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1.
J Ethnopharmacol ; 336: 118731, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39182698

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Calyptrochilum emarginatum (Afzel. Ex Sw.) Schltr. (Orchidaceae) is a traditional medicinal plant known for its antimicrobial properties and efficacy in managing convulsive fever and menstrual disorders and addressing conditions such as malaria, tuberculosis, and cough. AIM OF THE STUDY: The study aims to examine the memory-enhancing and neuroprotective properties of ethanol extract of Calyptrochilum emarginatum leaves (EECEL) in scopolamine-induced amnesia mice model. MATERIALS AND METHODS: Forty-two male mice were divided into six groups (n = 7). Group 1 served as control, administered distilled water (10 mL/kg, p. o), group 2 received scopolamine only (3 mg/kg, i. p.), groups 3 to 6 received pretreatments of EECEL (50, 100, and 200 mg/kg, p. o.) and donepezil (1 mg/kg, p. o.) 30 min before scopolamine (3 mg/kg), for seven days. Following treatments, behavioral (learning and memory) assessments were carried out, while biochemical (acetylcholinesterase activity, oxidative stress markers, inflammatory cytokines markers) and histological evaluations were done after euthanasia. RESULTS: Scopolamine significantly impaired spatial, long term and recognition memory. Nevertheless, administration of EECEL (50, 100, and 200 mg/kg orally) enhanced memory function in mice, as observed in the Y maze [F (5, 30) = 20.23, p < 0.0001], Morris water maze [F (10, 90) = 3.105, p = 0.0019; [F (5, 30) = 21.13, p < 0.0001]], and novel object recognition tasks [F (5, 30) = 37.22, p < 0.0001)]. Scopolamine-treated mice exhibited significant dysfunction in the cholinergic system, as evidenced by elevated AChE activity [0.099 ± 0.005 vs. 0.063 ± 0.004 mol/min/g] with an elevation in oxidative stress. On the other hand, administration of EECEL counteracted these consequences by reducing AChE activity, mitigating oxidative damage, reducing pro-inflammatory cytokines, and preventing degeneration of neurons. CONCLUSION: The results demonstrated that EECEL effectively mitigates scopolamine-induced memory impairment via an oxido-inflammatory mechanism and modulation of the central cholinergic system.


Asunto(s)
Amnesia , Etanol , Fármacos Neuroprotectores , Orchidaceae , Extractos Vegetales , Hojas de la Planta , Escopolamina , Animales , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratones , Amnesia/tratamiento farmacológico , Amnesia/inducido químicamente , Etanol/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/aislamiento & purificación , Orchidaceae/química , Estrés Oxidativo/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Modelos Animales de Enfermedad , Memoria/efectos de los fármacos , Solventes/química , Donepezilo/farmacología , Donepezilo/uso terapéutico
2.
Brain Behav ; 14(5): e3507, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38688895

RESUMEN

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues. METHODS: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 µL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor. RESULTS: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M1 mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions. CONCLUSION: Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.


Asunto(s)
Acetilcolinesterasa , Amnesia , Factor Neurotrófico Derivado del Encéfalo , Aceites Volátiles , Rosa , Escopolamina , Animales , Ratas , Amnesia/inducido químicamente , Amnesia/tratamiento farmacológico , Amnesia/metabolismo , Aceites Volátiles/farmacología , Aceites Volátiles/administración & dosificación , Masculino , Rosa/química , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Acetilcolinesterasa/metabolismo , Receptor Muscarínico M1/metabolismo , Ratas Wistar , Nootrópicos/farmacología , Modelos Animales de Enfermedad , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Cognición/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos
3.
Drug Des Devel Ther ; 18: 967-978, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562518

RESUMEN

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.


Asunto(s)
Amnesia Anterógrada , Dexmedetomidina , Insuficiencia Respiratoria , Humanos , Amnesia/inducido químicamente , Amnesia Anterógrada/inducido químicamente , Benzodiazepinas , Broncoscopía/efectos adversos , Dexmedetomidina/efectos adversos , Hipnóticos y Sedantes/efectos adversos , Intubación Intratraqueal/efectos adversos , Insuficiencia Respiratoria/inducido químicamente , Sufentanilo , Vigilia , Método Doble Ciego
4.
Metab Brain Dis ; 39(4): 589-609, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38351421

RESUMEN

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.


