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Investigative Ophthalmology & Visual... Jul 2024Glucocorticoid-induced glaucoma (GIG) is a prevalent complication associated with glucocorticoids (GCs), resulting in irreversible blindness. GIG is characterized by the...
PURPOSE
Glucocorticoid-induced glaucoma (GIG) is a prevalent complication associated with glucocorticoids (GCs), resulting in irreversible blindness. GIG is characterized by the abnormal deposition of extracellular matrix (ECM) in the trabecular meshwork (TM), elevation of intraocular pressure (IOP), and loss of retinal ganglion cells (RGCs). The objective of this study is to investigate the effects of nicotinamide riboside (NR) on TM in GIG.
METHODS
Primary human TM cells (pHTMs) and C57BL/6J mice responsive to GCs were utilized to establish in vitro and in vivo GIG models, respectively. The study assessed the expression of ECM-related proteins in TM and the functions of pHTMs to reflect the effects of NR. Mitochondrial morphology and function were also examined in the GIG cell model. GIG progression was monitored through IOP, RGCs, and mitochondrial morphology. Intracellular nicotinamide adenine dinucleotide (NAD+) levels of pHTMs were enzymatically assayed.
RESULTS
NR significantly prevented the expression of ECM-related proteins and alleviated dysfunction in pHTMs after dexamethasone treatment. Importantly, NR protected damaged ATP synthesis, preventing overexpression of mitochondrial reactive oxygen species (ROS), and also protect against decreased mitochondrial membrane potential induced by GCs in vitro. In the GIG mouse model, NR partially prevented the elevation of IOP and the loss of RGCs. Furthermore, NR effectively suppressed the excessive expression of ECM-associated proteins and mitigated mitochondrial damage in vivo.
CONCLUSIONS
Based on the results, NR effectively enhances intracellular levels of NAD+, thereby mitigating abnormal ECM deposition and TM dysfunction in GIG by attenuating mitochondrial damage induced by GCs. Thus, NR has promising potential as a therapeutic candidate for GIG treatment.
Topics: Animals; Niacinamide; Pyridinium Compounds; Glucocorticoids; Mice, Inbred C57BL; Mitochondria; Mice; Glaucoma; Extracellular Matrix; Intraocular Pressure; Humans; Disease Models, Animal; Trabecular Meshwork; Cells, Cultured; Retinal Ganglion Cells; Reactive Oxygen Species; Dexamethasone; Male
PubMed: 38949632
DOI: 10.1167/iovs.65.8.1 -
Obstetrics and Gynecology Jul 2024
Randomized Controlled Trial
Topics: Humans; Infant, Newborn; Female; Pregnancy; Respiratory Distress Syndrome, Newborn; Infant, Premature; Prenatal Care; Glucocorticoids
PubMed: 38949545
DOI: 10.1097/AOG.0000000000005619 -
Obstetrics and Gynecology Jul 2024
Randomized Controlled Trial
Topics: Humans; Infant, Newborn; Female; Pregnancy; Respiratory Distress Syndrome, Newborn; Infant, Premature; Prenatal Care; Glucocorticoids
PubMed: 38949543
DOI: 10.1097/AOG.0000000000005589 -
A&A Practice Jul 2024Lumbar sympathetic blocks (LSBs) are used to treat sympathetically mediated pain in the lower extremities, kidneys, ureters, and genitals. LSBs use local anesthetic to...
Lumbar sympathetic blocks (LSBs) are used to treat sympathetically mediated pain in the lower extremities, kidneys, ureters, and genitals. LSBs use local anesthetic to block the sympathetic system to modulate pain response. In this case report, an avid runner was diagnosed with synovial plica syndrome. His pain was refractory to arthroscopic plica excision, physical therapy, nonsteroidal anti-inflammatory drugs, and intraarticular steroid injections. He received 3 rounds of LSB resulting in significant and sustained pain relief. This case suggests that LSB successfully treated knee pain from synovial plica syndrome and there may be a sympathetic component to this disease state.
