Mineral and electrolyte metabolism最新文献

Mitogenic growth factors stimulate cell growth by initiating a signaling cascade leading to the activation of the cyclin-dependent kinases (cdks), phosphorylation of pRb, and subsequent entry of the cell into the S phase. Transforming growth factor-beta (TGF-beta) is a potent antimitogen in a wide variety of cells and is postulated to inhibit cell cycle progression by blocking the late G1 activation of the cdks, thereby preventing pRb phosphorylation and S phase entry. The loss of TGF-beta sensitivity in many transformed cells coupled with recent data demonstrating a deregulation of cyclins, cdks, and cdk inhibitors in many types of cancer has attracted much attention to the molecular mechanism of TGF-beta-mediated growth arrest. Despite these recent advances, further research is required to elucidate how these effects of TGF-beta on the cyclins, cdks, and cdk inhibitors are linked to the TGF-beta receptor complex and the Smad proteins.

The relationships between tubular hypertrophy/hyperplasia, procollagen alpha1(IV) mRNA levels, and the development of tubular basement membrane thickening were studied in male Sprague-Dawley rats subjected to subtotal renal ablation and sacrificed 2 or 15 days later. Tubular hypertrophy and hyperplasia were demonstrable at 2 days, however no increment in procollagen alpha1 (IV) mRNA levels was discerned at that time, demonstrating a dissociation between mRNA levels for classical type IV collagen and tubular enlargement. At 15 days, tubular procollagen alpha1(IV) mRNA levels did increase approximately 2-fold (p < 0.002), localizing predominantly in proximal tubules in the deep cortex and outer medullary stripe. At this time point, there was still no significant correlation to tubular enlargement, but there was a significant correlation to tubular basement membrane thickening (r = 0.89, p < 0.01). These studies demonstrated that an increase in mRNA for classical type IV collagen is not required for the development of hypertrophy, and that the increment is a better marker for matrix expansion than it is for hypertrophy.

Chronic renal failure is associated with an abnormal growth hormone/insulin-like growth factor-1 axis. In addition, nutritional status strongly regulates this axis. Because these hormones are involved in growth in children and maintenance of a normal body composition in adults, experimental and clinical studies have tested the metabolic effects of these recombinant growth factors. Various conditions in which these growth factors have been administered have been reported, such as the recovery of acute renal failure, protein metabolism in chronic renal failure, growth improvement in uremic children, the increase in renal function in nondialyzed uremic patients, and the potential treatment of malnutrition in adult maintenance dialysis patients.

Diabetes mellitus with onset during childhood usually presents as overt ketoacidemia. Pediatricians now inquire specifically about diabetes mellitus in children with nonspecific signs of illness and perform urinary dipstick testing. The present study was therefore performed to assess the possible influence of this strategy on the initial presentation and management of diabetes mellitus. The charts of 61 consecutive children with newly diagnosed diabetes mellitus (positive glucosuria and ketonuria and capillary glucose >14 mmol/l), who had been admitted between 1991 and 1996 at the Department of Pediatrics, University of Bern, Switzerland, were therefore reviewed. Twenty-six out of the 61 patients were nonacidemic (blood pH 7.36 or more). Children with and without acidemia did not differ with respect to age, history of polydipsia and polyuria, plasma glucose and circulating glycated hemoglobin A1c. The degree of dehydration and the amount of fluid required for its correction and the total insulin dosage were more prominent in the group of patients with acidemia. The study demonstrates that childhood diabetes mellitus is nowadays often recognized as nonacidemic hyperglycemia and that in these patients a reduced initial fluid repair and total insulin dosage is recommended.

Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis.