Feeding of palm oil fatty acids or rapeseed oil throughout lactation: Effects on mammary gene expression and milk production in Norwegian dairy goats.

Lipid added as rapeseed or palm oil to the diet of dairy goats over 8 mo of one lactation alters fat secretion and milk fatty acid (FA) and protein composition. In this study, we examined the contribution of mammary gene expression to these changes and included 30 multiparous goats of Norwegian dairy goat breed for a 230-d experimental period, with indoor feeding from 1 to 120 d in milk (DIM), mountain grazing from 120 to 200 DIM, and indoor feeding from 200 to 230 DIM. After an initial period (1-60 DIM) when the control diet was given to all goats, the animals were subdivided into 3 groups of 10 goats. Treatments (60-230 DIM) were basal concentrate (control) alone or supplemented with either 8% (by weight) hydrogenated palm oil enriched with palmitic acid (POFA) or 8% (by weight) rapeseed oil (RSO). Milk was sampled individually from all animals throughout lactation, at 60, 120, 190, and 230 DIM for milk yield and composition. On d 60, 120, 190, and 230, mammary tissue was collected by biopsy to measure mRNA abundance of 19 key genes. None of the 19 genes involved in milk protein, apoptosis, lipid metabolism, transcription factors, and protein of the milk fat globule membrane, as measured by mRNA abundance, were affected by the lipid supplements, although POFA increased milk fat content, and POFA and RSO affected milk FA composition. Over the experimental period (120-230 DIM), the mRNA abundance of 13 of the 19 studied genes was affected by lactation stage. For some genes, expression either gradually increased from 120 to 230 DIM (CSN2, CASP8, CD36, GLUT4) or increased from 120 to 200 and then remained stable (XDH), or decreased (CSN3, G6PD, SREBF1, PPARG1) or increased only at 230 DIM (SCD1, SCD5, ELF3). For a second group of genes (CSN1, LALBA, FABP3, FASN, LPL, MFGE8), expression was stable over the lactation period. Our results suggest that factors other than gene expression, such as substrate availability or posttranscriptional regulation of these genes, could play an important role in the milk fat and FA responses to dietary fat composition in the goat. In conclusion, mammary gene expression in goats was more regulated by stage of lactation than by the dietary treatments applied.

Feeding of palm oil fatty acids or rapeseed oil throughout lactation: Effects on energy status, body composition, and milk production in Norwegian dairy goats.

The objective of this experiment was to examine how supplements of rapeseed oil or palm oil fatty acids would affect milk production and composition, body lipid stores, and energy balance in 30 multiparous goats of Norwegian dairy goat breed. The experiment lasted 230 d, with 1 to 120 d in milk (DIM) for indoor feeding (P1), 120 to 200 DIM for mountain grazing (P2), and 200 to 230 DIM for indoor feeding (P3). Grass silage was fed according to appetite during indoor feeding periods. After an adjustment period (1-60 DIM) when the control diet was given to the goats, the animals were subdivided into 3 groups of 10 goats. Treatments (60-230 DIM) were (1) basal concentrate (control; no added fat); (2) control concentrate with 8% (added on air-dry basis) hydrogenated palm oil enriched with palmitic acid (POFA); and (3) control concentrate with 8% (added on air-dry basis) rapeseed oil (RSO). Individual energy balances based on energy intake and milk production were estimated on 10, 30, 60, 90, 120, 200, and 230 DIM. At the same times, body weight (BW), body condition score (BCS), body mass index, and body tissue stores using computed tomography were monitored. Silage intake was depressed by POFA throughout the experimental period. Reduced BW and body mass index were observed in the POFA and RSO groups, whereas no effect on BCS or body composition was observed throughout lactation. Generally, a minor decrease in BW was observed from 10 to 120 DIM (only 0.6 kg on average) and the total amount of body lipid was reduced by 4.4 kg. During the mountain grazing period, a further reduction in body lipid stores (2.7 kg) was observed, and BW was reduced by 3.9 kg in the same period. The goats mobilized, on average, 72% of their fat reserves during the first 200 DIM. In this period, dietary fat supplementation did not reduce the mobilization of adipose tissue but resulted in greater milk fat yield (2 kg more, on average, compared with the control group). Milk yield was not affected by POFA or RSO supplementation. Milk fat content was higher in the POFA group than in the control and RSO groups. Milk protein and lactose contents were not affected by lipid supplements. In late lactation, a rapid accumulation of fat deposits followed the intense mobilization during the grazing period. Dietary lipid supplements had no effect on milk fat yield at this stage. Milk production depends heavily on the ability to mobilize body lipid stores, and neither POFA nor RSO supplements at rates used in our study affected this mobilization.

