SpecialEscherichia coli serotypes among enterotoxigenic strains from diarrhoea in adults and children

106 enterotoxigenicEscherichia coli strains from children and adults from many parts of the world were serotyped for O and H antigens. Some OH types,i.e. O6H16, O8H9, O15H11, O25H42, O78H11 and O78H12, were found repeatedly from different geographical locations. Some of these OH serotypes were only found rarely among more than 20000E. coli strains collected over many years from different locations and sources. It is suggested that these special OH serotypes represent clones which have been selected to the special conditions in the small intestine and selected to carry the plasmids necessary to provoke diarrhoea.     

Increased prevalence and altered species composition of filamentous fungi in respiratory specimens from cystic fibrosis patients

Filamentous fungi cultured from respiratory tract specimens submitted to the department of clinical microbiology, Aarhus University Hospital, during 2010 were identified by morphology and by internal transcribed spacer (ITS) sequencing. Of 343 fungal isolates, discrepancies between identification methods were observed for four isolates (1.2%), while identification to species was achieved only with ITS sequencing for 16 isolates (4.7%). Filamentous fungi were isolated from 15% of cystic fibrosis (CF) respiratory samples in contrast to 2% of non‐CF samples. From CF patients, a total of nine different species were found in 188 samples from 48 patients, whereas from non‐CF patients, 24 different species were found in 155 samples from 111 patients. CF was associated with a significant overrepresentation of Aspergillus fumigatus and Scedosporium species; in contrast, the frequency of Penicillium spp. and other putative contaminants were significantly increased in non‐CF patients. The altered species variation of filamentous fungi in CF respiratory specimens is contradictory to a scenario of incidentally inhaled spores, trapped in the viscous airway mucus of these patients and subsequently expectorated; rather, our data most likely reflect both an increased prevalence and an increased proportion of truly colonizing fungi in this patient group.     

The effect of growth hormone on the insulin-like growth factor system during fasting

The present study investigates the possible stimulatory effect of endogenous GH on IGF and IGF-binding protein (IGFBP) levels during fasting. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state; 2) after 40 h of fasting; 3) after 40 h of fasting with somatostatin suppression of GH; and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement. The two somatostatin experiments were identical in terms of hormone replacement (except for GH). Short-term fasting led to a 50% reduction in free IGF-I. The reduction in free IGF-I was paralleled by an increase in IGFBP-1, an increase in the complex formation of IGFBP-1 and IGF-I, and a modest reduction in IGFBP-3 proteolysis. GH deprivation during fasting led to a 35% reduction in total IGF-I and a 70% reduction in free IGF-I. GH replacement increased free and total IGF-I to levels similar to those observed during plain fasting and decreased IGFBP-1, however, without affecting IGFBP-1-bound IGF-I. Finally, IGFBP-3 proteolysis was slightly increased by GH replacement. In conclusion, the major new finding of the present study is that the GH hypersecretion seen during short-term fasting is not merely secondary to a reduction in IGF bioactivity.     

Renal insulin-like growth factor I and growth hormone receptor binding in experimental diabetes and after unilateral nephrectomy in the rat

Summary We have measured specific binding of insulin-like growth factor I and growth hormone to renal plasma membranes from control, streptozotocin-diabetic, insulin-treated diabetic, uninephrectomised and combined diabetic-uninephrectomised male Wistar rats. Control, insulin-treated and uninephrectomised rats had similar body weights after 7 days (243±2 g), whereas diabetic and diabetic-uninephrectomised animals were significantly lighter (219±4 and 203±4 g, p<0.05). Blood glucose concentrations were similar in the diabetic and diabetic-uninephrectomised animals (around 26 mmol/l) but significantly lower in the insulin-treated group. Right kidney weight increased by 14% in the control, insulin-treated and sham-nephrectomised animals, by 33% in the diabetic group, 38% in the nephrectomised animals and 60% in the diabetic-nephrectomised group. The renal content of insulin-like growth factor I was similar and stable in the control, insulin-treated and sham-nephrectomised animals (208±14 ng/g wet weight) but rose to a peak of 669±35 ng/g in the diabetic group (p<0.001), 871±34 ng/g in the nephrectomised animals (p<0.001) and 1012±43 ng/g in the diabetic-uninephrectomised group (p<0.001). Maximum binding of insulin-like growth factor I fell on day 1 in the diabetic group (8.3±1.4 vs 5.2±0.71× 10^– mol/l; p<0.01) but thereafter was identical to control animals. In the insulin-treated animals, maximum binding rose to 11.0±1.1×10^–11 mol/l, significantly different from control and diabetic animals (p<0.01). Growth hormone binding fell acutely in both the diabetic and diabetic-nephrectomised animals (3.13±0.58 and 2.83±0.21 vs 7.77±0.68×10^–12 mol/l; p<0.001 for both). Following uninephrectomy, maximum binding of insulin-like growth factor I and growth hormone was unchanged from control values. We conclude that the rise in renal content of insulin-like growth factor I which precedes the compensatory growth seen after induction of diabetes and uninephrectomy is not due to alterations in insulin-like growth factor I receptor binding and is independent of growth hormone binding.     

