Effects of glucagon-like peptide 1 (7–36 amide) on whole-body protein metabolism in healthy man

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-¹³C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P  < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO₂ production during GLP-1 administration ( P  < 0.0005). Plasma insulin increased after 3 h of GLP-1 infusion to 1486 ± 145 pmol L⁻¹ vs. 185 ± 12 pmol L⁻¹ for saline ( P  < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.     

Increased lymphatic vascular density is seen before colorectal cancers reach stage II and growth factor FGF‐2 is downregulated in tumor tissue compared with normal mucosa

Lymphangiogenesis is an important event in progression of colorectal cancer (CRC), and the estimated lymphatic vascular density (LVD) probably indicates facilitated lymphatic tumor cell invasion and metastasis. However, at what time point during tumor progression this process is triggered, is unclear. The aim of this study was twofold. Firstly, to examine LVD in paired samples of CRC tissue and normal mucosa with specific emphasis on possible difference in LVD between tumors stages II and III, and secondly, the expression of the lymphangiogenic growth factor fibroblast growth factor‐2 (FGF‐2). Eighteen patients were studied. Immunostaining for podoplanin was performed to highlight lymphatic vessels. FGF‐2 mRNA expression was determined by quantitative real‐time RT‐PCR, whereas protein expression was quantitatively assessed by densitometric analysis of Western blot signal intensity. The immunoblots were further validated by FGF‐2 immunostaining of histological sections. LVD was significantly increased in tumor tissue compared with the normal mucosa but no changes in LVD between stages II and III CRC was observed. FGF‐2 was found to be downregulated both at the mRNA and protein level in tumor tissues compared with normal mucosa. Lymphangiogenesis was triggered early in tumor development. An increased LVD was established before the tumor reached stage II. FGF‐2 was downregulated in tumor tissue. The importance of this finding remains unclear.     

C‐type natriuretic peptide in prostate cancer

C‐type natriuretic peptide (CNP) is expressed in the male reproductive organs in pigs. To examine whether the human prostate also expresses the CNP gene, we measured CNP and N‐terminal proCNP in prostate cancer tissue extracts and performed immunohistochemical biopsy staining. Additionally, proCNP‐derived peptides were quantitated in plasma from patients with prostate cancer. Blood was collected from healthy controls and patients before surgery for localized prostate cancer. Tissue extracts were prepared from tissue biopsies obtained from radical prostatectomy surgery. N‐terminal proCNP, proCNP (1–50) and CNP were measured in plasma and tissue extracts. Biopsies were stained for CNP‐22 and N‐terminal proCNP. Tissue extracts from human prostate cancer contained mostly N‐terminal proCNP [median 5.3 pmol/g tissue (range 1.0–12.9)] and less CNP [0.14 pmol/g tissue (0.01–1.34)]. Immunohistochemistry demonstrated the presence of the peptides in prostatic epithelial cells. The N‐terminal proCNP concentrations in plasma were marginally lower in patients with localized prostate cancer compared with control subjects [13.8 pmol/l (11.0–17.2) vs. 15.1 pmol/l (10.4–23.2), p=0.002] but not enough to justify the use of N‐terminal proCNP as a cancer marker. Further research is needed to establish whether measurement of proCNP‐derived peptides may offer clinical information.     

Urinary Excretion of Kallikrein before and after Operation for Aldosterone-producing Adenoma

ABSTRACT. Hesse B, Rasmussen S, Lund JO, Christensen P, Damkjær Nielsen M. (Department of Clinical Physiology, Glostrup Hospital, and Institute for Experimental Medicine, Copenhagen, Denmark.) Urinary excretion of kallikrein before and after operation for aldosterone-producing adenoma. Urinary kallikrein excretion (UKal), determined by the esterase method, was measured in 10 normotensive volunteers, 10 patients with essential hypertension and in 7 patients with primary aldosteronism before and after operative removal of the adenoma. UKal values were low in 5 of the patients with essential hypertension. Preoperative UKal values in the patients with aldosteronism did not differ significantly from those of the normal subjects, but decreased in all after operation in parallel with changes in urinary excretion of tetrahydroaldosterone and plasma aldosterone concentration. The study supports the assumption of an association between the renal kallikrein-kinin system and the mineralo-corticoid state in man.     

PSEUDOHYPOALDOSTERONISM Clinical, Biochemical and Morphological Studies in a Long-term Follow-up

ABSTRACT. A boy with pseudohypoaldosteronism was followed from birth to the age of 7 years. Failure to thrive, vomiting, dehydration, hyponatraemia and urinary sodium loss were prominent findings. Urinary excretion of corticosteroid metabolites was normal. Before treatment, excessively high plasma renin concentration was found, associated with a marked activation of aldosterone secretion. A renal biopsy showed pronounced hypertrophy of the juxtaglomerular apparatus. Persisting metabolic acidosis and an insufficient urinary acidifying capacity suggested the presence of distal renal tubular acidosis. Treatment with sodium bicarbonate and sodium chloride from 19 to 31 months of age resulted in normal growth and normal physical and mental development. The plasma electrolytes were normalized but a pronounced activation of the renin–aldosterone system persisted after therapy, and on sodium restriction this system responded with a considerable further activation.     

OBSERVER VARIATION IN THE SCINTIGRAPHIC DIAGNOSIS OF SOLITARY COLD THYROID LESIONS

In order to evaluate the reproducibility of the diagnosis of solitary cold thyroid lesions, two specialists in nuclear medicine and two specialists in endocrinology independently twice read 240 thyroid 99mTc pertechnetate scintigrams. No significant difference or interaction between the results obtained from the right and the left lobe was found. A solitary cold lesion was diagnosed in 100 of the 480 lobes; however, in only 30 did all four observers agree upon the diagnosis. Interobserver variation was determined by pairwise comparison of observers. The observed agreement was between 0.91 and 0.94. After adjusting for expected chance agreement, kappa values between 0.57 and 0.70 were found. Intraobserver variation was smaller than interobserver variation, revealing agreement rates of 0.93-0.96 and kappa values between 0.71 and 0.77. Agreement was related to large lesions, lesions located centrally in the lobe, and ovoid-shaped lesions. Clinicians should be aware to what extent they can rely on the information they use in their decisions. The considerable inconsistency in the evaluation of cold lesions on thyroid scintigrams should be taken into consideration, and calls in question the value of using thyroid scintigrams for deciding whether a patient should be referred for operation or biopsy.     

Energy intake and physical activity during pregnancy in relation to maternal fat accretion and infant birthweight

Summary. During the second pregnancy of 56 Swedish women resulting in a term birth, energy intake and physical activity were measured for 3 days at weeks 17 and 33. The values were related to maternal lean body mass, pregnancy weight gain, maternal fat accretion and infant birth-weight by multiple linear regression analyses. A significant regression coefficient was found for energy intake at week 17 on maternal fat accretion. Energy intake was not significantly correlated with infant birthweight, not even when physical activity and maternal lean body mass were taken into account. Thus in a well-nourished Swedish population, energy intake is positively related to maternal fat accretion but not to the birthweight of term infants.