Effects of 12 weeks of treatment with fermented milk on blood pressure, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind placebo-controlled study.

OBJECTIVE: Studies have indicated a blood pressure (BP)-lowering effect of milk-derived peptides in non-diabetic individuals, but the cardiometabolic effects of such peptides in patients with type 2 diabetes (T2D) are not known. We investigated the effect of milk fermented with Lactobacillus helveticus on BP, glycaemic control and cardiovascular risk factors in T2D. DESIGN: A randomised, double-blinded, prospective, placebo-controlled study. METHODS: In one arm of a factorial study design, 41 patients with T2D were randomised to receive 300 ml milk fermented with L. helveticus (Cardi04 yogurt) (n=23) or 300 ml artificially acidified milk (placebo yogurt) (n=18) for 12 weeks. BPs were measured over 24-h, and blood samples were collected in the fasting state and during a meal test before and after the intervention. RESULTS: Cardi04 yogurt did not reduce 24-h, daytime or nighttime systolic or diastolic BPs compared with placebo (P>0.05). Daytime and 24-h heart rate (HR) were significantly reduced in the group treated by Cardi04 yogurt compared with the placebo group (P<0.05 for both). There were no differences in HbA1c, plasma lipids, C-reactive protein, plasminogen activator inhibitor-1, tumour necrosis factor alpha, tissue-type plasminogen activator: Ag, and von Willebrand factor: Ag between the groups. The change in fasting blood glucose concentration differed significantly between the two groups with a larger increase in the placebo group (P<0.05). CONCLUSIONS: Ingestion of milk fermented with L. helveticus compared with placebo for 12 weeks did not significantly reduce BP in patients with T2D. Our finding of lower HRs and fasting plasma glucose levels in T2D patients during ingestion of fermented milk needs further validation.

Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study.

AIMS/HYPOTHESIS: Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c) and cardiovascular risk factors in type 2 diabetes. METHODS: Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n = 20) or placebo (n = 21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA(1c) and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements. RESULTS: Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049 ± 17,659 vs 27,270 ± 32,004 pmol/l × min (p = 0.838). In the placebo group AUC for insulin decreased from 27,392 ± 14,348 pmol/l × min to 22,938 ± 11,936 pmol/l × min (p = 0.002). Esomeprazole treatment (n = 20) caused a ninefold increase in the AUC for gastrin. HbA(1c) increased from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.3 ± 0.8% (56 ± 6 mmol/mol) in the esomeprazole-treated group and from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.4 ± 0.8% (57 ± 6 mmol/mol) in the placebo group (n = 21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p > 0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p < 0.05). No change in BP was seen in the patients treated with esomeprazole. CONCLUSIONS/INTERPRETATION: Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Treatment with a proton pump inhibitor improves glycaemic control in Psammomys obesus, a model of type 2 diabetes.

AIMS/HYPOTHESIS: Gastrin has been implicated in islet growth/neogenesis, and proton pump inhibitors (PPIs) have been shown to increase endogenous gastrin levels in animals and humans. Therefore, we investigated the effect of PPIs in a model of type 2 diabetes, Psammomys obesus. METHODS: P. obesus (morning blood glucose [mBG] 16.9 +/- 0.6 mmol/l) were treated with vehicle or different doses (1-15 mg/kg) of lansoprazole for 17 days. RESULTS: Treatment with lansoprazole resulted in up to ninefold dose-dependent increases in endogenous gastrin levels (p < 0.05 for 10 mg/kg lansoprazole vs vehicle). There was a significant reduction in mBG levels in all animals in the high-dose lansoprazole groups during the 17 day treatment period, whereas there was no significant improvement in mBG in animals in the vehicle groups. The mBG at end of study was 18.2 +/- 2.1, 8.7 +/- 2.2 (p < 0.01), and 6.1 +/- 2.3 (p < 0.001) mmol/l for vehicle and lansoprazole 10 and 15 mg/kg, respectively. The animals treated with 15 mg/kg lansoprazole, compared with vehicle, had a 2.3-fold increase in the intensity of insulin staining in beta cells (p=0.0002) and 50% higher beta cell mass (p=0.04). CONCLUSIONS/INTERPRETATIONS: The PPI lansoprazole had significant glucose-lowering effects in an animal model of type 2 diabetes, an effect that is most likely mediated through an increase in endogenous gastrin levels.

