Differential regulation of morphine antinociceptive effects by endogenous enkephalinergic system in the forebrain of mice

<p>Abstract</p> <p>Background</p> <p>Mice lacking the preproenkephalin (<it>ppENK</it>) gene are hyperalgesic and show more anxiety and aggression than wild-type (WT) mice. The marked behavioral changes in <it>ppENK </it>knock-out (KO) mice appeared to occur in supraspinal response to painful stimuli. However the functional role of enkephalins in the supraspinal nociceptive processing and their underlying mechanism is not clear. The aim of present study was to compare supraspinal nociceptive and morphine antinociceptive responses between WT and <it>ppENK </it>KO mice.</p> <p>Results</p> <p>The genotypes of bred KO mice were confirmed by PCR. Met-enkephalin immunoreactive neurons were labeled in the caudate-putamen, intermediated part of lateral septum, lateral globus pallidus, intermediated part of lateral septum, hypothalamus, and amygdala of WT mice. Met-enkephalin immunoreactive neurons were not found in the same brain areas in KO mice. Tail withdrawal and von Frey test results did not differ between WT and KO mice. KO mice had shorter latency to start paw licking than WT mice in the hot plate test. The maximal percent effect of morphine treatments (5 mg/kg and 10 mg/kg, i.p.) differed between WT and KO mice in hot plate test. The current source density (CSD) profiles evoked by peripheral noxious stimuli in the primary somatosenstory cortex (S1) and anterior cingulate cortex (ACC) were similar in WT and KO mice. After morphine injection, the amplitude of the laser-evoked sink currents was decreased in S1 while the amplitude of electrical-evoked sink currents was increased in the ACC. These differential morphine effects in S1 and ACC were enhanced in KO mice. Facilitation of synaptic currents in the ACC is mediated by GABA inhibitory interneurons in the local circuitry. Percent increases in opioid receptor binding in S1 and ACC were 5.1% and 5.8%, respectively.</p> <p>Conclusion</p> <p>The present results indicate that the endogenous enkephalin system is not involved in acute nociceptive transmission in the spinal cord, S1, and ACC. However, morphine preferentially suppressed supraspinal related nociceptive behavior in KO mice. This effect was reflected in the potentiated differential effects of morphine in the S1 and ACC in KO mice. This potentiation may be due to an up-regulation of opioid receptors. Thus these findings strongly suggest an antagonistic interaction between the endogenous enkephalinergic system and exogenous opioid analgesic actions in the supraspinal brain structures.</p

Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH 2

Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts

Traditional Chinese Medicine for Metabolic Syndrome via TCM Pattern Differentiation: Tongue Diagnosis for Predictor

Metabolic syndrome is a morbid condition, which is manifested by central obesity, abnormal glucose tolerance, lipodystrophy, and hypertension. Traditional Chinese medicine (TCM) clarifies that obesity is classified as phlegm-dampness. It is often accompanied with qi stagnation and blood stasis. One hundred and two overweight adults, who did not receive lipid-lowering drugs, were enrolled for analysis. The exclusion criteria were adults having malignancy disease, DM, and renal disease or who were pregnant or lactating. The study was divided into two groups: metabolic syndrome group (MetS) and nonmetabolic syndrome group (nMetS). The modern tongue analysis and heart rate variability devices for data analysis and Council on Nutrition Appetite Questionnaire (CNAQ) for appetite evaluation were used. Obesity patients with metabolic syndrome obviously have lower CNAQ score. The 6 items of CNAQ between two groups have significant difference in variation (P<0.001). The nMetS average was above 28 scores (96%) and the MetS was all in 17–28 scores. The tongue appearance showed that MetS group have white coating different from the nMetS group with white and yellow coating (P<0.05). However the HRV is not different from nMetS group significantly. Our results try to explore the relationship between the TCM pattern, nutrition appetite, and heart rate variability in metabolic syndrome patients

Analysis of Agreement on Traditional Chinese Medical Diagnostics for Many Practitioners

In Traditional Chinese Medicine (TCM) diagnostics, it is an important issue to study the degree of agreement among several distinct practitioners. In order to study the reliability of TCM diagnostics, we have to design an experiment to simultaneously deal with both of the cases when the data is ordinal and when there are many TCM practitioners. In this study, we consider a reliability measure called “Krippendorff's alpha” to investigate the agreement of tongue diagnostics in TCM. Besides, since it is not easy to obtain a large data set with patients rated simultaneously by many TCM practitioners, we use the renowned “bootstrapping” to obtain a 95% confidence interval for the Krippendorff's alpha. The estimated Krippendorff's alpha for the agreement among ten physicians that discerned fifteen randomly chosen patients is 0.7343, and the 95% bootstrapping confidence interval for the true alpha coefficient is [0.6570, 0.7349]. The data was collected and analyzed at the Department of Traditional Chinese Medicine, Changhua Christian Hospital (CCH) in Taiwan

Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: Oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder

The present study used the preproenkephalin knockout (ppENK) mice to test whether the endogenous enkephalins deficit could facilitate the anxiety- and depressive-like symptoms of posttraumatic stress disorder (PTSD). On Day 1, sixteen wildtype (WT) and sixteen ppENK male mice were given a 3 mA or no footshock treatment for 10 seconds in the footshock apparatus, respectively. On Days 2, 7, and 13, all mice were given situational reminders for 1 min per trial, and the freezing response was assessed. On Day 14, all mice were tested in the open field test, elevated plus maze, light/dark avoidance test, and forced swim test. Two hours after the last test, brain tissues were stained to examine c-fos expression in specific brain areas. The present results showed that the conditioned freezing response was significant for different genotypes (ppENK vs WT). The conditioned freezing effect of the ppENK mice was stronger than those of the WT mice. On Day 14, the ppENK mice showed more anxiety- and depressive-like responses than WT mice. The magnitude of Fos immunolabeling was also significantly greater in the primary motor cortex, bed nucleus of the stria terminalis-lateral division, bed nucleus of the stria terminalis-supracapsular division, paraventricular hypothalamic nucleus-lateral magnocellular part, central nucleus of the amygdala, and basolateral nucleus of the amygdala in ppENK mice compared with WT mice. In summary, animals with an endogenous deficit in enkephalins might be more sensitive to PTSD-like aversive stimuli and elicit stronger anxiety and depressive PTSD symptoms, suggesting an oversensitivity hypothesis of enkephalin deficit-induced PTSD

Complete genomic sequence of the temperate bacteriophage ΦAT3 isolated from Lactobacillus casei ATCC 393

AbstractThe complete genomic sequence of a temperate bacteriophage ΦAT3 isolated from Lactobacillus (Lb.) casei ATCC 393 is reported. The phage consists of a linear DNA genome of 39,166 bp, an isometric head of 53 nm in diameter, and a flexible, noncontractile tail of approximately 200 nm in length. The number of potential open reading frames on the phage genome is 53. There are 15 unpaired nucleotides at both 5′ ends of the ΦAT3 genome, indicating that the phage uses a cos-site for DNA packaging. The ΦAT3 genome was grouped into five distinct functional clusters: DNA packaging, morphogenesis, lysis, lysogenic/lytic switch, and replication. The amino acid sequences at the NH2-termini of some major proteins were determined. An in vivo integration assay for the ΦAT3 integrase (Int) protein in several lactobacilli was conducted by constructing an integration vector including ΦAT3 int and the attP (int-attP) region. It was found that ΦAT3 integrated at the tRNAArg gene locus of Lactobacillus rhamnosus HN 001, similar to that observed in its native host, Lb. casei ATCC 393

LrrA, a novel leucine-rich repeat protein involved in cytoskeleton remodeling, is required for multicellular morphogenesis in Dictyostelium discoideum

AbstractCell sorting by differential cell adhesion and movement is a fundamental process in multicellular morphogenesis. We have identified a Dictyostelium discoideum gene encoding a novel protein, LrrA, which composes almost entirely leucine-rich repeats (LRRs) including a putative leucine zipper motif. Transcription of lrrA appeared to be developmentally regulated with robust expression during vegetative growth and early development. lrrA null cells generated by homologous recombination aggregated to form loose mounds, but subsequent morphogenesis was blocked without formation of the apical tip. The cells adhered poorly to a substratum and did not form tight cell–cell agglomerates in suspension; in addition, they were unable to polarize and exhibit chemotactic movement in the submerged aggregation and Dunn chamber chemotaxis assays. Fluorescence-conjugated phalloidin staining revealed that both vegetative and aggregation competent lrrA− cells contained numerous F-actin-enriched microspikes around the periphery of cells. Quantitative analysis of the fluorescence-stained F-actin showed that lrrA− cells exhibited a dramatically increase in F-actin as compared to the wild-type cells. When developed together with wild-type cells, lrrA− cells were unable to move to the apical tip and sorted preferentially to the rear and lower cup regions. These results indicate that LrrA involves in cytoskeleton remodeling, which is needed for normal chemotactic aggregation and efficient cell sorting during multicellular morphogenesis, particularly in the formation of apical tip

