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Pharmacological Research Jul 2024Coronavirus disease 2019 (COVID-19) affected people worldwide, and fever is one of the major symptoms of this disease. Although Acetaminophen (APAP) is a common...
Coronavirus disease 2019 (COVID-19) affected people worldwide, and fever is one of the major symptoms of this disease. Although Acetaminophen (APAP) is a common fever-reducing medication, it can also mediate liver injury. However, the role of PGC-1α in regulating mitochondrial quality control by lactate dehydrogenase B (LDHB), a vital enzyme catalyzing the conversion of lactate to pyruvate, in APAP-induced hepatotoxicity, is unclear. Here, gene expression omnibus data of patients with APAP-induced liver injury were used to explore gene expression profiles. AML12 cells and C57/BL6 mice were used to establish models of APAP-induced acute liver injury. SIRT1 and PGC-1α were overexpressed in vitro via lentiviral transfection to establish stable cell lines. The results showed that APAP treatment decreased SIRT1/PGC-1α/LDHB expression and increased protein lactylation, mitochondrial lactate levels, and pathological damage in liver mitochondria. PGC-1α upregulation or activation ameliorated APAP-induced damage in the cells and liver. Furthermore, PGC-1α overexpression increased LDHB synthesis, reduced lactylation, and induced a switch from lactate to pyruvate production. These results suggest that PGC-1α and LDHB play a role in APAP-induced liver injury by regulating mitochondrial quality control and lactate metabolic reprogramming. Therefore, the PGC-1α/LDHB axis is a potential therapeutic target for APAP-induced liver injury.
Topics: Animals; Acetaminophen; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Chemical and Drug Induced Liver Injury; Mice, Inbred C57BL; Mice; Humans; Male; L-Lactate Dehydrogenase; Lactic Acid; Mitochondrial Proteins; Cell Line; Mitochondria, Liver; Sirtuin 1; Isoenzymes
PubMed: 38810904
DOI: 10.1016/j.phrs.2024.107228 -
World Neurosurgery: X Jul 2024To formulate the most current, evidence-based recommendations for the role of medication, physical medicine, and rehabilitation in the management of acute low back pain... (Review)
Review
OBJECTIVES
To formulate the most current, evidence-based recommendations for the role of medication, physical medicine, and rehabilitation in the management of acute low back pain lasting <4 weeks.
METHODS
A systematic literature search in PubMed and Google Scholar databases was performed from 2012 to 2022 using the search terms "acute low back pain," "drugs," "bed rest," "physical medicine," rehabilitation." Standardized screening criteria resulted in a total of 39 articles that were analyzed, including 16 RCTs, 8 prospective studies, 6 retrospective studies, and 9 systematic reviews. This up-to-date information was reviewed and presented at two separate meetings of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. Two rounds of the Delphi method were utilized to vote on the statements and arrive at a positive or negative consensus.
RESULTS AND CONCLUSION
The WFNS Spine Committee finalized twelve recommendation guidelines on the role of medication, physical medicine and rehabilitation in the management of acute LBP. We advocate for a uniform approach to the treatment of these patients, including proper patient education and utilizing drugs with proven efficacy and minimal side effects. First-line pharmacologic agents are acetaminophen and NSAIDs; muscle relaxants can be used for spasms and pain reduction, and opioids should be minimized. Continued activity, rather than bed rest, is recommended, and lumbar spine orthotics may be used to reduce pain and augment functional status. Thermotherapy, cryotherapy, TENs, spinal manipulative therapy, and acupuncture may all be used as adjuncts to improve acute LBP.
PubMed: 38807862
DOI: 10.1016/j.wnsx.2024.100273 -
Cureus Apr 2024Osteoarthritis management primarily focuses on targeting pain. Conventional modalities for pain management include acetaminophen, non-steroidal anti-inflammatory drugs...
