ABSTRACT
The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments - riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) - were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders.
ABSTRACT
AIMS: Iron deficiency anemia (IDA) is one of the disorders recently associated with an increase in insulin resistance (IR) and, consequently, diabetes mellitus (DM) affection by causing oxidative stress. In this study, we look at how IDA may contribute to developing type II diabetes mellitus (T2DM), controlling diabetes, and reducing IR in women with T2DM. METHODS: In this single group, clinical interventional study, we enrolled 40 women with T2DM and IDA. Before and after intervention with ferrous sulfate tablets, their blood glucose (BG) levels and IR levels were evaluated. This study was approved by the Ethics Committee of Qom University of Medical Sciences (ethics code: IR.MUQ.REC.1397.031) and registered at the Iranian Center for Clinical Trials (No. IRCT20170215032587N3). A significant level was considered p <0.05. RESULT: The mean age of patients was 48.18 ± 4.6 years, with 5.3-5.8 years duration of T2DM. After the intervention, the mean fasting blood glucose (FBG) level reached 198.53 ± 48.11 to 170.93 ± 37.41, which was significant (p <0.0001). Also, hemoglobin A1C level reached from 8.49 ± 0.9 to 7.96 ± 0.58, which was significant (p <0.0001). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) demonstrating a significant reduction of IR levels after intervention with ferrous sulfate tablets (p <0.018). CONCLUSIONS: IDA treatment in patients with T2DM can significantly reduce the BG and IR levels. To better control BG, checking iron status and its correction may provide better clinical outcomes in these patients. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20170215032587N3.
ABSTRACT
BACKGROUND: Due to the presence of postoperative pain in patients undergoing anorectal surgery, and since the pain affects the quality of life of patients, we aimed to compare the analgesic effectiveness of oral magnesium with oral ketorolac to choose the right analgesic drug for these patients. METHODS: This study was a double-blind, randomized clinical trial performed on 104 candidates undergoing anorectal surgery. Patients were randomly divided into two groups. Group 1 received oral magnesium (250 mg daily), and group 2 received oral ketorolac (10 mg daily). The medicine was given to the patient 2 hours after the operation and every 12 hours for 10 days. Pain measurements were recorded at 24-hour intervals after surgery based on the visual analog scale and numerical rating scale. RESULTS: This study found that postoperative pain was reduced in patients taking magnesium tablets, similar to the ketorolac group. A similar decreasing trend was observed in the group receiving ketorolac; however, the reduction was more pronounced in the magnesium group and was statistically significant on days 1, 3, and 5 (p < 0.001). However, insignificant differences were noted between the two groups on the seventh (p = 0.093) and tenth (p = 0.088) postoperative days. CONCLUSION: Taking magnesium tablets after surgery has a suitable analgesic effect, which is similar to oral ketorolac tablets from the fifth day onwards, but in the initial days, it is less effective than ketorolac statistically.