Yttrium oxide (Y2O3) as an inert marker in digestibility studies with dogs, blue foxes and mink fed diets containing different protein sources.

The study evaluated the use of yttrium oxide (Y(2)O(3)) as an inert marker in studies of apparent total tract digestibility in dogs, blue foxes and mink. Comparison was made with total faecal collection, and use of chromic oxide (Cr(2)O(3)) as marker respectively. Four experimental diets were added 0.1 g/kg yttrium oxide and 10 g/kg chromic oxide and fed to four animals of each species. Faecal recovery of yttrium oxide was 94.4% (SEM +/- 1.0), and of chromic oxide 105.8% (SEM +/- 1.5). The digestibilities of dry matter, crude protein, crude fat, starch and total carbohydrates obtained by total collection and yttrium oxide as marker showed close similarity, and in most cases not significant differences, independent of species and diets. In dogs, overall digestibilities of main nutrients with chromic oxide as marker were not significantly different from overall means obtained with yttrium oxide (p > 0.05). Overall digestibility of dry matter, crude protein and total carbohydrates in blue foxes and mink was significantly higher with chromic oxide than with yttrium oxide (p < 0.05). In dogs and blue foxes, digestibilities of individual amino acids determined by use of yttrium oxide were not different from values obtained using total collection of faeces, both within diets and for overall mean (p > 0.05). Overall amino acid digestibilities in dogs determined with chromic oxide as marker were similar to corresponding figures for yttrium oxide, whereas use of chromic oxide resulted in significantly higher digestibilites for a number of amino acids compared with yttrium oxide in foxes and mink (p < 0.05). The digestibilities of most main nutrients and amino acids revealed no interaction between diet and method (p > 0.05). The study showed that yttrium oxide can be used in low concentration in the feed, and allows high accuracy of analyses and thereby precise digestibility determination. It is concluded that yttrium oxide is an alternative inert marker to chromic oxide in the studied species.

Transfer of (85)Sr and (134)Cs from diet to reindeer foetuses and milk.

Sr-85 and (134)Cs in aqueous solution of the chlorides were administered daily to four pregnant reindeer during the last part of gestation. Radionuclide concentrations were determined in calves sacrificed at birth, and secretion of the nuclides was measured in milk. Although the gastrointestinal absorption of (85)Sr was low, an apparently higher transfer of the absorbed fraction of (85)Sr than (134)Cs from the mother to the foetus led to similar accumulation of (85)Sr and (134)Cs in foetuses. At birth 1.4-1.6 and 1.5-2.5% of the total administered activities of (85)Sr and (134)Cs, respectively, were present in the calves' bodies. Transfer coefficients (F (m)) for (85)Sr and (134)Cs from feed to milk were estimated at 0.0218+/-0.0026 and 0.185+/-0.025 day kg(-1), respectively, and the observed ratio (OR(milk-diet)) for (85)Sr was 0.124+/-0.037. Transfer of radiostrontium to reindeer milk was in agreement with previously reported relationships between Ca intake and radiostrontium transfer in ruminants. These relationships suggest that the transfer of radiostrontium to foetuses and milk of free-ranging reindeer can be 3-4 times higher than observed in this experiment (due to lower Ca intake with natural forage), but the transfer to milk will not be as high as that of ionic (134)Cs. The concentrations of (85)Sr in milk suggested that the does mobilized skeletal stores of Ca and (85)Sr for milk production, although the diet appeared to satisfy the Ca requirements. In reindeer with radiostrontium intake during the whole year, radiostrontium concentrations in milk will therefore be higher than indicated by the F (m) value observed in our study. No differences in half-times for (85)Sr and (134)Cs secretion in milk were detected. Both nuclides were secreted with short- and long-term half-times of 1-2 and 12-19 days, respectively. For (85)Sr, 80-90% of the activity was excreted with the short half-time, whereas the corresponding value for (134)Cs was 30-50%.

Physiological parameters that affect the transfer of radiocaesium to ruminants.

Recently there has been a renewed interest in biological scaling relationships between parameters, such as those between, for example, body mass, dry matter intake and biological half-times of radionuclides that are useful in predicting the transfer of radiocaesium to different animal species, particularly to wild animals. However, there is still a considerable unexplained variability in transfer coefficient estimates between individuals of the same species. This paper discusses the physiological parameters that affect the transfer of radiocaesium to ruminants, and it shows how a better understanding of these parameters may help to reduce the within-species variability in radiocaesium transfer coefficients. In light of the improved understanding during the past 10-15 years of the importance of source-dependent bioavailability on absorption of radiocaesium from the gastrointestinal tract, it is concluded that further studies are required on the effects of feed digestibility and physiological factors on absorption and endogenous faecal excretion of radiocaesium to better understand the variability in transfer coefficients.

Absorption, retention and tissue distribution of radiocaesium in reindeer: effects of diet and radiocaesium source.

Radiocaesium absorption and retention in reindeer (Rangifer tarandus) calves was compared in groups fed diets containing different proportions of lichen and concentrates, and different chemical forms of radiocaesium ((134)CsCl in solution or fallout from the Chernobyl accident). Daily intakes of fallout radiocaesium were 15-23 kBq, while daily intakes of (134)CsCl ranged from 70 kBq to 1,160 kBq. The half-life for radiocaesium in red blood cells (RBC) in animals fed with a pure lichen diet exceeded that in animals fed with a combined diet of lichen and concentrates by 40% (17.8+/-0.7 days vs. 12.7+/-0.4 days). Corresponding differences in the half-lives for urinary and faecal excretion were about 60% and 40%, respectively. Transfer coefficients (F(f)) to reindeer meat were estimated to be 0.25+/-0.01 days kg(-1) for fallout radiocaesium and 1.04+/-0.03 days kg(-1) for (134)CsCl, reflecting differences in both radiocaesium bioavailability and retention. The bioavailability of the Chernobyl radiocaesium in lichen in 1988 was estimated at ca. 35% compared to (134)CsCl.

Long-term consequences for Northern Norway of a hypothetical release from the Kola nuclear power plant.

The spatial and temporal variation in radiocaesium and (90)Sr doses to two population groups of the two Northernmost counties of Norway, Troms and Finnmark, following a hypothetical accident at the Kola nuclear power plant (KNPP) have been estimated using a model implemented within a geographical information system. The hypothetical accident assumes a severe loss of coolant accident at the KNPP coincident with meteorological conditions causing significant radionuclide deposition in the two counties. External doses are estimated from ground deposition and the behaviour of the different population groups, and internal doses from predicted food product activity concentrations and dietary consumption data. Doses are predicted for reindeer keepers and other Norwegian inhabitants, taking account of existing (137)Cs and (90)Sr deposition but not including the remedial effect of any countermeasures that might be used. The predicted doses, arising mainly from radiocaesium, confirm the Arctic Monitoring and Assessment Programme assessment that residents of the Arctic are particularly vulnerable to radiocaesium contamination, which could persist for many years. External doses are predicted to be negligible compared to ingestion doses. Ingestion doses for reindeer keepers are predicted to exceed 1 mSv y(-1) for several decades primarily due to their high consumption of reindeer meat. Other Norwegians would also be potentially exposed to doses exceeding 1 mSv y(-1) for several years, especially if they consume many local products. Whilst reindeer production is the most important exposure pathway, freshwater fish, lamb meat, dairy products, mushrooms and berries are also significant contributors to predicted ingestion doses. Radionuclide fluxes, defined as the total output of radioactivity in food from an area for a unit time, are dominated by reindeer meat. The results show the need for an effective emergency response, with appropriate countermeasures, should an accident of the scale considered in this paper occur at the KNPP.

Plasma urea, creatinine, and urea: creatinine ratio in reindeer (Rangifer tarandus tarandus) and in Svalbard reindeer (Rangifer tarandus platyrhynchus) during defined feeding conditions and in the field.

