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Cureus May 2024Background Rituximab, a chimeric monoclonal antibody targeting the CD20 protein on the surface of B cells, is used to treat several rheumatologic and oncologic diseases....
Implementation of an Accelerated Infusion Protocol (90-Minute Infusion) of Rituximab and Its Safety in Patients With Autoimmune Rheumatic Diseases at a Tertiary Veterans Affairs Center.
Background Rituximab, a chimeric monoclonal antibody targeting the CD20 protein on the surface of B cells, is used to treat several rheumatologic and oncologic diseases. The standard infusion duration of rituximab is four hours. Objective Evaluating the safety of administering the accelerated 90-minute protocol at our Veterans Affairs center to patients with rheumatologic diseases and monitoring for any infusion-related reactions. This study is unique as it examines infusion rates faster than those most described (120 minutes). Methods Patients treated with rituximab for autoimmune diseases between June 2020 and June 2022 at our center were included in the study. Our patients were over 18 years of age, met the inclusion criteria, and had received previous rituximab infusions without prior infusion-related reactions. They received the accelerated protocol of 90 minutes over their next cycles and were monitored for any reactions during their infusions. Results A total of 34 patients receiving 76 infusions were included in the analysis. Most of the patients were males (n = 27). The most prevalent indication for rituximab infusion was rheumatoid arthritis (n = 20). Out of 76 infusions, only two infusion-related reactions were recorded (2.6% incidence). The first patient had itching and a sore throat, indicating a grade 1A reaction. The second patient developed chest pain and dyspnea, which resolved with diphenhydramine and albuterol. For both, the infusion was completed after appropriate management. Conclusion The incidence of infusion-related reactions during the accelerated 90-minute rituximab infusion was remarkably low and well-tolerated by our rituximab-experienced patients. Only two infusions were complicated by a reaction, an incidence comparable to or even lower than other reported 120-minute infusion protocols. This protocol is time- and cost-efficient, allowing for more infusions per chair per day at our center.
PubMed: 38887351
DOI: 10.7759/cureus.60558 -
Chemosphere Jun 2024There is global demand for novel ecotoxicity testing tools that are based on alternative to animal models, have high throughput potential, and may be applicable to a...
There is global demand for novel ecotoxicity testing tools that are based on alternative to animal models, have high throughput potential, and may be applicable to a wide diversity of taxa. Here we scaled up a microplate-based cell-free neurochemical testing platform to screen 800 putative endocrine disrupting chemicals from the U.S. Environmental Protection Agency's ToxCast e1k library against the glutamate (NMDA), muscarinic acetylcholine (mACh), and dopamine (D2) receptors. Each assay was tested in cellular membranes isolated from brain tissues from a representative bird (zebra finch = Taeniopygia castanotis), mammal (mink = Neogale vison), and fish (rainbow trout = Oncorhynchus mykiss). The primary objective of this short communication was to make the results database accessible, while also summarising key attributes of assay performance and presenting some initial observations. In total, 7200 species-chemical-assay combinations were tested, of which 453 combinations were classified as a hit (radioligand binding changed by at least 3 standard deviations). There were some differences across species, and most hits were found for the D2 and NMDA receptors. The most active chemical was C.I. Solvent Yellow 14 followed by Diphenhydramine hydrochloride, Gentian Violet, SR271425, and Zamifenacin. Nine chemicals were tested across multiple plates with a mean relative standard deviation of the specific radioligand binding data being 24.6%. The results demonstrate that cell-free assays may serve as screening tools for large chemical libraries especially for ecological species not easily studied using traditional methods.
PubMed: 38851506
DOI: 10.1016/j.chemosphere.2024.142562 -
Chemosphere Jun 2024Diphenhydramine (DPH) is an antihistamine drug. It has been frequently detected in the environment, because it is not completely degraded in wastewater treatment plants....
Diphenhydramine (DPH) is an antihistamine drug. It has been frequently detected in the environment, because it is not completely degraded in wastewater treatment plants. Recent studies have shown the adverse effects of DPH exposure to various aquatic organisms; however, its chronic effects on fish have been poorly elucidated. In this study, several pairs of mature Japanese medaka (Oryzias latipes) were exposed to DPH for a long period to determine the effects of DPH exposure on the subsequent generations, number of spawned and fertilized eggs, expression of sex-related genes, feeding behavior, embryo development, hatching rate, malformations among the hatched larvae, and mortality rate. The number of spawned eggs significantly decreased, when the parent fish were continuously exposed to 31.6 μg/L DPH for over 46 days. DPH exposure also altered the feeding behavior of medaka individuals, and increased the larval mortality rate. The effects of DPH exposure to fish may occur to some extent in the actual aquatic environment, although the risk evaluations in the field are limited.
