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The Korean Journal of Pain Jul 2024Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine...
BACKGROUND
Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats.
METHODS
This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG.
RESULTS
After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance ( < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS ( < 0.001), while simultaneously causing a decrease in TAS levels ( < 0.001).
CONCLUSIONS
The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.
PubMed: 38946696
DOI: 10.3344/kjp.24042 -
Orthopaedic Surgery Jul 2024The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to...
OBJECTIVES
The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population.
METHODS
Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test.
RESULTS
Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission.
CONCLUSION
Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.
PubMed: 38946692
DOI: 10.1111/os.14150 -
Cancer Discovery Jul 2024Despite its long history of toxicity and limited efficacy, IL2 has re-entered the clinic as a companion to the recently FDA-approved tumor infiltrating lymphocyte...
Despite its long history of toxicity and limited efficacy, IL2 has re-entered the clinic as a companion to the recently FDA-approved tumor infiltrating lymphocyte therapy. In back-to-back articles, Moynihan and Kaptein introduce a new fusion protein that delivers a biased IL2 mutein to CD8 T cells. See related article by Moynihan et al., p. 1206 (6). See related article by Kaptein et al., p. 1226 (7).
Topics: Humans; Interleukin-2; Neoplasms; CD8-Positive T-Lymphocytes; Lymphocytes, Tumor-Infiltrating
PubMed: 38946323
DOI: 10.1158/2159-8290.CD-24-0558 -
The Bone & Joint Journal Jul 2024
Topics: Humans; Aspirin; Thromboembolism; Platelet Aggregation Inhibitors; Venous Thromboembolism
PubMed: 38946290
DOI: 10.1302/0301-620X.106B7.BJJ-2024-0621 -
Acta Dermatovenerologica Croatica : ADC Mar 2024Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking. (Observational Study)
Observational Study
The Safety Profiles of Adalimumab, Infliximab, Etanercept, Secukinumab and Ustekinumab in Psoriasis - A 30-month Observational Cohort Prospective Study of Adverse Events in Biologic Therapy.
BACKGROUND
Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking.
METHODS
A total of 124 patients with psoriasis were followed up for 30 months; 74 received anti-TNF-alpha inhibitors (adalimumab, etanercept, infliximab), 33 were on ustekinumab, and 17 were treated with secukinumab. The rates of adverse events in these groups were recorded and statistically analyzed.
RESULTS
Infliximab-treated patients showed a high occurrence of asymptomatic, but increased liver enzymes, fatigue, and respiratory as well as dermatologic infections. Adalimumab-treated patients were more often affected by musculoskeletal disorders and infections of all types. Patients treated with secukinumab presented with higher rates of cardiovascular disorders as well as respiratory and dermatologic infections. The group receiving etanercept was more often diagnosed with musculoskeletal and reproductive disorders, specifically menstrual disorders. The rates of therapy discontinuation and serious adverse events did not reach statistically significant values.
CONCLUSION
A higher incidence of adverse events was observed among adalimumab-, and infliximab-treated patients, with ustekinumab found to have the safest profile. Our results demonstrate that a personalized approach, including evaluation of a patient's risk profile, is necessary before commencing a biologic. Further research is warranted to confirm the findings of our study.
Topics: Humans; Psoriasis; Female; Male; Ustekinumab; Prospective Studies; Adalimumab; Infliximab; Middle Aged; Adult; Etanercept; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Cohort Studies; Dermatologic Agents
PubMed: 38946182
DOI: No ID Found -
Iranian Biomedical Journal Dec 2023Despite the widespread use of opioids to manage severe pain, its systemic administration results in side effects. Among the subcutaneous and transdermal drug delivery...
BACKGROUND
Despite the widespread use of opioids to manage severe pain, its systemic administration results in side effects. Among the subcutaneous and transdermal drug delivery systems developed to deal with adverse effects, microneedles have drawn attention due to their rapid action, high drug bioavailability, and improved permeability. SUF is an effective injectable opioid for treating severe pain. In this study, we investigated the analgesic effects of SUF using dissolvable microneedles.