Topics: Humans; Male; Autonomic Nerve Block; Knee Joint; Syndrome
PubMed: 38949224
DOI: 10.1213/XAA.0000000000001810 -
JPMA. the Journal of the Pakistan... Jun 2024
Topics: Humans; Carpal Tunnel Syndrome; Treatment Failure; Glucocorticoids; Injections, Intra-Articular
PubMed: 38949007
DOI: 10.47391/JPMA.11142 -
JPMA. the Journal of the Pakistan... Jun 2024To compare the efficacy of tocotrienol and tocopherol in the management of patients with atherosclerotic cardiovascular diseases. (Comparative Study)
Comparative Study
OBJECTIVE
To compare the efficacy of tocotrienol and tocopherol in the management of patients with atherosclerotic cardiovascular diseases.
METHODS
The systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines 2020, and comprised literature search from 2002 till January 5, 2023, on PubMed, Google Scholar, Cochrane Library, Google, Wiley-Inter Science Library, Medline, SpringerLink, Taylor and Francis databases. The search was conducted using key words, such as: "tocopherol", "tocotrienol", "vitamin E", "dyslipidaemia", "cardiovascular diseases" "cardioprotective", "hypercholesterolemia" and "atherosclerosis" along with Boolean operators. Human clinical studies regarding the use of tocotrienol or tocopherol or comparison of its efficacy in patients having atherosclerosis, dyslipidaemia leading to cardiovascular diseases, and studies including details of efficacy of any of the four alpha, beta, gamma, delta isomers of tocopherol or tocotrienol were included. Pertinent data from the eligible studies was retrieved and reviewed.
RESULTS
Of the 516 articles identified, 26 (5%) articles met eligibility criteria. Of them 5(19%) were subjected to detailed analysis. Tocotrienol showed significant anti-oxidant efficacy at (250 mg/d) by decreasing cholesterol and serum inflammatory biomarkers i.e C-reactive protein (40%), malondialdehyde (34%), gamma-glutamyl transferase (22%) (p<0.001). Total anti-oxidant status (TAS) levels raised 22% (p<0.001) and Inflammatory cytokines i.e resistin, interleukin (IL)-1, IL-12, Interferon-gamma were decreased 15-17% (p<0.05-0.01) respectively by tocotrienol. Several microRNA (miRNA-133a, miRNA-223, miRNA-214, miRNA-155) were modulated by δ-tocotrienol. Whereas, tocopherol showed heterogeneity of results by either decreasing or increasing the risk of mortality in atherosclerotic cardiovascular diseases.
CONCLUSION
Compared to tocopherol, tocotrienol was found to be safe and potential candidate for improving cardiovascular health in the management of atherosclerotic cardiovascular diseases.
Topics: Humans; Tocotrienols; Atherosclerosis; Tocopherols; Antioxidants; Cardiovascular Diseases; Dyslipidemias; Cholesterol
PubMed: 38948984
DOI: 10.47391/JPMA.9227 -
HemaSphere Jul 2024Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T...
Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, = 0.12) and tisa-cel (44% vs. 36%, = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, = 0.79), ICANS G ≥3 (15% vs. 17%, = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.
PubMed: 38948924
DOI: 10.1002/hem3.86 -
International Journal of Chronic... 2024Vitamin D deficiency (VDD, 25-hydroxyvitamin D < 20 ng/mL) has been reported associated with exacerbation of chronic obstructive pulmonary disease (COPD) but sometimes... (Observational Study)
Observational Study
PURPOSE
Vitamin D deficiency (VDD, 25-hydroxyvitamin D < 20 ng/mL) has been reported associated with exacerbation of chronic obstructive pulmonary disease (COPD) but sometimes controversial. Research on severe vitamin D deficiency (SVDD, 25-hydroxyvitamin D < 10 ng/mL) in exacerbation of COPD is limited.
PATIENTS AND METHODS
We performed a retrospective observational study in 134 hospitalized exacerbated COPD patients. 25-hydroxyvitamin D was modeled as a continuous or dichotomized (cutoff value: 10 or 20 ng/mL) variable to evaluate the association of SVDD with hospitalization in the previous year. Receiver operator characteristic (ROC) analysis was performed to find the optimal cut-off value of 25-hydroxyvitamin D.
RESULTS
In total 23% of the patients had SVDD. SVDD was more prevalent in women, and SVDD group tended to have lower blood eosinophils counts. 25-hydroxyvitamin D level was significantly lower in patients who were hospitalized in the previous year (13.6 vs 16.7 ng/mL, = 0.044), and the prevalence of SVDD was higher (38.0% vs 14.3%, = 0.002). SVDD was independently associated with hospitalization in the previous year [odds ratio (OR) 4.34, 95% CI 1.61-11.72, = 0.004] in hospitalized exacerbated COPD patients, whereas continuous 25-hydroxyvitamin D and VDD were not ( = 0.1, = 0.9, separately). The ROC curve yielded an area under the curve of 0.60 (95% CI 0.50-0.71) with an optimal 25-hydroxyvitamin D cutoff of 10.4 ng/mL.
