Vasodilative effects of prostaglandin E1 derivate on arteries of nerve roots in a canine model of a chronically compressed cauda equina

<p>Abstract</p> <p>Background</p> <p>Reduction of blood flow is important in the induction of neurogenic intermittent claudication (NIC) in lumbar spinal canal stenosis. PGE₁improves the mean walking distance in patients with NIC type cauda equina compression. PGE₁derivate might be effective in dilating blood vessels and improving blood flow in nerve roots with chronically compressed cauda equina. The aim of this study was to assess whether PGE₁derivate has vasodilatory effects on both arteries and veins in a canine model of chronic cauda equina compression.</p> <p>Methods</p> <p>Fourteen dogs were used in this study. A plastic balloon inflated to 10 mmHg was placed under the lamina of the 7th lumbar vertebra for 1 week. OP-1206-cyclodextrin clathrate (OP-1206-CD: prostaglandin E₁derivate) was administered orally. The blood vessels of the second or third sacral nerve root were identified using a specially designed surgical microscope equipped with a video camera. The diameter of the blood vessels was measured on video-recordings every 15 minutes until 90 minutes after the administration of the PGE₁derivate.</p> <p>Results</p> <p>We observed seven arteries and seven veins. The diameter and blood flow of the arteries was significantly increased compared with the veins at both 60 and 75 minutes after administration of the PGE₁derivate (p < 0.05). Blood flow velocity did not change over 90 minutes in either the arteries or veins.</p> <p>Discussion</p> <p>The PGE₁derivate improved blood flow in the arteries but did not induce blood stasis in the veins. Our results suggest that the PGE₁derivate might be a potential therapeutic agent, as it improved blood flow in the nerve roots in a canine model of chronic cauda equina compression.</p

Quantitative radiologic criteria for the diagnosis of lumbar spinal stenosis: a systematic literature review

Background: Beside symptoms and clinical signs radiological findings are crucial in the diagnosis of lumbar spinal stenosis (LSS). We investigate which quantitative radiological signs are described in the literature and which radilogical criteria are used to establish inclusion criteria in clincical studies evaluating different treatments in patients with lumbar spinal stenosis. Methods: A literature search was performed in Medline, Embase and the Cochrane library to identify papers reporting on radiological criteria to describe LSS and systematic reviews investigating the effects of different treatment modalities. Results: 25 studies reporting on radiological signs of LSS and four systematic reviews related to the evaluation of different treatments were found. Ten different parameters were identified to quantify lumbar spinal stenosis. Most often reported measures for central stenosis were antero-posterior diameter (< 10 mm) and cross-sectional area (< 70 mm2) of spinal canal. For lateral stenosis height and depth of the lateral recess, and for foraminal stenosis the foraminal diameter were typically used. Only four of 63 primary studies included in the systematic reviews reported on quantitative measures for defining inclusion criteria of patients in prognostic studies. Conclusions: There is a need for consensus on well-defined, unambiguous radiological criteria to define lumbar spinal stenosis in order to improve diagnostic accuracy and to formulate reliable inclusion criteria for clinical studies

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

<p>Abstract</p> <p>Background</p> <p>Several polymorphisms of genes involved in the immunological recognition of <it>Helicobacter pylori </it>and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding <it>Angiotensin converting enzyme </it>(<it>ACE</it>), <it>Nod-like receptor 1 </it>(<it>NOD1</it>), <it>Toll-like receptor 4 </it>(<it>TLR4</it>) and <it>FAS/FASL</it>.</p> <p>Methods</p> <p>Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. <it>ACE I/D </it>(rs4646994), <it>NOD1 796G>A </it>(rs5743336), <it>TLR4 3725G>C </it>(rs11536889), <it>FAS 1377G>A </it>(rs2234767), <it>FAS 670A>G </it>(rs1800682) and <it>FASL 844T>C </it>(rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.</p> <p>Results</p> <p>Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for <it>NOD1 796G/G </it>genotype to be associated with increased risk of HRAG (62.4% <it>vs</it>. 54.5% in controls, <it>p </it>= 0.082). <it>FAS 670G/G </it>genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (<it>p </it>= 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. <it>NOD1 796G>A </it>and <it>TLR4 3725G>C </it>gene polymorphisms were also not associated with <it>Helicobacter pylori </it>infection.</p> <p>Conclusions</p> <p><it>ACE, NOD1, TRL4 </it>and <it>FAS/FASL </it>gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.</p

Novel mutations in TLR genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection

<p>Abstract</p> <p>Background</p> <p>Toll like receptors (TLR) play the central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in the TLR1, TLR2 and TLR4 genes may change the ability to recognize PAMPs and cause altered responsiveness to the bacterial pathogens.</p> <p>Results</p> <p>The study presents association between TLR gene mutations and increased susceptibility to <it>Mycobacterium avium </it>subsp. <it>paratuberculosis </it>(MAP) infection. Novel mutations in TLR genes (TLR1- Ser150Gly and Val220Met; TLR2 – Phe670Leu) were statistically correlated with the hindrance in recognition of MAP legends. This correlation was confirmed subsequently by measuring the expression levels of cytokines (IL-4, IL-8, IL-10, IL-12 and IFN-γ) in the mutant and wild type moDCs (mocyte derived dendritic cells) after challenge with MAP cell lysate or LPS. Further <it>in silico </it>analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR (leucine rich repeat) motifs.</p> <p>Conclusion</p> <p>The most critical positions that may alter the pathogen recognition ability of TLR were: the 9^thamino acid position in LRR motif (TLR1–LRR10) and 4^thresidue downstream to LRR domain (exta-LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection.</p

Recent advances of metabolomics in plant biotechnology

Biotechnology, including genetic modification, is a very important approach to regulate the production of particular metabolites in plants to improve their adaptation to environmental stress, to improve food quality, and to increase crop yield. Unfortunately, these approaches do not necessarily lead to the expected results due to the highly complex mechanisms underlying metabolic regulation in plants. In this context, metabolomics plays a key role in plant molecular biotechnology, where plant cells are modified by the expression of engineered genes, because we can obtain information on the metabolic status of cells via a snapshot of their metabolome. Although metabolome analysis could be used to evaluate the effect of foreign genes and understand the metabolic state of cells, there is no single analytical method for metabolomics because of the wide range of chemicals synthesized in plants. Here, we describe the basic analytical advancements in plant metabolomics and bioinformatics and the application of metabolomics to the biological study of plants