Variation in plasma urea and creatinine concentration and plasma urea:creatinine ratio (U:C) were studied in semidomestic free-ranging reindeer (Rangifer tarandus tarandus) on the Norwegian mainland, in wild Svalbard reindeer (Rangifer tarandus platyrhynchus), and in captive reindeer maintained either on a lichen-based diet or a protein-rich concentrate to investigate whether these parameters could be used as indicators of the nutritional status of reindeer. In the mainland animals, plasma creatinine concentration was high in winter and early spring and decreased by two-thirds toward the summer. The overall range in mean plasma creatinine concentration (+/-SE) was from 90+/-1.26 to 280+/-2.88 micromol/L. Mean plasma urea concentration (+/-SE) varied from 2.46+/-0.10 in winter up to 17.44+/-0.29 mmol/L in summer and autumn. Month of sampling explained 65% and 90% of the variation in plasma urea and creatinine concentrations, respectively, indicating that seasonality in the diet had the greatest influence on these parameters. Reindeer given lichens as the only feed showed an increase in plasma creatinine and a decrease in plasma urea concentration. Food restriction caused a temporary elevation in urea level but had no significant effect on plasma creatinine concentration. The slight effect of energy intake on urea and creatinine levels was supported by the fact that severe undernutrition in the Svalbard reindeer population had only a small effect on plasma urea and creatinine levels. Protein-rich pellet feed increased plasma urea from around 3 mmol/L to above 10 mmol/L and reduced creatinine concentrations to less than 100 micromol/L, suggesting that the protein content of forage is an important determinant of these blood parameters. Mean U:C ratio (+/-SE) in plasma varied from 8.9+/-0.28 to 120.8+/-1.88. Ratios above 20 appeared when protein intake was low and energy intake was restricted or when protein intake was high. Low ratios occurred when protein intake was low but energy intake adequate. Plasma urea and creatinine concentrations and the U:C ratio showed complex dynamics that were affected by both season and the protein and feed intake. We conclude that they appear to be difficult to interpret as single measures of nutritional status of reindeer.

Tolerance to the nephrotoxic component of Narthecium ossifragum in sheep: the effects of repeated oral doses of plant extracts.

Young adult sheep were dosed with extracts of Narthecium ossifragum plants by the oral or parenteral routes and the resulting nephrotoxicity was assessed from the increases in the concentrations of creatinine and urea in the serum. Following single intraruminal or intraperitoneal doses of extracts derived from 30 g N. ossifragum (wet weight) per kg live weight (kg lw), serum creatinine concentrations increased from about 100 micromol/L to between 260 and 510 micromol/L. The serum urea concentrations increased from about 5-8 mmol/L to between 11 and 66 mmol/L in individual sheep. Daily intraruminal administration of 5-30 g/kg lw to three sheep over a 10- or 15-day period increased creatinine concentrations from 100 micromol/L to 300-760 micromol/L, and urea concentrations from 5-8 mmol/L to 35 mmol/L. A single intraperitoneal challenge dose of 30 g/kg lw, delivered 7 or 12 days after the final intraruminal dose, did not lead to increased serum creatinine or urea concentrations, indicating that oral treatment had apparently resulted in an increased tolerance to the nephrotoxic principle(s) in N. ossifragum.

Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetes.

AIM: The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design. METHODS: Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 +/- 7 years (mean +/- s.d.), HbA1c 8.1 +/- 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo. RESULTS: Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 +/- 11/8 vs. 130/76 +/- 12/6 mmHg, p < 0.05). A significant decline in GFR (133 +/- 23 vs. 140 +/- 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 +/- 3.5 vs. 26.2 +/- 3.6%, p < 0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 +/- 0.53 vs. 2.98 +/- 0.93 mg/kg/min) and insulin-stimulated states (6.84 +/- 2.52 vs. 6.97 +/- 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 +/- 0.34 vs. 1.33 +/- 0.18, mg/kg/min, p < 0.01) and during insulin stimulation (2.89 +/- 0.75 vs. 2.40 +/- 0.62 mg/kg/min, p < 0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups. CONCLUSIONS: Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients.

Effects of the amylin analogue pramlintide on hepatic glucagon responses and intermediary metabolism in Type 1 diabetic subjects.

