Uncategorized

Dexmedetomidine could be an ideal adjuvant to propofol during gastrointestinal endoscopy because it provides both analgesia and sedation without respiratory depression. This study investigates the effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy METHODS: 90 adult patients were randomly assigned to Group Control , Group DEX0.5 (0.5 μg/kg dexmedetomidine), or Group DEX1.0 (1.0 μg/kg dexmedetomidine) . Anaesthesia during endoscopy was implemented by plasma target-controlled infusion (TCI) of propofol with different doses of dexmedetomidine. TCI concentration of the first patient for each group was 2.5 μg/ml and the consecutive adjacent concentration gradient was 0.5 μg/mL. EC of propofol by TCI for gastrointestinal endoscopy was determined by using the modified Dixon's up-and-down method. Cardiovascular variables were also measured.

Cognitive behavioral therapy for chronic pain (CBT-CP) is an evidence-based treatment for improving functioning and pain intensity for people with chronic pain with extensive evidence of effectiveness. However, there has been relatively little investigation of the factors associated with successful implementation and uptake of CBT-CP, particularly clinician and system level factors. This formative evaluation examined barriers and facilitators to the successful implementation and uptake of CBT-CP from the perspective of CBT-CP clinicians and referring primary care clinicians.

Polymyalgia rheumatica and giant cell arteritis are systemic inflammatory conditions of the elderly. Polymyalgia rheumatica classically presents as a bilateral proximal muscle pain and stiffness syndrome. Biceps tenosynovitis is the commonest pathology in polymyalgia rheumatica. However according to literature, erosive sternoclavicular arthritis is a rare association of polymyalgia rheumatica. Giant cell arteritis is an inflammatory granulomatous arteritis predominantly involving large cerebral arteries. Thus, its classic clinical presentation includes severe headache with scalp tenderness, jaw claudication, and sudden painless loss of vision. Urological manifestations (prostatic vasculitis and epididymo-orchitis) were seldom reported in giant cell arteritis.

As one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA), interstitial lung disease (ILD) is still challenging due to unrevealed pathophysiological mechanism. To address this question, in the present study, we used the classical collagen-induced arthritis (CIA) mouse model to determine the related-immune mechanism of lung injury and possible pharmacological treatment for RA-ILD. At the peak of arthritis, we found CIA mice developed apparent lung injury, characterized by interstitial thickening, inflammatory cell infiltration, and lymphocyte follicle formation. Additionally, the endothelial injury occurred as the number of endothelial cells (ECs) and their CD31 expression decreased. Along with those, monocytes, predominantly Ly6C monocytes with pro-inflammatory phenotype, were also increased. While in the remission period of arthritis, ECs gradually increased with retrieved CD31 expression, leading to decreased infiltrating monocytes, but boosted Ly6C population. Ly6C monocytes were prone to locate around damaged ECs, promoted ECs proliferation and vascular tube formation, and lessened the expression of adhesion molecules. In addition, we evaluated angiotensin II type 2 receptor (Agtr2), which has been demonstrated to be protective against lung injury, could be beneficial in RA-ILD. We found elevated Agtr2 in CIA lung tissue, and activation of Agtr2, within its specific agonist C21, alleviated the pulmonary inflammation in vivo, reduced ECs injury, and promoted monocytes conversion from Ly6C to Ly6C monocytes in vitro. Our data reveal a potential pathological mechanism of RA-ILD that involves ECs damage and inflammatory monocytes infiltration and provide a potential drug target, Agtr2, for RA-ILD treatment.

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract (GI). Currently, the treatment options for IBD are limited. It has been reported that a novel bioactive mitochondrial-derived peptide (MOTS-c) encoded in the mitochondrial 12S rRNA, suppresses inflammatory response by enhancing the phagocytosis of macrophages. The aim of this study was to investigate the protective effects of MOTS-c against dextran sulfate sodium (DSS)-induced colitis. The results showed that intraperitoneal (i.p.) administration of MOTS-c significantly ameliorated the symptoms of DSS-induced experimental colitis, such as body weight loss, colon length shortening, diarrhea, and histological damage. MOTS-c down-regulated the expression of pro-inflammatory cytokines, decreased the plasma levels of myeloperoxidase, and inhibited the activation of macrophages and recruitment of neutrophils. Moreover, treatment with MOTS-c exhibited anti-apoptotic effects and significantly suppressed the phosphorylation of AMPKα1/2, ERK, and JNK. Notably, oral administration of MOTS-c did not result in any significant improvements. Screening of cell penetrating peptides was performed, (PRR)5 was linked to the C-terminus of MOTS-c through a linker to synthesize a new molecule (termed MP) with better penetration into the colon epithelium. In vitro experiments revealed the longer half-life of MP than MOTS-c, and in vivo experiments showed that oral administration of MP significantly ameliorated DSS-induced colitis. CONCLUSION: The present results demonstrate a protective role of MOTS-c in experimental IBD.

