Application of Stem Cells Shows Antiinflammatory Effect in an Irradiated Random Pattern Flap Model.

BACKGROUND: In reconstructive surgery, local flaps might develop tissue necrosis or partial flap loss especially after previous irradiation, which may be necessary in many tumor entities. The application of stem cells seems promising to improve flap perfusion and might be a possible solution to optimize flap survival. METHODS: Twenty rats received harvesting of bilateral random pattern fasciocutaneous flaps. The right flaps received 20 Gy ionizing radiation 4 weeks prior to the surgery, while the left flaps served as the non-irradiated control. After flap harvest, four different stem cell mixtures (5 × 106 ASC, ASC-HUVEC, MSC, MSC-HUVEC) were applied under both right and left flaps using 1 mL fibrin glue as the delivery vehicle. Flap size and its necrotic area were examined clinically. Two weeks after the surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis (Interleukin 6, HIF-1α and VEGF), were performed. RESULTS: Application of ASCs, ASCs-HUVECs and MSCs resulted in a lower number of CD68-stained cells compared to the no cell group. The expression of Hif1α was higher in the ASC group compared to those in the MSC and previously treated no cell groups. Treatment with MSCs and MSCs-HUVECs prevented shrinking of the flaps in this series. CONCLUSION: Application of ASCs, MSCs and ASCs-HUVECs was shown to have an antiinflammatory effect. Treatment with MSCs and MSCs-HUVECs can prevent early shrinking of the flaps.

Heart rate and heart rate variability in subjectively reported insomnia.

According to epidemiological studies, insomnia is associated with cardiovascular mortality. However, it is yet to be determined whether this link is mediated by known cardiovascular risk factors. The current study aimed at investigating the association between primary insomnia, defined as subjectively reported sleep disturbance in the absence of any other pathology or substance intake, and alterations in polysomnographically determined nocturnal heart rate (HR) and heart rate variability (HRV). A total of 4,581 nocturnal short-term electrocardiographic recordings (5 min each) from 104 participants (58 with primary insomnia, 46 healthy controls) were evaluated for HR as well as for time and frequency domain measures of HRV. In the primary insomnia group, we found a lower wake-to-sleep HR reduction and a lower standard deviation of RR intervals (SDNN) compared to healthy controls. However, between-group differences in resting HR were not found, and previous results of an increase in sympathovagal balance and a decrease in parasympathetic nocturnal activity in objectively determined insomnia could not be confirmed in our sample of self-report insomnia patients. When restricting our analyses to insomnia patients with objectively determined short sleep duration, we found reduced parasympathetic activity as indicated by decreased high frequency power of HRV, as well as decreased root mean square of successive RRI differences (RMSSD) and percentage of successive RRIs that differ by more than 50 ms (pNN50) values. A lower wake-to-sleep HR reduction and alterations in HRV variables might, at least partially, mediate the increased rates of cardiovascular morbidity and mortality observed in insomnia patients.

Different role of CD30 in the development of acute and chronic airway inflammation in a murine asthma model.

CD30 is a costimulatory molecule of the TNF receptor superfamily, expressed on activated T and B cells. Previously, we have shown in a murine asthma model the crucial role of CD30 signaling for the development of this Th2-cell-mediated disease. In the present study, we investigated the role of CD30 in the maintenance of the immune response. In contrast to the acute model, in the chronic model CD30(-/-) mice developed a severe asthma-like phenotype with eosinophilic inflammation and high serum IgE levels. Collagen content, ECM protein deposition and proliferation of smooth muscle cells as signs for airway remodeling were equally increased in both CD30(-/-) and WT mice. Reduced expression of the costimulatory molecule OX40 on CD3(+) T cells in the acute and up-regulation in the chronic model indirectly supported a compensatory role of OX40 for CD30 signaling. In accordance, application of agonistic OX40 antibody restored the asthma phenotype in CD30(-/-) mice in the acute model, whereas chronic airway inflammation was reduced in the presence of an inhibitory anti-OX40 ligand antibody. These data demonstrate that the crucial role of CD30 signaling in the development of acute asthma may be taken over by other costimulatory molecules like OX40 after long-term exposure to the antigen.

Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera.

Purpose: Posterior scleral remodeling accompanies myopia. In guinea pigs developing myopia, the region around the optic nerve (peripapillary zone, PPZ) rapidly expands followed by inhibition in eye size in the periphery. We studied the differential gene expression in the sclera that accompanies these changes. Methods: Guinea pigs were form-deprived (FD) for 2 weeks to induce myopia, while the fellow eye served as a control. After 2 weeks, the PPZ and the peripheral temporal sclera were isolated in representative animals to extract the RNA. RNA sequencing was undertaken using an Illumina HiSeq 2000, with differential expression analyzed using Voom and pathways analyzed using the Ingenuity Pathway Analysis tool. RNA from additional PPZ and peripheral temporal sclera in FD and fellow eyes was used for validation of gene expression using quantitative real-time PCR (qRT-PCR). Results: In myopic sclera, 348 genes were differentially expressed between PPZ and the peripheral temporal region (corrected P < 0.05), of which 61 were differentially expressed in the PPZ between myopic and control eyes. Pathway analyses of these gene sets showed the involvement of Gαi signaling along with previously reported gamma-aminobutyric acid (GABA) and glutamate receptors among numerous novel pathways. The expression pattern of three novel genes and two myopia-related genes was validated using qRT-PCR. Conclusions: Gene expression changes are associated with the rapid elongation that occurs around the optic nerve region during the development of myopia. A prominent change in Gαi signaling, which affects cAMP synthesis and thus collagen levels, may be critical in mediating the regional changes in myopic sclera.