1,721,032 research outputs found
The role of neuroinflammatory modulation on POCD development following surgery
Full text linkThe effects of peripheral surgery-induced inflammation and the role of the proinflammatory
cytokine interleukin 1-beta (IL-1β) on cognitive function in mouse in
several different contexts are explored.
Lipopolysaccharide (LPS)-induced inflammation, but not isoflurane-induced
anaesthesia, results in memory impairment in mouse, causing a permanent retrograde
amnesia in contextual fear-conditioning tests. Blocking the action of IL-1β reduces
the hippocampal memory deficit induced by LPS.
Peripheral orthopaedic surgery results in inflammation in the brain and
cognitive impairment in a mouse model of orthopaedic surgery. Such surgery is
associated with increased levels of IL-1β in the serum and in the hippocampus. It also
induces hippocampal microgliosis without being associated with an increase in
apoptosis. Injection of an interleukin 1 receptor antagonist (IL1-ra) results in reduced
microgliosis and reduced IL-1β levels in the serum and in the hippocampus.
The inflammatory response to such surgical insult also results in impairment of
remote (pre-frontal cortex (PFC)) localised memory in mouse as assessed by two tests
of contextual remote memory. Such impairment is not accompanied by an increase in
IL-1β in the PFC. There is also a reduction in the level of hippocampal brain derived
neurotrophic factor (BDNF) which may contribute to the impairment of memory after
such surgery.
The murine anxiety response to peripheral orthopaedic surgery, as assessed
using the social interaction test, shows that surgery does not increase anxiety in our
animal model of peripheral surgery. Nor does such surgery affect olfactory memory
under the conditions presented on the olfactory habituation-dishabituation task.
A sub-pyrogenic dose of LPS alone fails to impair memory function. However,
when the same is administered prior to peripheral surgery, it exacerbates surgery-induced
cognitive dysfunction as assessed by fear-conditioning tests. It causes a
concomitant additional increase in the levels of IL-1β in both plasma and
hippocampus of those animals
Xenon-anaesthesia and beyond: pros-contras
No full textXenon is a colourless and odourless noble gas, licensed for human use as an anaesthetic gas as well as a radiological marker. The MAC of this gas is about 63% but Xenon anaesthesia is associated with fast recovery of cognitive function and cardiovascular stability. Nevertheless, Postoperative nausea and vomiting (PONV) incidence for xenon anaesthesia is very high. Xenon has been reported to have cytoprotective effects that may have therapeutic values in both CNS protection, and in organ graft preservation. Currently, there are few studies about the effect of Xenon on ischaemia reperfusion injury of transplantable organs and insufficient clinical data upon its effect on intracranial and cerebral perfusion pressure. We shortly review pros and contras of Xenon, as an anaesthetic agent
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Anaesthetics affect cancer cell biology through cellular signalling and metabolic modulations
Full text linkSurgery remains the first-line treatment for most cancer types. However, anaesthetic use during surgery may influence cancer cell biology and hence affect cancer recurrence. The current PhD study project objective is to evaluate the effects of two general anaesthetics, sevoflurane (inhalational) and propofol (intravenous), on cancer cells. This study intends to understand the impact of anaesthetics on cancer recurrence following surgery and ultimately provide the research rationale of clinical study/trials for improving cancer surgical outcomes.
Propofol inhibited lung, colonic, renal, and ovarian cancer cell malignancy in a dose- dependent manner through regulating PEDF* and HIF-1α expressions. Propofol also altered the metabolites of lung, colonic, renal, and ovarian cancer cells that inhibited the lung and ovarian cancer cell glucose metabolism. It was demonstrated that propofol inhibited lung cancer cell malignancy through downregulating GLUT1 and MPC1, thus disturbing glucose metabolism. These processes induced the high PEDF expression, which downregulated HIF-1α via the Akt pathways, thus regulated pro- and anti-tumour genes. However, propofol neither inhibited brain cancer cell malignancy nor affected the above molecular entities.
In contrast, sevoflurane enhanced colonic, renal and ovarian cancer cell malignancy through upregulating VEGFA. Sevoflurane upregulated GLUT1, MPC1 and GLUD1, which enhanced ovarian cancer cellular glucose metabolism. These changes inhibited PEDF expression, and its reduction resulted in upregulating HIF-1α via the Erk pathway, which upregulated two pro-tumour gene-encoded proteins, namely CXCL12 and CXCR4. However, propofol had the opposite effect on these cellular signalling and metabolic pathways in ovarian cancer cells. In summary, this PhD project demonstrated that sevoflurane may have pro-tumour while propofol might have anti-cancer properties. According to laboratory evidence found in the current study, propofol, unlike sevoflurane, may benefit cancer surgery patients. The work presented in this thesis may provide a foundation for further clinical studies to optimise the anaesthesia regimen for better surgical outcomes following cancer surgery.Open Acces
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Bv8 mediates myeloid cell migration and enhances malignancy of colorectal cancer
No full textColorectal cancer (CRC) is the third most predominant malignancy in the world. Although the
importance of immune system in cancer development has been well established, the
underlying mechanisms remain to be investigated further. My PhD project studied a novel
protein prokineticin 2 (Prok2, also known as Bv8) as a key pro-tumoural factor in CRC
progression in in vitro and ex vivo settings.
