Evaluation of analgesic, anti-inflammatoryand antipyretic activities of the ethanol extract from Speranskia tuberculate

Background: Speranskia tuberculata (Bunge) Baill, has been used to prevent and treat many diseases in Chinese folk medicine, nevertheless, few investigations had been reported.Materials and Methods: Animals were orally administered STE at the doses of 125, 250, 500 mg/kg. The analgesic effect was estimated in mice by hot-plate test and the acetic acid-induced writhing test. The anti-inflammatory effect was assessed using rat paw edema model elicited by fresh egg white and the mouse ear edema model caused by dimethylbenzene. The antipyretic effect was determined using the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute oral toxicity of STE was studied.Results: STE significantly and dose-dependently reduced the number of writhing responses in mice, prolonged reaction time of mice against heat stimulation, depressed egg white-induced paw edema in rats and the dimethylbenzene-caused ear edema in mice, but did not alleviate LPS-induced pyrexia in rats. No death of mice was observed when orally administered STE up to 52.8 g/kg (approximately 2080 times of clinical dose used).Conclusion: STE possesses evident analgesic and anti-inflammatory activities, but has no antipyretic effect. Furthermore STE has a favorable safety. These findings support the applications of Speranskia tuberculata as an analgesic and anti-inflammatory drug in folk medicine.Key Words: Herb, pain, inflammation, Pyrexia, Safet

Lumbar spinal stenosis: an update on the epidemiology, diagnosis and treatment

Lumbar spinal stenosis (LSS) is a common spinal disorder in the older population, and the clinical syndrome consisting of pain in the buttock or lower extremity, with or without low back pain and corresponding imaging findings of narrowing of spaces around neural and vascular elements in the lumbar spine. The diagnosis depends on history, symptoms, physical examination, radiographies. Varieties of non-operative and operative options are available for LSS patients. In this article, an update on the epidemiology, diagnosis and treatment of LSS was reviewed.published_or_final_versio

Construction of stiffness and flexibility for substructure-based model updating

2013-2014 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Simultaneous quantitative assessment of circulating cell-free mitochondrial and nuclear DNA by multiplex real-time PCR

Quantification of circulating nucleic acids in plasma and serum could be used as a non-invasive diagnostic tool for monitoring a wide variety of diseases and conditions. We describe here a rapid, simple and accurate multiplex real-time PCR method for direct synchronized analysis of circulating cell-free (ccf) mitochondrial (mtDNA) and nuclear (nDNA) DNA in plasma and serum samples. The method is based on one-step multiplex real-time PCR using a FAM-labeled MGB probe and primers to amplify the mtDNA sequence of the ATP 8 gene, and a VIC-labeled MGB probe and primers to amplify the nDNA sequence of the glycerinaldehyde-3-phosphate-dehydrogenase (GAPDH) gene, in plasma and serum samples simultaneously. The efficiencies of the multiplex assays were measured in serial dilutions. Based on the simulation of the PCR reaction kinetics, the relative quantities of ccf mtDNA were calculated using a very simple equation. Using our optimised real-time PCR conditions, close to 100% efficiency was obtained from the two assays. The two assays performed in the dilution series showed very good and reproducible correlation to each other. This optimised multiplex real-time PCR protocol can be widely used for synchronized quantification of mtDNA and nDNA in different samples, with a very high rate of efficiency

The Shapes of Cooperatively Rearranging Regions in Glass Forming Liquids

The shapes of cooperatively rearranging regions in glassy liquids change from being compact at low temperatures to fractal or ``stringy'' as the dynamical crossover temperature from activated to collisional transport is approached from below. We present a quantitative microscopic treatment of this change of morphology within the framework of the random first order transition theory of glasses. We predict a correlation of the ratio of the dynamical crossover temperature to the laboratory glass transition temperature, and the heat capacity discontinuity at the glass transition, Delta C_p. The predicted correlation agrees with experimental results for the 21 materials compiled by Novikov and Sokolov.Comment: 9 pages, 6 figure

Non-monotonic temperature evolution of dynamic correlations in glass-forming liquids

The viscosity of glass-forming liquids increases by many orders of magnitude if their temperature is lowered by a mere factor of 2-3 [1,2]. Recent studies suggest that this widespread phenomenon is accompanied by spatially heterogeneous dynamics [3,4], and a growing dynamic correlation length quantifying the extent of correlated particle motion [5-7]. Here we use a novel numerical method to detect and quantify spatial correlations which reveal a surprising non-monotonic temperature evolution of spatial dynamical correlations, accompanied by a second length scale that grows monotonically and has a very different nature. Our results directly unveil a dramatic qualitative change in atomic motions near the mode-coupling crossover temperature [8] which involves no fitting or indirect theoretical interpretation. Our results impose severe new constraints on the theoretical description of the glass transition, and open several research perspectives, in particular for experiments, to confirm and quantify our observations in real materials.Comment: 7 page

Lower bounds on the dilation of plane spanners

(I) We exhibit a set of 23 points in the plane that has dilation at least $1.4308$, improving the previously best lower bound of $1.4161$ for the worst-case dilation of plane spanners. (II) For every integer $n\geq13$, there exists an $n$-element point set $S$ such that the degree 3 dilation of $S$ denoted by $\delta_0(S,3) \text{ equals } 1+\sqrt{3}=2.7321\ldots$ in the domain of plane geometric spanners. In the same domain, we show that for every integer $n\geq6$, there exists a an $n$-element point set $S$ such that the degree 4 dilation of $S$ denoted by $\delta_0(S,4) \text{ equals } 1 + \sqrt{(5-\sqrt{5})/2}=2.1755\ldots$ The previous best lower bound of $1.4161$ holds for any degree. (III) For every integer $n\geq6$, there exists an $n$-element point set $S$ such that the stretch factor of the greedy triangulation of $S$ is at least $2.0268$.Comment: Revised definitions in the introduction; 23 pages, 15 figures; 2 table

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed