Renal insufficiency-induced bone loss is associated with an increase in bone size and preservation of strength in rat proximal femur

Chronic renal insufficiency (CRI) results in phosphate retention and secondary hyperparathyroidism, the treatment of which is largely based on the use of calcium salts as phosphate binders. Advanced CRI causes bone fragility, but information about bone geometry and strength in moderate CRI is scarce. We assigned 39 8-week-old male Sprague-Dawley rats to sham-operation (Sham) or 5/6 nephrectomy (NTX). Four weeks later, the rats were randomized to 0.3% calcium (Sham, NTX) or 3.0% calcium diet (Sham + Calcium, NTX + Calcium). After 8 weeks, the animals were sacrificed, plasma samples collected, and femora excised for neck and midshaft analyses: dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and biomechanical testing. The NTX increased plasma urea and PTH 1.6-fold and 3.6-fold, respectively, whereas high calcium intake suppressed PTH to 30% of controls. Total femoral bone mineral content decreased (-6.3%) in the NTX group, while this deleterious effect was reversed by high calcium diet. In the site-specific analysis of the femoral neck, the volumetric bone density (-6.5%) was decreased in the NTX group but not NTX + Calcium group. However, in the nephrectomized rats, there was also a concomitant increase in the cross-sectional area (+15%), and, despite the decrease in bone density, the mechanical strength of the femoral neck was maintained. In the midshaft, NTX decreased cortical volumetric bone density (-1.2%), but similar to the femoral neck, no differences were found in the mechanical strength. In conclusion, a decrease in bone mass in moderate experimental CRI was associated with a concomitant increase in bone size, and maintenance of mechanical competence. Although high calcium diet suppressed plasma PTH to under normal physiological levels, it prevented the CRI-induced loss of bone mass without an adverse influence on bone strength.     

Dicarboxylic acid bis(L-prolyl-pyrrolidine) amides as prolyl oligopeptidase inhibitors

New dicarboxylic acid bis(L-prolyl-pyrrolidine) amides were synthesized, and their inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. As compared with earlier described prolyl oligopeptidase inhibitors, these new compounds have in common an L-prolyl-pyrrolidine moiety, but the typical lipophilic acyl end group is replaced by another L-prolyl-pyrrolidine moiety connected symmetrically with a short dicarboxylic acid linker. These compounds are a new type of peptidomimetic prolyl oligopeptidase inhibitor.     

All snoring is not adenoids in young children

OBJECTIVE: To determine the prevalence of snoring in young children and to assess age, growth, previous surgery therapy, respiratory problems and sleep-related symptoms in relation to child's snoring, and to evaluate the relationship between child's snoring and parents' snoring and smoking. CHILDREN AND METHODS: A cross-sectional study evaluated 2100 children 1-6 years of age in Helsinki, Finland. Child's frequency of snoring on a five-point scale (never to every night) and age, height, weight and body mass index, previous adenotonsillectomies, tympanostomies, allergic rhinitis and respiratory infections were determined as was frequency of parental snoring and smoking. Sleep problems were determined based on Finnish or Swedish modified version of the sleep disturbance scale for Children. RESULTS: Of the 2100 eligible children, 1471 (71%) returned questionnaires. Children always or often snoring numbered 92 (6.3%), sometimes snoring, 183 (12.4%), and never or occasionally snoring, 1196 (81.3%). No difference in age (p=0.06) or gender (p=0.39) existed between snorers and non-snorers. History of previous adenotonsillectomies (p<0.001), allergic rhinitis (p<0.001), recurrent respiratory infections (p<0.001), and otitis media (p<0.001) were more common among snorers than among occasional or never-snorers. Nocturnal symptoms such as breathing problems, sleep hyperhydrosis, sleep-wake transition disorders, and daytime somnolence were associated with children's snoring. Frequency of children's snoring was also associated with parental snoring (p<0.001) and smoking (p<0.001). CONCLUSIONS: Snoring is common among young children and is associated with previous adenotonsillectomy, allergic rhinitis, respiratory infections, nocturnal symptoms, and parents' snoring and smoking. The high prevalence of snoring among children with adenotonsillectomy raises the question whether adenotonsillectomy alone is adequate treatment for snoring in young children.     

Hydrocortisone and indomethacin negatively modulate EGF-R signaling in human fetal intestine

Concomitant use of hydrocortisone and the nonspecific cyclo-oxygenase (COX)-inhibitor indomethacin increases the risk for intestinal perforations in preterm infants. We determined whether this was associated with insufficient epidermal growth factor receptor (EGF-R) signaling. We tested the effect of EGF, hydrocortisone, and indomethacin on its activation, cell proliferation and migration, COX-2 expression, and prostaglandin E2 (PGE2) production. Human small intestine epithelial cell line FHsInt74 and EGF-R-deficient mice [EGF-R (-/-)] were used as models. The data revealed that EGF-R signaling had a bimodal positive effect on fetal enterocyte: 1) it increased cell proliferation and migration synergistically with hydrocortisone and 2) up-regulated COX-2 mRNA expression and subsequent PGE2 production. Correlating with this, COX-2 protein expression was down-regulated in EGF-R (-/-) intestine. Despite a positive effect on cell proliferation with EGF, hydrocortisone blunted the stimulatory effect of EGF on COX-2 expression and PGE2 production. Addition of indomethacin even further inhibited the EGF-stimulated PGE2 synthesis. The data suggest that concomitant use of indomethacin and hydrocortisone on preterm infants, who physiologically synthesize only low levels of EGF-R ligands, may lead to intestinal problems related to failure in cytoprotective and regenerative events.     

Sleep problems and daytime tiredness in Finnish preschool‐aged children‐a community survey

Background Sleep is important to the well‐being and development of children. Specially, small children are vulnerable to the effects of inadequate sleep. However, not much is known about the frequency of all types of sleep problems and daytime tiredness in preschool‐aged children. Objective To evaluate the prevalence of a wide spectrum of sleep problems, daytime tiredness and associations between these in 3‐ to 6‐year‐old Finnish children. Methods A population‐based study where parents of 3‐ to 6‐year‐old children (n= 904) living in Helsinki filled in the Sleep Disturbance Scale for Children (SDSC). Results Of the children, 45% had at least one sleep‐related problem occurring at least three times a week: 14.1% were unwilling to go to bed, 10.2% had difficulties in falling asleep, 10.2% had bruxism, 6.4% sleep talking, 2.1% sleep terrors, 8.2% had sleep‐related breathing problem, 11.2% had excessive sweating while falling asleep and 12.9% excessive sweating during sleep. Age and gender were related to phenotype of the sleeping problems. In multiple regression analysis, the difficulties in initiating and maintaining sleep were most strongly associated with tiredness in the morning and during the day. Conclusions Different types of sleep problems are frequent in preschool‐aged children. Poor sleep quality is associated with morning and daytime tiredness. In screening for sleep problems in children, attention should be paid not only to sleep amount but also to sleep quality.