The Effect of Low-Intensity Pulsed Ultrasound on Bone Regeneration and the Expression of Osterix and Cyclooxygenase-2 during Critical-Size Bone Defect Repair.

Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that utilizes low-intensity pulsed waves. Its effect on bones that heal by intramembranous ossification has not been sufficiently investigated. In this study, we examined LIPUS and the autologous bone, to determine their effect on the healing of the critical-size bone defect (CSBD) of the rat calvaria. The bone samples underwent histological, histomorphometric and immunohistochemical analyses. Both LIPUS and autologous bone promoted osteogenesis, leading to almost complete closure of the bone defect. On day 30, the bone volume was the highest in the autologous bone group (20.35%), followed by the LIPUS group (19.12%), and the lowest value was in the control group (5.11%). The autologous bone group exhibited the highest intensities of COX-2 (167.7 ± 1.1) and Osx (177.1 ± 0.9) expression on day 30. In the LIPUS group, the highest intensity of COX-2 expression was found on day 7 (169.7 ±1.6) and day 15 (92.7 ± 2.2), while the highest Osx expression was on day 7 (131.9 ± 0.9). In conclusion, this study suggests that LIPUS could represent a viable alternative to autologous bone grafts in repairing bone defects that are ossified by intramembranous ossification.

Upper-lower limb and breathing exercise program for improving sleep quality and psychological status in multiple sclerosis: a pilot randomized controlled trial.

PURPOSE: To examine the feasibility and possible effect of an 8-week exercise program on sleep quality, insomnia and psychological distress in individuals with multiple sclerosis (MS). METHODS: Twenty-four individuals with MS were recruited into a controlled pre-post feasibility study and divided into 2 groups: exercise (n = 13; Expanded Disability Status Scale (EDSS): 1.0-7.5) and a related control group with no exercise (n = 11; EDSS: 1.0-7.0). The exercise group performed combined upper limb, lower limb and breathing exercises in a controlled group (2d/week, 60 min/session) for 8 weeks. Participants were administered measures to evaluate sleep quality (Pittsburgh Sleep Quality Index, PSQI), insomnia severity (Insomnia Severity Index, ISI), psychological distress (Clinical Outcomes in Routine Evaluation-Outcome Measure, CORE-OM) and additionally impact of fatigue (Modified Fatigue Impact Scale, MFIS) after 8-weeks. RESULTS: Insomnia severity measured with ISI (F(1;22)=5.95, p = 0.023, η p 2 = 0.213, 90% CI = 0.02-0.42) and psychological distress measured with the CORE-OM (F(1;22)=4.82, p = 0.039, η p 2 = 0.179, 90% CI = 0.01-0.40) showed statistically significant group-by-time interaction. Sleep quality measured with the PSQI showed statistically significant group-by-time interaction only in an aspect of daytime sleep dysfunction (F(1;22)=5.33, p = 0.031, η p 2 = 0.195, 90% CI = 0.01-0.40). The fatigue impact measured with the MFIS showed statistically significant group-by-time interaction in physical (F(1;22)=6.80, p = 0.016, η p 2 = 0.236, 90% CI = 0.02-0.44) and cognitive aspects (F(1;22)=9.12, p = 0.006, η p 2 = 0.293, 90% CI = 0.05-0.49), and total score (F(1;22)=11.29, p = 0.003, η p 2 = 0.339, 90% CI = 0.08-0.52). CONCLUSIONS: Our 8-week program reduced insomnia severity, psychological distress and some aspects of fatigue (physical; cognitive; total), and improved sleep quality in an aspect of daytime sleep dysfunction in a small group of individuals with MS. Good feasibility and significant positive changes from baseline warrant further exploratory work.

Serum Levels of Inflammatory and Fibrotic Cytokines in Patients with Carpal Tunnel Syndrome and Hip Osteoarthritis.

A certain percentage of carpal tunnel syndrome (CTS) is associated with inflammatory conditions. Osteoarthritis (OA) increases the risk of CTS, and both diseases are common in the general population. Moreover, OA and CTS are often present in the same patients. Since inflammation and fibrosis are found in both conditions, the question is whether circulating inflammatory cytokines and cytokines involved in fibrosis in OA and CTS patients could serve as indicators of coexisting CTS and OA pathology. This investigation was performed on 31 CTS patients, 29 hip OA patients, and 15 healthy volunteers. Blood samples were collected, and serum levels of TGF-ß1, BMP-7, IL-1ß, and TNFα were measured using the ELISA method. The statistical analysis was performed to reveal the most significant differences in the serum levels of these cytokines. Statistical significance was set at p-values ≤ 0.05. The serum level of TGF-ß1 was the highest in CTS patients (16.36 pg/mL) and significantly different compared to OA and healthy control. Analysis of the cytokine serum level in the subdivided group revealed that serum levels of TGF-ß1 and BMP-7 were significantly higher in CTS+/OA+ patients as well as BMP-7 in the OA+/CTS+ group. There was no significant difference in serum levels of the inflammatory cytokines TNFα and IL-1ß among all groups. This study showed that in the end stage of CTS and OA, serum levels of inflammatory cytokines (IL1-ß and TNFα) were not altered, while the serum levels of TGF-ß1 and BMP-7 were significantly higher, especially in patients with coexisting OA and CTS. These findings suggest the possible values of TGF-ß1 and BMP-7 as a predictive factor for the comorbidity of CTS and OA.

Gender-Related Differences in BMP Expression and Adult Hippocampal Neurogenesis within Joint-Hippocampal Axis in a Rat Model of Rheumatoid Arthritis.

BMPs regulate synovial quiescence and adult neurogenesis in the hippocampus in non-stress conditions. However, changes in BMP expression that are induced by inflammation during rheumatoid arthritis (RA) have not yet been reported. Here, we show that signalling with synovial BMPs (BMP-4 and -7) mediates the effect of systemic inflammation on adult neurogenesis in the hippocampus during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Moreover, we show gender differences in BMP expressions and their antagonists (Noggin and Gremlin) during PIA and their correlations with the clinical course and IL-17A and TNF-α levels in serum. Our results indicate gender differences in the clinical course, where male rats showed earlier onset and earlier recovery but a worse clinical course in the first two phases of the disease (onset and peak), which correlates with the initial increase of serum IL-17A level. The clinical course of the female rats worsened in remission. Their prolonged symptoms could be a reflection of an increased TNF-α level in serum during remission. Synovial inflammation was greater in females in PIA-remission with greater synovial BMP and antagonist expressions. More significant correlations between serum cytokines (IL-17A and TNF-α), and synovial BMPs and their antagonists were found in females than in males. On the other hand, males showed an increase in hippocampal BMP-4 expression during the acute phase, but both genders showed a decrease in antagonist expressions during PIA in general. Both genders showed a decrease in the number of Ki-67+ and SOX-2+ and DCX+ cells and in the ratio of DCX+ to Ki67+ cells in the dentate gyrus during PIA. However, in PIA remission, females showed a faster increase in the number of Ki67+, SOX-2+, and DCX+ cells and a faster increase in the DCX/Ki67 ratio than males. Both genders showed an increase of hippocampal BMP-7 expression during remission, although males constantly showed greater BMP-7 expression at all time points. Our data show that gender differences exist in the BMP expressions in the periphery-hippocampus axis and in the IL-17A and TNF-α levels in serum, which could imply differences in the mechanisms for the onset and progression of the disease, the clinical course severity, and adult neurogenesis with subsequent neurological complications between genders.