BACKGROUND AND OBJECTIVE: Evidence from randomized controlled trials in early infancy suggest that prenatal supplementation with Ω-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease characterized by an immunoglobulin E (IgE) response. We aimed to determine whether protective effects were evident in the 6-year-old offspring of women supplemented with n-3 rich fish oil during pregnancy.

Our systematic review and meta-analysis was suggestive of benefits of increased n-3 LC-PUFAs in the maternal diet and outcomes of childhood allergic disease. However, due to the inconsistency in results, the hypothesis linking maternal n-3 LC-PUFA intake to childhood allergic disease cannot unequivocally be confirmed or rejected.

Senescence compromises the ability of chondrocytes to maintain and repair articular cartilage. We hypothesized that oxidative stress and telomere loss contribute to chondrocyte senescence. To test this hypothesis, we compared the growth of human articular cartilage chondrocytes incubated in 5% O2 and 21% O2. Cells grown in 5% O2 reached 60 population doublings (PD) before senescing, but growth in 21% O2 induced DNA damage and premature senescence at less than 40 PD. Human telomerase reverse transcriptase (hTERT)-transduction failed to prevent chondrocyte senescence in 21% O2, but allowed 1 of 3 chondrocyte strains to exceed 90 PD in 5% O2. These results show that oxidative stress causes premature chondrocyte senescence. They may help explain the increased risk of osteoarthritis with age and after joint trauma and inflammation, and suggest that minimizing oxidative damage will help produce optimal results for chondrocyte transplantation.

Objective Although the majority of the ATP in chondrocytes is made by glycolysis rather than by oxidative phosphorylation in mitochondria there is evidence to suggest that reactive oxygen species produced by mitochondrial electron transport help to maintain cellular redox balance in favor of glycolysis. The objective of this study was to test this hypothesis by determining if rotenone, which inhibits electron transport and blocks oxidant production inhibits glycolytic ATP synthesis. Design Bovine osteochondral explants were treated with rotenone, an electron transport inhibitor; or oligomycin an ATP synthase inhibitor; or 2-fluoro-2-deoxy-D-glucose, a glycolysis inhibiter; or peroxide, an exogenous oxidant; or mitoquinone, a mitochondria-targeted anti-oxidant. Cartilage extracts were assayed for ATP, NAD+, and NADH, and culture medium was assayed for pyruvate and lactate after 24 hours of treatment. Imaging studies were used to measure superoxide production in cartilage. Results Rotenone and 2-fluoro-2-deoxy-D-glucose caused a significant decline in cartilage ATP (p < 0.001). In contrast, ATP levels were not affected by oligomycin. Peroxide treatment blocked rotenone effects on ATP, while treatment with MitoQ significantly suppressed ATP levels. Rotenone and 2-fluoro-2-deoxy-D-glucose caused a significant decline in pyruvate, but not in lactate production. NADH:NAD+ ratios decreased significantly in both rotenone and 2-fluoro-2-deoxy-D-glucose-treated explants (p < 0.05). Rotenone also significantly reduced superoxide production Conclusions These findings showing a link between glycolysis and electron transport are consistent with previous reports on the critical need for oxidants to support normal chondrocyte metabolism. They suggest a novel role for mitochondria in cartilage homeostasis that is independent of oxidative phosphorylation.

A model of gram-negative lethal endotoxin shock, involving continuous peritoneal infusion of lipopolysaccharide (LPS), has been applied to wild-type (WT) mice and mice with a severe deficiency of endothelial protein C receptor (EPCR ␦/␦ ). The survival of EPCR ␦/␦ mice was significantly diminished as compared to WT mice after administration of LPS via this route. Heart rates and central blood pressures also were significantly more depressed in EPCR ␦/␦ mice, indicating that the receptor-based protein C (PC) pathway functions in regulation of hemodynamic properties in the mouse. Further, heart muscle damage was more severe in EPCR ␦/␦ mice as compared to WT mice after endotoxin administration, as revealed by the more elevated plasma myoglobin levels in EPCR ␦/␦ mice and by microscopic examination of stained heart sections. Neutrophil infiltration was more pronounced in heart tissue of EPCR ␦/␦ mice, perhaps in response to the greatly increased expression level of the chemokine, MIP-2, which also significantly more up-regulated in the LPS-treated EPCR ␦/␦ mouse cohort. In conclusion, a severe deficiency of EPCR adversely affects survival of mice subjected to continuous infusion of endotoxin, via contributions of more responsive hemodynamic and cardiac alterations, thus suggesting that, among its other functions, the PC-based receptor system has a cardioprotective role after acute inflammatory challenge.

