ABSTRACT
Aim To investigate the anti-neuropathic pain effect of DXL-A-22 and further to explore the potential mechanisms. Methods The anti-neuropathic pain effect was evaluated by chronic constriction injury (CCI) model. The potential anti-neuropathic pain mechanisms of DXL-A-22 was studied by Western blot and qPCR. The acute toxicity was evaluated by ultimate test. Results DXL-A-22 (2,1,0. 5 mg . kg-1 ,i. g.) dose-dependently elevated the mechanical withdrawal threshold (MWT) and the paw withdrawal latency (PWL) in CCI rats (P < 0. 05, P < 0. 01), the percentage of pain threshold elevation (PTE%) and the percentage of Maximal Possible Effect (MPE%) was 108%,86%,71% and 77%,56%,43% respectively on day 7 post-operation. DXL-A-22 (2 mg . kg-1 ,i. g.) significantly reduced the expression of p-CaMK II α, p-CREB, p-JAK2, p-STAT3 proteins and TNF-α mRNA, c-Fos mRNA in DRG (P < 0. 05, P < 0.01), and the percent inhibition was 37%, 48%, 35%,58%, 39% and 32% respectively. The expression of TNF-α mRNA and c-Fos mRNA in spinal pord was reduced by 47% and 72% respectively in CCI rats (P <0. 01). Acute toxicity test showed that DXL-A-22 had no obvious toxicity reaction. Conclusions Spirocyclopiperazinium salt compound DXL-A-22 exerts significant antinociceptive effect on CCI model. The anti-neuropathic pain effect of DXL-A-22 may be related to the inhibition of CaMK II α/CREB and JAK2/STAT3 signaling pathways, and the inhibition of the mRNA expression of TNF-α and c-Fos.
ABSTRACT
OBJECTIVE: To evaluate how bone mineral density in the calcaneus measured by a dual energy X-ray laser (DXL) correlates with bone mineral density in the spine and hip in Turkish women over 40 years of age and to determine whether calcaneal dual energy X-ray laser variables are associated with clinical risk factors to the same extent as axial bone mineral density measurements obtained using dual energy x-ray absorbtiometry (DXA). MATERIALS AND METHODS: A total of 2,884 Turkish women, aged 40-90 years, living in Ankara were randomly selected. Calcaneal bone mineral density was evaluated using a dual energy X-ray laser Calscan device. Subjects exhibiting a calcaneal dual energy X-ray laser T- score <-2.5 received a referral for DXA of the spine and hip. Besides dual energy X-ray laser measurements, all subjects were questioned about their medical history and the most relevant risk factors for osteoporosis. RESULTS: Using a T-score threshold of -2.5, which is recommended by the World Health Organization (WHO), dual energy X-ray laser calcaneal measurements showed that 13 percent of the subjects had osteoporosis, while another 56 percent had osteopenia. The mean calcaneal dual energy X-ray laser T-score of postmenopausal subjects who were smokers with a positive history of fracture, hormone replacement therapy (HRT), covered dressing style, lower educational level, no regular exercise habits, and low tea consumption was significantly lower than that obtained for the other group (p<0.05). A significant correlation was observed between the calcaneal dual energy X-ray laser T-score and age (r=-0.465, p=0.001), body mass index (BMI) (r=0.223, p=0.001), number of live births (r=-0.229, p=0.001), breast feeding time (r=-0.064, p=0.001), and age at menarche (r=-0.050, p=0.008). The correlations between calcaneal DXL and DXA T-scores (r=0.340, p=0.001) and calcaneal DXL and DXA Z-scores (r=0.360, p=0.001) at the spine, and calcaneal DXL and DXA T- ...