There is considerable clinical evidence that topiramate (TPM) has a high potential in the treatment of refractory and super-refractory status epilepticus (RSE, SRSE). Because TPM is only approved for oral administration, it is applied as suspension via a nasogastric tube for SE treatment. However, this route of administration is impractical in an emergency setting and leads to variable absorption with unpredictable plasma levels and time to peak concentration. Thus, the development of an intravenous (i.v.) solution for TPM is highly desirable. Here we present data on two parenteral formulations of TPM that are currently being developed. One of these solutions is using sulfobutylether-β-cyclodextrin (SBE-β-CD; Captisol®) as an excipient. A 1% solution of TPM in 10% Captisol® has been reported to be well tolerated in safety studies in healthy volunteers and patients with epilepsy or migraine, but efficacy data are not available. The other solution uses the FDA- and EMA-approved excipient amino sugar meglumine. Meglumine is much more effective to dissolve TPM in water than Captisol®. A 1% solution of TPM can be achieved with 0.5-1% of meglumine. While the use of Captisol®-containing solutions is restricted in children and patients with renal impairment, such restrictions do not apply to meglumine. Recently, first-in-human data were reported for a meglumine-based solution of TPM, indicating safety and efficacy when used as a replacement for oral administration in a woman with epilepsy. Based on the multiple mechanisms of action of TPM that directly target the molecular neuronal alterations that are thought to underlie the loss of efficacy of benzodiazepines and other anti-seizure medications during prolonged SE and its rapid brain penetration after i.v. administration, we suggest that parenteral (i.v.) TPM is ideally suited for the treatment of RSE and SRSE. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Gelsemiumelegans(Gardner. & Chapm.) Benth. has long been considered a traditional Chinese medicine effective against rheumatoid pain, cancer, cirrhosis, and skin diseases. Koumine (KM), the most abundant alkaloid in G.elegans Benth., demonstrates a variety of biological effects, including antitumor, analgesic, anxiolytic, anti-inflammatory, antidepressant, antioxidant, immunoregulatory, and hepatoprotective effects. Furthermore, the relatively low toxicity of KM makes it a promising drug candidate. This study aimed to investigate the protective effects of KM and its possible mechanisms using a concanavalin A (Con A)-induced autoimmune hepatitis (AIH) model in mice. Mice were orally administered different doses of KM for 14 d before Con A tail vein injections. The effects of KM on serum biochemical markers and liver histopathology were then evaluated 12 h after Con A exposure. The Nrf2 and NF-κB signaling pathways and alterations in gut microbiota were determined using western blotting, immunohistochemistry, and 16S rRNA sequencing to explore the underlying mechanisms of KM exposure. KM pretreatment dose-dependently decreased serum liver injury markers (Alanine aminotransferase, and aspartate aminotransferase) and cytokine levels (Tumor necrosis factor-α and interleukin-6), as well as the liver pathological damage triggered by Con A. Furthermore, the results of the multi-technique analysis indicated that KM activated the Nrf2 pathway, upregulated the expression of anti-oxidation factors HO-1 and Nrf2, and downregulated the expression of Keap1. Moreover, the NF-κB signaling pathway was inhibited. Interestingly, pre-treatment with KM also significantly improved the composition of the gut microbiota probably because it increases the richness of probiotics. Our findings suggest that KM pretreatment could attenuate Con A-induced AIH, the Nrf2 and NF-κB signaling pathways, and that gut microbiota are involved in the process of the hepatoprotective effect. This study provides a theoretical basis for the development of KM as an effective agent against AIH.

Trigeminal neuralgia (TN) is a stubborn head and face neuropathic pain with complex pathogenesis. Patients with TN have a significantly increased risk of central neurodegeneration, which manifests as cognitive impairment and memory loss, but the specific mechanism underlying central nervous degeneration is still unclear. This study aimed to explore central neurodegeneration and its possible mechanism of action in TN rats based on changes in the brain fatty acid content and microglia-related neuroinflammation. Using a TN neuropathic pain model established by us, we found that TN rats have obvious cognitive impairment. Furthermore, changes in the brain fatty acid content were analyzed using gas chromatography-mass spectrometry (GC-MS). It was found that the docosahexaenoic acid (DHA) content in the central nervous system (CNS) of TN rats was significantly decreased compared to that in the CNS of Sham rats. An important component in maintaining brain cognition, DHA also plays a key role in regulating central neuroinflammation. Here, by continuous supplementation of DHA, the CNS DHA content was increased to a certain extent in TN rats. The cognitive impairment of TN rats was improved after restoring the central DHA level; this may be related to the improvement of neuroinflammation through the DHA-mediated regulation of microglial polarization. Overall, this study provides a theoretical basis for explaining the pathogenesis of central neurodegeneration in TN. It also suggests DHA as a target for protecting the CNS of patients with TN from damage.

Dementia is an urgent public health problem worldwide, and the determination of the contribution of pain to cognitive decline or dementia is significant for the prevention of dementia.

This review synthesizes recent findings related to the biopsychosocial processes that underlie racial disparities in chronic pain, while highlighting opportunities for interventions to reduce disparities in pain treatment among BIPOC.