Immunostaining of human samples collected from cancer patients indicated myeloid cell
infiltration (especially neutrophils) and Bv8 accumulation in colorectal tumour tissue. Bv8
shows chemotactic effects on human neutrophils through real-time chemotaxis assay, with
neutrophils presenting a Bv8 gradient-dependent movement pattern. CRC cells produced
reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF) that were
triggered by myeloid cells and Bv8. ROS and VEGF acted as pro-angiogenesis buffer in myeloid
cell-infiltrated CRC microenvironment. Moreover, leukocytes from studied patients with
malignant tumours were more susceptible to produce ROS compared to patients with benign
tumours. Myeloid cell or Bv8 enhanced energy consumption of glycolysis ATP and
mitochondria ATP of CRC cells. Interestingly, cell-cell interaction between myeloid cells and
CRC cells increased CRC cell viability but decreased the viability of myeloid cells (U937 cells).
On the other hand, Bv8 showed no effect on cell viability and proliferation of CRC cells. ERK
signalling pathway in CRC cells was activated by both Bv8 and co-cultured myeloid cells,
indicating its regulatory role in Bv8-induced effects on CRC cells. Further data potentially
suggested that Bv8 was negatively regulated in the tumour microenvironment of CRC, being
maintained at a delicate level with a maximum pro-tumoural potential. In conclusion, my PhD
PhD Thesis Xiaomeng Li
5
project presents the vital roles of Bv8 in myeloid cell infiltration and CRC development,
suggesting that Bv8 is a potential therapeutic target for cancer-related immunotherapy.Open Acces
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.
No full textBACKGROUND: Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)-associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ). OBJECTIVE: We asked whether isoflurane and propofol have differential effects on the tau/Aβ ratio (the primary outcome), and individual AD biomarkers. We also examined whether genetic/intraoperative factors influenced perioperative changes in AD biomarkers. METHODS: Patients undergoing neurosurgical/otolaryngology procedures requiring lumbar cerebrospinal fluid (CSF) drain placement were prospectively randomized to receive isoflurane (n = 21) or propofol (n = 18) for anesthetic maintenance. We measured perioperative CSF sample AD markers, performed genotyping assays, and examined intraoperative data from the electronic anesthesia record. A repeated measures ANOVA was used to examine changes in AD markers by anesthetic type over time. RESULTS: The CSF tau/Aβ ratio did not differ between isoflurane- versus propofol-treated patients (p = 1.000). CSF tau/Aβ ratio and tau levels increased 10 and 24 h after drain placement (p = 2.002×10-6 and p = 1.985×10-6, respectively), mean CSF p-tau levels decreased (p = 0.005), and Aβ levels did not change (p = 0.152). There was no interaction between anesthetic treatment and time for any of these biomarkers. None of the examined genetic polymorphisms, including ApoE4, were associated with tau increase (n = 9 polymorphisms, p > 0.05 for all associations). CONCLUSION: Neurosurgery/otolaryngology procedures are associated with an increase in the CSF tau/Aβ ratio, and this increase was not influenced by anesthetic type. The increased CSF tau/Aβ ratio was largely driven by increases in tau levels. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations
Anaesthetics influence leukaemia cell biology and malignancy: Mechanisms and Implications
Full text linkAcute lymphoblastic leukaemia (ALL) is the most common type of cancer in children. During ALL treatments, general anaesthetics are often used on patients undergoing painful procedures. General anaesthetics have been shown to influence cancer cell biology in solid cancer models. However, no study has been published regarding the effects of anaesthetics on leukaemia. To further our understanding, the objective of this thesis is to compare the effects of two commonly used general anaesthetics (intravenous: propofol and inhalational: sevoflurane) on ALL in vitro and in vivo.
Propofol and sevoflurane reduce proliferation, CXCR4 expression, osteopontin (OPN) secretion and migration of leukaemia cells in vitro. In addition, both anaesthetics reduce homing and migration of leukaemia cells in vivo. Upon further investigation, hypoxia-inducible factor-1 alpha (HIF-1α) is responsible for induced molecular changes in leukaemia cells. HIF-1α is reduced by propofol in a dose-dependent manner, and its effect is relatively short-term (<24 hours). On the other hand, HIF-1α is inhibited by sevoflurane in a time-dependent manner with more sustainable effects lasting more than 24 hours. The reduction of HIF-1α expression by propofol is likely due to the inhibition of the phosphorylation of ERK and AKT. Sevoflurane only decreases the phosphorylation of ERK. Chemoresistance study reveals both propofol and sevoflurane enhance the cytotoxic effect of the chemotherapeutic agent (Ara-C). Both anaesthetics are shown to potentiate caspase-based apoptotic pathways when given together with Ara-C to leukaemia cells.
In addition to HIF-1α, OPN is shown to regulate anaesthetic induced molecular changes in leukaemia cells in vitro. Upon further investigation, OPN forms an auto feedback loop with HIF-1α in leukaemia cells, regulating CXCR4 expression, migration and chemoresistance of leukaemia cells in vitro.
In summary, our data demonstrate both propofol and sevoflurane may potentially reduce the malignancy of ALL.Open Acces
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