in the emptying rate between patients studied preoperatively (T 75 = 48 +/- 21.8 min) and those investigated after a Billroth I gastroduodenostomy (T 75 = 45 +/- 15.8 min). However, the emptying rate was significantly retarded in the Roux-en-Y patients as compared to those studied preoperatively (T 75 + T 50 + T 25). In the former group, an initial retardation of emptying of the meal was most apparent (T 75 = 89 +/- 81.7 min). Due to a high standard deviation, the difference between the Roux-en-Y and gastroduodenostomy groups did not reach statistical significance. Our results would indicate that retarded gastric emptying is not a regular phenomenon after a Roux-en-Y gastrojejunostomy provided that a selective gastric vagotomy had been performed and the investigation been carried out at least 6 months after the operation.
The absorption of acetylsalicylic (ASA) acid from enteric coated tablets was studied in relation to gastric emptying and in-vivo disintegration. ASA tablets labelled with 51Cr were given to six healthy subjects under fasting and non-fasting conditions. The position and disintegration of the 51Cr-labelled tablets was followed by external radiation measurement and the amount of salicylic acid in blood and urine was analysed. The absorption of ASA from the studied enteric coated tablets was usually correlated with gastric emptying and in-vivo disintegration. However in some cases the absorption can be delayed between 10-20 h even if gastric emptying and disintegration of the tablet have occurred.
Thirteen healthy subjects participated in the study. Three meals of equal energy content consisting of hamburgers and mashed potatoes, polished rice or white beans were studied. The various meals were labelled with 2.6 MBq 51Cr and gastric emptying was studied by a movable NaI (T1) detector. Blood glucose and plasma insulin were measured after an overnight fast and after ingestion of the testmeal. Gastric emptying of mashed potatoes was faster than that of polished rice (P less than 0.02) and of white beans (P less than 0.05). Blood glucose and plasma insulin responses to the meal with mashed potatoes were greater than to that with polished rice (P less than 0.01), which also produced a greater glucose response than that with white beans (P less than 0.01). The correlation coefficient (rs) between difference in gastric emptying and difference in blood glucose or plasma insulin response was 0.95 (P less than 0.01) when comparing meals of mashed potatoes and polished rice. No correlation was found between gastric emptying and blood glucose or plasma insulin after the white bean meal. We conclude that glucose and insulin responses to potatoes and rice are strongly related to gastric emptying rate, but other factors dominate the control of these responses to white beans.
The intratumor distribution of the capillary permeability surface area product (PS) correlated to the intratumor distribution of vascular space and of blood flow was studied by labeled albumin in a transplantable rat fibrosarcoma. A wide heterogeneity in intratumor distribution of PS was found. The tumor PS values were not significantly correlated to tumor vascular space or to blood flow values. This might suggest that intravascularly administered drugs could reach a comparative high intratissue concentration also in less vascularized tumor areas.