METHODS
SUF polymeric dissolvable microneedles were constructed through the mold casting method and characterized by SEM and FTIR analysis. Its mechanical strength was also investigated using a texture analyzer. Fluorescence microscopy was applied in vitro to measure the penetration depth of microneedle arrays. Irritation and microchannel closure time, drug release profile, and hemocompatibility test were conducted for the validation of microneedle efficiency. Hot plate test was also used to investigate the analgesic effect of microneedle in an animal model.
RESULTS
Local administration of SUF via dissolving microneedles had an effective analgesic impact. One hour after administration, there was no significant difference between the subcutaneous and the microneedle groups, and the mechanical properties were within acceptable limits.
CONCLUSION
Microneedling is an effective strategy in immediate pain relief compared to the traditional methods.
PubMed: 38946039
DOI: 10.61186/ibj.4062 -
Yakugaku Zasshi : Journal of the... 2024An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the...
An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an "infodemic" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.
Topics: Humans; Antipyretics; Pharmacists; COVID-19 Vaccines; Male; Female; Middle Aged; Adult; Acetaminophen; Japan; Surveys and Questionnaires; Professional Role; Vaccination; Aged; Young Adult; Nonprescription Drugs; COVID-19
PubMed: 38945850
DOI: 10.1248/yakushi.23-00183 -
Food Research International (Ottawa,... Aug 2024To improve the color stability of anthocyanins (ACNs) in blueberry fermented beverage, the intermolecular copigmentation between ACNs and 3 different phenolic compounds,...
To improve the color stability of anthocyanins (ACNs) in blueberry fermented beverage, the intermolecular copigmentation between ACNs and 3 different phenolic compounds, including (-)-epigallocatechin gallate (EGCG), ferulic acid (FA), and gallic acid (GA) as copigments, was compared in the model and the real blueberry fermented beverage, respectively. The copigmented ACNs by EGCG presented a high absorbance (0.34 a.u.) and redness (27.09 ± 0.17) in the model blueberry fermented beverage. The copigmentation by the participation of the 3 different phenolic compounds showed all a spontaneous exothermic reaction, and the Gibbs free energy (ΔG°) of the system was lowest (-5.90 kJ/mol) using EGCG as copigment. Furthermore, the molecular docking model verified that binary complexes formed between ACNs and copigments by hydrogen bonds and π-π stacking. There was a high absorbance (1.02 a.u.), percentage polymeric color (PC%, 68.3 %), and good color saturation (C*ab, 43.28) in the real blueberry fermented beverage aged for 90 days, and more malvidin-3-O-glucoside had been preserved in the wine using EGCG as copigment. This finding may guide future industrial production of blueberry fermented beverage with improved color.
Topics: Anthocyanins; Blueberry Plants; Fermentation; Coumaric Acids; Molecular Docking Simulation; Gallic Acid; Phenols; Color; Catechin; Fruit and Vegetable Juices; Fruit
PubMed: 38945622
DOI: 10.1016/j.foodres.2024.114632 -
The Journal of Dermatological Treatment Dec 2024In the global phase 3 POETYK PSO-1 and PSO-2 trials, significantly greater proportions of deucravacitinib-treated patients met the coprimary endpoints (PASI 75, sPGA... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
In the global phase 3 POETYK PSO-1 and PSO-2 trials, significantly greater proportions of deucravacitinib-treated patients met the coprimary endpoints (PASI 75, sPGA 0/1) at Week 16 versus placebo or apremilast-treated patients. This analysis evaluated onset of action and maintenance of response in patients randomized to deucravacitinib and placebo only.
METHODS
Adults with moderate to severe plaque psoriasis at baseline were randomized 1:2:1 to oral placebo, deucravacitinib, or apremilast. Onset of action was determined through changes from baseline in mean PASI, BSA, BSA × sPGA, and DLQI. Maintenance of response was assessed using PASI 75, PASI 90, PASI 100, sPGA 0/1, and sPGA 0 response rates through Week 52 in patients who were treated continuously with deucravacitinib, crossed over from placebo to deucravacitinib at Week 16, or received deucravacitinib and achieved PASI 75 by Week 24.
