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Auris, Nasus, Larynx Jun 2024Idiopathic sudden sensorineural hearing loss (ISSNHL) is characterized by abruptly appearing hearing loss, sometimes accompanied by vertigo. Vascular pathologies (e.g.,... (Review)
Review
Idiopathic sudden sensorineural hearing loss (ISSNHL) is characterized by abruptly appearing hearing loss, sometimes accompanied by vertigo. Vascular pathologies (e.g., cochlear ischemia, or cochlear infarction) are one of the most likely causes of ISSNHL. This review aims to present current understanding of inner ear anatomy, clinical features of ISSNHL, and its treatment strategies. The labyrinthine artery is the only end artery supplying blood to the inner ear, and it has three branches: the anterior vestibular artery, the main cochlear artery, and the vestibulo-cochlear artery (VCA). Occlusion of the VCA can be caused by a variety of factors. The VCA courses through a narrow bone canal. ISSNHL is usually diagnosed after excluding retrocochlear pathologies of sudden sensorineural hearing loss (SSNHL), such as vestibular schwannoma. Therefore, a head MRI or assessing auditory brainstem responses are recommended for patients with SSNHL. Severe SSNHL patients with high CHADS scores, an index of stroke risk, have a significantly lower rate of vestibular schwannoma than severe SSNHL patients with low CHADS scores, suggesting that severe ISSNHL in individuals at high risk of stroke is caused by vascular impairments. Intralabyrinthine hemorrhage causes SSNHL or vertigo, as in ISSNHL. The diagnosis of intralabyrinthine hemorrhage requires careful interpretation of MRI, and a small percentage of patients diagnosed with ISSNHL may in fact have intralabyrinthine hemorrhage. Many studies have reported an association between ISSNHL and atherosclerosis or cardiovascular risk factors (e.g., diabetes mellitus, hypertension, dyslipidemia and cardiovascular disease), and subsequent risk of stroke in patients with ISSNHL may be elevated compared to controls. Increased hearing level on the healthy ear side, high Framingham risk score, high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, and severe white matter lesions may be poor prognostic factors for patients with ISSNHL. The association between thrombosis-related genes and susceptibility to ISSNHL has been reported in many studies (e.g., coagulation factor 2, coagulation factor 5, plasminogen activator inhibitor-1, platelet-associated genes, a homocysteine metabolism-related enzyme gene, endothelin-1, nitric oxide 3, phosphodiesterase 4D, complement factor H, and protein kinase C-eta). Treatment of ISSNHL with the aim of mitigating the vascular impairment in the inner ear includes systemically administered steroids, intratympanic steroid injections, hyperbaric oxygen therapy, prostaglandin E1, defibrinogenation therapy, and hydrogen inhalation therapy, but there is currently no evidence-based treatment for ISSNHL. Breakthroughs in the unequivocal diagnosis and treatment of ISSNHL due to vascular impairment are crucial to improve quality of life.
PubMed: 38850720
DOI: 10.1016/j.anl.2024.05.009 -
BMJ Open Gastroenterology Jun 2024The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH.
METHODS
In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis.
RESULTS
A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25-64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months' treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group.
CONCLUSION
Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group.
TRIAL REGISTRATION NUMBER
NCT05804305.
Topics: Humans; Male; Female; Non-alcoholic Fatty Liver Disease; Middle Aged; Double-Blind Method; Adult; Misoprostol; Interleukin-6; Treatment Outcome; Insulin Resistance; Liver Cirrhosis; Liver Function Tests; Liver
PubMed: 38844374
DOI: 10.1136/bmjgast-2023-001342 -
Archivos Espanoles de Urologia May 2024Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic disease, and its aetiology and pathogenesis remain unclear. This study aimed to identify...
BACKGROUND
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic disease, and its aetiology and pathogenesis remain unclear. This study aimed to identify potential urine and serum biomarkers in patients with IC/BPS to further understand the pathogenesis and diagnosis of the disease.
