Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610C Mice With and Without Weight‐Bearing Exercise

Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder associated with reduced bone mineral density and skeletal fragility. Bone is inherently mechanosensitive, with bone strength being proportional to muscle mass and strength. Physically active healthy children accrue more bone than inactive children. Children with type I OI exhibit decreased exercise capacity and muscle strength compared with healthy peers. It is unknown whether this muscle weakness reflects decreased physical activity or a muscle pathology. In this study, we used heterozygous G610C OI model mice (+/G610C), which model both the genotype and phenotype of a large Amish OI kindred, to evaluate hindlimb muscle function and physical activity levels before evaluating the ability of +/G610C mice to undergo a treadmill exercise regimen. We found +/G610C mice hindlimb muscles do not exhibit compromised muscle function, and their activity levels were not reduced relative to wild‐type mice. The +/G610C mice were also able to complete an 8‐week treadmill regimen. Biomechanical integrity of control and exercised wild‐type and +/G610C femora were analyzed by torsional loading to failure. The greatest skeletal gains in response to exercise were observed in stiffness and the shear modulus of elasticity with alterations in collagen content. Analysis of tibial cortical bone by Raman spectroscopy demonstrated similar crystallinity and mineral/matrix ratios regardless of sex, exercise, and genotype. Together, these findings demonstrate +/G610C OI mice have equivalent muscle function, activity levels, and ability to complete a weight‐bearing exercise regimen as wild‐type mice. The +/G610C mice exhibited increased femoral stiffness and decreased hydroxyproline with exercise, whereas other biomechanical parameters remain unaffected, suggesting a more rigorous exercise regimen or another exercise modality may be required to improve bone quality of OI mice. © 2015 American Society for Bone and Mineral Research.     

Evaluation of nutrient intakes of rural elders in eleven southern states based on sociodemographic and life style indicators

Nutrient intakes of 2893 rural free-living elderly persons aged 65 and older residing in 11 southern states were studied. Data being reported herein include food intake by a 24-hr recall, meal preparation settings and use of dietary supplements and socioeconomic variables. High percentages of monthly income were spent on food, particularly among black females and participation rates in community service programs, including senior centers and home delivered meals, were low. Caloric intakes by rural males were 1603 and 1365 kcal, respectively, for whites and blacks; 1270 and 1259 kcal for white and black females, respectively. Means for most of the nutrients equalled or exceeded the RDAs for this age group except energy and calcium. Age had little influence on nutrient intake. Race showed as a significant determinant on the nutrient intake index computed from 11 key nutrient intakes; however, the significant effect of race disappeared when either income or educational level was used as covariate. Thus, the disparities in intakes between the black and white elders were due partly to income rather than race. Of these rural elders, 46.5% consumed meals alone. Eating alone per se did not have a significant impact on nutrient consumption, but 35.2% of those eating alone indicated that they ate less, had fewer choices or ate more. Dietary supplements were used by 33.9% of rural elders, and their intakes of several nutrients were higher than by nonusers. More effort by community services to reach rural elders is needed, particularly those in the low socioeconomic spectrum.     

Production of beta-defensin antimicrobial peptides by maxillary sinus mucosa.

beta-Defensins are endogenous cationic peptides with broad-spectrum antimicrobial activity that are thought to play a role in the innate immune response. Two human beta-defensins, beta-defensin-1 (HBD-1) and beta-defensin-2 (HBD-2), have been identified. These peptides have recently been characterized in several human tissues. The presence of these peptides in the paranasal sinuses has not been investigated. We examined maxillaary sinus secretions from six patients with sinusitis and 10 patients without signs, symptoms, or radiologic evidence of sinus disease for the presence of beta-defensins. Cationic peptides were extracted from antral lavage specimens and examined for the presence of HBD-1 and HBD-2 by Western blot. Normal maxillary sinus epithelium was obtained from two patients and analyzed by RT-PCR for the presence of HBD-1 and HBD-2 mRNA. Tissue immunostaining for the two peptides was also used. Western blot analysis identified HBD-1 in two of 10 patients in the control group and in three of six patients in the sinusitis group. HBD-2 was identified in one of 10 patients in the control group and in four of six patients in the sinusitis group. RT-PCR revealed HBD-1 mRNA in one of two normal controls tested. Immunostaining localized HBD-1 and HBD-2 to the epithelial cell cytoplasm. This is the first demonstration of HBD-1 and HBD-2 production in the paranasal sinuses. In the present study, HBD-1 and HBD-2 were detected more frequently in the maxillary sinus fluid of patients with inflamed sinuses than in normal controls.     

Novispirin G10-induced lung toxicity in a Klebsiella pneumoniae infection model

Mammalian cathelicidins are a class of innate antimicrobial peptides isolated from leukocytes and epithelial cells that aid host defense against bacterial infections. Synthetic analogs of cathelicidins offer the promise of potent broad-spectrum antimicrobial efficacy. We developed a combined lung infection and ex vivo whole-blood assay model to characterize the toxicity and efficacy of synthetic cathelicidin-derived peptides. Male C57BL/6 mice were administered saline or Klebsiella pneumoniae by intratracheal instillation. Five hours later, the Klebsiella-infected mice were instilled with saline, tobramycin (1 mg/kg of body weight or 10 mg/kg), novispirin G10 (0.4 mg/kg), or a combination of tobramycin (1 mg/kg) and G10 (0.4 mg/kg). At 24 h, bronchoalveolar lavage fluid (BAL) was collected for analysis of culturable bacteria and for markers of inflammation and lung toxicity. Blood samples were analyzed for circulating cytokines. Recovery of Klebsiella from the lung, recruitment of neutrophils, and production of interleukin-6 (IL-6) in BAL samples were highly correlated (r=0.68 and 0.84, respectively; P<0.01). Animals treated with G10 or G10 plus tobramycin had increased hemoglobin (P<0.001) and protein (P<0.001) levels compared to those for Klebsiella-infected or tobramycin-alone-treated animals. The levels of circulating IL-6 in mice infected with Klebsiella were 1000- to 10,000-fold higher than in the noninfected controls. The highest levels of IL-6 were measured in mice given G10 alone or in combination with tobramycin. These studies demonstrated that G10 was relatively nontoxic in saline-treated mice but was highly toxic in mice infected with Klebsiella. This finding establishes the importance of investigating candidate antimicrobial agents in an in vivo infection model.     

Chronic airway obstruction in children: evaluation with cine-CT

The radiographic diagnosis of airway lesions, especially laryngomalacia and tracheomalacia, often is imprecise. Endoscopy, which allows detailed examination of the upper airway, is an invasive procedure requiring sedation or anesthesia. A prospective study was undertaken to show the value of cine-CT (Imatron) scanning in diagnosing airway lesions in children. Eleven patients, aged 10 days to 4 years old, with a history of stridor were evaluated by both cine-CT and flexible fiberoptic endoscopy. Cine-CT studies of 12 children imaged for other reasons and without clinical evidence of airway disease served as controls to assess normal airway motion. Endoscopy identified 13 abnormalities, 11 of which were identified by cine-CT. Cine-CT has the capacity to image common causes of chronic stridor in children. It is rapid, noninvasive, and requires no sedation in most children. Although additional work is needed to clarify the role of cine-CT, this study suggests that cine-CT is a sensitive and specific imaging technique for evaluation of chronic stridor in infants and children.