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Food Chemistry: X Jun 2024The presence of veterinary drug residues in aquatic products represents a significant challenge to food safety. The current detection methods, limited in both scope and...
The presence of veterinary drug residues in aquatic products represents a significant challenge to food safety. The current detection methods, limited in both scope and sensitivity, underscore the urgent need for more advanced techniques. This research introduces a swift and potent screening technique using high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) and a refined QuEChERS protocol, allowing simultaneous qualitative and semi-quantitative analysis of 192 residues. A comprehensive database, employing full scan mode and data-dependent secondary mass spectroscopy, enhances screening accuracy. The method involves efficient extraction using 90% acetonitrile, dehydration with NaSO, and acetic acid, followed by cleanup using dispersive solid-phase extract sorbent primary secondary amine. It is suitable for samples with varying fat content, offering detection limits ranging from 0.5 to 10 μg/kg, high recovery rates (60-120%), and low relative standard deviations (<20%). Practical application has validated its effectiveness for multi-residue screening, marking a significant advancement in food safety evaluation.
PubMed: 38855097
DOI: 10.1016/j.fochx.2024.101504 -
Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models.Cell Death & Disease May 2024Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in...
Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux in NPC1 cells resulted in mitochondrial dysfunction due to impairment of mitophagy, leading to the depletion of both the reduced and oxidised forms of NAD as identified via metabolic profiling. Consequently, exhaustion of the NAD pools triggered mitochondrial depolarisation and apoptotic cell death. Our chemical screening identified two FDA-approved drugs, celecoxib and memantine, as autophagy activators which effectively restored autophagic flux, NAD levels, and cell viability of NPC1 cells. Of biomedical relevance, either pharmacological rescue of the autophagy deficiency or NAD precursor supplementation restored NAD levels and improved the viability of NPC1 patient fibroblasts and induced pluripotent stem cell (iPSC)-derived cortical neurons. Together, our findings identify the autophagy-NAD axis as a mechanism of cell death and a target for therapeutic interventions in NPC1 disease, with a potential relevance to other neurodegenerative disorders.
Topics: Niemann-Pick Disease, Type C; Humans; Autophagy; NAD; Induced Pluripotent Stem Cells; Fibroblasts; Mitochondria; Memantine; Neurons; Cell Death; Cell Survival; Mitophagy; Apoptosis
PubMed: 38821960
DOI: 10.1038/s41419-024-06770-y -
Alzheimer's Research & Therapy May 2024A large proportion of nursing home (NH) residents suffer from dementia and effects of conventional anti-dementia drugs on their health is poorly known. We aimed to... (Observational Study)
Observational Study
BACKGROUND
A large proportion of nursing home (NH) residents suffer from dementia and effects of conventional anti-dementia drugs on their health is poorly known. We aimed to investigate the associations between exposure to anti-dementia drugs and mortality among NH residents.
METHODS
This retrospective longitudinal observational study involved 329 French NH and the residents admitted in these facilities since 2014 and having major neurocognitive disorder. From their electronic health records, we obtained their age, sex, level of dependency, Charlson comorbidity index, and Mini mental examination score at admission. Exposure to anti-dementia drugs was determined using their prescription into 4 categories: none, exposure to acetylcholinesterase inhibitors (AChEI) alone, exposure to memantine alone, exposure to AChEI and memantine. Survival until the end of 2019 was studied in the entire cohort by Cox proportional hazards. To alleviate bias related to prescription of anti-dementia drugs, we formed propensity-score matched cohorts for each type of anti-dementia drug exposure, and studied survival by the same method.
RESULTS
We studied 25,358 NH residents with major neurocognitive disorder. Their age at admission was 87.1 + 7.1 years and 69.8% of them were women. Exposure to anti-dementia drugs occurred in 2,550 (10.1%) for AChEI alone, in 2,055 (8.1%) for memantine alone, in 460 (0.2%) for AChEI plus memantine, whereas 20,293 (80.0%) had no exposure to anti-dementia drugs. Adjusted hazard ratios for mortality were significantly reduced for these three groups exposed to anti-dementia drugs, as compared to reference group: HR: 0.826, 95%CI 0.769 to 0.888 for AChEI; 0.857, 95%CI 0.795 to 0.923 for memantine; 0.742, 95%CI 0.640 to 0.861 for AChEI plus memantine. Results were consistent in propensity-score matched cohorts.
CONCLUSION
The use of conventional anti-dementia drugs is associated with a lower mortality in nursing home residents with dementia and should be widely used in this population.
Topics: Humans; Memantine; Nursing Homes; Female; Male; Dementia; Longitudinal Studies; Aged, 80 and over; Cholinesterase Inhibitors; Retrospective Studies; Aged; Homes for the Aged; France
PubMed: 38812028
DOI: 10.1186/s13195-024-01481-0 -
Narra J Apr 2024Numerous prior studies have identified therapeutic targets that could effectively combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection,...