AIMS: Hepatic glycogen stores have been shown to be depleted, and glucagon stimulated hepatic glucose production reduced, in Type 1 diabetic subjects. Co-administration of amylin and insulin has been shown to replete hepatic glycogen stores in diabetic animal models. The aim of the present study was to investigate the effect of amylin replacement on hepatic glucagon responsiveness in humans. METHODS: Thirteen Type 1 diabetic men were studied in a double-blind, placebo-controlled, cross-over study after 4 weeks of subcutaneous pramlintide (30 microg q.i.d.) or placebo administration. Following an overnight fast, plasma glucose was kept above 5 mmol/l (baseline 210-240 min) with an insulin infusion rate of 0.25 mU x kg(-1) x min(-1). To control portal glucagon levels, somatostatin was infused at a rate of 200 microg/h. Basal growth hormone (2 ng x kg(-1) x min(-1)) and glucagon (0.7 ng x kg(-1) x min(-1)) were replaced. Glucagon infusion was increased to 2.1 ng x kg(-1) x min(-1) at 240-360 min (step 1) and to 4.2 ng x kg(-1) x min(-1) at 360-420 min (step 2). RESULTS: Baseline plasma glucose (5.59+/-0.16 vs. 5.67+/-0.25 mmol/l) and endogenous glucose production (EGP) (1.32+/-0.22 vs. 1.20+/-0.13 mg x kg(-1). min(-1)) were similar and the response to glucagon was unaffected by pramlintide (glucose: step 1; 6.01+/-0.31 vs. 5.94+/-0.38 mmol/l, step 2; 6.00+/-0.37 vs. 5.96+/-0.50 mmol/l, EGP: step 1; 1.91+/-0.18 vs. 1.83+/-0.15 mg x kg(-1) x min(-1), step 2; 2.08+/-0.17 vs. 1.96+/-0.16 ng x kg(-1) x min(-1), pramlintide vs. placebo). Glucose disposal rates were similar at baseline (2.44+/-0.13 vs. 2.28+/-0.09 mg x kg(-1) x min(-1), pramlintide vs. placebo) as well as during the glucagon challenge (P-values all > 0.2). CONCLUSIONS: Co-administration of pramlintide and insulin to Type 1 diabetic subjects for 4 weeks does not change the plasma glucose or endogenous glucose production response to a glucagon challenge, following an overnight fast. In addition, pramlintide administration does not appear to alter insulin-mediated glucose disposal.

Fluxes of radiocaesium in selected rural study sites in Russia and Ukraine.

Food production and food harvesting systems common in the areas contaminated by the Chernobyl accident in Russia and Ukraine can be grouped into three major categories: collective farm produce, private farming produce and foods collected from natural ecosystems. The contribution of each of these sources to radiocaesium intake by people living in rural settlements in the mid 1990s has been estimated at two major study sites, one in each country. The collective farm system provided the smallest contribution (7-14%) to the intake of radiocaesium at both sites. Natural food was the major contributor to intake at the Russian site (83%). Whereas private farm produce was the major contributor (68%) at the Ukrainian study site. The difference between the two sites was mainly because private milk production was stopped at the Russian site due to the contamination in 1986. A retrospective assessment of the situation 1 year after the accident shows that collective farming could have been a minor contributor to radiocaesium intake (8%), whilst private farming would have been the major contributor wherever private milk production and consumption continued. The extent to which inhabitants consume natural foods from forests has a considerable effect on their radiocaesium intake. The comparative importance of food products from natural ecosystems increases with time due to the long effective ecological half-lives of radiocaesium in unimproved pastures and forests. Estimation of the fluxes of radiocaesium from the different production and harvesting systems showed that the contribution from private farming and food harvesting from natural ecosystems may be significant, contributing 14-30% to the total fluxes of radiocaesium from an area even if the quantity of food produced in these systems is small. However, the major contributor to the flux exported from an area was the collective farming system, accounting for about 70-86% of the total.

The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus.