METHODS
Patients with IC/BPS diagnosed and treated in the First Hospital of Hebei Medical University from 1 July 2021 to 30 July 2023 were selected. The urine and serum biomarkers of 50 patients with IC/BPS were investigated and compared with the urine and serum samples of 50 healthy controls. IBM SPSS Statistics 26.0 was used for statistical analysis of the recorded data by using chi-square test, -test and logistic regression analysis.
RESULTS
Overall, 50 patients with IC/BPS (mean age, 54.20 ± 8.15 years) were included in the study. Those with history of urinary diseases, anxiety or depression were susceptible to IC/BPS. Levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), nerve growth factor, and prostaglandin E2 (PGE2) in urine, as well as IL-8, TNF-α, and PGE2 in serum, were found to significantly increase in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). These differences were statistically significant ( < 0.05). Multifactor analysis showed that anxiety, depression, IL-6, IL-8, TNF-α and PEG2 are risk factors for patients with IC/BPS.
CONCLUSIONS
Multiple biomarkers were identified in the urine and serum of patients with IC/BPS, suggesting a potential close relationship to the pathogenesis of IC/BPS.
Topics: Humans; Cystitis, Interstitial; Biomarkers; Middle Aged; Female; Male; Adult; Tumor Necrosis Factor-alpha; Interleukin-6
PubMed: 38840277
DOI: 10.56434/j.arch.esp.urol.20247704.48 -
BMJ Open Jun 2024Public training in cardiopulmonary resuscitation and treatment in emergency and intensive care unit have made tremendous progress. However, cardiac arrest remains a... (Observational Study)
Observational Study
INTRODUCTION
Public training in cardiopulmonary resuscitation and treatment in emergency and intensive care unit have made tremendous progress. However, cardiac arrest remains a major health burden worldwide, with brain damage being a significant contributor to disability and mortality. Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly localised in the central nervous system, has been previously shown to inhibit postischemia neuronal apoptosis. Therefore, we aim to observe whether serum L-PGDS can serve as a potential biomarker and explore its role in determining the severity and prognosis of patients who have achieved restoration of spontaneous circulation (ROSC).
METHODS AND ANALYSIS
This is a prospective observational study. The participants (n = 60) who achieve ROSC will be distributed into two groups (non-survivor and survivor) based on 28-day survival. Healthy volunteers (n = 30) will be enrolled as controls. Each individual's relevant information will be extracted from Electronic Medical Record System in Xinhua Hospital, including demographic characteristics, clinical data, laboratory findings and so on. On days 1, 3 and 7 after ROSC, blood samples will be drawn and batch tested on the level of serum neuron-specific enolase, soluble protein 100β, L-PGDS, procalcitonin, tumour necrosis factor-alpha and interleukin-6. The cerebral performance category score was assessed on the 28th day after ROSC.
ETHICS AND DISSEMINATION
This study was performed with the approval of the Clinical Ethical Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-C-2023-130-1). The results will be published in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
Chinese Clinical Trial Registry (ChiCTR2300078564).
Topics: Humans; Prospective Studies; Intramolecular Oxidoreductases; Lipocalins; Heart Arrest; Biomarkers; Prognosis; Male; Cardiopulmonary Resuscitation; Female; Predictive Value of Tests; Adult; Middle Aged; Observational Studies as Topic
PubMed: 38839386
DOI: 10.1136/bmjopen-2023-083136 -
Bioorganic Chemistry Aug 2024Targeting protein kinases that regulate signalling pathways in inflammation is an effective pharmacological approach to alleviate uncontrolled inflammatory diseases. In...
