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Proceedings of the National Academy of... Nov 2023Neurotransmitter receptors are increasingly recognized to play important roles in anti-tumor immunity. The expression of the ion channel N-methyl-D-aspartate receptor...
Neurotransmitter receptors are increasingly recognized to play important roles in anti-tumor immunity. The expression of the ion channel N-methyl-D-aspartate receptor (NMDAR) on macrophages was reported, but the role of NMDAR on macrophages in the tumor microenvironment (TME) remains unknown. Here, we show that the activation of NMDAR triggered calcium influx and reactive oxygen species production, which fueled immunosuppressive activities in tumor-associated macrophages (TAMs) in the hepatocellular sarcoma and fibrosarcoma tumor settings. NMDAR antagonists, MK-801, memantine, and magnesium, effectively suppressed these processes in TAMs. Single-cell RNA sequencing analysis revealed that blocking NMDAR functionally and metabolically altered TAM phenotypes, such that they could better promote T cell- and Natural killer (NK) cell-mediated anti-tumor immunity. Treatment with NMDAR antagonists in combination with anti-PD-1 antibody led to the elimination of the majority of established preclinical liver tumors. Thus, our study uncovered an unknown role for NMDAR in regulating macrophages in the TME of hepatocellular sarcoma and provided a rationale for targeting NMDAR for tumor immunotherapy.
Topics: Humans; Tumor-Associated Macrophages; Neoplastic Processes; Memantine; Liver Neoplasms; Sarcoma; Tumor Microenvironment
PubMed: 37967215
DOI: 10.1073/pnas.2302126120 -
PloS One 2023To evaluate the effects of conservation agriculture (CA) on SOC pools and their lability, field experiments (2015-2020) were conducted on contrasting soils under...
To evaluate the effects of conservation agriculture (CA) on SOC pools and their lability, field experiments (2015-2020) were conducted on contrasting soils under subtropical climates. The experiment on non-calcareous soils, was comprised of tillage (minimum [MT] vs. conventional [CT]) in main plots, cropping systems (Wheat [Triticum aestivum]-Aus and Aman rice [Oryza sativa L.], WRR; Lentil [Lens culinaris]-Aus and Aman rice, LRR; and Mustard [Brassica nigra]- Boro and Aman rice, MRR) in the sub-plots, and crop residue (with or without 20% residue) in the sub-sub plots. The experiment on calcareous soils, was comprised of tillage (strip-till, ST; no-till, NT; and CT) and crop residue (high residue, HR at 50% by height vs. low residue, LR at 15%). Results showed that the MT had higher SOC contents by 18.8% than the CT in non-calcareous soils. Likewise, SOC was 12.5% and 6.7% higher in the NT and ST, respectively, than in the CT in calcareous soils. Significantly higher particulate organic (POC), permanganate oxidizable (POXC), and microbial biomass carbon (MBC) were observed in the MT, NT, and ST than in the CT at both locations. Reduced tillage with residue retention under LRR had a higher SOC, including labile C pools compared to WRR and MRR systems. Similarly, carbon management index (1.2-1.5 and 1.0-1.2) in both soils had significant positive correlations with SOC lability via POXC, POC, and MBC pools, indicating a SOC sequestration potential. In conclusion, our results showed positive effects of CA on SOC and its lability across soils.
Topics: Soil; Oryza; Carbon; Crops, Agricultural; Agriculture; Lens Plant; Triticum; Amantadine
PubMed: 37939097
DOI: 10.1371/journal.pone.0293257 -
Case Reports in Psychiatry 2023Tardive dyskinesia (TD) is characterized by abnormal and involuntary movements that generally occur after prolonged exposure to neuroleptic medications. In this article,...
Tardive dyskinesia (TD) is characterized by abnormal and involuntary movements that generally occur after prolonged exposure to neuroleptic medications. In this article, we present the case of a 29-year-old man with schizophrenia who developed TD following treatment with haloperidol. Despite various attempts with benzodiazepines, amantadine, and anticholinergics, the dyskinesias persisted. However, after 2 years of treatment with olanzapine alone, a progressive improvement occurred, leading to the complete disappearance of the dyskinesias. We also provide a brief review of reported cases of antipsychotic-induced TD that has improved with olanzapine.
PubMed: 37908858
DOI: 10.1155/2023/6688623 -
Molecules (Basel, Switzerland) Oct 2023Homotaurine (HOM) is considered a promising drug for the treatment of Alzheimer's and other neurodegenerative diseases. In the present work, a new high-performance...
