Plos One
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Evidence is conflicting with regards to the role of vitamin D in statin induced myalgia (SIM). Studies so far have assessed cross-sectional association and were limited by study sample selected predominantly from cardiology clinics. In this retrospective cohort study we assessed the association between vitamin D and SIM and attempted to establish a serum vitamin D cutoff to identify patients at risk for developing SIM. ⋯ Low vitamin D level at statin initiation is associated with SIM, levels ≤15 ng/ml have a high predictive accuracy for SIM. Randomized controlled trials are needed to validate our results.
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Opioids, acting at μ opioid receptors, are commonly used for pain management. Chronic opioid treatment induces cellular adaptations, which trigger long-term side effects, including constipation mediated by enteric neurons. We tested the hypothesis that chronic opioid treatment induces alterations of μ opioid receptor signaling in enteric neurons, which are likely to serve as mechanisms underlying opioid-induced constipation. ⋯ This study showed that opioids induce endocytosis- and dynamin-dependent MAPK/ERK activation in enteric neurons and that chronic morphine treatment triggers changes at the receptor level and downstream signaling resulting in MAPK/ERK-dependent CREB activation. Blockade of this signaling pathway prevents the development of gastrointestinal motility impairment induced by chronic morphine treatment. These findings suggest that alterations in μ opioid receptor downstream signaling including MAPK/ERK pathway in enteric neurons chronically treated with morphine contribute to the development of opioid-induced constipation.
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Clinical Trial
Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol.
Recent studies using electroencephalography (EEG) suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC). Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA), deep sedation (SED), loss (LOC) and return of consciousness (ROC) by gathering full 10/20 system human EEG data in ten healthy male subjects. ⋯ However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back) connectivity suggests a propofol concentration dependent association and is not directly related to the level of consciousness per se.
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Clinical Trial
Spinal fMRI reveals decreased descending inhibition during secondary mechanical hyperalgesia.
Mechanical hyperalgesia is one distressing symptom of neuropathic pain which is explained by central sensitization of the nociceptive system. This sensitization can be induced experimentally with the heat/capsaicin sensitization model. The aim was to investigate and compare spinal and supraspinal activation patterns of identical mechanical stimulation before and after sensitization using functional spinal magnetic resonance imaging (spinal fMRI). ⋯ Comparison of voxel-based activation patterns during mechanical stimulation before/after sensitization showed deactivations in RVM and activations in superficial ipsilateral dGM. This study revealed increased spinal activity and decreased activity in supraspinal centers involved in pain modulation (SRD, RVM, DLPT) during secondary mechanical hyperalgesia suggesting facilitation of nociception via decreased endogenous inhibition. Results should help prioritize approaches for further in vivo studies on pain processing and modulation in humans.
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Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication of liver transplantation. For early detection of AKI, various urinary biomarkers such as monocyte chemotactic protein-1, liver-type fatty acid-binding protein, interleukin-18, osteopontin, cystatin C, clusterin and neutrophil gelatinase-associated lipocalin (NGAL) have been identified. Here, we attempt to identify urinary biomarkers for the early detection of tacrolimus-induced AKI in liver transplant patients. ⋯ The area under the receiver operating characteristics curve of urinary NGAL was 0.876 (95% confidence interval, 0.800-0.951; P<0.0001), which was better than those of the other six urinary biomarkers. In addition, the urinary levels of NGAL at postoperative day 1 (p = 0.0446) and day 7 (p = 0.0006) can be a good predictive marker for tacrolimus-induced AKI within next 6 days, respectively. In conclusion, urinary NGAL is a sensitive biomarker for tacrolimus-induced AKI, and may help predict renal event caused by tacrolimus therapy in liver transplant patients.