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Diabetes & Vascular Disease Research 2023Diabetes patients frequently experience diabetic neuropathy (DN), a microvascular complication that significantly reduces patients' quality of life. Memantine has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Diabetes patients frequently experience diabetic neuropathy (DN), a microvascular complication that significantly reduces patients' quality of life. Memantine has demonstrated potential benefits for neuropathic pains in preclinical studies. This study aimed to assess the efficacy of memantine in the management of peripheral neuropathy in patients with type 2 diabetes mellitus (T2DM).
METHOD
This randomized clinical trial includes 143 diabetic patients (aged between 18 and 75 years) with a confirmed diagnosis of diabetic neuropathy. Patients were randomly assigned to receive memantine 5 mg twice daily for 1 week, followed by 10 mg twice daily plus gabapentin 300 mg daily ( = 72) or just gabapentin 300 mg daily ( = 71) for 8 weeks. The DN4 questionnaire, monofilament, tuning fork, and Tip-therm tests were used to measure neuropathy at baseline and after the 8-week intervention.
RESULTS
The mean score of the DN4 questionnaire in the memantine group was significantly lower than the control group (. value: .001). The number of patients with diabetic neuropathy remarkably decreased in the memantine group at the end of the study based on the performed tests (. value: .001).
CONCLUSION
Memantine functions as a beneficial agent in the management of diabetic neuropathy, which would significantly improve the quality of life in diabetic patients.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Diabetic Neuropathies; Gabapentin; Memantine; Diabetes Mellitus, Type 2; Quality of Life
PubMed: 37495223
DOI: 10.1177/14791641231191093 -
PloS One 2024Technological advancements have long played crucial roles in rice productivity and food security in Bangladesh. Seasonal variation over time and regional differences in...
Technological advancements have long played crucial roles in rice productivity and food security in Bangladesh. Seasonal variation over time and regional differences in rice production, however, pose a threat to agricultural sustainability but remain unexplored. We performed a spatial-temporal mapping of rice cultivation area, production, and yield from 2006-2007 to 2019-2020 using secondary data for disaggregating 64 districts in Bangladesh. Growth and multivariate approaches were employed to analyze time-series data. Results showed that Mymensingh had the highest rice cultivated area and production, while Bandarban had the lowest. The 14 years highest average rice yield was found in Gopalganj and Dhaka (3.63 tons/ha), while Patuakhali (1.73 tons/ha) had the lowest. For the Aus, Aman, and Boro, the rice cultivation area in 19 districts, 11 districts, and 13 districts declined significantly. The overall rice production increased significantly in most districts. For the Aus, Aman, and Boro seasons, the rice yield in 54, 50, and 37 districts demonstrated a significant upward trend, respectively. The adoption rate of modern varieties has risen dramatically. However, there are notable variances between regions and seasons. A significant increasing trend in Aus (0.007% to 0.521%), Aman (0.004% to 0.039%), and Boro (0.013% to 0.584%) were observed in 28, 34, and 36 districts, respectively, with an increase of 1% adaptation of HYV. Predictions revealed that rice cultivation area and production of Aus, Aman, and Boro seasons will be increased in most of the regions of Bangladesh by 2030. Based on spatiotemporal cluster analysis, the five identified cluster groupings illustrated that clusters lack spatial cohesion and vary greatly seasonally. This suggests increasing rice production by expanding cultivable land, adopting high-yielding varieties, and integrating faster technological advancement in research and extension. The findings will assist scientists in developing region-specific production technologies and policymakers in designing decentral region-specific policies to ensure the future sustainability of rice production.
Topics: Oryza; Bangladesh; Agriculture; Seasons; Amantadine
PubMed: 38489334
DOI: 10.1371/journal.pone.0300648 -
RSC Advances Aug 2023A series of ten novel compounds were synthesized by incorporating a 1,3 thiazole core into amantadine and their structures were validated using different analytical and...
A series of ten novel compounds were synthesized by incorporating a 1,3 thiazole core into amantadine and their structures were validated using different analytical and spectral methods such as FTIR, EI-MS, H NMR, and C NMR. The antibacterial and enzyme inhibitory properties of these newly synthesized compounds were evaluated. Remarkably, the compounds exhibited significant antibacterial activity against and . Additionally, the inhibitory activities of the synthesized compounds, against α-amylase, α-glucosidase, and urease were investigated. Among the tested compounds, compound 6d demonstrated potent and selective inhibition of α-amylase IC = 97.37 ± 1.52 μM, while acarbose was used as positive control and exhibited IC = 5.17 ± 0.25 μM. Compound 6d and 6e exhibited prominent inhibition against α-glucosidase IC = 38.73 ± 0.80 μM and 41.63 ± 0.26 μM respectively. Furthermore, compound 6d inhibited urease with exceptional efficacy IC = 32.76 μM, while positive control thiourea showed more prominent activity having IC = 1.334 μM. Molecular docking studies disclosed the binding mechanism and affinity of these new inhibitors within the binding sites of various amino acids. To investigate the association between molecular structural characteristics and inhibitory actions of synthesized derivatives, preliminary structure-activity relationship (SAR) studies were performed. These findings indicated that compounds 6a, 6c, 6d and 6e are potential candidates for hit-to-lead follow-up in the drug-discovery process for treating diabetes and hyperglycemia.
