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Cureus Apr 2024Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often...
Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often translates to limited treatment options for patients and, occasionally, challenges in obtaining a definitive diagnosis. SPS also impacts patients' mental health, social and economic involvement, and overall quality of life. A 43-year-old man was initially being seen for lumbar radicular pain. A clinical diagnosis of SPS was made by a neurologist and confirmed by in-clinic follow-ups and anti-glutamic acid decarboxylase (anti-GAD) antibody testing. The Pain Management doctor agreed with this diagnosis and offered intravenous (IV) ketamine treatment, which he has found to positively impact the treatment of similar disorders. After an initial 10-day infusion, the patient reported improvement in pain and function. For almost two years, the patient received intravenous immunoglobulin (IVIg) and IV ketamine treatments to manage their condition and maintain pain control as well as quality of life. When the patient's symptoms began worsening after IVIg infusions, the decision to withdraw IVIg infusions and continue ketamine infusions was made. After discontinuing IVIg infusions, the patient reported improvement in function and pain level and continues to receive monthly two-day ketamine boosters. Outside of the infusions, the patient was able to discontinue the use of fentanyl patches and continued taking ketamine lozenges, oxycodone-acetaminophen, and dextromethorphan for at-home pain management. The patient's symptoms continue to be managed effectively with their current regimen, enabling their return to work and experiencing an enhanced quality of life. This case illustrates the potential benefits of IV ketamine treatment for patients with treatment-resistant SPS and similar neurologic and autoimmune disorders. Understanding and examining treatment alternatives for rare syndromes is crucial for achieving optimal patient outcomes. Additionally, documenting such cases offers valuable insights into the mechanism of ketamine, extending beyond these syndromes.
PubMed: 38817534
DOI: 10.7759/cureus.59397 -
Reproductive Toxicology (Elmsford, N.Y.) Aug 2024Paracetamol is suggested to have endocrine disrupting properties possibly affecting fetal programming of reproductive health that might lead to impaired semen quality...
Paracetamol is suggested to have endocrine disrupting properties possibly affecting fetal programming of reproductive health that might lead to impaired semen quality and changes in reproductive hormones. In this longitudinal study, we included 1058 young adult men born 1998-2000 into the Danish National Birth Cohort with follow-up at 18-21 years of age. The exposure, maternal intake of paracetamol, was modelled in three ways: dichotomized, trimester-specific, and as duration of exposure categorized into: short (1-2 weeks), medium (3-9 weeks) or long duration (>9 weeks) vs. no intake. Outcomes included semen characteristics, self-measured testis volume, and reproductive hormone levels. We used negative binominal regression to estimate the percentage difference and 95% confidence interval (CI) for each outcome. In total, 547 (48%) sons were prenatally exposed to paracetamol due to maternal intake at least once. Maternal intake of paracetamol during pregnancy was not associated with any of the biomarkers in the dichotomized or trimester-specific exposure models. For duration of exposure, sons of mothers with long duration of maternal intake of paracetamol showed tendencies towards lower semen concentration (-14% [95% CI: -31%; 8%]), a higher proportion of nonprogressive and immotile spermatozoa (8% [95% CI: -4%; 21%]) and higher DNA Fragmentation Index (16% [95% CI: -1%; 36%]) compared to son of mothers with no intake. Maternal intake of paracetamol during pregnancy was not clearly associated with biomarkers of male fecundity in adult sons. However, it cannot be ruled out that long duration of maternal intake of paracetamol might be associated with impaired semen characteristics.
Topics: Acetaminophen; Humans; Male; Female; Pregnancy; Young Adult; Biomarkers; Adolescent; Prenatal Exposure Delayed Effects; Fertility; Analgesics, Non-Narcotic; Longitudinal Studies; Denmark; Testis; Semen Analysis
PubMed: 38815769
DOI: 10.1016/j.reprotox.2024.108626 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
Annals of Medicine Dec 2024Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.
METHODS
We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.
RESULTS
We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity between the studies was low.
CONCLUSIONS
Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
Topics: Humans; Tension-Type Headache; Analgesics; Adult; Network Meta-Analysis; Ibuprofen; Acetaminophen; Bayes Theorem; Treatment Outcome; Diclofenac; Randomized Controlled Trials as Topic; Naproxen; Ketoprofen; Anti-Inflammatory Agents, Non-Steroidal; Female; Male
PubMed: 38813682
DOI: 10.1080/07853890.2024.2357235 -
Heliyon May 2024APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG...
APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG (Kaempferol-3-sophoroside-7-glucoside) is a kaempferol derivative that was separated from plant species belonging to different genera. This study explored the protective effects of KSG on ALI (acute liver injury) caused by APAP overdose in mice and elucidated its possible mechanisms. The results showed that KSG pretreatment alleviated APAP-induced hepatic damage as it reduced hepatic pathological lesions as well as the serum parameters of liver injury. Moreover, KSG opposed APAP-associated oxidative stress and augmented hepatic antioxidants. KSG suppressed the inflammatory response as it decreased the genetic and protein expression as well as the levels of inflammatory cytokines. Meanwhile, KSG enhanced the mRNA expression and level of anti-inflammatory cytokine, IL-10 (interleukin-10). KSG repressed the activation of NF-κB (nuclear-factor kappa-B), besides it promoted the activation of Nrf2 signaling. Additionally, KSG markedly hindered the elevation of ASK-1 (apoptosis-signal regulating-kinase-1) and JNK (c-Jun-N-terminal kinase). Furthermore, KSG suppressed APAP-induced apoptosis as it decreased the level and expression of Bax (BCL2-associated X-protein), and caspase-3 concurrent with an enhancement of anti-apoptotic protein, Bcl2 in the liver. More thoroughly, Computational studies reveal indispensable binding affinities between KSG and Keap1 (Kelch-like ECH-associated protein-1), ASK1 (apoptosis signal-regulating kinase-1), and JNK1 (c-Jun N-terminal protein kinase-1) with distinctive tendencies for selective inhibition. Taken together, our data showed the hepatoprotective capacity of KSG against APAP-produced ALI via modulation of Nrf2/NF-κB and JNK/ASK-1/caspase-3 signaling. Henceforth, KSG could be a promising hepatoprotective candidate for ALI.
PubMed: 38813141
DOI: 10.1016/j.heliyon.2024.e31448 -
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