BackgroundOxaliplatin, a widely used anticancer drug against metastatic colorectal cancer, can induce acute peripheral neuropathy, which is characterized by cold and mechanical allodynia. Activation of glial cells (e.g. astrocytes and microglia) and increase of pro-inflammatory cytokines (e.g. IL-1β and TNF-α) in the spinal cord play a crucial role in the pathogenesis of neuropathic pain. Our previous study demonstrated that Gyejigachulbu-Tang (GBT), a herbal complex formula, alleviates oxaliplatin-induced neuropathic pain in rats by suppressing spinal glial activation. However, it remains to be elucidated whether and how Buja (Aconiti Tuber), a major ingredient of GBT, is involved in the efficacy of GBT.MethodsCold and mechanical allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) in Sprauge-Dawley rats were evaluated by a tail immersion test in cold water (4 °C) and a von Frey hair test, respectively. Buja (300 mg/kg) was orally administrated for five consecutive days after the oxaliplatin injection. Glial activation in the spinal cord was quantified by immunohistochemical staining using GFAP (for astrocytes) and Iba-1 (for microglia) antibodies. The amount of spinal pro-inflammatory cytokines, IL-1β and TNF-α, were measured by ELISA.ResultsSignificant behavioral signs of cold and mechanical allodynia were observed 3 days after an oxaliplatin injection. Oral administration of Buja significantly alleviated oxaliplatin-induced cold and mechanical allodynia by increasing the tail withdrawal latency to cold stimuli and mechanical threshold. Immunohistochemical analysis showed the activation of astrocytes and microglia and the increase of the IL-1β and TNF-α levels in the spinal cord after an oxaliplatin injection. Administration of Buja suppressed the activation of spinal astrocytes without affecting microglial activation and down-regulated both IL-1β and TNF-α levels in the spinal cord.ConclusionsOur results indicate that Buja has a potent anti-allodynic effect in a rat model of oxaliplatin-induced neuropathic pain, which is associated with the inhibition of activation of astrocytes and release of pro-inflammatory cytokines in the spinal cord. Thus, our findings suggest that administration of Buja could be an alternative therapeutic option for the management of peripheral neuropathy, a common side-effect of oxaliplatin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1556-z) contains supplementary material, which is available to authorized users.

Oxaliplatin, a chemotherapy drug used to treat colorectal cancer, induces specific sensory neurotoxicity signs that are aggravated by cold and mechanical stimuli. Here we examined the preventive effects of Bee Venom (BV) derived phospholipase A2 (bvPLA2) on oxaliplatin-induced neuropathic pain in mice and its immunological mechanism. The cold and mechanical allodynia signs were evaluated by acetone and von Frey hair test on the hind paw, respectively. The most significant allodynia signs were observed at three days after an injection of oxaliplatin (6 mg/kg, i.p.) and then decreased gradually to a normal level on days 7–9. The oxaliplatin injection also induced infiltration of macrophages and upregulated levels of the pro-inflammatory cytokine interleukin (IL)-1β in the lumbar dorsal root ganglia (DRG). Daily treatment with bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days prior to the oxaliplatin injection markedly inhibited the development of cold and mechanical allodynia, and suppressed infiltration of macrophages and the increase of IL-1β level in the DRG. Such preventive effects of bvPLA2 were completely blocked by depleting regulatory T cells (Tregs) with CD25 antibody pre-treatments. These results suggest that bvPLA2 may prevent oxaliplatin-induced neuropathic pain by suppressing immune responses in the DRG by Tregs.

IL-8 might be a potential therapeutic target in chronic radicular neuropathic pain because of disc herniation, CXCL8 inhibitor could be one of its promising therapeutic agents.

The Sasang constitutional medicine (SCM), a medical tradition originating from Korea, is distinguished from the traditional Chinese medicine in its philosophical background, theoretical development and especially, the fundamental rationale that analyzes the structure and function of the human body within a quadrifocal scheme. In SCM, the structure of the body is comprehended within the Sasang quadrifocal scheme, and the function of the body is understood within the context of the energy–fluid metabolism and the water–food metabolism controlled by the four main organs (lung, spleen, liver and kidney). Also, the concept of Seong–Jeong is used to explain the structural and functional variations between different constitutional types that arise from the constitutional variations in organ system scheme, which are in turn caused by deviations in the constitutional Seong–Jeong. Therefore, understanding the SCM perspective of the human body is essential in order to fully appreciate the advantages of the constitutional typological system (which focuses on individual idiosyncrasies) found in SCM.

Abstract. Network security is considered one of the obstacles that prevent the wide deployment of ad-hoc wireless networks. Among many security problems, authentication is the most fundamental problem that has to be solved before any others. Some previous solutions requiring centralized entities were not scalable and others requiring physical encounter took a long time. We propose a new architecture, called the Secure Overlay Network (SON), for fully distributed authentication. The SON has scalability because it is constructed in a self-organizing manner. The SON also has NPC-reachability which makes the SON robust against Sybil attacks, and guarantees authentication service between any two nodes in the SON. Both NPC-reachability and simulation results confirm the effectiveness of our architecture.

Two forms of iron superoxide dismutase (SOD) were purified from cell extract (CE) and culture filtrate (CF) of Mycobacterium bovis BCG, respectively. The molecular weight of both enzymes was estimated to be approximately 84,000 by gel filtration, whereas that of their subunits was 21,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that each of purified enzymes is composed of four identical subunits. The specific activities of CE SOD and CF SOD were 3,850 and 4,040, respectively. The purified enzymes were not joined by disulfide bonds and were, to some extent, resistant to sodium dodecyl sulfate. Their activities were lost by H2O2, but not by azide and cyanide, indicating iron SODs. Enzyme activities were detectable over a broad range of pHs, from 5.0 to 9.0, and were stable for 6 months at −20°C. Each value of pI was 4.5. In Western blots, both enzymes reacted with sera of tuberculosis patients, but not with normal sera. The N-terminal amino acid sequences of CE SOD and CF SOD were the same, suggesting that there is no N-terminal signal sequence.