Homotaurine (HOM) is considered a promising drug for the treatment of Alzheimer's and other neurodegenerative diseases. In the present work, a new high-performance liquid chromatography with fluorescence detection (HPLC-FLD) (λex. = 340 nm and λem. = 455 nm) method was developed and validated for the study of substance permeability in the central nervous system (CNS). Analysis was performed on a RP-C18 column with a binary gradient elution system consisting of methanol-potassium phosphate buffer solution (pH = 7.0, 0.02 M) as mobile phase. Samples of homotaurine and histidine (internal standard) were initially derivatized with ortho-phthalaldehyde (OPA) (0.01 M), N-acetylcysteine (0.01 M) and borate buffer (pH = 10.5; 0.05 M). To ensure the stability and efficiency of the reaction, the presence of different nucleophilic reagents, namely (a) 2-mercaptoethanol (2-ME), (b) N-acetylcysteine (NAC), (c) tiopronin (Thiola), (d) 3-mercaptopropionic acid (3-MPA) and (e) captopril, was investigated. The method was validated (R = 0.9999, intra-day repeatability %RSD < 3.22%, inter-day precision %RSD = 1.83%, limits of detection 5.75 ng/mL and limits of quantification 17.43 ng/mL, recovery of five different concentrations 99.75-101.58%) and successfully applied to investigate the in vitro permeability of homotaurine using Franz diffusion cells. The apparent permeability (P) of HOM was compared with that of memantine, which is considered a potential therapeutic drug for various CNSs. Our study demonstrates that homotaurine exhibits superior permeability through the simulated blood-brain barrier compared to memantine, offering promising insights for enhanced drug delivery strategies targeting neurological conditions.
Topics: Acetylcysteine; Chromatography, High Pressure Liquid; Memantine; o-Phthalaldehyde; Indicators and Reagents; Tiopronin; Reproducibility of Results
PubMed: 37894565
DOI: 10.3390/molecules28207086 -
American Journal of Ophthalmology Case... Dec 2023To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and...
PURPOSE
To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and outcomes of amantadine-induced corneal edema.
OBSERVATIONS
A 36-year-old woman presented with a 6-week history of gradually progressive bilateral painless visual loss with visual acuity (VA) of 20/350 and 20/300 in the right and left eye, respectively. Examination showed bilateral diffuse central corneal edema with multiple Descemet membrane folds without endothelial guttata, keratic precipitates or intraocular inflammation. This did not respond to hypertonic saline drops and empirical treatment for presumed herpetic endotheliitis with oral acyclovir. Medication review revealed the use of amantadine 100mg daily for the past 10 years, prescribed by her neurologist for fatigue. Despite discontinuing amantadine, corneal edema was irreversible due to a markedly reduced endothelial cell count of 625 (right) and 680 cells/mm (left).
CONCLUSIONS AND IMPORTANCE
This case highlights the need to consider amantadine as a cause of unexplained bilateral non-guttae corneal edema. A literature review of 33 case reports revealed broadly similar features of amantadine-induced corneal edema; whilst most cases had favorable outcomes with median VA 20/25 (interquartile range IQR 20/20-20/30) and complete resolution of corneal edema within 30 days (IQR 14-35) of amantadine discontinuation, most experienced low endothelial cell density 759 cells/mm (IQR 621-1078). Taken together, screening specular microscopy ought to be considered for those in whom amantadine is likely required long-term.
PubMed: 37840541
DOI: 10.1016/j.ajoc.2023.101881 -
Journal of Medical Case Reports Oct 2023Huntington's disease is an autosomal dominant inherited disorder characterized by personality changes (such as irritability and restlessness) and psychotic symptoms...
BACKGROUND
Huntington's disease is an autosomal dominant inherited disorder characterized by personality changes (such as irritability and restlessness) and psychotic symptoms (such as hallucinations and delusions). When the personality changes become noticeable, involuntary movements (chorea) also develop. The disease is caused by the CAG repeat expansion in the coding region of the HTT gene, and the diagnosis is based on the presence of this expansion. However, there is currently no effective treatment for the progression of Huntington's disease and its involuntary motor symptoms. Herein, we present a case in which memantine was effective in treating the chorea movements of Huntington's disease.
CASE PRESENTATION
A 75-year-old Japanese woman presented to the hospital with involuntary movements of Huntington's disease that began when she was 73 years old. In a cerebral blood flow test (N-isopropyl-p-iodoamphetamine-single-photon emission computed tomography), decreased blood flow was observed in the precuneus (anterior wedge) and posterior cingulate gyrus. Usually, such areas of decreased blood flow are observed in patients with Alzheimer's-type dementia. So, we administered memantine for Alzheimer's-type dementia, and this treatment suppressed the involuntary movements of Huntington's disease, and the symptoms progressed slowly for 7 years after the onset of senility. In contrast, her brother died of complications of pneumonia during the course of Huntington's disease.
CONCLUSIONS
We recorded changes in parameters such as the results of the N-isopropyl-p-iodoamphetamine-single-photon emission computed tomography and gait videos over 7 years. Treatment with memantine prevented the chorea movement and the progression of Huntington's disease. We believe this record will provide clinicians with valuable information in diagnosing and treating Huntington's disease.
