54 research outputs found

    Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling

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    Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1ÎČ) or tumor necrosis factor alpha (TNF-α) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 ”M), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 ”M AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease

    Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

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    The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & NemĂ©sio 2007; Donegan 2008, 2009; NemĂ©sio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

    The Trichoptera barcode initiative: a strategy for generating a species-level Tree of Life

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    DNA barcoding was intended as a means to provide species-level identifications through associating DNA sequences from unknown specimens to those from curated reference specimens. Although barcodes were not designed for phylogenetics, they can be beneficial to the completion of the Tree of Life. The barcode database for Trichoptera is relatively comprehensive, with data from every family, approximately two-thirds of the genera, and one-third of the described species. Most Trichoptera, as with most of life’s species, have never been subjected to any formal phylogenetic analysis. Here, we present a phylogeny with over 16 000 unique haplotypes as a working hypothesis that can be updated as our estimates improve. We suggest a strategy of implementing constrained tree searches, which allow larger datasets to dictate the backbone phylogeny, while the barcode data fill out the tips of the tree. We also discuss how this phylogeny could be used to focus taxonomic attention on ambiguous species boundaries and hidden biodiversity. We suggest that systematists continue to differentiate between ‘Barcode Index Numbers’ (BINs) and ‘species’ that have been formally described. Each has utility, but they are not synonyms. We highlight examples of integrative taxonomy, using both barcodes and morphology for species description. This article is part of the themed issue ‘From DNA barcodes to biomes’

    The History, Present, and Future of Spine Surgery in Switzerland

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    Effect of 17beta-estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats

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    The effect of 17beta-estradiol on the secondary damage following spinal cord injury (SCI) was examined in male rats subjected to moderate compression. Two doses of 17beta-estradiol (0.1 or 4 mg/kg) were injected i.p. immediately after spinal cord compression. Functional outcome was observed during 4 weeks following injury with two different tests. Release of cytokines (IL-1alpha, IL-1beta and IL-6) was assessed 6 h, 3 days and 1 week post-injury. Reactive astrocytes expressing the glial fibrillary acidic protein GFAP and vimentin, and diffusion of CD68-positive inflammatory cells were examined from 3 days to 4 weeks following SCI. Treatment with 17beta-estradiol significantly increased locomotor function from the first week until 4 weeks post-SCI. The injured spinal cord of 17beta-estradiol-treated rats expressed more IL-1alpha, IL-1beta and IL-6 than controls 6 h after injury. Moreover, 17beta-estradiol-treated rats showed reactive astrocytes as soon as 3 days following SCI, with increased GFAP expression, smaller lesion areas and more limited diffusion of CD68-positive cells after 1 week post-injury compared to controls. The number of CD68-positive cells was also reduced in 17beta-estradiol-treated rats one week post-SCI. However, these differences between 17beta-estradiol-treated and control rats disappeared after 4 weeks. These results suggest that 17beta-estradiol protects the spinal cord by stimulating early cytokines release and astroglial responses. These stimulations may prevent the area of damage from expanding and inflammatory cells to spread in the surrounding tissue during the critical first week following SCI. Although transient, these effects improved the locomotor recovery that was sustained over 4 weeks after injury

    Inflammaging in the intervertebral disc

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    Degeneration of the intervertebral disc – triggered by ageing, mechanical stress, traumatic injury, infection, inflammation and other factors – has a significant role in the development of low back pain. Back pain not only has a high prevalence, but also a major socio-economic impact. With the ageing population, its occurrence and costs are expected to grow even more in the future. Disc degeneration is characterized by matrix breakdown, loss in proteoglycans and thus water content, disc height loss and an increase in inflammatory molecules. The accumulation of cytokines, such as interleukin (IL)-1ÎČ, IL-8 or tumor necrosis factor (TNF)-α, together with age-related immune deficiency, leads to the so-called inflammaging – low-grade, chronic inflammation with a crucial role in pain development. Despite the relevance of these molecular processes, current therapies target symptoms, but not underlying causes. This review describes the biological and biomechanical changes that occur in a degenerated disc, discusses the connection between disc degeneration and inflammaging, highlights factors that enhance the inflammatory processes in disc pathologies and suggests future research avenues.ISSN:2514-183

    Beurteilung funktioneller EinschrĂ€nkungen bei degenerativen Erkrankungen der LendenwirbelsĂ€ule: Wer hat Recht – der Arzt, der Patient oder der objektive Test?

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    Zusammenfassung. Zur exakten Erfassung von Schmerzen, funktionellen EinschrĂ€nkungen und gesundheitsbezogener LebensqualitĂ€t bei Patienten mit degenerativen WirbelsĂ€ulenerkrankungen existiert eine Reihe validierter Messinstrumente. Neben der Beurteilung durch den Therapeuten sowie «subjektiven» patientenorientierten Messmethoden (PROMs) wurde in den vergangenen Jahren der «Timed Up and Go»(TUG)-Test systematisch untersucht und als krankheitsspezifisches Messinstrument validiert. Heute kann eine objektive funktionelle EinschrĂ€nkung (OFI = Objective Functional Impairment) in wenigen Sekunden und kostenfrei mithilfe einer Smartphone-Applikation bestimmt werden. Die Bestimmung von Z- oder T-Werten, die TUG-Testergebnisse in Relation zur Populationsnorm setzen, ermöglichen eine alters- und geschlechtsadjustierte Ergebnisinterpretation. Diese Übersichtsarbeit fasst die aktuellen Erkenntnisse zu objektiven Messmethoden bei degenerativen WirbelsĂ€ulenpathologien inklusive deren Vor- und Nachteile zusammen und vergleicht sie mit den bisherigen Beurteilungsmethoden fĂŒr funktionelle Outcomes. </jats:p

    Regional Versus General Anesthesia: Effect of Anesthetic Techniques on Clinical Outcome in Lumbar Spine Surgery: A Prospective Randomized Controlled Trial.

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    BACKGROUND There are only a few prospective clinical trials investigating the effects of different anesthetic techniques on clinical outcomes after lumbar spine surgery. The purpose of this study was to evaluate clinical outcomes in patients receiving general (GA) and regional anesthesia (RA) for lumbar spine surgery. METHODS This was a single-center, 2-arm, trial in which 100 patients undergoing lumbar spine surgery were randomized to receive either RA or GA (50 per group). The primary endpoint was morphine consumption during the first postoperative 48 hours. In addition, anesthesia time, transition time (defined as time from end of surgery to admission to the postoperative anesthesia care unit), visual analogue scale (VAS) for pain, and patient satisfaction at hospital discharge were recorded. RESULTS There was no difference in the primary endpoint (cumulative morphine consumption at 48 h) between the 2 anesthesia types. Anesthesia and transition times were significantly shorter in the RA compared with the GA group-anesthesia time 125.4±23.6 minutes for GA versus 99.4±13.5 minutes for RA, transition time 22.5 minutes for GA versus 10.0 minutes for RA (both P<0.001). The VAS for pain on arrival to the postoperative anesthetic care unit was lower for patients who received RA compared with GA (crude and adjusted, both <0.001). 84% of patients in the RA group were completely satisfied compared with 74% in the GA group (P<0.001). There was a significant difference in the sex analysis for VAS for pain over time; females reported higher VAS for pain from the preoperative assessment to 6 weeks after the operation (P<0.001). CONCLUSIONS There was no difference in postoperative morphine consumption in patients receiving GA and RA for lumbar spine surgery. RA was associated with shorter anesthesia and transition times, lower VAS for pain at arrival at the postoperative anesthesia care unit, and higher patient satisfaction at hospital discharge
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