RESULTS
Deucravacitinib showed significantly higher increases in mean percent change from baseline in PASI versus placebo by Week 1. Significant improvement versus placebo was observed in all other efficacy measures by Week 8. Efficacy with deucravacitinib was maintained through Week 52.
CONCLUSION
Deucravacitinib displayed efficacy as early as 1 week and clinical responses were maintained over 52 weeks in patients with moderate to severe plaque psoriasis.
Topics: Humans; Psoriasis; Male; Female; Middle Aged; Adult; Double-Blind Method; Severity of Illness Index; Treatment Outcome; Thalidomide; Cross-Over Studies
PubMed: 38945549
DOI: 10.1080/09546634.2024.2371045 -
Journal of Ethnopharmacology Jun 2024Pain and inflammation are the most frequent reasons for which people seek medical care. Currently available analgesics against these conditions produce fatal adverse...
Analgesic and anti-inflammatory activities of NPK500 capsules, a Cassia sieberiana DC. - based herbal analgesic medicine used to treat dysmenorrhea and peptic ulcer, is mediated through the inhibition of PGE2 and iNOS.
ETHNOPHARMACOLOGICAL RELEVANCE
Pain and inflammation are the most frequent reasons for which people seek medical care. Currently available analgesics against these conditions produce fatal adverse effects. NPK500 capsules is an alternative herbal analgesic employed to treat dysmenorrhea, peptic ulcer and pain. NPK500 is produced from Cassia sieberiana. A plant used in traditional medicine to treat pain and inflammation.
AIM OF THE STUDY
This study reports the analysis, phytochemical characterization and mechanism of analgesic and anti-inflammatory activities of two NPK500 capsules, called old and new NPK500 capsules (ONPK500 and NNPK500) respectively.
MATERIALS AND METHODS
Physicochemical, organoleptic, GC-MS and LC-MS methods were employed to analyze the NPK500 capsules. Analgesic activity was evaluated using tail immersion, Randall-Selitto and acetic acid induced writing tests. Anti-inflammatory activity was evaluated using carrageenan-induced rat paw inflammation. Additionally, pro-inflammatory mediators such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase 1 and 2 (COX-2 and COX-1) were quantified in the sera of the rats using Enzyme Linked Immunosorbent Assay (ELISA) kits.
RESULTS
Thirteen major compounds were characterized in the NNPK500 capsules via the GC-MS and LC-MS spectroscopies. Kaempferol was the major compound characterized in addition to physcion, β-sitosterol 3-O-β-D-glucopyranoside, betulinic acid and nine others. Physicochemical and organoleptic indices of the capsules were also derived for its authentication and quality control. Furthermore, NNPK500 0.5-1.5 mg/kg p.o. produce significant (P < 0.5) analgesic activity (160-197%) higher than that of ONPK500 (109.8%) and Morphine (101%) in the tail immersion test. The analgesic activity of NNPK500 0.5-1.5 mg/kg p.o. (171.0 - 258.3%) and ONPK500 (179.5%) were also significant (P < 0.01) and higher than that of Aspirin (103.00%) in the Randall-Selitto test. Both capsules also demonstrated significant (P < 0.5) analgesic and anti-inflammatory activities in the acetic acid-induced writhing and carrageenan-indued paw edema tests respectively. The two NPK500 capsules also, significantly (P < 0.5) inhibited PGE2 and iNOS but not COX-2 and COX-1 in the carrageenan-indued paw edema test.
CONCLUSION
These results show that NNPK500 and ONPK500 capsules possessed potent analgesic and anti-inflammatory activities via inhibition of PGE2 and iNOS as a result of their chemical constituents. NPK500 capsules thus, relief acute pain and inflammation without causing gastrointestinal, renal or hepatic injuries, since they did not inhibit COX-1.
PubMed: 38945468
DOI: 10.1016/j.jep.2024.118510