Osteoarthritis management primarily focuses on targeting pain. Conventional modalities for pain management include acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and intra-articular corticosteroid injections. However, these approaches may provide minimal pain relief and can be contraindicated for some patients, highlighting the ongoing need for alternative pain management. Colchicine, commonly used in the management of gout, has emerged as a potential option for pain management in osteoarthritis. There are implications of colchicine use for knee and hand osteoarthritis but remains inconclusive. In this context, we present a case of a 68-year-old diabetic woman with glenohumeral osteoarthritis and associated right shoulder pain. Due to minimal pain relief from previous treatments, the patient was given a combination trial of colchicine and acetaminophen for three months. After completion of this treatment, the patient experienced significant pain relief and improved functionality. The aim of this case is to highlight the efficacy of colchicine as a possible treatment option for managing shoulder pain in osteoarthritis.
PubMed: 38807809
DOI: 10.7759/cureus.59181 -
BMC Chemistry May 2024Ten novel spectrophotometric approaches were developed for the initial examination of the Hydroxychloroquine and Paracetamol medications. These procedures are...
Ten novel spectrophotometric approaches were developed for the initial examination of the Hydroxychloroquine and Paracetamol medications. These procedures are straightforward, specific, easy to use, and provide exact and accurate results. The determination was conducted through the utilization of several approaches, including zero order (dual wavelength, zero crossing, advanced absorption subtraction and spectrum subtraction), derivative (first derivative of zero crossing), ratio (ratio difference, ratio derivative) and mathematical (bivariate, simultaneous equation, and Q-absorbance) techniques. After undergoing validation in accordance with ICH criteria, it was established that each of these methods achieved acceptable levels of precision, repeatability, robustness, and accuracy. The advantages and disadvantages of each method are demonstrated, and the proposed and reported methodologies were statistically compared.
PubMed: 38807212
DOI: 10.1186/s13065-024-01187-2 -
Scientific Reports May 2024In pursuit of an efficient visible light driven photocatalyst for paracetamol degradation in wastewater, we have fabricated the ZnO/g-CN S-Scheme photocatalysts and...
In pursuit of an efficient visible light driven photocatalyst for paracetamol degradation in wastewater, we have fabricated the ZnO/g-CN S-Scheme photocatalysts and explored the optimal percentage to form a composite of graphitic carbon nitride (g-CN) with zinc oxide (ZnO) for enhanced performance. Our study aimed to address the urgent need for a catalyst capable of environmentally friendly degradation of paracetamol, a common pharmaceutical pollutant, using visible light conditions. Here, we tailored the band gap of a photocatalyst to match solar radiation as a transformative advancement in environmental catalysis. Notably, the optimized composite, containing 10 wt.% g-CN with ZnO, demonstrated outstanding paracetamol degradation efficiency of 95% within a mere 60-min exposure to visible light. This marked enhancement represented a 2.24-fold increase in the reaction rate compared to lower wt. percentage composites (3 wt.% g-CN) and pristine g-CN. The exceptional photocatalytic activity of the optimized composite can be attributed to the band gap narrowing that closely matched the maximum solar radiation spectrum. This, coupled with efficient charge transfer mechanisms through S-scheme heterojunction formation and an abundance of active sites due to increased surface area and reduced particle size, contributed to the remarkable performance. Trapping experiments identified hydroxyl radicals as the primary reactive species responsible for paracetamol photoreduction. Furthermore, the synthesized ZnO/g-CN composite exhibited exceptional photostability and reusability, underscoring its practical applicability. Thus, this research marks a significant stride towards the development of an effective and sustainable visible light photocatalyst for the removal of pharmaceutical contaminants from aquatic environments.
PubMed: 38806502
DOI: 10.1038/s41598-024-60306-0 -
Yonago Acta Medica May 2024Patients taking multiple drugs and various health foods often develop acute hepatitis. We hypothesized that the interaction between health foods and drug metabolism was...
BACKGROUND
Patients taking multiple drugs and various health foods often develop acute hepatitis. We hypothesized that the interaction between health foods and drug metabolism was the cause of severe liver injury in these patients. Therefore, we studied changes in the activity of the drug-metabolizing enzyme, cytochrome P450 (CYP), using slimming health food extracts and elucidated the molecular mechanism of liver injury onset through hepatotoxicity evaluation.
