Reed et al. Spinal Mobilization Prevents NGF-Induced PainConclusion: SM prevents the development of local (trunk) NGF-induced mechanical hyperalgesia and distant (hindpaw) allodynia, in part, through attenuation of CGRP expression in lumbar DRG sensory neurons. NGF decreases rat exploratory behavior and increases spontaneous pain for which passive SM acts to mitigate these painrelated behavioral changes. These initial study findings suggest that beginning daily SM soon after injury onset might act to minimize or prevent the development of LBP by reducing production of pain-related neuropeptides.
We compared the effects of an 8‐week iso‐caloric high‐protein (HP) diet versus a combined exercise regimen (Comb‐Ex) in individuals with long‐standing spinal cord injury (SCI). Effects on metabolic profiles, markers of inflammation, and signaling proteins associated with glucose transporter 4 (GLUT‐4) translocation in muscles were evaluated. Eleven participants with SCI completed the study (HP diet: n = 5; Comb‐Ex: n = 6; 46 ± 8 years; C5‐T12 levels; American Spinal Injury Association Impairment Scale A or B). The Comb‐Ex regimen included upper body resistance training (RT) and neuromuscular electrical stimulation‐induced‐RT for paralytic quadriceps muscles, interspersed with high‐intensity (80–90% VO2 peak) arm cranking exercises 3 days/week. The HP diet included ~30% total energy as protein (carbohydrate to protein ratio <1.5, ~30% energy from fat). Oral glucose tolerance tests and muscle biopsies of the vastus lateralis (VL) and deltoid muscles were performed before and after the trial. Fasting plasma glucose levels decreased in the Comb‐Ex (P < 0.05) group compared to the HP‐diet group. A decrease in areas under the curve for insulin and TNF‐α concentrations was observed for all participants regardless of group assignment (time effect, P < 0.05). Although both groups exhibited a quantitative increase in insulin sensitivity as measured by the Matsuda Index, the change was clinically meaningful only in the HP diet group (HP diet: pre, 4.6; post, 11.6 vs. Comb‐Ex: pre, 3.3; post, 4.6). No changes were observed in proteins associated with GLUT‐4 translocation in VL or deltoid muscles. Our results suggest that the HP‐diet and Comb‐Ex regimen may improve insulin sensitivity and decrease TNF‐α concentrations in individuals with SCI.
This study compares the effects of an 8-wk isocaloric high-protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and nonparalytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber-type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-wk interventions. A total of 11 participants (C5-T12 levels, 21.8 ± 6.3 yr postinjury; 6 Comb-Ex and 5 HP diet) completed the study. Comb-Ex training occurred 3 days/wk and consisted of upper body resistance training (RT) in addition to neuromuscular electrical stimulation (NMES)-induced-RT for paralytic VL muscle. Strength training was combined with high-intensity arm-cranking exercises (1-min intervals at 85-90%, V̇o) for improving cardiovascular endurance. For the HP diet intervention, protein and fat each comprised 30%, and carbohydrate comprised 40% of total energy. Clinical tests and muscle biopsies were performed 24 h before and after the last exercise or diet session. The Comb-Ex intervention increased Type IIa myofiber distribution and CSA in VL muscle and Type I and IIa myofiber CSA in deltoid muscle. In addition, Comb-Ex increased lean thigh mass, V̇o, and upper body strength ( P < 0.05). These results suggest that exercise training is required to promote favorable changes in paralytic and nonparalytic muscles in individuals with long-standing SCI, and adequate dietary protein consumption alone may not be sufficient to ameliorate debilitating effects of paralysis. NEW & NOTEWORTHY This study is the first to directly compare the effects of an isocaloric high-protein diet and combination exercise training on clinical and molecular changes in paralytic and nonparalytic muscles of individuals with long-standing spinal cord injury. Our results demonstrated that muscle growth and fiber-type alterations can best be achieved when the paralyzed muscle is sufficiently loaded via neuromuscular electrical stimulation-induced resistance training.
Ultraviolet (UV) irradiation of the skin is related to the development of skin cancer. UVB also causes DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), which can result in stable mutations. Toll-like receptor 4 (TLR4), a component of innate immunity, plays a key role in cancer. Previous studies from our laboratory have observed that TLR4 deficiency resulted in the repair of UVB-induced DNA damage, inhibition of UVB-induced immune suppression, and carcinogenesis. In this study, we determined the efficacy of TLR4 antagonist TAK-242 in regulation of UVB-induced DNA damage, inflammation, and tumor development. Our results indicate that TAK-242 treatment increased the expression of xeroderma pigmentosum group A (XPA) mRNA, resulting in the repair of UVB-induced CPDs in skin of SKH-1 mice. Treatment with TAK-242 also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) in UVB-exposed skin of SKH-1 mice. Cutaneous carcinogenesis was significantly reduced in mice treated with TAK-242 in comparison to vehicle-treated mice. The proinflammatory cytokines IL-1β, IL-6, and TNF-α were also found to be significantly greater in vehicle-treated mice than TAK-242-treated mice. Finally, treatment with TAK-242 augmented anti-tumor immune responses in mice. Our data provide further evidence that activation of the TLR4 pathway promotes the development of UV-induced non-melanoma skin cancer mediated at least in part on its negative effects on DNA damage. Moreover, treatment with the TLR4 inhibitor TAK-242 may be effective for prevention of skin cancer.
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