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Journal of Molecular Modeling Oct 2023The aggregation and adsorption of amantadine and sodium dodecyl sulfate on the boron nitride nanotubes in aqueous system were investigated, employing the classical...
CONTEXT
The aggregation and adsorption of amantadine and sodium dodecyl sulfate on the boron nitride nanotubes in aqueous system were investigated, employing the classical molecular dynamics method. The aqueous system containing amantadine and sodium dodecyl sulfate was investigated by self-diffusion of the molecules, with particular emphasis on their center of mass mean square displacement. The radial distribution function and dipole moment measurement were used to analyze the water effect on the aggregation and molecular interaction between amantadine and sodium dodecyl sulfate in the complex. In turn, the amantadine molecules are able to develop water monolayers at the aqueous solution but show no noticeable aggregated adsorption in the fluid. In contrast, sodium dodecyl sulfate self-aggregation on the boron nitride nanotube efficiently occurs, and so the effect of sodium dodecyl sulfate on aggregated adsorption of amantadine was studied. Our results show that in the presence of sodium dodecyl sulfate at critical micelle concentration, its effect on the aggregation of amantadine was enhanced onto boron nitride nanotube compared to just pure sodium dodecyl sulfate or amantadine on boron nitride nanotube. Our simulations show a remarkable restructuring and enhanced orientation of the water molecules around sodium dodecyl sulfate and amantadine adsorbed on boron nitride nanotube.
METHOD
All molecular dynamics simulations were done using NAMD-2.9 package with CHARMM-36 force field. The nanotube PDB file was made by VMD with (12, 12) indexes. The nanotube atoms were considered to be fixed and periodic during the simulation process, and the ends did not cap with hydrogens. The initial PDB file of components was saved from ChemOffice software, and the webservers to obtain the charge and topology files were Reddb and Swiss Param webservers. The VMD software was used for structural visualizations and graphical analysis.
PubMed: 37807012
DOI: 10.1007/s00894-023-05736-9 -
The American Journal of Geriatric... Dec 2023Alzheimer's disease or Related Dementia (ADRD) is known to disturb pain perception and reduce the ability to report it, resulting in underestimation by practitioners and...
OBJECTIVE
Alzheimer's disease or Related Dementia (ADRD) is known to disturb pain perception and reduce the ability to report it, resulting in underestimation by practitioners and sub-optimal medical management. The aim of this study was to estimate the prevalence of all types of CP among people with ADRD.
DESIGN
Nationwide cross-sectional study.
SETTINGS
French community-dwelling and nursing home residents.
PARTICIPANTS
People with ADRD, >40 years old, treated with cholinesterase inhibitors or memantine, or with a diagnosis/long-term illness of ADRD and matched with a comparison sample.
SETTINGS
French community-dwelling and nursing home residents.
PARTICIPANTS
People with ADRD, >40 years old, treated with cognitive stimulants (cholinesterase inhibitors and memantine) or with a diagnosis/long-term illness of ADRD and matched with a comparison sample (non-ADRD).
MEASUREMENTS
The capture-recapture method was performed to provide estimates of the prevalence of CP. People treated with analgesic drugs for ≥6 months consecutively or with a medical diagnosis of CP (ICD-10 codes) or referred to a pain center were considered as having CP.
RESULTS
A total of 48,288 individuals were included, of which 16,096 had ADRD and 32,192 without ADRD. The estimated prevalence of CP in people with ADRD was from 57.7% [52.9;63.3] to 57.9%[53.0;63.9], and slightly higher than the non-ADRD sample (from 49.9%[47.0;53.2] to 50.4%[47.3;53.9], p <0.001).
CONCLUSIONS
The prevalence of CP among people living with ADRD was at least the same as or better than individuals without ADRD. This result should alert practitioners' attention to the need for effective pain assessment and management in this population who has difficulties to express and feel pain.