Topics: Animals; Oryzias; Reproduction; Water Pollutants, Chemical; Diphenhydramine; Male; Female; Larva; Feeding Behavior
PubMed: 38697572
DOI: 10.1016/j.chemosphere.2024.142163 -
Medicina (Kaunas, Lithuania) Apr 2024Ocrelizumab is an effective medication for multiple sclerosis. However, infusion-related reactions (IRRs) are a concern for patients and may lead to discontinuation of... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Ocrelizumab is an effective medication for multiple sclerosis. However, infusion-related reactions (IRRs) are a concern for patients and may lead to discontinuation of ocrelizumab. To minimize IRRs, pre-medications are administered. However, from our experience, these medications, especially diphenhydramine, can cause marked drowsiness. The primary objective of this study was to evaluate whether cetirizine is non-inferior to diphenhydramine in limiting the proportion and severity of reactions from ocrelizumab infusions. Twenty participants were serially randomized in a 1:1 ratio to receive 10 mg of cetirizine or 25 mg of diphenhydramine orally prior to their first three ocrelizumab infusions. The rate of IRRs in this study was similar across both treatment groups with no increase in the risk of severity, and no grade 3 IRRs. Further, patients receiving cetirizine experienced a reduction in fatigue. While there was not a significant difference in global satisfaction, this score increased over time in the cetirizine arm while it remained unchanged in the diphenhydramine arm. Overall, our results suggest that cetirizine does not increase the risk of infusion-related reactions compared to diphenhydramine.
Topics: Humans; Diphenhydramine; Cetirizine; Female; Male; Adult; Middle Aged; Antibodies, Monoclonal, Humanized; Infusions, Intravenous; Multiple Sclerosis
PubMed: 38674305
DOI: 10.3390/medicina60040659 -
Biomedicine & Pharmacotherapy =... Jun 2024The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in...
The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.
Topics: Serum Albumin, Bovine; Molecular Docking Simulation; Histamine H1 Antagonists; Animals; Glycation End Products, Advanced; Glycosylation; Cattle; Receptors, Histamine H1
PubMed: 38663107
DOI: 10.1016/j.biopha.2024.116632 -
The Journal of Pediatric Pharmacology... Apr 2024Care coordination for children and youth with special health care needs and medical complexity (CYSHCN-CMC), especially medication management, is difficult for...
OBJECTIVE
Care coordination for children and youth with special health care needs and medical complexity (CYSHCN-CMC), especially medication management, is difficult for providers, parents/caregivers, and -patients. This report describes the creation of a clinical pharmacotherapy practice in a pediatric long-term care facility (pLTCF), application of standard operating procedures to guide comprehensive medication management (CMM), and establishment of a collaborative practice agreement (CPA) to guide drug therapy.
METHODS
In a prospective case series, 102 patients characterized as CYSHCN-CMC were included in this pLTCF quality improvement project during a 9-month period.
RESULTS
Pharmacists identified, prevented, or resolved 1355 drug therapy problems (DTP) with an average of 13 interventions per patient. The patients averaged 9.5 complex chronic medical conditions with a -median length of stay of 2815 days (7.7 years). The most common medications discontinued due to pharmacist assessment and recommendation included diphenhydramine, albuterol, sodium phosphate enema, ipratropium, and metoclopramide. The average number of medications per patient was reduced from 23 to 20. A pharmacoeconomic analysis of 244 of the interventions revealed a monthly direct cost savings of $44,304 ($434 per patient per month) and monthly cost avoidance of $48,835 ($479 per patient per month). Twenty-eight ED visits/admissions and 61 clinic and urgent care visits were avoided. Hospital -readmissions were reduced by 44%. Pharmacist recommendations had a 98% acceptance rate.
CONCLUSIONS
Use of a CPA to conduct CMM in CYSHCN-CMC decreased medication burden, resolved, and prevented adverse events, reduced health care-related costs, reduced hospital readmissions and was well-accepted and implemented collaboratively with pLTCF providers.
PubMed: 38596413
DOI: 10.5863/1551-6776-29.2.119 -
Experimental & Molecular Medicine Apr 2024Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of...
Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.
Topics: Animals; Autophagy; Mice; Transcriptome; Humans; Protein Biosynthesis; Disease Models, Animal; Muscle, Skeletal; Gene Expression Profiling; Sarcopenia; Muscular Dystrophy, Duchenne
PubMed: 38556548
DOI: 10.1038/s12276-024-01189-z -
International Journal of Molecular... Mar 2024Arrestins are known to be involved not only in the desensitization and internalization of G protein-coupled receptors but also in the G protein-independent activation of...
