Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats—part 1: morphological and functional aspects

Musculoskeletal injuries are very frequent and are responsible for causing pain and impairment of muscle function, as well as significant functional limitations. In the acute phase, the most prescribed treatment is with non-steroidal anti-inflammatory drugs (NSAIDs), despite their questionable effectiveness. However, the use of photobiomodulation therapy (PBMT) in musculoskeletal disorders has been increasing in the last few years, and this therapy appears to be an interesting alternative to the traditional drugs. The objective of the present study was to evaluate and compare the effects of PBMT, with different application doses, and topical NSAIDs, under morphological and functional parameters, during an acute inflammatory process triggered by a controlled model of musculoskeletal injury induced via contusion in rats. Muscle injury was induced by means of a single trauma to the animals’ anterior tibialis muscle. After 1 h, the rats were treated with PBMT (830 nm; continuous mode, with a power output of 100 mW; 3.57 W/cm²; 1 J–35.7 J/cm², 3 J–107.1 J/cm², and 9 J–321.4 J/cm²; 10, 30, and 90 s) or diclofenac sodium for topical use (1 g). Morphological analysis (histology) and functional analysis (muscle work) were performed, 6, 12, and 24 h after induction of the injury. PBMT, with all doses tested, improved morphological changes caused by trauma; however, the 9 J (321.4 J/cm²) dose was the most effective in organizing muscle fibers and cell nuclei. On the other hand, the use of diclofenac sodium produced only a slight improvement in morphological changes. Moreover, we observed a statistically significant increase of muscle work in the PBMT 3 J (107.1 J/cm²) group in relation to the injury group and the diclofenac group (p < 0.05). The results of the present study indicate that PBMT, with a dose of 3 J (107.1 J/cm²), is more effective than the other doses of PBMT tested and NSAIDs for topical use as a means to improve morphological and functional alterations due to muscle injury from contusion.     

Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats—part 2: biochemical aspects

Muscle injuries trigger an inflammatory process, releasing important biochemical markers for tissue regeneration. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice to promote pain relief due to muscle injury. NSAIDs exhibit several adverse effects and their efficacy is questionable. Photobiomodulation therapy (PBMT) has been demonstrated to effectively modulate inflammation induced from musculoskeletal disorders and may be used as an alternative to NSAIDs. Here, we assessed and compared the effects of different doses of PBMT and topical NSAIDs on biochemical parameters during an acute inflammatory process triggered by a controlled model of contusion-induced musculoskeletal injury in rats. Muscle injury was induced by trauma to the anterior tibial muscle of rats. After 1 h, rats were treated with PBMT (830 nm, continuous mode, 100 mW of power, 35.71 W/cm²; 1, 3, and 9 J; 10, 30, and 90 s) or diclofenac sodium (1 g). Our results demonstrated that PBMT, 1 J (35.7 J/cm²), 3 J (107.1 J/cm²), and 9 J (321.4 J/cm²) reduced the expression of tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2) genes at all assessed times as compared to the injury and diclofenac groups (p < 0.05). The diclofenac group showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). COX-2 protein expression remained unchanged with all therapies except with PBMT at a 3-J dose at 12 h (p < 0.05 compared to the injury group). In addition, PBMT (1, 3, and 9 J) effectively reduced levels of cytokines TNF-α, interleukin (IL)-1β, and IL-6 at all assessed times as compared to the injury and diclofenac groups (p < 0.05). Thus, PBMT at a 3-J dose was more effective than other doses of PBMT and topical NSAIDs in the modulation of the inflammatory process caused by muscle contusion injuries.     

Increased cytokine release from peripheral blood cells after acute stroke.

Cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha can play pathogenetic or protective roles in stroke. They are increased in the brain after experimental ischemia and in the CSF of patients with stroke. However, their presence in the periphery is still controversial. To determine the source and time-course of cytokines in blood of stroke patients, IL-6 and TNF-alpha release from blood cells and serum levels were determined in 40 patients on days 1 through 2, 4, 10, 30, and 90 after stroke. Twenty healthy age-matched volunteers were used as controls. IL-6 and TNF-alpha release from stimulated blood cells was increased in stroke patients, compared to controls. A peak response (+224%) was observed at day 4 for IL-6, while TNF-alpha release was largely and significantly increased (about three-fold compared to controls) from day 1 to 2 until day 90 after stroke. The increase in IL-6 release was significantly higher in ischemic, compared to hemorrhagic strokes, at days 1 and 4. Circulating IL-6 was increased at each time point. The ischemic processes in the CNS induces a long-lasting activation of IL-6 and TNF-alpha production in peripheral blood cells, which are a major source of serum cytokines after stroke.     

Maternal and placental risk factors associated with the development of necrotizing enterocolitis (NEC) and its severity

Background/purposeAntenatal factors play an important role in NEC. This study aimed to identify antenatal risk factors associated with the development of NEC, the role of the placental alterations, and the presence of prenatal signs predisposing to a severe NEC.Materials/methodsData of NEC patients including antenatal findings [preeclampsia, diabetes, cholestasis, abnormal antenatal umbilical artery flow (AAUF), clinical chorioamnionitis (CC), and histology of placentas] were compared to unaffected cases between 2002 and 2016 in a single center. Unaffected infants were matched for gestational age. Newborns with cardiovascular diseases were excluded. Bivariate and multivariate analyses were performed.ResultsWe identified 136 cases and 134 controls. The group of mothers of NEC-neonates had a higher prevalence of preeclampsia, CC, and AAUF. Histology of Placentas from 123/136 cases and 126/133 unaffected newborns was available. Chorioamnionitis was significantly more present in NEC cases vs controls. There weren't differences in vascular anomalies and necrotic alterations. Multivariate analysis identified AAUF, CC and histological chorioamnionitis (HC) as predictors of NEC. Bivariate tests show that preeclampsia and HC occurred more often in severe cases of NEC.ConclusionThis study suggests that AAUF, CC, and HC can independently predict the risk of NEC. Preeclampsia and HC seem associated to more severe cases.Level of evidenceIIIA.     

A new integrated dual time-point amyloid PET/MRI data analysis method

Purpose

In the initial evaluation of patients with suspected dementia and Alzheimer’s disease, there is no consensus on how to perform semiquantification of amyloid in such a way that it: (1) facilitates visual qualitative interpretation, (2) takes the kinetic behaviour of the tracer into consideration particularly with regard to at least partially correcting for blood flow dependence, (3) analyses the amyloid load based on accurate parcellation of cortical and subcortical areas, (4) includes partial volume effect correction (PVEC), (5) includes MRI-derived topographical indexes, (6) enables application to PET/MRI images and PET/CT images with separately acquired MR images, and (7) allows automation.

Methods

A method with all of these characteristics was retrospectively tested in 86 subjects who underwent amyloid (¹⁸F-florbetaben) PET/MRI in a clinical setting (using images acquired 90–110 min after injection, 53 were classified visually as amyloid-negative and 33 as amyloid-positive). Early images after tracer administration were acquired between 0 and 10 min after injection, and later images were acquired between 90 and 110 min after injection. PVEC of the PET data was carried out using the geometric transfer matrix method. Parametric images and some regional output parameters, including two innovative “dual time-point” indexes, were obtained.

Results

Subjects classified visually as amyloid-positive showed a sparse tracer uptake in the primary sensory, motor and visual areas in accordance with the isocortical stage of the topographic distribution of the amyloid plaque (Braak stages V/VI). In patients classified visually as amyloid-negative, the method revealed detectable levels of tracer uptake in the basal portions of the frontal and temporal lobes, areas that are known to be sites of early deposition of amyloid plaques that probably represented early accumulation (Braak stage A) that is typical of normal ageing. There was a strong correlation between age and the indexes of the new dual time-point amyloid imaging method in amyloid-negative patients.

Conclusions

The method can be considered a valuable tool in both routine clinical practice and in the research setting as it will standardize data regarding amyloid deposition. It could potentially also be used to identify early amyloid plaque deposition in younger subjects in whom treatment could theoretically be more effective.