Topics: Humans; Chronic Pain; Memantine; Prevalence; Cross-Sectional Studies; Cholinesterase Inhibitors; Alzheimer Disease
PubMed: 37468390
DOI: 10.1016/j.jagp.2023.06.015 -
Medicine May 2024This study aims to investigate the effect of amantadine use on neurological outcomes and mortality in patients with severe traumatic brain injury (TBI) (Glasgow coma... (Observational Study)
Observational Study
This study aims to investigate the effect of amantadine use on neurological outcomes and mortality in patients with severe traumatic brain injury (TBI) (Glasgow coma score [GCS] between 3 and 8) who have been followed up on mechanical ventilators in the intensive care unit (ICU). Data from the hospital's electronic records were retrospectively searched. Patients over 18 years of age, with severe brain trauma (GCS between 3-8), who were treated with endotracheal intubation and invasive mechanical ventilation at admission to the ICU, and who were treated with Amantadine hydrochloride at least once in the first week of follow-up were included in the study. To evaluate the patients' neurological outcomes, the GCS and FOUR scores were used. GCS and FOUR scores were recorded on the 1st, 3rd, and 7th days of the first week. In addition, the score difference between the 1st and 7th day was calculated for both scores. The patients were divided into 2 groups: those receiving amantadine treatment (Group A, n = 44) and the control group (Group C, n = 47). The median age of all patients was 39 (18-81) (P = .425). When Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day GCS values (P = .474, P = .483, and P = 329, respectively). However, the difference in GCS values between day 1 and day 7 (∆ GCS 7-1) was statistically significant (P = .012). Similarly, when Group A and Group C were compared, no statistically significant results were found between the 1st, 3rd, and 7th day FOUR score values (P = .948, P = .471, and P = .057, respectively). However, the FOUR score values between day 1 and day 7 (∆ FOUR score 7-1) were statistically significant (P = .004). There was no statistically significant difference among the groups in terms of ICU length of stay, duration of non-ICU hospital stay, and length of hospital stay (P = .222, P = .175, and P = .067, respectively). Amantadine hydrochloride may help improve neurological outcomes in patients with severe TBI. However, further research is needed to investigate this topic.
Topics: Humans; Amantadine; Respiration, Artificial; Male; Female; Middle Aged; Adult; Retrospective Studies; Intensive Care Units; Aged; Glasgow Coma Scale; Adolescent; Aged, 80 and over; Brain Injuries, Traumatic; Young Adult; Treatment Outcome; Craniocerebral Trauma
PubMed: 38758901
DOI: 10.1097/MD.0000000000038172 -
Journal of Ethnopharmacology Apr 2024In elderly people, Alzheimer's disease (AD) is the most common form of dementia. It has been shown that traditional Chinese medicine (TCM) based on phytomedicines...
ETHNOPHARMACOLOGICAL RELEVANCE
In elderly people, Alzheimer's disease (AD) is the most common form of dementia. It has been shown that traditional Chinese medicine (TCM) based on phytomedicines enhances the therapeutic effects of modern medicine when taken in conjunction with them. Modern medicine N-methyl-D-aspartate receptor (NMDA) antagonist memantine (Mm) are mainly used in the clinical treatment of AD. TCM Cerebralcare Granule® (CG) has long been an effective treatment for headaches, dizziness, and other symptoms. In this study, we employ a blend of CG and Mm to address Alzheimer's disease-like symptoms and explore their impacts and underlying mechanisms.
AIM OF THE STUDY
The objective of our study was to observe the effects of CG combined with Memantine (Mm) on learning and memory impairment of AD mice induced by D-galactose and to explore the mechanism at work.
MATERIALS AND METHODS
CG and Mm were combined to target multiple pathological processes involved in AD. For a thorough analysis, we performed various experiments such as behavioral detection, pathological detection, proteomic detection, and other experimental methods of detection.