The results of this study introduce a novel participant in the asthmatic response and indicate that factor Xa functions in airway remodeling in asthma by stimulating mucin production, through regulation of amphiregulin expression and collagen deposition.

BackgroundRandomized controlled trials of prenatal omega (ω-3) long chain polyunsaturated fatty acid (LCPUFA) supplementation are suggestive of some protective effects on allergic sensitization and symptoms of allergic disease in childhood. Due to the nature of the atopic march, investigation of any effects of this prenatal intervention may be most informative when consistently assessed longitudinally during childhood.MethodsFollow-up of children (n = 706) with familial risk of allergy from the Docosahexaenoic Acid to Optimize Mother Infant Outcome (DOMInO) trial. The intervention group received fish oil capsules (900 mg of ω-3 LCPUFA) daily from <21 weeks’ gestation until birth; the control group received vegetable oil capsules without ω-3 LCPUFA. This new longitudinal analysis reports previously unpublished data collected at 1 and 3 years of age. The allergic disease symptom data at 1, 3 and 6 years of age were consistently reported by parents using the "International Study of Asthma and Allergies in Childhood" (ISAAC) questionnaire. Sensitization was determined by skin prick test to age specific, common allergen extracts.ResultsChanges over time in symptoms of allergic disease with sensitization (IgE-mediated) and sensitization did not differ between the groups; interaction p = 0.49, p = 0.10, respectively. Averaged across the 1, 3 and 6-year assessments, there were no significant effects of prenatal ω-3 LCPUFA supplementation on IgE-mediated allergic disease symptoms (adjusted relative risk 0.88 (95% CI 0.69, 1.12), p = 0.29) or sensitization (adjusted relative risk 0.97 (95% CI 0.82, 1.15), p = 0.76). Sensitization patterns to common allergens were consistent with the atopic march, with egg sensitization at 1 year strongly associated with house dust mite sensitization at 6 years, (p < 0.0001).DiscussionAlthough there is some evidence to suggest that maternal supplementation with 900mg ω-3 LCPUFA has a protective effect on early symptoms of allergic disease and sensitization in the offspring, we did not observe any differences in the progression of disease over time in this longitudinal analysis. Further investigation into the dose and timing of ω-3 LCPUFA supplementation, including long-term follow up of children using consistent outcome reporting, is essential to determine whether this intervention may be of benefit as a primary prevention strategy for allergic disease.ConclusionMaternal supplementation with 900 mg of ω-3 LCPUFA did not change the progression of IgE-mediated allergic disease symptoms or sensitization throughout childhood from 1 to 6 years.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN); DOMInO trial ACTRN12605000569606, early childhood allergy follow up ACTRN12610000735055 and 6-year allergy follow up ACTRN12615000498594.

Tissue engineering potentially offers new treatments for disorders of the temporomandibular joint which frequently afflict patients. Damage or disease in this area adversely affects masticatory function and speaking, reducing patients' quality of life. Effective treatment options for patients suffering from severe temporomandibular joint disorders are in high demand because surgical options are restricted to removal of damaged tissue or complete replacement of the joint with prosthetics. Tissue engineering approaches for the temporomandibular joint are a promising alternative to the limited clinical treatment options. However, tissue engineering is still a developing field and only in its formative years for the temporomandibular joint. This review outlines the anatomical and physiological characteristics of the temporomandibular joint, clinical management of temporomandibular joint disorder, and current perspectives in the tissue engineering approach for the temporomandibular joint disorder. The tissue engineering perspectives have been categorized according to the primary structures of the temporomandibular joint: the disc, the mandibular condyle, and the glenoid fossa. In each section, contemporary approaches in cellularization, growth factor selection, and scaffold fabrication strategies are reviewed in detail along with their achievements and challenges.