Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation

<p>Abstract</p> <p>Background</p> <p>Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 μl, i.p.).</p> <p>Results</p> <p>Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid-induced nociception (0-60 minutes post-injection) and the enhancement in the number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid injection. Also, the expression of spinal phosphorylated extracellular signal-regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre-administration. Interestingly, intrathecal introduction of PD98059, an ERK upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain responses.</p> <p>Conclusions</p> <p>These results demonstrate that minocycline effectively inhibits acetic acid-induced acute abdominal nociception via the inhibition of neuronal p-ERK expression in the spinal cord, and that minocycline may have therapeutic potential in suppressing acute abdominal pain.</p

Detecting Bladder Biomarkers for Closed-Loop Neuromodulation: A Technological Review

Neuromodulation was introduced for patients with poor outcomes from the existing traditional treatment approaches. It is well-established as an alternative, novel treatment option for voiding dysfunction. The current system of neuromodulation uses an open-loop system that only delivers continuous stimulation without considering the patient’s state changes. Though the conventional open-loop system has shown positive clinical results, it can cause problems such as decreased efficacy over time due to neural habituation, higher risk of tissue damage, and lower battery life. Therefore, there is a need for a closed-loop system to overcome the disadvantages of existing systems. The closed-loop neuromodulation includes a system to monitor and stimulate micturition reflex pathways from the lower urinary tract, as well as the central nervous system. In this paper, we reviewed the current technological status to measure biomarker for closed-loop neuromodulation systems for voiding dysfunction

S6 kinase 1 plays a key role in mitochondrial morphology and cellular energy flow

Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1 KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondria' fraction. In addition, there was no evidence for autophagy and mitophagy induction in S6K1 depleted cells. Glycolysis and mitochondrial respiratory activity was higher in S6K1-KO MEFs, whereas OxPhos ATP production was not altered. However, inhibition of Drp1 by Mdivi1 (Drp1 inhibitor) resulted in higher OxPhos ATP production and lower mitochondrial membrane potential. Taken together the depletion of S6K1 increased Drpl-mediated fission, leading to the enhancement of glycolysis. The fission form of mitochondria resulted in lower yield for OxPhos ATP production as well as in higher mitochondrial membrane potential. Thus, these results have suggested a potential role of S6K1 in energy metabolism by modulating mitochondrial respiratory capacity and mitochondrial morphology.

Experimental Study on Flow Control Characteristics of Synthetic Jets over a Blended Wing Body Configuration

Nov. 20-22, 2013, Sunport Hall Takamatsu, Takamatsu, JAPANThis paper presents experimental investigations on the characteristics of synthetic jets over blended wing body configuration. Flow control experiments were performed by using piezoelectrically driven synthetic jet under various flow conditions. In the first step, baseline characteristics of blended wing body configuration were analyzed when synthetic jet was off. Pressure distribution and separated-flow region on the wing surface were examined by changing the angle of attack. Flow control experiments were carried out by synthetic jet to demonstrate the flow control performance in the post-stall regime. Comparative studies were also conducted for a stalled condition. Aerodynamic coefficient was examined by changing synthetic jet operating condition, such as jet oscillation frequency and jet module locations. Based on various comparisons, it was observed that synthetic jet operating conditions have significantly influence on the development of leading-edge vorticies, that is to say, flow control performance of synthetic jet.This research was supported by Defense Acquisition Program Administration and Agency for Defense Development (UC100031JD).OAIID:oai:osos.snu.ac.kr:snu2013-01/104/0000004648/20SEQ:20PERF_CD:SNU2013-01EVAL_ITEM_CD:104USER_ID:0000004648ADJUST_YN:NEMP_ID:A001138DEPT_CD:446CITE_RATE:0FILENAME:api280_bhl_130913.pdfDEPT_NM:기계항공공학부EMAIL:[email protected]:

Neuroprotective Effects of a Traditional Multi-Herbal Medicine Kyung-Ok-Ko in an Animal Model of Parkinson's Disease: Inhibition of MAPKs and NF-κB Pathways and Activation of Keap1-Nrf2 Pathway

Kyung-Ok-Ko (KOK), a traditional multi-herbal medicine, has been widely used in Oriental medicine as a restorative that can enforce vitality of whole organs and as a medicine that can treat age-related symptoms including lack of vigor and weakened immunity. However, the beneficial effect of KOK on neurological diseases such as Parkinson's diseases (PD) is largely unknown. Thus, the objective of this study was to examine the protective effect of KOK on neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-treatment with KOK at 1 or 2 g/kg/day (p.o.) showed significant mitigating effects on neurological dysfunction (motor and welfare) based on pole, rotarod, and nest building tests. It also showed effects on survival rate. These positive effects of KOK were related to inhibition of loss of tyrosine hydroxylase–positive neurons, reduction of MitoSOX activity, increased apoptotic cells, microglia activation, and upregulation of inflammatory factors [interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide], and reduced blood-brain barrier (BBB) disruption in the substantia nigra pars compacta (SNpc) and/or striatum after MPTP intoxication. Interestingly, these effects of KOK against MPTP neurotoxicity were associated with inhibition of phosphorylation of mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways along with up-regulation of nuclear factor erythroid 2-related factor 2 pathways in SNpc and/or striatum. Collectively, our findings suggest that KOK might be able to mitigate neurotoxicity in MPTP-induced mouse model of PD via multi-effects, including anti-neuronal and anti-BBB disruption activities through its anti-inflammatory and anti-oxidative activities. Therefore, KOK might have potential for preventing and/or treating PD

Integrating Metal-Oxide-Decorated CNT Networks with a CMOS Readout in a Gas Sensor

We have implemented a tin-oxide-decorated carbon nanotube (CNT) network gas sensor system on a single die. We have also demonstrated the deposition of metallic tin on the CNT network, its subsequent oxidation in air, and the improvement of the lifetime of the sensors. The fabricated array of CNT sensors contains 128 sensor cells for added redundancy and increased accuracy. The read-out integrated circuit (ROIC) was combined with coarse and fine time-to-digital converters to extend its resolution in a power-efficient way. The ROIC is fabricated using a 0.35 μm CMOS process, and the whole sensor system consumes 30 mA at 5 V. The sensor system was successfully tested in the detection of ammonia gas at elevated temperatures