METHODS
For cytotoxicity testing, health food extract samples were added to HepG2 cells derived from hepatic parenchymal cells and culture medium, and cell viability was calculated 48 h after culture. To evaluate CYP3A4 induction, 3-1-10 cells constructed with a reporter linked to CYP3A4 gene were used, and reporter activity was measured 48 h after culture.
RESULTS
In the chronological order of the slimming health food intake history of the patient, niacinamide and extracts strongly inhibited HepG2 cell viability. In contrast, dietary supplements A and extract strongly induced CYP3A4 reporter activity.
UNLABELLED
To confirm CYP3A4 induction in humans, humanized CYP3A/pregnane X receptor (PXR) mice were treated with forskolin. CYP3A4 mRNA expression levels were elevated 3.9 times compared to that of the control group ( < 0.05).
CONCLUSION
extract showed the strongest transcriptional activation of CYP3A4 gene. In a mouse model of human-type drug metabolism, forskolin induced CYP3A4 transcription. Thus, we concluded that CYP3A4 induction by is one of the causes of crucial hepatocellular injury, which is a type of liver injury caused by the active metabolite of acetaminophen produced by CYP3A4.
PubMed: 38803590
DOI: 10.33160/yam.2024.05.004 -
Cureus Apr 2024Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac...
A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).
Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and 14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and 14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14) (p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.
PubMed: 38800230
DOI: 10.7759/cureus.58859 -
Spectrochimica Acta. Part A, Molecular... Oct 2024Raman spectroscopy is a well-established method for chemical identification, with a wide variety of applications. The two major limitations are that fluorescence can...
Raman spectroscopy is a well-established method for chemical identification, with a wide variety of applications. The two major limitations are that fluorescence can hamper detection, and that Raman imaging is slow; it typically takes multiple hours to measure even a small surface area. We have developed a multimodal setup that mitigates these limitations. The setup has a point-scanning mode that allows for time-gated as well as continuous Raman spectroscopy, and both modes use an 80 MHz, 532 nm excitation laser with up to 20 W of power. The fluorescence suppression capabilities of the setup were demonstrated by comparing time-gated to continuous detection of a Dracaena leaf. Raman bands showed a 4-8 times improvement in signal-to-background ratio, and one band that was invisible in the continuous measurement, became visible in the time-gated measurement. The setup also has a 4-band simultaneously detected wide-field mode. Using a set of beam splitters, the Raman signal from the sample is split. This signal is imaged onto four separate cameras, each with a specific band-pass filter. The wide-field data were processed using principal component analysis with k-means clustering. To illustrate the wide-field capabilities of the setup, a 1mm sample containing aspirin, caffeine and paracetamol was measured using 10 W excitation power. A 10-second measurement enabled identification of the compounds, and a 1-second measurement showed promising results. This brings the setup close to real-time imaging, showing great potential for applications in quality control or for measuring samples that change over time.
PubMed: 38795525
DOI: 10.1016/j.saa.2024.124388 -
Pharmaceuticals (Basel, Switzerland) May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.
PubMed: 38794197
DOI: 10.3390/ph17050627 -
Sensors (Basel, Switzerland) May 2024The purpose of this paper is to demonstrate a new discovery regarding the interaction between materials and very low radio frequencies. Specifically, we observed a...
The purpose of this paper is to demonstrate a new discovery regarding the interaction between materials and very low radio frequencies. Specifically, we observed a feedback response on an inertia active sensor when specific frequencies (around 2-4 kHz) are used to irradiate targeted pharmaceutical samples like aspirin or paracetamol drugs. The characteristics of this phenomenon, such as excitation and relaxation time, the relation between deceleration and a material's quantity, and signal amplitude, are presented and analyzed. Although the underlying physics of this phenomenon is not yet known, we have shown that it has potential applications in remote identification of compounds, detection, and location sensing, as well as identifying substances that exist in plants without the need for any processing. This method is fast, accurate, low-cost, non-destructive, and non-invasive, making it a valuable area for further research that could yield spectacular results in the future.
Topics: Acetaminophen; Electromagnetic Phenomena; Aspirin; Pharmaceutical Preparations; Radio Waves
PubMed: 38793913
DOI: 10.3390/s24103059