Rapamycin is a potent immunosuppressant with antitumoral properties widely used in the field of renal transplantation. To test the hypothesis that the antiproliferative and antiangiogenic activity of rapamycin interferes with the normal structure and function of growth plate and impairs longitudinal growth, 4-week-old male rats (n = 10/group) receiving 2 mg/kg per day of intraperitoneal rapamycin (RAPA) or vehicle (C) for 14 days were compared. Rapamycin markedly decreased bone longitudinal growth rate (94 ± 3 vs. 182 ± 3 μm/day), body weight gain (60.2 ± 1.4 vs. 113.6 ± 1.9 g), food intake (227.8 ± 2.6 vs. 287.5 ± 3.4 g), and food efficiency (0.26 ± 0.00 vs. 0.40 ± 0.01 g/g). Signs of altered cartilage formation such as reduced chondrocyte proliferation (bromodeoxiuridine-labeled cells 32.9 ± 1.4 vs. 45.2 ± 1.1%), disturbed maturation and hypertrophy (height of terminal chondrocytes 26 ± 0 vs. 29 ± 0 μm), and decreased cartilage resorption (18.7 ± 0.5 vs. 31.0 ± 0.8 tartrate-resistant phosphatase alkaline reactive cells per 100 terminal chondrocytes), together with morphological evidence of altered vascular invasion, were seen in the growth plate of RAPA animals. This study indicates that rapamycin can severely impair body growth in fast-growing rats and distort growth-plate structure and dynamics. These undesirable effects must be kept in mind when rapamycin is administered to children.

Growth retardation is a major manifestation of chronic kidney disease (CKD) in pediatric patients. The involvement of the various pathogenic factors is difficult to evaluate in clinical studies. Here, we present an experimental model of adenine-induced CKD for the study of growth failure. Three groups ( n = 10) of weaning female rats were studied: normal diet (control), 0.5% adenine diet (AD), and normal diet pair fed with AD (PF). After 21 days, serum urea nitrogen, creatinine, parathyroid hormone (PTH), weight and length gains, femur osseous front advance as an index of longitudinal growth rate, growth plate histomorphometry, chondrocyte proliferative activity, bone structure, aorta calcifications, and kidney histology were analyzed. Results are means ± SE. AD rats developed renal failure (serum urea nitrogen: 70 ± 6 mg/dl and creatinine: 0.6 ± 0.1 mg/dl) and secondary hyperparathyroidism (PTH: 480 ± 31 pg/ml). Growth retardation of AD rats was demonstrated by lower weight (AD rats: 63.3 ± 4.8 g, control rats: 112.6 ± 4.7 g, and PF rats: 60.0 ± 3.8 g) and length (AD rats: 7.2 ± 0.2 cm, control rats: 11.1 ± 0.3 cm, and PF rats: 8.1 ± 0.3 cm) gains as well as lower osseous front advances (AD rats: 141 ± 13 μm/day, control rats: 293 ± 16 μm/day, and PF rats: 251 ± 10 μm/day). The processes of chondrocyte maturation and proliferation were impaired in AD rats, as shown by lower growth plate terminal chondrocyte height (21.7 ± 2.3 vs. 26.2 ± 1.9 and 23.9 ± 1.3 μm in control and PF rats) and proliferative activity index (AD rats: 30 ± 2%, control rats: 38 ± 2%, and PF rats: 42 ± 3%). The bone primary spongiosa structure of AD rats was markedly disorganized. In conclusion, adenine-induced CKD in young rats is associated with growth retardation and disturbed endochondral ossification. This animal protocol may be a useful new experimental model to study growth in CKD.

The contribution of human metapneumovirus (hMPV) relative to that of other respiratory viruses as a cause of respiratory infections in children less than 1 year old has been evaluated. From October 2003 to April 2004, nasopharyngeal samples from 211 children less than 1 year old were analyzed to detect respiratory viruses. Respiratory syncytial virus (RSV) was the predominant virus isolated (96 children [45.5%]), followed by influenza A virus, parainfluenza virus, adenovirus, cytomegalovirus, and herpes simplex virus type 1, which were only occasionally detected. From January 2004 to April 2004, a nested retrotranscription-PCR, using in-house primers directed to the matrix protein gene of hMPV, was carried out on samples in which no other viruses were detected. hMPV was detected in 18 (16.2%) children, indicating that this virus was the second-most-frequent cause of viral respiratory infections in children less than 1 year old. The rate of hospitalization for RSV- and hMPV-infected children was higher than 75%. While RSV had a peak from December to February, hMPV was increasingly detected from January to April. The mean age of hMPV-infected children (6.44 ± 3.64 [mean ± standard deviation] months) was significantly higher than that of RSV-infected children (3.99 ± 2.96 [mean ± standard deviation] months). On the other hand, 64.3% of the RSV-infected children and 12.5% of the hMPV-infected children showed high levels of C-reactive protein. Although several authors have reported that clinical symptoms of hMPV-positive patients mirrored those of RSV-positive patients, differences between the two viruses can be found.