Exercise during energy restriction mitigates bone loss but not alterations in estrogen status or metabolic hormones

Summary

Energy restriction causes bone loss, increasing stress fracture risk. The impact of exercise during energy restriction on bone and endocrine factors is examined. Exercise with energy restriction did not influence endocrine factors, but did mitigate some bone loss seen with energy restriction in sedentary rats.

Introduction

Chronic dietary energy restriction (ER) leads to bone loss and increased fracture risk. Strictly controlled trials of long-term ER with and without vigorous exercise are required to determine whether exercise loading can counterbalance ER-induced bone loss. The aim of this current project is to elucidate the impact of exercise and ER on bone mass, estrogen status, and metabolic hormones.

Methods

Twenty-four virgin female Sprague-Dawley rats (n?=?8/group) were divided into three groups—ad libitum fed?+?exercise (Adlib?+?EX), 40 % energy restricted?+?exercise (ER?+?EX), and 40 % energy restricted?+?sedentary (ER?+?SED). Energy availability between ER groups was equal. Treadmill running was performed 4 days/week at 70 % VO_2max for 12 weeks.

Results

Fat and lean mass and areal bone mineral density (aBMD) were lower after 12 weeks (p?<?0.05) for ER?+?EX vs Adlib?+?EX, but ER?+?EX aBMD was higher than ER?+?SED (p?<?0.0001). Serum leptin and a urinary estrogen metabolite, estrone-1-glucuronide (E1G), were lower at week 12 (p?=?0.0002) with ER, with no impact of exercise. Serum insulin-like growth factor I (IGF-I) declined (p?=?0.02) from baseline to week 12 in both ER groups. ER?+?EX exhibited higher cortical volumetric bone mineral density (vBMD) at the midshaft tibia (p?=?0.006) vs ER?+?SED.

Conclusion

Exercise during ER mitigated some, but not all, of the bone loss observed in sedentary ER rats, but had little impact on changes in urinary E1G and serum IGF-I and leptin. These data highlight the importance of both adequate energy intake and the mechanical loading of exercise in maintaining bone mass.

     

IL-13 induces expression of CD36 in human monocytes through PPARgamma activation

The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)gamma pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARgamma pathway was demonstrated using transfection of a PPARgamma expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARgamma, and in peritoneal macrophages from PPARgamma-conditional null mice. We also show that CD36 induction by IL-13 via PPARgamma is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-Delta12,14-prostaglandin J2, an endogenous PPARgamma ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARgamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARgamma in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARgamma ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.     

Inactivated Francisella tularensis live vaccine strain protects against respiratory tularemia by intranasal vaccination in an immunoglobulin A-dependent fashion

Francisella tularensis is a gram-negative intracellular bacterium that is considered to be a potential category A biological weapon due to its extreme virulence. Although vaccination with the attenuated live vaccine strain (LVS) of F. tularensis can protect against lethal challenge, use of inactivated or subunit forms as vaccine candidates for induction of protective antibody responses has not been fully evaluated. In the present study, we examined whether immune protection in the lung could be stimulated by intranasal administration of inactivated LVS together with interleukin-12 (IL-12) as an adjuvant. LVS was inactivated by heat, paraformaldehyde treatment, or exposure to UV, and inactivation of the preparations was confirmed by assessing bacterial growth and the survival of mice after direct inoculation. We found that mucosal vaccination with inactivated LVS provided 90 to 100% protection in mice after lethal intranasal challenge with 10(4) CFU of LVS, and this protection was dependent on inclusion of exogenous IL-12 during vaccine administration. Survival of vaccinated mice after live bacterial challenge was correlated with reduced bacterial burden, decreased pulmonary inflammation, increased serum antibody titers, and lower levels of gamma interferon (IFN-gamma), tumor necrosis factor alpha, and IL-6 in the lungs, livers, and spleens. Whereas NK cells were primarily responsible for the production of IFN-gamma in unvaccinated, challenged animals, vaccinated mice had increased levels of lung IFN-gamma+ CD4+ T cells after challenge. Significantly, mice genetically deficient in immunoglobulin A (IgA) expression were unable to survive lethal challenge after vaccination. These results are the first results to demonstrate that IgA-mediated protection against lethal respiratory tularemia occurs after mucosal vaccination with inactivated F. tularensis LVS.     

Detection of Rickettsia rickettsii and Bartonella henselae in Rhipicephalus sanguineus ticks from California

Sixty-two questing adult Rhipicephalus sanguineus (Latreille) ticks were collected by direct removal from blades of turfgrass and adjacent concrete walkways at a suburban home in Riverside County, CA, and tested for the presence of Rickettsia, Bartonella, and Ehrlichia DNA. Polymerase chain reaction (PCR) was used to amplify fragments of the 17-kDa antigen gene and the rOmpA gene of the spotted fever group rickettsiae. One male tick contained R. rickettsii DNA; its genotype differed from R. rickettsii isolates found in Montana and Arizona that cause Rocky Mountain spotted fever and from Hlp#2 and 364D serotypes. One male tick and one female tick contained B. henselae DNA. No Ehrlichia platys or Ehrlichia canis DNAs were detected using nested PCR for their 16S rRNA genes. These findings extend the area where Rickettsia rickettsii may be vectored by Rh. sanguineus. Rh. sanguineus also may be infected with Bartonella henselae, a human pathogen that is typically associated with fleas and causes cat scratch disease.     

Bone formation after sinus augmentation with engineered bone

Objectives: The aim of the following investigation was to quantify the resorption rate of tissue-engineered bone grafts in the maxillary sinus using volume measurements. MATERIAL AND METHODS: Sinus floor augmentation using autologous bone grafts from the iliac crest (n=17, group 1) was compared with commercially produced transplants of human cells seeded on polyglycolid-polylactid (PLGA) scaffolds (Oral Bone) (n=14, group 2). RESULTS: The total resorption rate for autologous transplants 3 months post operation was 29%, while the tissue-engineered bone showed a resorption rate of 90%. The autologous bone had a bone density of up to 266-551 Hounsfield units (HU), while sufficient mineralization of tissue-engineered bone was found in only one case (152 HU). CONCLUSION: In this clinical study, the use of autologous cancellous bone grafts in sinus augmentation was more reliable than scaffolds containing cultured osteoblasts. Further tissue-engineered bone transplants should be examined to draw general conclusions about the use of tissue-engineered grafts compared with autologous bone grafts for maxillary sinus augmentation.