RESULTS
It was found that the combination of CG and Mm was significantly effective for improving learning and memory in AD mice as well as brain pathology. The serum and hippocampal tissue of AD mice were significantly enhanced with catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) levels were decreased with this treatment. In AD mice, a combination of Mm and CG (CG + Mm) significantly increased the levels of the anti-inflammatory factors IL-4 and IL-10, decreased the levels of pro-inflammatory factors (IL-6, IL-1β) and tumor necrosis factor-alpha (TNF-α), improved synaptic plasticity by restoring synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) expression in the hippocampus, enhanced Aβ phagocytosis of microglia in AD mice, and increased mitochondrial respiratory chain enzyme complexes I, II, III, and IV, lead to an increase in the number of functionally active NMDA receptors in the hippocampus. Proteomic analysis GO analysis showed that the positive regulation gene H3BIV5 of G protein coupled receptor signal pathway and synaptic transmission was up-regulated, while the transsynaptic signal of postsynaptic membrane potential and regulation-related gene Q5NCT9 were down-regulated. Most proteins showed significant enriched signal transduction pathway profiles after CG + Mm treatment, based on the KEGG pathway database.
CONCLUSION
The data supported the idea that CG and Mm could be more effective in treating AD mice induced by D-galactose than Mm alone. We provided a basis for the clinical use of CG with Mm.
Topics: Humans; Mice; Animals; Aged; Alzheimer Disease; Memantine; Galactose; Proteomics; Hippocampus; Antioxidants
PubMed: 38142875
DOI: 10.1016/j.jep.2023.117609 -
The Canadian Journal of Neurological... Nov 2023To describe the development and initial experience of a clinical research program in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Canada: The...
OBJECTIVE
To describe the development and initial experience of a clinical research program in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Canada: The Rossy PSP Centre, to share the data acquisition tools adopted, and to report preliminary results.
METHODS
Extensive demographic and longitudinal clinical information is collected every 6 months using standardized forms. Biofluids are collected for biobanking and genetic analysis, and many patients are enrolled in neuroimaging research protocols. Brain donation is an important component of the program, and standardized processing protocols have been established, including very short death to autopsy times in patients undergoing medical assistance in dying.
RESULTS
Between Oct 2019 and Dec 2021, 132 patients were screened, 91 fulfilling criteria for PSP and 19 for CBS; age 71 years; 41% female; duration 5 years, age-of-onset 66 years. The most common symptoms at onset were postural instability and falls (45%), cognitive-behavioral changes (22%), and Parkinsonism (9%). The predominant clinical phenotype was Richardson syndrome (82%). Levodopa and amantadine resulted in partial and short-lasting benefit.
CONCLUSIONS
The Rossy PSP Centre has been established to advance clinical and basic research in PSP and related tauopathies. The extent of the clinical data collected permits deep phenotyping of patients and allows for future clinical and basic research. Preliminary results showed expected distribution of phenotypes, demographics, and response to symptomatic treatments in our cohort. Longitudinal data will provide insight into the early diagnosis and management of PSP. Future steps include enrollment of patients in earlier stages, development of biomarkers, and fast-tracking well-characterized patients into clinical trials.
PubMed: 36600512
DOI: 10.1017/cjn.2022.332 -
Biomaterials Aug 2023Hydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but...
Hydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but various mechanical stimuli may cause premature hydrogel breakage and detachment, impeding their further clinical translation. Here we report a multifunctional mechanically-resilient self-healing hydrogel for effective UC treatment, which is synthesized through the host-guest interaction between dopamine/β-cyclodextrin-modified hyaluronic acid (HA-CD-DA) and amantadine-modified carboxymethyl chitosan (CMCS-AD). The excessive β-CD cavities allow the incorporation of dexamethasone (DEX), while the porous hydrogel network potentiates the encapsulation of basic fibroblast growth factor (bFGF) and L-alanyl-l-glutamine (ALG). DA moieties in HA components allow firm adhesion of the hydrogel to the ulcerative lesions after in-situ implantation, while the reversible host-guest interaction between CD and AD could enhance the persistence of hydrogel. The hydrogel demonstrated favorable biocompatibility and could continuously release DEX to induce M1-to-M2 repolarization of mucosal macrophages through inhibiting the toll-like receptor 4 (TLR4)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis. Furthermore, the co-delivered bFGF and ALG facilitates the regeneration of ulcerative mucosa and restore its barrier functions to ameliorate UC symptoms. The mechanically resilient hydrogel offers an integrative approach for UC therapy in the clinics.