Targeting protein kinases that regulate signalling pathways in inflammation is an effective pharmacological approach to alleviate uncontrolled inflammatory diseases. In this context, the natural product indirubin and its 6-bromo-substituted analogue 6-bromoindirubin-3 -glycerol-oxime ether (6BIGOE; 1) were identified as potent inhibitors of glycogen synthase kinase-3β (GSK-3β). These inhibitors suppress the release of pro-inflammatory cytokines and prostaglandins (PG) from human monocytes. However, indirubin derivatives target several protein kinases such as cyclin-dependent kinases (CDKs) which has been a major concern for their application in inflammation therapy. Here, we report on a library of 13 5-bromo-substituted indirubin derivatives that have been designed to improve potency and target selectivity. Side-by-side comparison of reference compound 1 (6BIGOE) with 5-bromo derivatives revealed its isomer 2 (5BIGOE), as the most potent derivative able to supress pro-inflammatory cytokine and PG release in lipopolysaccharide-stimulated human monocytes. Analysis of protein kinase inhibition in intact monocytes, supported by our in silico findings, proposed higher selectivity of 1 for GSK-3β inhibition with lesser potency against CDKs 8 and 9. In contrast, 2 supressed the activity of these CDKs with higher effectiveness than GSK-3β, representing additional targets of indirubins within the inflammatory response. Encapsulation of 1 and 2 into polymer-based nanoparticles (NP) improved their pharmacological potential. In conclusion, the 5- and 6-brominated indirubins 1 and 2 as dual GSK-3β and CDK8/9 inhibitors represent a novel concept for intervention with inflammatory disorders.
Topics: Humans; Monocytes; Indoles; Protein Kinase Inhibitors; Signal Transduction; Structure-Activity Relationship; Molecular Structure; Inflammation Mediators; Dose-Response Relationship, Drug; Lipopolysaccharides; Cytokines; Molecular Docking Simulation
PubMed: 38838619
DOI: 10.1016/j.bioorg.2024.107470 -
Parasites, Hosts and Diseases May 2024Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis...
Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis sinensis infection. Herein, we analyzed the structural and enzymatic properties of sigma-class GST (CsGST-σ) proteins to obtain insight into their antioxidant and immunomodulatory functions in comparison with mu-class GST (CsGST-μ) proteins. CsGST-σ proteins conserved characteristic structures, which had been described in mammalian hematopoietic prostaglandin D2 synthases. Recombinant forms of these CsGST-σ and CsGST-μ proteins expressed in Escherichia coli exhibited considerable degrees of GST and PGS activities with substantially different specific activities. All recombinant proteins displayed higher affinities toward prostaglandin H2 (PGS substrate; average Km of 30.7 and 3.0 μm for prostaglandin D2 [PGDS] and E2 synthase [PGES], respectively) than those toward CDNB (GST substrate; average Km of 1,205.1 μm). Furthermore, the catalytic efficiency (Kcat/Km) of the PGDS/PGES activity was higher than that of GST activity (average Kcat/Km of 3.1, 0.7, and 7.0×10-3 s-1μm-1 for PGDS, PGES, and GST, respectively). Our data strongly suggest that the C. sinensis sigma- and mu-class GST proteins are deeply involved in regulating host immune responses by generating PGD2 and PGE2 in addition to their roles in general detoxification.
Topics: Glutathione Transferase; Clonorchis sinensis; Animals; Intramolecular Oxidoreductases; Recombinant Proteins; Lipocalins; Escherichia coli; Prostaglandin H2; Kinetics
PubMed: 38835261
DOI: 10.3347/PHD.24004 -
Molecular Pain 2024Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked...
Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E (PGE)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.
Topics: Morphine; Animals; Nociceptors; Dinoprostone; Receptors, Opioid, mu; Analgesics, Opioid; Male; Rats; Ganglia, Spinal; Hyperalgesia; Rats, Sprague-Dawley; Dose-Response Relationship, Drug
PubMed: 38828868
DOI: 10.1177/17448069241260348 -
Journal of Musculoskeletal & Neuronal... Jun 2024To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y...
Effects of Combined Application of Percutaneous Vertebroplasty and Zoledronic Acid on Bone Mineral Density, Bone Metabolism, NPY and PGE2 in Elderly Patients with Osteoporotic Lumbar Vertebral Compression Fracture.
OBJECTIVE
To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y (NPY) and prostaglandin E2 (PGE2) in elderly patients with osteoporotic lumbar vertebral compression fracture (OVCF).
METHODS
The medical records of 118 elderly patients with OVCF who received treatment at our hospital from March 2018 to March 2020 were collected and analyzed retrospectively. Vertebral body height, spinal function, pain degree, and lumbar BMD were compared between the two groups upon admission and three years after the operation. Additionally, the levels of bone-specific alkaline phosphatase (BALP), 25-hydroxyvitamin D (25-(OH)D), beta collagen degradation fragments (β-CTx), neuropeptide Y (NPY), and prostaglandin E2 (PGE2) in the two groups were measured at admission and three years after the operation. Furthermore, complications in the two groups within three years after the operation were documented.