Asunto(s)
Amnesia , Curcumina , Modelos Animales de Enfermedad , Nanocápsulas , Animales , Curcumina/farmacología , Curcumina/administración & dosificación , Curcumina/uso terapéutico , Ratones , Masculino , Amnesia/tratamiento farmacológico , Amnesia/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Escopolamina
5.
BMC Infect Dis ; 24(1): 36, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166694

RESUMEN

BACKGROUND: The purpose of this study is to analyze the influencing factors associated with Long-COVID in patients infected with Omicron variant of COVID-19 in Changchun City, Jilin Province, China three months after discharge in March 2022. METHODS: In this study, we conducted a telephone follow-up based on the real-world data collected from the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun Tongyuan Shelter Hospital and Changchun Infectious Disease Hospital during the COVID-19 epidemic in Changchun in March 2022. We used the Global COVID-19 Clinical Platform Case Report Form for Post COVID condition as a follow-up questionnaire to collect the general information, past medical history, clinical symptoms, COVID-19 vaccine inoculation doses, and other relevant information to analyze the symptom characteristics of COVID-19 patients three months after discharge from the hospital and related factors affecting Long COVID. RESULTS: A total of 1,806 patients with COVID-19 were included in this study, 977 males and 829 females, with a mean age of 38.5 [30.0, 49.4] years, and the number of female patients suffering from Long COVID (50.87%) was greater than male patients (p = 0.023). The binary logistic regression analysis of factors influencing Long COVID showed that smoking history (OR (95%CI) = 0.551(0.425-0.714), p < 0.001, taking never smoking as a reference), allergy history (OR (95%CI) = 1.618 (1.086-2.413), p-value 0.018, taking no allergy as a reference), first symptoms (OR (95%CI) = 0.636 (0.501-0.807), p < 0.001, with no first symptoms as reference) and COVID-19 vaccine inoculation doses (OR (95%CI) = 1.517 (1.190-1.933), p-value 0.001, with ≤ 2 doses of COVID-19 vaccine inoculation doses as reference) constituted its influencing factors. The first symptoms of patients on admission mainly included fever (512 cases, 71.81%), cough (279 cases, 39.13%) and dry or itchy throat (211 cases, 29.59%). The most common symptoms of Long COVID were persistent fatigue (68 cases), amnesia (61 cases), insomnia (50 cases) and excessive sweating (50 cases). CONCLUSION: The first symptoms on admission were predominantly fever, cough and dry or itchy throat. The most common symptoms of Long COVID were persistent fatigue, amnesia, insomnia and excessive sweating, and female patients were at a higher risk of Long COVID.


Asunto(s)
COVID-19 , Trastornos del Inicio y del Mantenimiento del Sueño , Adulto , Femenino , Humanos , Masculino , Amnesia , Tos , COVID-19/epidemiología , Vacunas contra la COVID-19 , Estudios Transversales , Fatiga , Fiebre/epidemiología , Alta del Paciente , Síndrome Post Agudo de COVID-19 , SARS-CoV-2 , Persona de Mediana Edad
6.
J Orthop Surg Res ; 19(1): 34, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38183050

RESUMEN

OBJECTIVE: A comparative study of joint amnesia in patients undergoing total hip arthroplasty with the direct anterior approach and posterior approach was conducted through a comprehensive evaluation. METHODS: The literature on joint amnesia in postoperative patients who underwent total hip arthroplasty by the direct anterior approach and the posterior approach was systematically searched in PubMed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and VIP databases from the time of library construction until February 13, 2023. Meta-analysis was performed using RevMan 5.3 software after independent searching, screening of the literature, data extraction, and quality assessment of the included studies by two investigators in strict accordance with the guidelines for conducting meta-analyses. RESULTS: A total of one RCT and six cohort studies were included in this meta-analysis. Meta-analysis results indicated that at 1 month postoperatively (MD = 2.08, 95% CI (0.20, 3.96), P = 0.03), 3 months (MD = 10.08, 95% CI (1.20, 18.96), P = 0.03), and 1 year (MD = 6.74, 95% CI (1.30, 12.19), P = 0.02), DAA total hip arthroplasty was associated with better FJS compared to PA at 1 year postoperatively. However, there was no statistical significance in FJS between the two groups at 5 years postoperatively (MD = 1.35, 95% CI (- 0.58, 3.28), P = 0.17). CONCLUSION: Current evidence suggests that the degree of joint amnesia after THA for DAA was not found to be superior to that of PA. Further, these findings require confirmation by including a larger number of high-quality randomized controlled studies. STUDY DESIGN: Systematic review; Level of evidence, 3.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Amnesia/etiología , Bases de Datos Factuales , Periodo Posoperatorio , Control de Calidad
8.
Br J Anaesth ; 132(2): 421-422, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38052678

Asunto(s)
Amnesia , Memoria , Humanos
9.
Clin J Sport Med ; 34(1): 38-43, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37058611

RESUMEN

OBJECTIVES: 1) Evaluate the frequency of same-year, repeat concussions; (2) assess predictors of sustaining a repeat concussion; and (3) compare outcomes of athletes with repeat concussions with athletes with single concussion. DESIGN: A retrospective, case-control study. SETTING: Regional sports concussion center. PATIENTS: Adolescents sustaining a sport-related concussions (SRC) from November 2017 to October 2020. INDEPENDENT VARIABLES: Participants were dichotomized into 2 groups: (1) athletes with a single concussion; and (2) athletes with repeat concussions. MAIN OUTCOME MEASURES: Between group and within group analyses were completed to look for differences in demographics, personal and family history, concussion history, and recovery metrics between the 2 groups. RESULTS: Of 834 athletes with an SRC, 56 (6.7%) sustained a repeat concussion and 778 (93.3%) had a single concussion. Between group: Personal history of migraines (19.6% vs 9.5%, χ 2 = 5.795, P = 0.02), family history of migraines (37.5% vs 24.5%, χ 2 = 4.621, P = 0.03), and family history of psychiatric disorders (25% vs 13.1%, χ 2 = 6.224, P = 0.01) were significant predictors of sustaining a repeat concussion. Within group: Among those with a repeat concussion, initial symptom severity was greater (Z = -2.422; P = 0.02) during the repeat concussion and amnesia was more common (χ 2 = 4.775, P = 0.03) after the initial concussion. CONCLUSIONS: In a single-center study of 834 athletes, 6.7% suffered a same-year, repeat concussion. Risk factors included personal/family migraine history and family psychiatric history. For athletes with repeat concussions, initial symptom score was higher after the second concussion, yet amnesia was more common after the initial concussion.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Trastornos Migrañosos , Adolescente , Humanos , Traumatismos en Atletas/diagnóstico , Estudios Retrospectivos , Estudios de Casos y Controles , Conmoción Encefálica/complicaciones , Conmoción Encefálica/epidemiología , Conmoción Encefálica/diagnóstico , Amnesia/etiología , Atletas , Trastornos Migrañosos/complicaciones
10.
Eur J Trauma Emerg Surg ; 50(1): 157-172, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36707437

RESUMEN

PURPOSE: The primary aim was to compare the prevalence of acute and delayed intracranial haemorrhage (ICH) following mild traumatic brain injury (mTBI) in patients on antithrombotic medication referred to a clinic for oral and plastic maxillofacial surgery. The secondary aim was to evaluate the need for short-term hospitalisation based on initial radiological and clinical findings. METHODS: This was an observational retrospective single-centre study of all patients on antithrombotic medication who were admitted to our department of oral and plastic maxillofacial surgery with mTBI over a 5 year period. Demographic and anamnesis data, injury characteristics, antithrombotic medication, radiological findings, treatment, and outcome were analysed. Patients were divided into the following four groups based on their antithrombotic medication: (1) single antiplatelet users, (2) vitamin K antagonist users, (3) direct oral anticoagulant users, and (4) double antithrombotic users. All patients underwent an emergency cranial CT (CT0) at admission. Based on clinical and radiological evaluation, different treatment protocols were applied. Patients with positive CT0 findings and patients with secondary neurological deterioration received a control CT (CT1) before discharge. Acute and delayed ICH and patient's outcome during hospitalisation were evaluated using descriptive statistical analysis. RESULTS: A total of 696 patients (mean age, 71.6 years) on antithrombotic medication who presented at our department with mTBI were included in the analysis. Most injuries were caused by a ground-level fall (76.9%). Thirty-six patients (5.1%) developed an acute traumatic ICH, and 47 intracerebral lesions were detected by radiology-most of these in patients taking acetylsalicylic acid. No association was detected between ICH and antithrombotic medication (p = 0.4353). In total, 258 (37.1%) patients were admitted for 48 h in-hospital observation. The prevalence of delayed ICH was 0.1%, and the mortality rate was 0.1%. Multivariable analysis identified a Glasgow Coma Scale (GCS) of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea as clinical characteristics significantly associated with an increased risk of acute ICH, whereas age, sex, and trauma mechanism were not associated with ICH prevalence. Of the 39 patients who underwent a control CT1, most had a decreasing or at least constant intracranial lesion; in three patients, intracranial bleeding increased but was not clinically relevant. CONCLUSION: According to our experience, antithrombotic therapy does not increase the rate of ICH after mTBI. A GCS of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea are indicators of higher ICH risk. A second CT scan is more effective in patients with secondary neurological deterioration. Initial CT findings were not clinically relevant and should not indicate in-hospital observation.


