Structure and expression of the rat neuropeptide Y gene.

Neuropeptide Y is a 36-amino acid peptide that is abundant throughout the mammalian nervous system. It belongs to the same family of carboxyl-terminally amidated peptides as pancreatic polypeptide and peptide YY. We describe here the gene encoding the rat neuropeptide Y precursor. The gene spans 7.2 kilobase pairs and contains four exons. The exon organization is identical to the pancreatic polypeptide gene, although the amino acid sequences of the neuropeptide Y and pancreatic polypeptide precursors differ extensively. The predicted amino acid sequence of mature rat neuropeptide Y is identical to the human sequence. Also the sequence of the 30-amino acid carboxyl-terminal peptide of preproneuropeptide Y is highly conserved, which suggests that it is functionally important. Two neuropeptide Y alleles were found to differ at nine positions in 2.5 kilobase pairs at the 5' portion of the gene. No exon difference was found. One nucleotide substitution close to the gene promoter may influence the regulation of expression. Neuropeptide Y mRNA was found in all rat brain subregions tested, which shows that neuropeptide Y is synthesized throughout the brain. Developmentally, mRNA was detected in the rat brain as early as embryonic day 16 and increased rapidly to adult levels. The level of neuropeptide Y mRNA was also studied in several rat peripheral organs. Unexpectedly high levels were observed in heart and spleen. This mRNA may be synthesized in intrinsic ganglia and non-neuronal cells, respectively.     

Reduction of protein intake decreases glomerular filtration rate in young Type 1 (insulin-dependent) diabetic patients mainly in hyperfiltering patients

Summary The influence of different protein intake on renal function was studied in 16 Type 1 (insulin-dependent) diabetic patients, aged 15–23 years, with onset of diabetes before puberty and with a duration of diabetes between 5 and 20 years. The glomerular filtration rate, renal plasma flow, albumin excretion rate, and blood pressure were examined in a cross-over randomised order after 10 days on isocaloric diets with either 10% (i.e. 0.9±0.06 g·kg^–1·day^–1) or 20% (1.9±0.1 g·kg^–1·day^–1) of the calories as protein, the latter being equal to the recommended diet. Dietary compliance was evaluated using fractional phosphate excretion and overnight urea excretion. Glomerular filtration rate was lower after the low-protein diet compared to the usual protein diet (p<0.001). Patients with glomerular filtration rate above +2 SD of the normal mean on the usual protein diet (n=6) exhibited the steepest fall in glomerular filtration rate with a mean decrease of 20ml/min compared to 7 ml/min in those with initially normal glomerular filtration (p=0.01). Filtration fraction tended to decrease on low protein diet, more so in initially hyperfiltering patients (p=0.09). Renal plasma flow remained unchanged. In patients with elevated glomerular filtration rate on usual protein diet, albumin excretion rate and systolic, but not diastolic blood pressure, were decreased on low protein diet (p=0.03 and p=0.01, respectively) but not in initially normal-filtering patients. Mean blood glucose and serum fructosamine were unchanged on both diets. In conclusion, low protein diet decreases glomerular filtration rate independently of glycaemic control in young Type 1 diabetic patients and more so in hyperfiltering patients. This decline in glomerular filtration rate is accompanied by a decrease in albumin excretion rate and systolic blood pressure in hyper-filtering patients.     

Oral budesonide is as effective as oral prednisolone in active Crohn's disease

Background—The use of corticosteroids in activeCrohn's disease often becomes limited by side effects. Budesonide is apotent corticosteroid with low systemic bioavailability due to anextensive first pass liver metabolism.
Aims—To compare the efficacy and safety of twodosage regimens of budesonide and prednisolone in patients with activeCrohn's disease affecting the ileum and/or the ascending colon.
Patients and methods—One hundred and seventy eightpatients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn'sDisease Activity Index (CDAI) of 150 or less.
Results—After eight weeks of treatment, remissionoccurred in 60% of patients receiving budesonide once daily orprednisolone and in 42% of those receiving budesonide twice daily(p=0.062). The presence of glucocorticoid associated side effects wassimilar in all groups; however, moon face was more common in theprednisolone group (p=0.0005). The highest frequency of impairedadrenal function, as measured by a short ACTH test, was found in theprednisolone group (p=0.0023).
Conclusions—Budesonide CIR, administered at 9 mgonce daily or 4.5 mg twice daily, is comparable to prednisolone ininducing remission in active Crohn's disease. The single doseadministration is as promptly effective as prednisolone and representsa simpler and safer therapeutic approach, with a considerable reduction in side effects.

Keywords:adrenal function; CDAI; glucocorticoid; glucocorticoid associated side effects