Insulinotropic actions of intravenous glucagon-like peptide-1 (GLP-1) [7–36 amide] in the fasting state in healthy subjects

GLP-1 (7–36 amide) stimulates insulin and suppresses glucagon secretion in normal subjects and may, in pharmacological doses, normalize hyperglycaemia in type 2 diabetic patients. It is not known whether such pharmacological doses can actually lower blood glucose to hypoglycaemic levels. Therefore, in seven normal fasting subjects, GLP-1 (7–36 amide) was infused intravenously at 0.3, 0.9 and 2.7 pmol/kg per min for 30 min each. The plasma concentration of GLP-1 (7–36 amide) increased dose-dependently, but insulin secretion (insulin, C-peptide) was stimulated only marginally. Glucagon was slightly suppressed, and plasma glucose was reduced, but not into the hypoglycaemic range. In conclusion, when plasma glucose concentrations are in the normal fasting range, GLP-1 (7–36 amide) is not able to stimulate insulin secretion to a degree that causes hypoglycaemia. This should limit the risk of hypoglycaemic responses when GLP-1 (7–36 amide) is administered in pharmacological doses to reduce hyperglycaemia in type 2 diabetic patients.     

GLP-1 does not acutely affect insulin sensitivity in healthy man

Summary Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7–36 amide) may have the direct effect of increasing insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyperinsulinaemic (0.8 mU · kg⁻¹ · min⁻¹), euglycaemic (5 mmol/l) clamp. Somatostatin (450 μg/h) was infused to suppress endogenous insulin secretion, and growth hormone (3 ng · kg⁻¹ · min⁻¹) and glucagon (0.8 ng · kg⁻¹ · min⁻¹) were infused to maintain basal levels. GLP-1 (50 pmol · kg⁻¹ · h⁻¹) or 154 mmol/l NaCl (placebo) was infused after 3 h of equilibration, i.e. from 180-360 min. GLP-1 infusion resulted in GLP-1 levels of approximately 40 pmol/l. Plasma glucose, insulin, growth hormone, and glucagon levels were similar throughout the clamps. The rate of glucose infusion required to maintain euglycaemia was similar with or without GLP-1 infusion (7.69±1.17 vs 7.76±0.95 mg · kg⁻¹ · min⁻¹ at 150–180 min and 8.56±1.13 vs 8.55±0.68 mg · kg⁻¹ · min⁻¹ at 330–360 min) and there was no difference in isotopically determined hepatic glucose production rates (− 0.30±0.23 vs −0.16±0.22 mg · kg⁻¹ · min⁻¹ at 330–360 min). Furthermore, arteriovenous glucose differences across the forearm were similar with or without GLP-1 infusion (1.43±0.23 vs 1.8±0.29 mmol/l), (ANOVA;p>0.60, in all instances). In conclusion, GLP-1 (7–36 amide) administered for 3 h, leading to circulating levels within the physiological range, does not affect insulin sensitivity in healthy man.     

Variation between sheep in renal excretion of [14C]allantoin

The objectives of the present study were to investigate the recovery of [14C]allantoin in urine of sheep dosed intravenously and degradation of allantoin by rumen micro-organisms. The recovery of [14C]allantoin in the urine of eight sheep was measured during three periods in two experiments. Individual values of [14C]allantoin recovery varied from 66 to 95 % (mean value 83 (se 1.6) %). The recovery of [14C]allantoin showed no relation to the level of feed intake. There was some evidence that glomerular filtration rate was an important factor affecting the amount of urinary allantoin recovered in one experiment. Incomplete recovery of plasma [14C]allantoin in the urine indicated losses of plasma [14C]allantoin via non-renal routes. This is supported by the disappearance of 14C from rumen contents incubated in vitro with [14C]allantoin for 48 h (88 %) and the presence of 14C in saliva in vivo from sheep sampled after dosing with [14C]allantoin. However, the amount of 14C activity in the saliva was very low (equivalent to only 1.5 % of the total dose in sheep producing saliva at a rate of 15 litres/d). The proportion of renal and non-renal excretion of purine derivatives was found to be unpredictable both between and within individual animals. The factors responsible for this variability need to be identified, and existing models of excretion of purine derivatives may need to be modified accordingly to improve their accuracy of prediction. A single intravenous injection of [4,5-14C]allantoin provides a simple alternative to infusion methods used to measure the proportion of plasma allantoin excreted in the urine of sheep. Using this method it may be feasible to validate PD excretion models in other ruminant livestock.     

Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study

BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than the normal upper range and is accompanied by adverse effects such as joint pain and glucose intolerance. MATERIALS AND METHODS: We performed a 16-week open-labelled prospective pilot study in six male HALS patients using a s.c. low-dose hGH, 0.7 mg day(-1), aiming to examine the impact on total and free IGF-I and fat distribution. Glucose metabolism was examined by oral glucose tolerance tests and hyperinsulinaemic euglycaemic clamps. RESULTS: Total IGF-I increased twofold (P < 0.01) and free IGF-I increased 2.5-fold (P < 0.01) to the level of the normal upper range. HDL-cholesterol increased (P = 0.01). Patients reported improvements of lipodystrophy, which was supported by a decreased waist-to-thigh ratio (P = 0.01), and waist-to-hip ratio (P = 0.06). Ratio of peripheral to trunk soft tissue mass increased (P = 0.01, measured by dual-energy X-ray absorptiometry scans) and a trend towards reduction in percentage of trunk fat was suggested (P = 0.12). Total fat mass, exercise capacity, glucose tolerance, glucose disposal rate and immune status, respectively, did not change (all P > 0.5). The patients did not complain of arthralgia or other known GH-related side-effects. CONCLUSIONS: Sixteen weeks' treatment of lipodystrophic HIV-infected patients with hGH, 0.7 mg day(-1), increased total and free IGF-I twofold and appeared safe and tolerable. The potential of low-dose hGH in the treatment of HIV-lipodystrophy awaits examination by placebo-controlled, randomized trials.