Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model.</p> <p>Results</p> <p>Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord.</p> <p>Conclusions</p> <p>These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.</p

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

BACKGROUND: Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases. METHODS: Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11). RESULTS: The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p < 0.001) and 124% higher in IPF patients (p < 0.0001) compared with controls. ELN-441 had better diagnostic value in COPD patients (AUC 97%, p = 0.001) than in IPF patients (AUC 90%, p = 0.0001). The odds ratios for differentiating controls from COPD or IPF were 24 [2.06–280] for COPD and 50 [2.64–934] for IPF. CONCLUSIONS: MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings

Intrathecal Injection of Spironolactone Attenuates Radicular Pain by Inhibition of Spinal Microglia Activation in a Rat Model

Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation.Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn't affected.These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects

Percutaneous coronary intervention in patients with essential thrombocythemia: case reports and literature review

Essential thrombocythemia (ET) can cause systemic vascular thrombosis, but the involvement of coronary arteries is rare. This study is aimed to analyze the characteristics, treatment, and prognosis during follow-up in patients with ET after percutaneous coronary intervention (PCI). A total of eight patients with ET who had coronary heart disease and treated with PCI in our hospital from 2012 to 2018 were retrospectively studied. The basic clinical information with clinical data, data of coronary intervention, application of anti-platelet and platelet reducing drugs, and the results of long-term follow-up were recorded. There were five males and three females with a median age of 67 years. Clinical presentation was unstable angina in four cases, stable angina in one case, ST-elevation myocardial infarction in two cases, and non-ST elevation myocardial infarction in one case. The average platelet count was 722 × 109/L in admission, and hydroxyurea was used in seven cases. Coronary angiography suggested that all eight cases were single-vessel lesion. All the patients received PCI treatment, and Drug-eluting stent (DES) was used in all cases. Six were treated with one stent, one was treated with two stents and one was treated with three stents. After PCI, aspirin, and clopidogrel (or ticagrelor) were used in all cases. During the follow-up, one developed stent thrombus 2 months later, two developed stent restenosis 1 year later. In conclusion, PCI is an effective method of revascularization in patients with ET; but it may be associated with a higher rate of complications including stent thrombus and restenosis

The early transient dynamics reaction of KDP surface during nanosecond laser breakdown

The early kinetics of KDP surface after nanosecond laser induced breakdown was studied via time resolved pump and probe method. The plasma absorption region appears at the bottom of the pump laser’s rise edge, and expands continuously in the laser duration and fades after several nanoseconds. The shockwave, propagating in the air side, appears at the top of the rise edge. Its maximum velocity is in direct proportion to laser energy, achieving near the pulse peak and then decreasing rapidly. The propagation of shockwave in the free decaying phase matches well with the point explosion model