PubMed: 37614781
DOI: 10.1039/d3ra05330j -
Biomolecules Nov 2023L-DOPA is the mainstay of treatment for Parkinson's disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel...
L-DOPA is the mainstay of treatment for Parkinson's disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia (LID) are dopamine-depleted dopamine-transporter KO (DDD) mice. Treatment with α-methyl--tyrosine rapidly depletes their brain stores of DA and renders them akinetic. During sensitization in the open field (OF), their locomotion declines as vertical activities increase and upon encountering a wall they stand on one leg or tail and engage in climbing behavior termed "three-paw dyskinesia". We have hypothesized that L-DOPA induces a stereotypic activation of locomotion in DDD mice, where they are unable to alter the course of their locomotion, and upon encountering walls engage in "three-paw dyskinesia" as reflected in vertical counts or beam-breaks. The purpose of our studies was to identify a valid index of LID in DDD mice that met three criteria: (a) sensitization with repeated L-DOPA administration, (b) insensitivity to a change in the test context, and (c) stimulatory or inhibitory responses to dopamine D1 receptor agonists (5 mg/kg SKF81297; 5 and 10 mg/kg MLM55-38, a novel compound) and amantadine (45 mg/kg), respectively. Responses were compared between the OF and a circular maze (CM) that did not hinder locomotion. We found vertical counts and climbing were specific for testing in the OF, while oral stereotypies were sensitized to L-DOPA in both the OF and CM and responded to D1R agonists and amantadine. Hence, in DDD mice oral stereotypies should be used as an index of LID in screening compounds for PD.
Topics: Mice; Animals; Levodopa; Dopamine Agonists; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dyskinesia, Drug-Induced; Mice, Knockout; Parkinson Disease; Amantadine
PubMed: 38002340
DOI: 10.3390/biom13111658 -
Cureus Mar 2024Neuroleptic malignant syndrome (NMS) is a severe reaction to antipsychotic medications characterized by fever, muscle rigidity, altered mental status, and autonomic...
Neuroleptic malignant syndrome (NMS) is a severe reaction to antipsychotic medications characterized by fever, muscle rigidity, altered mental status, and autonomic dysfunction. Here, we describe the case of a 58-year-old female who presented with altered mental status two days after open reduction and internal fixation of the hip. A rapid response team was called when the patient appeared agitated with increased respiratory demand. After being intubated and moved to the ICU, she became febrile and rigid. A preliminary diagnosis of metabolic encephalopathy of unknown origin was made. Before being transported to the ICU, the patient was given multiple haloperidol doses in addition to her continued at-home medication, paroxetine, for major depressive disorder. The differential diagnosis included a workup for NMS, serotonin syndrome, and infectious processes. Once NMS was determined as the most likely etiology, all antipsychotic and serotonergic medications were discontinued. Then dantrolene and amantadine were administered, which resulted in clinically significant improvement. This case report demonstrates the importance of early identification of and intervention for NMS.
PubMed: 38686249
DOI: 10.7759/cureus.57276 -
MedRxiv : the Preprint Server For... Jun 2023Depression in Parkinson's disease (PD) is common, disabling and responds poorly to standard antidepressant medication. Motivational symptoms of depression, such as...
BACKGROUND
Depression in Parkinson's disease (PD) is common, disabling and responds poorly to standard antidepressant medication. Motivational symptoms of depression, such as apathy and anhedonia, are particularly prevalent in depression in PD and predict poor response to antidepressant treatment. Loss of dopaminergic innervation of the striatum is associated with emergence of motivational symptoms in PD, and mood fluctuations correlate with dopamine availability. Accordingly, optimising dopaminergic treatment for PD can improve depressive symptoms, and dopamine agonists have shown promising effects in improving apathy. However, the differential effect of antiparkinsonian medication on symptom dimensions of depression is not known.
AIMS
We hypothesised that there would be dissociable effects of dopaminergic medications on different depression symptom dimensions. We predicted that dopaminergic medication would specifically improve motivational symptoms, but not other symptoms, of depression. We also hypothesised that antidepressant effects of dopaminergic medications with mechanisms of action reliant on pre-synaptic dopamine neuron integrity would attenuate as pre-synaptic dopaminergic neurodegeneration progresses.
METHODS
We analysed data from a longitudinal study of 412 newly diagnosed PD patients followed over five years in the Parkinson's Progression Markers Initiative cohort. Medication state for individual classes of Parkinson's medications was recorded annually. Previously validated "motivation" and "depression" dimensions were derived from the 15-item geriatric depression scale. Dopaminergic neurodegeneration was measured using repeated striatal dopamine transporter (DAT) imaging.
RESULTS
Linear mixed-effects modelling was performed across all simultaneously acquired data points. Dopamine agonist use was associated with relatively fewer motivation symptoms as time progressed (interaction: β=-0.07, 95%CI [-0.13,-0.01], p=0.015) but had no effect on the depression symptom dimension (p=0.6). In contrast, monoamine oxidase-B (MAO-B) inhibitor use was associated with relatively fewer depression symptoms across all years (β=-0.41, 95%CI [-0.81,-0.01], p=0.047). No associations were observed between either depression or motivation symptoms and levodopa or amantadine use. There was a significant interaction between striatal DAT binding and MAO-B inhibitor use on motivation symptoms: MAO-B inhibitor use was associated with lower motivation symptoms in patients with higher striatal DAT binding (interaction: β=-0.24, 95%CI [-0.43, -0.05], p=0.012). No other medication effects were moderated by striatal DAT binding measures.
CONCLUSIONS
We identified dissociable associations between dopaminergic medications and different dimensions of depression in PD. Dopamine agonists may be effective for treatment of motivational symptoms of depression. In contrast, MAO-B inhibitors may improve both depressive and motivation symptoms, albeit the latter effect appears to be attenuated in patients with more severe striatal dopaminergic neurodegeneration, which may be a consequence of dependence on pre-synaptic dopaminergic neuron integrity.
PubMed: 37425947
DOI: 10.1101/2023.06.30.23292073 -
Annals of Palliative Medicine Nov 2023Improvements in radiation delivery and systemic therapies have resulted in few remaining indications for palliative whole brain radiation therapy (WBRT). Most centers...
BACKGROUND
Improvements in radiation delivery and systemic therapies have resulted in few remaining indications for palliative whole brain radiation therapy (WBRT). Most centers preferentially use stereotactic radiotherapy (SRT) and reserve WBRT for those with >15 lesions, leptomeningeal presentation, rapidly progressive disease, or limited estimated survival. Despite regional differences among preferred dose, fractionation, and treatment technique, we predict survival post-WBRT will remain poor-indicating appropriate application of WBRT in this era of SRT and improved systemic therapies.
METHODS
A multi-center, international retrospective analysis of patients receiving WBRT in 2022 was performed. Primary end point was survival after WBRT. De-identified data were analyzed centrally. Patients receiving WBRT as part of a curative regimen, prophylactically, or as bridging therapy were excluded. The collected data consisted of patient parameters including prescription dose and fractionation, use of neurocognitive sparing techniques and survival after WBRT. Survival was calculated via the Kaplan-Meier method.
RESULTS
Of 29,943 international RT prescriptions written at ten participating centers in 2022, 462 (1.5%) were for palliative WBRT. Participating centers were in the United States (n=138), the United Kingdom (n=111), Hong Kong (n=72), Italy (n=49), Belgium (n=45), Germany (n=27), Ghana (n=15), and Cyprus (n=5). Twenty-six different dose regimens were used. The most common prescriptions were for 3,000 cGy over 10 fractions (45.0%) and 2,000 cGy over 5 fractions (43.5%) with significant regional preferences (P<0.001). Prior SRT was delivered in 32 patients (6.7%), hippocampal avoidance (HA) was used in 44 patients (9.5%), and memantine was prescribed in 93 patients (20.1%). Survival ranged from 0 days to still surviving at 402 days post-treatment. The global median overall survival (OS) was 84 days after WBRT [95% confidence interval (CI): 68.0-104.0]. Actuarial survival at 7 days, 1 month, 3 months, and 6 months were 95%, 78%, 48%, and 32%, respectively. Twenty-seven patients (5.8%) were unable to complete their prescribed WBRT.
CONCLUSIONS
This moment-in-time analysis confirms that patients with poor expected survival are being appropriately selected for WBRT-illustrating the dwindling indications for WBRT-and demonstrates the variance in global practice. Since poor survival precludes patients from deriving benefit, memantine and HA are best suited in carefully selected cases.
Topics: Humans; Brain Neoplasms; Retrospective Studies; Memantine; Cranial Irradiation; Radiosurgery; Brain
PubMed: 37731303
DOI: 10.21037/apm-23-448 -
Experimental and Therapeutic Medicine May 2024Total saikosaponins (TSS) form a group of chemically and biologically active components that can be extracted from Bupleurum, with reported antidepressive,...
Total saikosaponins (TSS) form a group of chemically and biologically active components that can be extracted from Bupleurum, with reported antidepressive, anti-inflammatory, antiviral, antiendotoxin, antitumor, anti-pulmonary fibrosis and anti-gastric ulcer effects. Bupleurum or TSS is frequently utilized in clinical practice alongside other medications (such as entecavir, lamivudine, compound paracetamol and amantadine hydrochloride capsules), leading to an increased risk of drug-drug interactions. The cytochrome P450 (CYP) family serves a critical role in the metabolism of numerous essential drugs (such as tamoxifen, ibuprofen and phenytoin), where the majority of drug interactions involve CYP-mediated metabolism. It is therefore essential to understand the effects of key components of Bupleurum on CYPs when administering combination therapies containing TSS or Bupleurum. The present study aimed to investigate the effects of TSS on the mRNA and protein expression of CYP3A4 and CYP1A2 in HepaRG cells. The effects of TSS on the survival of HepaRG cells was investigated using the Cell Counting Kit-8 (CCK-8) method. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) analysis were used to assess the effects of different concentrations of TSS (0, 5, 10 and 15 µg/ml) on CYP3A4 and CYP1A2 mRNA and protein expression in HepaRG cells. Based on the CCK-8 assay results, it was observed that the cell viability remained above 80% when treated with 1, 5, 10 and 15 µg/ml TSS. Although there was a statistically significant reduced cell viability at TSS concentrations of 10 and 15 µg/ml compared with the control group, the findings indicated that TSS did not exhibit notable cytotoxic effects at these concentrations. Furthermore, RT-qPCR results revealed that compared with those in the control group, TSS at concentrations of 10 and 15 µg/ml reduced CYP3A4 mRNA expression but increased CYP1A2 mRNA expression in HepaRG cells at concentrations of 15 µg/ml. WB analysis found that TSS at concentrations of 10 and 15 µg/ml downregulated CYP3A4 protein expression in HepaRG cells while increasing CYP1A2 protein expression at concentrations of 15 µg/ml. Results in the present study suggest that TSS can inhibit CYP3A4 mRNA and protein expression, but exerts opposite effects on their CYP1A2 counterparts. These findings suggest that it is necessary to consider drug interactions between clinical preparations containing TSS or Bupleurum and drugs metabolized by CYP3A4 and CYP1A2 to avoid potential adverse drug reactions in clinical practice.
PubMed: 38590569
DOI: 10.3892/etm.2024.12505 -
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 -
BMC Geriatrics Feb 2024Since 2003 when memantine was first approved for use in the management of moderate-severe Alzheimer's dementia, its use has become more widespread and is being explored... (Review)
Review
BACKGROUND
Since 2003 when memantine was first approved for use in the management of moderate-severe Alzheimer's dementia, its use has become more widespread and is being explored in other diseases like neuropathic pain, epilepsy, and mood disorders. Our case uniquely highlights two important adverse effects in a patient who overdosed on memantine. One is hypertension, which is easy to overlook as a medication side effect. The other is echolalia which is the repetition of words and phrases spoken by another person. It is commonly seen in children with autism spectrum disorder and has been reported in older adults with head injuries, delirium, and neurocognitive disorders. The aim of this patient story is to highlight the importance of medication reconciliation with caregivers and knowledge of adverse drug reactions in patient management. This case report has been presented previously in the form of an abstract at the American Geriatrics Society Presidential poster session in May 2023.
CASE PRESENTATION
Our patient is an 86-year-old man with mild dementia and hypertension, who was brought to the emergency department (ED) due to abrupt onset of altered mental status and auditory hallucinations. Investigations including blood work, CT head and an electroencephalogram (EEG) did not reveal an etiology for this change in his condition. Due to elevated blood pressure on presentation, a nicardipine drip was started, and he was given IV midazolam to assist with obtaining imaging. While reviewing medications with his daughter, it was noted that sixty memantine pills were missing from the bottle. Poison control was contacted and they confirmed association of these features with memantine. With supportive care, his symptoms resolved in less than 100 h, consistent with the half-life of memantine. Notably, our patient was started on Memantine one month prior to this presentation.
CONCLUSIONS
Hypertensive urgency and echolalia were the most striking symptoms of our patient's presentation. Though hypertension is a known sign of memantine overdose, it can easily be contributed to medication non-compliance in patients with dementia, being treated for hypertension. According to our literature review, this the first case of memantine overdose presenting with echolalia, a sign that is not commonly associated with adverse reactions to medications. This highlights the importance of an early medication review, especially with caregivers of people with dementia.
Topics: Male; Humans; Aged; Aged, 80 and over; Memantine; Autism Spectrum Disorder; Echolalia; Alzheimer Disease; Dementia; Drug-Related Side Effects and Adverse Reactions; Hypertension
PubMed: 38302876
DOI: 10.1186/s12877-024-04658-2