RESULTS
After three years post-operation, the combination group showed a significantly greater improvement in vertebral body height compared to the control group (P<0.05). Moreover, the combination group exhibited a significantly lower Oswestry Disability Index (ODI) score compared to the control group (P<0.05).
CONCLUSION
In elderly patients with OVCF, the combined use of zoledronic acid and percutaneous vertebroplasty is effective in improving lumbar function, BMD, and bone metabolism indices, while reducing pain and the levels of NPY and PGE2.
Topics: Humans; Aged; Female; Fractures, Compression; Zoledronic Acid; Male; Vertebroplasty; Lumbar Vertebrae; Dinoprostone; Bone Density; Spinal Fractures; Neuropeptide Y; Osteoporotic Fractures; Aged, 80 and over; Bone Density Conservation Agents; Retrospective Studies; Combined Modality Therapy
PubMed: 38826002
DOI: No ID Found -
The Journal of Allergy and Clinical... May 2024Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs) and leukotrienes (LTs) with a pathophysiological role in established atopic disease....
INTRODUCTION
Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs) and leukotrienes (LTs) with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. We aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease.
METHODS
We quantified the levels of 21 eicosanoids in urine from children from the COPSAC (age 1 year, n=450) and VDAART (age 3 years, n=575) mother-child cohorts and analyzed the associations with development of wheeze/asthma, atopic dermatitis, and biomarkers of Type-2 inflammation, applying FDR5% multiple testing correction.
RESULTS
In both cohorts, analyses adjusted for environmental determinants showed that higher TXA2 eicosanoids in early life were associated with increased risk of developing atopic dermatitis (P
CONCLUSIONS
This study suggests that early life perturbations in the eicosanoid metabolism are present before the onset of atopic disease in childhood, which provides pathophysiological insight in the inception of atopic diseases.
PubMed: 38825025
DOI: 10.1016/j.jaci.2024.05.022 -
Prostaglandins, Leukotrienes, and... Feb 2024We examined the relationship between Apolipoprotein E (APOE) genotype and n-3 highly unsaturated fatty acid (HUFA) levels in participants of the seAFOod trial, who were... (Randomized Controlled Trial)
Randomized Controlled Trial
APOE genotype, eicosapentaenoic acid (EPA) supplementation and n-3 highly unsaturated fatty acid (HUFA) levels in patients with multiple colorectal polyps: A secondary analysis of the seAFOod polyp prevention trial.
INTRODUCTION
We examined the relationship between Apolipoprotein E (APOE) genotype and n-3 highly unsaturated fatty acid (HUFA) levels in participants of the seAFOod trial, who were undergoing colonoscopy surveillance after removal of colorectal polyps.
METHODS
Baseline and on-treatment (eicosapentaenoic acid [EPA] 2 g daily or placebo for 6 months) levels of n-3 HUFAs, and plasma 18-hydroxyeicosapentaenoic acid (HEPE), were analysed according to APOE genotype (based on polymorphisms rs429358 and rs7412) in 584 participants.
RESULTS
Before treatment, APOE2/2 individuals had lower levels, and APOE4/4 participants had higher levels, of n-3 HUFAs, including EPA, than APOE3/3 counterparts (P < 0.01 for the APOE2/2 versus APOE4/4 comparison). After EPA supplementation, n-3 HUFA levels were not significantly different when stratified by APOE genotype, although APOE4 carriers displayed lower plasma 18-HEPE levels than individuals without an APOE4 allele (P = 0.002).
CONCLUSIONS
APOE genotype is associated with differential n-3 HUFA and 18-HEPE levels in individuals with multiple colorectal polyps.
Topics: Humans; Eicosapentaenoic Acid; Female; Male; Middle Aged; Dietary Supplements; Fatty Acids, Omega-3; Apolipoproteins E; Genotype; Aged; Colonic Polyps; Seafood
PubMed: 38823349
DOI: 10.1016/j.plefa.2024.102623