Decreased Risk of Osteoporosis Incident in Subjects Receiving Chinese Herbal Medicine for Sjögren Syndrome Treatment: A Retrospective Cohort Study with a Nested Case-Control Analysis

Sjögren syndrome (SS) is a long-lasting inflammatory autoimmune disease that may cause diverse manifestations, particularly osteoporosis. Though usage of Chinese herbal medicine (CHM) can safely manage autoimmune disease and treatment-related symptoms, the relation between CHM use and osteoporosis risk in SS persons is not yet recognized. With that in mind, this population-level nested case-control study aimed to compare the risk of osteoporosis with and without CHM use. Potential subjects aged 20–70 years, diagnosed with SS between 2001 and 2010, were retrieved from a national health claims database. Those diagnosed with osteoporosis after SS were identified and randomly matched to those without osteoporosis. We capitalize on the conditional logistic regression to estimate osteoporosis risk following CHM use. A total of 1240 osteoporosis cases were detected and randomly matched to 1240 controls at a ratio of 1:1. Those receiving conventional care plus CHM had a substantially lower chance of osteoporosis than those without CHM. Prolonged use of CHM, especially for one year or more, markedly dwindled sequent osteoporosis risk by 71%. Integrating CHM into standard care may favor the improvement of bone function, but further well-designed randomized controlled trials to investigate the possible mechanism are needed

以數值方法探討卵礫石層的力學行為

Gravel formation involves the mixture of hard gravel and a soil matrix. Knowing the integrated mechanical characteristics of gravel formation is beneficial for engineering constructions and disaster prevention. This study adopts the software PFC2D, which is based on the discrete element method, to investigate the mechanical behavior of gravel formations. First, simulation is carried out through a biaxial test to adjust the micro parameters in PFC2D, and then multiple regression analysis is performed to establish the relationship between macro and micro parameters. Furthermore, with the reasonable micro parameters obtained, the particle size and content of gravel can changed to investigate how they influence mechanical behavior. The results show that the bigger particle size and the greater the content of gravel, the higher the values of shear strength, elastic modulus, Poisson’s ratio and friction angle, but the lower the value of cohesion. In other words, this kind of material has higher shear strength and stronger deformation resistance. These findings correspond with previous research results.卵礫石層是混合堅硬卵礫石與基質土壤之綜合體，了解卵礫石層整體力學性質，對工程建設與災害防治有極大幫助。本研究以台灣中部卵礫石層為對象，運用分離元素法為基礎之軟體PFC2D 探討卵礫石材料力學行為。首先進行雙軸試驗之模擬，校正PFC2D 微觀參數，接著利用複迴歸分析 (multiple regression model)建立宏觀參數與微觀參數間之關係。另外，以得到的合理微觀參數，改變卵礫石粒徑大小與含量，探討粒徑大小和含量對力學性質的影響。結果顯示當卵礫石粒徑越大與含量越多，其剪力強度、彈性模數、柏松比、摩擦角也會越大，但凝聚力略為下降。表示卵礫石粒徑大、含量高之材料，其抗剪強度大，變形性小，此結果與前人研究結果相符

Co-seismic signatures in magnetometer, geophone, and infrasound data during the Meinong Earthquake

This paper utilizes 10 stations of co-located seismometer, QuakeFinder/infrasound to observe co-seismic signatures triggered by the 6 February 2016 M 6.6 Meinong Earthquake. Each QuakeFinder system consists of a 3-axes induction magnetometer, an air conductivity sensor, a geophone, and temperature/relative humidity sensors. There are no obvious charges in the positive/negative ions, the temperature, and the humidity, while the magnetometer, the geophone, and infrasound data detect clear co-seismic signatures, similar to seismic waves recorded by seismometers. The magnetometers register high-frequency pulsations, like seismic waves, and superimpose with low-frequency variations, which could be caused by the magnetometer shaking/tilting and/or the underground water level change, respectively, upon the arrival of seismic waves. The spectrum centering around 2.0 Hz of the co-seismic geophone fluctuations is similar to that of the seismic waves. However, the energy of co-seismic geophone fluctuations (also magnetometer pulsations) yields an exponential decay to the distance of a station to the epicenter, while the energy of the seismic waves is inversely proportional to the square of the distance. This suggests that the mechanisms for detecting seismic waves of the QuakeFinder system and seismometers are different. In general, the geophone and magnetometer/infrasound system are useful to record high- and low-frequency seismic waves, respectively