To explore further the effects of the human amylin analog pramlintide on overall glycemic control and postprandial responses of circulating glucose, glucagon, and metabolic intermediates in type 1 diabetes mellitus, 14 male type 1 diabetic patients were examined in a double-blind, placebo-controlled, crossover study. Pramlintide (30 microg four times daily) or placebo were administered for 4 weeks, after which a daytime blood profile (8:30 AM to 4:30 PM) was performed. Serum fructosamine was decreased after pramlintide (314+/-14 micromol/L) compared with placebo (350+/-14 micromol/L, P = .008). On the profile day, the mean plasma glucose (8.3+/-0.7 v 10.2+/-0.8 mmol/L, P = .04) and postprandial concentrations (incremental areas under the curve [AUCs] from 0 to 120 minutes) were significantly decreased during pramlintide administration (P < .01 for both) despite comparable circulating insulin levels (359+/-41 v 340+/-35 pmol/L). Mean blood glycerol values were reduced (0.029+/-0.004 v 0.040+/-0.004 mmol/L, P = .01) and blood alanine levels were elevated (0.274+/-0.012 v 0.246+/-0.008 mmol/L, P = .03) after pramlintide versus placebo. Blood lactate concentrations did not differ during the two regimens. During pramlintide administration, the AUC (0 to 120 minutes) for plasma glucagon after breakfast was diminished (P = .02), and a similar trend was observed following lunch. In addition, peak plasma glucagon concentrations 60 minutes after breakfast (45.8+/-7.3 v 72.4+/-8.0 ng/L, P = .005) and lunch (47.6+/-9.0 v 60.9+/-8.2 ng/L, P = .02) were both decreased following pramlintide. These data indicate that pramlintide (30 microg four times daily) is capable of improving metabolic control in type 1 diabetics. This may relate, in part, to suppression of glucagon concentrations. Longer-term studies are required to ascertain whether these findings are sustained over time.

Muscle mass and function in thyrotoxic patients before and during medical treatment.

OBJECTIVE: Development of muscle weakness and atrophy are well known complications of thyrotoxicosis, although little is known about its clinical course. The present longitudinal study was therefore undertaken to monitor muscle mass and strength before and during treatment of hyperthyroidism. DESIGN AND PATIENTS: Five patients (2 male, 3 female; Age 41 +/- 6 years; BMI 22.2 +/- 1.1 kg/m2) with newly diagnosed hyperthyroidism were studied with respect to muscle area, muscle strength, body composition and substrate metabolism at baseline and after 1, 3, 6, 9 and 12 months of treatment. MEASUREMENTS: Midthigh muscle areas were assessed by computed tomography (CT), while bioelectrical impedance analysis (BIA) was used for assessment of body composition. The isometric strength of the biceps brachialis and quadriceps muscles was assessed by means of a dynamometer and the maximal static ins- and ex-piratory mouth pressures were measured with a respiratory pressure module. RESULTS: Prior to treatment thyrotoxic patients all displayed elevated levels of total and free T3 and T4 together with suppressed TSH. BMI, fat mass and lean body mass increased significantly during the treatment period, while energy expenditure (EE) decreased. Thigh muscle areas increased by 24% (101.5 +/- 11.5 vs. 125.3 +/- 13.1 cm2, P < 0.05) from entry to peak. Peak time was 9 +/- 0.9 months. During treatment a significant (P < 0.01) increase in muscle strength was observed; arm capacity increased by 48%, while leg capacity increased by 51%. Peak time (months) was: Right arm: 8 +/- 3, left arm: 7 +/- 2, right leg: 5 +/- 3, left leg: 9 +/- 2. Respiratory muscle strength, expressed as maximal ins- or ex-piratory mouth pressure, was significantly impaired among patients at entry. A significant increase in inspiratory and expiratory strength was found from entry to peak (P < 0.05), as inspiratory strength increased by 35% and expiratory by 19%. Inspiratory strength peaked after 7 +/- 1 months, expiratory muscle strength after 6 +/- 1 months. CONCLUSIONS: In conclusion we find that in patients with thyrotoxicosis muscle mass is reduced by approximately 20% and muscle strength by approximately 40% and that between 5 and 9 months elapse before normal muscle mass and function are reestablished.

The use of hexacyanoferrates in different forms to reduce radiocaesium contamination of animal products in Russia.