Numerous prior studies have identified therapeutic targets that could effectively combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including the angiotensin-converting enzyme 2 (ACE2) receptor, RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro). In parallel, antiviral compounds like abacavir, acyclovir, adefovir, amantadine, amprenavir, darunavir, didanosine, oseltamivir, penciclovir, and tenofovir are under investigation for their potential in drug repurposing to address this infection. The aim of the study was to determine the effect of modifying the functional groups of the aforementioned antivirals in silico. Using the genetic optimization for ligand docking algorithm on software Maestro (version 11.1), the modified antivirals were docked onto ACE2 receptor, RdRp, and Mpro. Using QuickProp (Maestro v11.1), PASS (prediction of activity spectra for the substances), and altogether with SwissADME, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) of the modified antivirals, as well as their bioavailability and the predicted activity spectra, were determined. Discovery studio software was used to undertake post-docking analysis. Among the 10 antivirals, N(CH) derivative of darunavir, N(CH) derivative of amprenavir and NCH derivative of darunavir exhibited best binding affinities with ACE2 receptor (docking scores: -10.333, -9.527 and -9.695 kJ/mol, respectively). Moreover, NCH derivative of abacavir (-6.506 kJ/mol), NO derivative of didanosine (-6.877 kJ/mol), NCH derivative of darunavir (-7.618 kJ/mol) exerted promising affinity to Mpro. In conclusion, the results of the in silico screenings can serve as a useful information for future experimental works.
Topics: Antiviral Agents; Humans; Molecular Docking Simulation; SARS-CoV-2; Drug Repositioning; COVID-19 Drug Treatment; Models, Molecular; COVID-19; Angiotensin-Converting Enzyme 2; Pneumonia, Viral; Pandemics
PubMed: 38798846
DOI: 10.52225/narra.v4i1.319 -
The Science of the Total Environment Jul 2024The presence of contaminants of emerging concern in aquatic ecosystems represents an ever-increasing environmental problem. Aquatic biota is exposed to these...
The presence of contaminants of emerging concern in aquatic ecosystems represents an ever-increasing environmental problem. Aquatic biota is exposed to these contaminants, which can be absorbed and distributed to their organs. This study focused on the assessment, distribution, and ecological risk of 32 CECs in a Spanish river impacted by effluents from a wastewater treatment plant, analyzing the organs and plasma of common carp. Environmental concentrations in water and sediment were examined at sites upstream and downstream of the wastewater treatment plant. The two downstream sites showed 15 times higher total concentrations (12.4 μg L and 30.1 μg L) than the two upstream sites (2.08 μg L and 1.66 μg L). Half of the CECs were detected in fish organs, with amantadine having the highest concentrations in the kidney (158 ng g w.w.) and liver (93 ng g w.w.), followed by terbutryn, diazepam, and bisphenol F in the brain (50.2, 3.82 and 1.18 ng g w.w.). The experimental bioaccumulation factors per organ were compared with the bioconcentration factors predicted by a physiologically based pharmacokinetic model, obtaining differences of one to two logarithmic units for most compounds. Risk quotients indicated a low risk for 38 % of the contaminants. However, caffeine and terbutryn showed an elevated risk for fish. The mixed risk quotient revealed a medium risk for most of the samples in the three environmental compartments: surface water, sediment, and fish.
Topics: Water Pollutants, Chemical; Wastewater; Animals; Environmental Monitoring; Geologic Sediments; Risk Assessment; Carps; Rivers; Spain; Fishes
PubMed: 38768727
DOI: 10.1016/j.scitotenv.2024.173358 -
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 -
Tremor and Other Hyperkinetic Movements... 2024Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval,...
BACKGROUND
Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus.
METHODS
Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies.
RESULTS
The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus.
CONCLUSION
Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.
Topics: Humans; Male; Amantadine; Multiple System Atrophy; Ocular Motility Disorders; Aged
PubMed: 38737300
DOI: 10.5334/tohm.832 -
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 -
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 -
World Journal of Clinical Cases Apr 2024Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical form of dementia characterized by memory deficits and psychomotor slowing. However, HAD...
BACKGROUND
Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical form of dementia characterized by memory deficits and psychomotor slowing. However, HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease (CJD), particularly in patients with acquired immune deficiency syndrome (AIDS).
CASE SUMMARY
We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure. The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins. His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern. Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination. Initially, symptomatic treatment and administration of amantadine were pursued for presumed CJD, but the patient's condition continued to deteriorate. By contrast, the patient's condition improved following anti-HIV therapy. This individual is also the only patient with this prognosis to have survived over 4 years. Thus, the diagnosis was revised to HAD.
CONCLUSION
In the diagnostic process of rapidly progressive dementia, it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty. The 14-3-3 protein should not be regarded as the definitive marker for CJD. Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision, especially in AIDS patients with potential CJD. Ultimately, a trial of diagnostic treatment may be considered when additional testing is not feasible.
PubMed: 38680258
DOI: 10.12998/wjcc.v12.i12.2065