Topics: Male; Female; Humans; Aged; Huntington Disease; Chorea; Memantine; Alzheimer Disease; Iofetamine; Dyskinesias
PubMed: 37840138
DOI: 10.1186/s13256-023-04161-z -
Neuropharmacology Feb 2024The great potential for NMDA receptor modulators as druggable targets in neurodegenerative disorders has been met with limited success. Considered one of the rare... (Review)
Review
The great potential for NMDA receptor modulators as druggable targets in neurodegenerative disorders has been met with limited success. Considered one of the rare exceptions, memantine has consistently demonstrated restorative and prophylactic properties in many AD models. In clinical trials memantine slows the decline in cognitive performance associated with AD. Here, we provide an overview of the basic properties including pharmacological targets, toxicology and cellular effects of memantine. Evidence demonstrating reductions in molecular, physiological and behavioural indices of AD-like impairments associated with memantine treatment are also discussed. This represents both an extension and homage to Dr. Chris Parson's considerable contributions to our fundamental understanding of a success story in the AD treatment landscape.
Topics: Humans; Memantine; Alzheimer Disease; Receptors, N-Methyl-D-Aspartate; Cognition
PubMed: 37832633
DOI: 10.1016/j.neuropharm.2023.109737 -
Indian Journal of Anaesthesia Sep 2023
PubMed: 37829788
DOI: 10.4103/ija.ija_78_23 -
PloS One 2023Bangladesh has been ranked as one of the world's top countries affected by climate change, particularly in terms of agricultural crop sector. The purpose of this study...
Bangladesh has been ranked as one of the world's top countries affected by climate change, particularly in terms of agricultural crop sector. The purpose of this study is to identify spatial and temporal changes and trends in long-term climate at local and national scales, as well as their implications for rice yield. In this study, Modified Mann-Kendall and Sen's slope tests were used to detect significant trends and the magnitude of changes in temperature and rainfall. The temperature and rainfall data observed and recorded at 35 meteorological stations in Bangladesh over 65-years in the time span between the years 1949 and 2013 have been used to detect these changes and trends of variation. The results show that mean annual Tmean, Tmin, and Tmax have increased significantly by 0.13°C, 0.13°C, and 0.13°C/decade, respectively. The most significant increasing trend in seasonal temperatures for the respective Tmean, Tmin, and Tmax was 0.18°C per decade (post-monsoon), 0.18°C/decade (winter), and 0.23°C/decade (post-monsoon), respectively. Furthermore, the mean annual and pre-monsoon rainfall showed a significant increasing trend at a rate of 4.20 mm and 1.35 mm/year, respectively. This paper also evaluates climate variability impacts on three major rice crops, Aus, Aman, and Boro during 1970-2013. The results suggest that crop yield variability can be explained by climate variability during Aus, Aman, and Boro seasons by 33, 25, and 16%, respectively. Maximum temperature significantly affected the Aus and Aman crop yield, whereas rainfall significantly affected all rice crops' yield. This study sheds light on sustainable agriculture in the context of climate change, which all relevant authorities should investigate in order to examine climate-resilient, high-yield crop cultivation.
Topics: Temperature; Oryza; Climate Change; Bangladesh; Meteorology; Crops, Agricultural; Amantadine
PubMed: 37824463
DOI: 10.1371/journal.pone.0292668 -
The Journal of International Medical... Oct 2023Long-term use of antipsychotics or other dopamine antagonists can result in the extrapyramidal side effect of tardive dyskinesia (TD).Case presentation: An 18-year-old...
BACKGROUND
Long-term use of antipsychotics or other dopamine antagonists can result in the extrapyramidal side effect of tardive dyskinesia (TD).Case presentation: An 18-year-old female patient experienced abnormal speech and behavior and because of an equivocal diagnosis, she was given daily doses of 300 mg of quetiapine and 60 mg of ziprasidone. She had used these medications for 2 years before the appearance of involuntary abnormal movements. These movements, which were classified as TD, steadily worsened and markedly interfered with her daily life. Following a trial-and-error course of therapy with vitamin E, vitamin B6, amantadine, valproic acid sodium, lorazepam, and diazepam, the drugs were gradually reduced and stopped, yet the aberrant movements persisted. Finally, the patient was given olanzapine, clonazepam, baclofen, and gabapentin. The Abnormal Involuntary Movement Scale was used to assess changes in the patient's condition. Her TD was efficiently managed through co-administration of olanzapine, clonazepam, baclofen, and gabapentin.
CONCLUSIONS
The possibility of TD inducing by antipsychotic use is a clinical concern, even though atypical antipsychotics decrease the incidence of extrapyramidal side effects, and it cannot be entirely excluded. This report provides useful insights into the management of TD and will help clinicians manage similar cases.
Topics: Humans; Female; Adolescent; Olanzapine; Tardive Dyskinesia; Clonazepam; Gabapentin; Baclofen; Antipsychotic Agents
PubMed: 37812512
DOI: 10.1177/03000605231195154