Hexacyanoferrates have been identified as highly effective radiocaesium binders which effectively reduce radiocaesium uptake and transfer to milk and meat. In Russia a hexacyanoferrate called ferrocyn has been produced for use as a countermeasure. In 1989-1992, experiments were undertaken in Russia to study the effectiveness of four different ferrocyn materials as 137Cs binders, their potential toxicity, effect on production rates of cow milk, effect on animal health and ease of implementation in routine agricultural practice. Four different ferrocyn delivery forms have been used: 98% pure powder, sustained release rumen boli (15% ferrocyn), salt licks (10% ferrocyn) and sawdust with 10% ferrocyn adsorbed (bifege). In initial experiments with different cows, sheep and pigs these four ferrocyn materials were effective in reducing radiocaesium transfer to animal products. Daily administration of ferrocyn powder at a rate of 3-5 g per cow reduced 137Cs transfer by up to 90% in milk. One single administration of three boli per cow (containing 30 g ferrocyn per boli) reduced 137Cs transfer by 50-75% for a period of 2 months. Salt licks containing 10% ferrocyn (0.22 kg ferrocyn per 2.2 kg briquette provided once) reduced transfer of 137Cs up to twofold for up to 10 days whilst bifege, given at a rate of 30-60 g day-1 (3-6 g day-1 ferrocyn), reduced 137Cs transfer by 90-95%. However, large-scale application of these ferrocyn materials on collective and private farms in agricultural trials in 1994 resulted in a lower effectiveness. Therefore, in 1996 a comparative assessment of the application of the four ferrocyn forms was made under carefully controlled conditions. The results fully validated the previous experimental data, and showed the importance of meeting recommended procedures for treatment, particularly when hexacyanoferrates are administered on a day-to-day basis.

Generic relationship between calcium intake and radiostrontium transfer to the milk of dairy ruminants.

The hypothesis is tested that there is a generic relationship between the calcium intake and the transfer of radiostrontium to milk which can be used for all dairy ruminants. In addition to the daily calcium intake, the relationship also requires values for the strontium to calcium observed ratio, which describes the discrimination in transfer of the two elements to milk (a value of 0.11 is used), and the calcium concentration in milk. The relationship had previously only been validated for dairy cattle as there were insufficient data for other ruminant species. Here, we present recently available data for dairy goats, and also a limited amount of data for sheep derived from the literature. From the comparison between these data and predicted values, we conclude that it is possible to derive a generic model of the transfer of radiostrontium to the milk of dairy ruminants.

[Substrate metabolism in untreated and treated thyrotoxicosis]. / Substratomsaetning ved tyreotoksikose før og efter medicinsk behandling.

Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying biochemical mechanisms are incompletely understood. In order to elucidate these metabolic events further, we studied 12 patients with newly diagnosed diffuse (10 patients) or nodular (two patients) toxic goitre (ten women, two men; age 42.8 +/- 3.2 yr; BMI: 21.6 +/- 0.7 kg/m2) before ("TOX") and after ("TRE") 11.2 +/- 1.0 weeks treatment with methimazole and compared these patients to a control group ("CTR") of 11 subjects (nine women, two men; age 40.5 +/- 3.9 yr; BMI 22.5 +/- 1.0 kg/m2). All were studied for three hours in the basal state, using indirect calorimetry, isotope dilution for measurement of glucose turnover and the forearm technique for assessment of muscle metabolism. Prior to treatment patients with thyrotoxicosis were characterized by: Increased (p < 0.05) levels of T3 (3.75 +/- 0.23 [TOX], 1.89 +/- 0.08 [TRE] and 1.75 +/- 0.11 [CTR] nmol/l), resting energy expenditure (130.5 +/- 3.5 [TOX], 107.7 +/- 2.7 [TRE] and 106.3 +/- 3.1 [CTR] percent of predicted), protein oxidation (0.67 +/- 0.03 [TOX], 0.54 +/- 0.06 [TRE] and 0.46 +/- 0.05 [CTR] mg/kg/min), lipid oxidation (1.34 +/- 0.08 [TOX], 1.00 +/- 0.06 [TRE] and 1.02 +/- 0.04 [CTR] mg/kg/min), endogenous glucose production (2.51 +/- 0.13 [TOX], 1.86 +/- 0.12 [TRE] and 1.85 +/- 0.12 [CTR] mg/kg/min), non-oxidative glucose turnover (1.28 +/- 0.16 [TOX], 0.75 +/- 0.18 [TRE] and 0.71 +/- 0.11 [CTR] mg/kg/min) and a 50% increase in total forearm blood flow. Glucose oxidation (1.23 +/- 0.09 [TOX], 1.13 +/- 0.10 [TRE] and 1.13 +/- 0.09 [CTR] mg/kg/min), exchange of substrates in the muscles of the forearm and circulating levels of insulin, C-peptide, growth hormone or glucagon were not influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to seven of the patients for two days did not affect circulating levels of thyroid hormones, energy expenditure or glucose turnover rates. These results suggest that all major fuel sources contribute to the hypermetabolism of thyrotoxicosis and that augmented non-oxidative glucose metabolism may further aggravate the condition. All abnormalities recede with medical treatment of the disease.