Topics: Humans; Colitis, Ulcerative; Hydrogels; Biocompatible Materials; Mucous Membrane; Inflammation
PubMed: 37276796
DOI: 10.1016/j.biomaterials.2023.122184 -
Journal of Feline Medicine and Surgery May 2024Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a... (Review)
Review
Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care.Clinical approach:Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways.Aim:This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions.Evidence base:The review draws on current literature, where available, along with the author's extensive experience and research.
Topics: Cats; Animals; Neuralgia; Cat Diseases; Pain Management; Analgesics; Combined Modality Therapy
PubMed: 38710218
DOI: 10.1177/1098612X241246518 -
European Journal of Neurology Jan 2024Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae.
METHODS
Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15.
RESULTS
We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated.
CONCLUSION
The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.
Topics: Humans; COVID-19; SARS-CoV-2; Sleepiness; Amantadine; Double-Blind Method; Fatigue; Treatment Outcome
PubMed: 37584095
DOI: 10.1111/ene.16045 -
Clinics and Practice Jul 2023The usual adverse events of amantadine are dizziness, dry mouth, and peripheral edema. Postmarketing experience has revealed abnormal movements such as tremors,...
The usual adverse events of amantadine are dizziness, dry mouth, and peripheral edema. Postmarketing experience has revealed abnormal movements such as tremors, involuntary muscle contractions, and gait abnormalities. Herein, we report a case of an elderly male who presented with generalized twitching associated with amantadine. A 64-year-old male presenting with jerking movements within one day of onset was admitted. Sudden and involuntary distal lower and upper limb muscle twitching was observed. The subject presented subsequent brief movements when attempting to stand or hold arms antigravity. He was diagnosed with Parkinson's disease three years ago. Eight days before the presentation to the emergency department, he consulted with his primary care physician, who prescribed amantadine to improve his motor symptoms. On the seventh day, he developed brisk abnormal movements. Laboratory exams, neuroimaging, and electroencephalogram were unremarkable. Amantadine was discontinued. After three days, the patient reported that his jerking movements had fully recovered. To the authors' knowledge, 22 individuals with amantadine-associated myoclonus had already been reported in the literature. The pathophysiology of amantadine-induced myoclonus is probably related to serotoninergic pathways. Myoclonus secondary to amantadine was slightly more common in men. The population affected was elderly, with a mean and median age of 67.7 and 64 years.
PubMed: 37489424
DOI: 10.3390/clinpract13040075 -
Seminars in Neurology Oct 2023Patients with prolonged disorders of consciousness (DOCs) longer than 28 days may continue to make significant gains and achieve functional recovery. Occasionally, this...
Patients with prolonged disorders of consciousness (DOCs) longer than 28 days may continue to make significant gains and achieve functional recovery. Occasionally, this recovery trajectory may extend past 3 (for nontraumatic etiologies) and 12 months (for traumatic etiologies) into the chronic period. Prognosis is influenced by several factors including state of DOC, etiology, and demographics. There are several testing modalities that may aid prognostication under active investigation including electroencephalography, functional and anatomic magnetic resonance imaging, and event-related potentials. At this time, only one treatment (amantadine) has been routinely recommended to improve functional recovery in prolonged DOC. Given that some patients with prolonged or chronic DOC have the potential to recover both consciousness and functional status, it is important for neurologists experienced in prognostication to remain involved in their care.
Topics: Humans; Consciousness; Consciousness Disorders; Electroencephalography; Amantadine; Prognosis; Chronic Disease
PubMed: 37758177
DOI: 10.1055/s-0043-1775792