Arrestins are known to be involved not only in the desensitization and internalization of G protein-coupled receptors but also in the G protein-independent activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), to regulate cell proliferation and inflammation. Our previous study revealed that the histamine H receptor-mediated activation of ERK is dually regulated by G proteins and arrestins. In this study, we investigated the roles of G proteins and arrestins in the H receptor-mediated activation of JNK in Chinese hamster ovary (CHO) cells expressing wild-type (WT) human H receptors, the G protein-biased mutant S487TR, and the arrestin-biased mutant S487A. In these mutants, the Ser487 residue in the C-terminus region of the WT was truncated (S487TR) or mutated to alanine (S487A). Histamine significantly stimulated JNK phosphorylation in CHO cells expressing WT and S487TR but not S487A. Histamine-induced JNK phosphorylation in CHO cells expressing WT and S487TR was suppressed by inhibitors against H receptors (ketotifen and diphenhydramine), G proteins (YM-254890), and protein kinase C (PKC) (GF109203X) as well as an intracellular Ca chelator (BAPTA-AM) but not by inhibitors against G protein-coupled receptor kinases (GRK2/3) (cmpd101), β-arrestin2 (β-arrestin2 siRNA), and clathrin (hypertonic sucrose). These results suggest that the H receptor-mediated phosphorylation of JNK is regulated by G-protein/Ca/PKC-dependent but GRK/arrestin/clathrin-independent pathways.
Topics: Animals; Cricetinae; Humans; Arrestin; Arrestins; beta-Arrestins; CHO Cells; Clathrin; Cricetulus; Extracellular Signal-Regulated MAP Kinases; G-Protein-Coupled Receptor Kinases; GTP-Binding Proteins; Histamine; Phosphorylation; Protein Kinase C; Receptors, Histamine H1; Signal Transduction
PubMed: 38542369
DOI: 10.3390/ijms25063395 -
Cureus Feb 2024The H-antihistamine diphenhydramine antagonizes cholinesterase inhibitor poisoning in various animal species. One aspect of acute antidotal actions of diphenhydramine is... (Review)
Review
The H-antihistamine diphenhydramine antagonizes cholinesterase inhibitor poisoning in various animal species. One aspect of acute antidotal actions of diphenhydramine is increasing the median lethal doses (LD50) of toxicants. The objective of this meta-analysis was to assess the antidotal action of diphenhydramine against short-term toxicity (LD50) of cholinesterase inhibitors in experimental animals. The experimental studies selected were according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. They were conducted in laboratory animals (mice, rats, and chicks) to determine acute LD50 values of cholinesterase inhibitors (organophosphates, carbamates, and imidocarb) under the influence of diphenhydramine vs. controls. Twenty-eight records were selected from 12 studies on mice (n= 242), rats (n= 27), and young chicks (n= 128). The forest plot of randomized two-group meta-analysis assessed effect size, subgroup analysis, drapery prediction, heterogeneity, publication bias-funnel plot as well as one-group proportions meta-analysis of percent protection. Diphenhydramine significantly increased the combined effect size (i.e. increased LD50) in intoxicated experimental animals in comparison to controls (-3.71, standard error (SE) 0.36, 95%CI -4.46, -2.97). The drapery plot proposed a wide range of confidence intervals. The I index of heterogeneity of the combined effect size was high at 81.03% (= 142.3, p < 0.0001). Galbraith regression also indicated data heterogeneity; however, the normal quantile plot indicated no outliers. Subgroup analysis indicated significantly high heterogeneity with organophosphates (I = 63.72%) and carbamates (I = 76.41%), but low with imidocarb (I = 51.48%). The funnel plot and Egger regression test (t= -13.7, p < 0.0001) revealed publication bias. The median of the diphenhydramine protection ratio was 1.655, and the related forest plot of one group proportion meta-analysis revealed a statistically high level of protection (0.594, SE 0.083, 95%CI 0.432, 0.756), with high heterogeneity (I= 99.86). The risk of bias assessment was unclear, while the total score (16 out of 20) of each study leaned towards the side of the low risk of bias. In conclusion, the meta-analysis of LD50 values indicated that diphenhydramine unequivocally protected experimental animals from the acute toxicity of cholinesterase inhibitors. The drug could be an additional antidote against acute poisoning induced by cholinesterase inhibitors, but a word of caution: it is not to be considered as a replacement for the standard antidote atropine sulfate. Further studies are needed to examine the action of diphenhydramine on adverse chronic effects of cholinesterase inhibitors.
PubMed: 38505441
DOI: 10.7759/cureus.54403 -
Scientific Reports Mar 2024The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg...
The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO⋅5HO) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D, D, 5HT, H, and M-M). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (- 10.2 kcal/mol) toward the M receptors and an elevated binding affinity toward the receptors 5HT (- 8.1 kcal/mol), M (- 7.7 kcal/mol), M (- 8.7 kcal/mol), and H (- 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA.
Topics: Animals; Antiemetics; Molecular Docking Simulation; Ondansetron; Vomiting; Receptors, Muscarinic; Abietanes
PubMed: 38503897
DOI: 10.1038/s41598-024-57173-0