CONCLUSION
SVDD probably showed a more stable association with hospitalization in the previous year in hospitalized exacerbated COPD patients. Reasons for lower eosinophil counts in SVDD group needed further exploration.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Vitamin D Deficiency; Female; Male; Retrospective Studies; Vitamin D; Aged; Prevalence; Disease Progression; Risk Factors; Middle Aged; Severity of Illness Index; Biomarkers; ROC Curve; Hospitalization; Time Factors; Odds Ratio; Aged, 80 and over; Area Under Curve; Logistic Models; Chi-Square Distribution; Patient Admission; Multivariate Analysis
PubMed: 38948911
DOI: 10.2147/COPD.S461029 -
Postepy Psychiatrii Neurologii Mar 2024Tolosa-Hunt syndrome (THS) is a rare cause of painful ophtalmoplegia with different clinical manifestations. It is described as a unilateral periorbital headache with...
PURPOSE
Tolosa-Hunt syndrome (THS) is a rare cause of painful ophtalmoplegia with different clinical manifestations. It is described as a unilateral periorbital headache with concomitant dysfunction of at least one out of the IIIrd, IVth and VIth cranial nerves due to the granulomatous inflammation of periorbital structures, but no underlying cause has been established.
CASE DESCRIPTION
We present six patients referred to the Neurology Department due to a unilateral headache with ipsilateral paresis of at least one cranial nerve responsible for eye movements. The THS diagnostic criteria of the International Headache Disorders Classification (ICHD-3) were applied and analysed. Few patients had atypical clinical manifestations according to these criteria.
COMMENT
Diagnosing THS may prove very challenging. There is a lack of specific markers for the disorder, whereas diagnostic criteria leave a wide area for misdiagnosis. The diagnostic approach should be focused on the exclusion of other pathologies because typical steroid therapy may prove fatal in otherwise benign cases.
PubMed: 38948688
DOI: 10.5114/ppn.2023.135176 -
Frontiers in Endocrinology 2024Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism....
BACKGROUND
Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism. This study aimed to investigate differences in the serum metabolic profiles of patients with PCOS compared with healthy controls, in addition to investigating the effects of compound oral contraceptive (COC) treatment in patients with PCOS.
MATERIALS AND METHODS
50 patients with PCOS and 50 sex-matched healthy controls were recruited. Patients with PCOS received three cycles of self-administered COC treatment. Clinical characteristics were recorded, and the laboratory biochemical data were detected. We utilized ultra-performance liquid chromatography-high-resolution mass spectrometry to study the serum metabolic changes between patients with PCOS, patients with PCOS following COC treatment, and healthy controls.
RESULT
Patients with PCOS who received COC treatment showed significant improvements in serum sex hormone levels, a reduction in luteinising hormone levels, and a significant reduction in the levels of biologically active free testosterone in the blood. Differential metabolite correlation analysis revealed differences between PCOS and healthy control groups in N-tetradecanamide, hexadecanamide, 10E,12Z-octadecadienoic acid, and 13-HOTrE(r); after 3 months of COC treatment, there were significant differences in benzoic acid, organic acid, and phenolamides. Using gas chromatography-mass spectrometry to analyse blood serum in each group, the characteristic changes in PCOS were metabolic disorders of amino acids, carbohydrates, and purines, with significant changes in the levels of total cholesterol, uric acid, phenylalanine, aspartic acid, and glutamate.
CONCLUSION
Following COC treatment, improvements in sex hormone levels, endocrine factor levels, and metabolic levels were better than in the group of PCOS patients receiving no COC treatment, indicating that COC treatment for PCOS could effectively regulate the levels of sex hormones, endocrine factors, and serum metabolic profiles.
Topics: Humans; Polycystic Ovary Syndrome; Female; Metabolomics; Adult; Young Adult; Case-Control Studies; Metabolome; Testosterone; Contraceptives, Oral; Contraceptives, Oral, Combined; Biomarkers
PubMed: 38948525
DOI: 10.3389/fendo.2024.1354214