Asunto(s)
Conmoción Encefálica , Humanos , Anciano , Conmoción Encefálica/complicaciones , Fibrinolíticos/efectos adversos , Estudios Retrospectivos , Mareo/inducido químicamente , Mareo/complicaciones , Mareo/tratamiento farmacológico , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/epidemiología , Anticoagulantes/efectos adversos , Hospitalización , Tomografía Computarizada por Rayos X/efectos adversos , Inconsciencia/inducido químicamente , Inconsciencia/complicaciones , Inconsciencia/tratamiento farmacológico , Cefalea/inducido químicamente , Cefalea/complicaciones , Cefalea/tratamiento farmacológico , Amnesia/inducido químicamente , Amnesia/complicaciones , Amnesia/tratamiento farmacológico , Náusea/inducido químicamente , Náusea/complicaciones , Náusea/tratamiento farmacológico
11.
Neuropsychologia ; 191: 108728, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37939875

RESUMEN

To understand the neural basis of episodic memory it is necessary to appreciate the significance of the fornix. This pathway creates a direct link between those temporal lobe and medial diencephalic sites responsible for anterograde amnesia. A collaboration with Andrew Mayes made it possible to recruit and scan 38 patients with colloid cysts in the third ventricle, a condition associated with variable fornix damage. Complete fornix loss was seen in three patients, who suffered chronic long-term memory problems. Volumetric analyses involving all 38 patients then revealed a highly consistent relationship between mammillary body volume and the recall of episodic memory. That relationship was not seen for working memory or tests of recognition memory. Three different methods all supported a dissociation between recollective-based recognition (impaired) and familiarity-based recognition (spared). This dissociation helped to show how the mammillary body-anterior thalamic nuclei axis, as well as the hippocampus, is vital for episodic memory yet is not required for familiarity-based recognition. These findings set the scene for a reformulation of temporal lobe and diencephalic amnesia. In this revised model, these two regions converge on overlapping cortical areas, including retrosplenial cortex. The united actions of the hippocampal formation and the anterior thalamic nuclei on these cortical areas enable episodic memory encoding and consolidation, impacting on subsequent recall.


Asunto(s)
Memoria Episódica , Humanos , Diencéfalo/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Amnesia/diagnóstico por imagen , Recuerdo Mental , Tubérculos Mamilares/diagnóstico por imagen
12.
Int J Mol Sci ; 24(16)2023 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-37628900

RESUMEN

The role of histamine H3 receptors (H3Rs) in memory and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer's disease (AD), is well-accepted. Therefore, the procognitive effects of acute systemic administration of H3R antagonist E169 (2.5-10 mg/kg, i.p.) on MK801-induced amnesia in C57BL/6J mice using the novel object recognition test (NORT) were evaluated. E169 (5 mg) provided a significant memory-improving effect on MK801-induced short- and long-term memory impairments in NORT. The E169 (5 mg)-provided effects were comparable to those observed with the reference phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and were abrogated with the H3R agonist (R)-α-methylhistamine (RAMH). Additionally, our results demonstrate that E169 ameliorated MK801-induced memory deficits by antagonism of H3Rs and by modulation of the level of disturbance in the expression of PI3K, Akt, and GSK-3ß proteins, signifying that E169 mitigated the Akt-mTOR signaling pathway in the hippocampus of tested mice. Moreover, the results observed revealed that E169 (2.5-10 mg/kg, i.p.) did not alter anxiety levels and locomotor activity of animals in open field tests, demonstrating that performances improved following acute systemic administration with E169 in NORT are unrelated to changes in emotional response or in spontaneous locomotor activity. In summary, these obtained results suggest the potential of H3R antagonists such as E169, with good in silico physicochemical properties and stable retained key interactions in docking studies at H3R, in simultaneously modulating disturbed brain neurotransmitters and the imbalanced Akt-mTOR signaling pathway related to neurodegenerative disorders, e.g., AD.


Asunto(s)
Enfermedad de Alzheimer , Antagonistas de los Receptores Histamínicos H3 , Animales , Ratones , Ratones Endogámicos C57BL , Glucógeno Sintasa Quinasa 3 beta , Fosfatidilinositol 3-Quinasas , Maleato de Dizocilpina , Antagonistas de los Receptores Histamínicos H3/farmacología , Antagonistas de los Receptores Histamínicos H3/uso terapéutico , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasa , Serina-Treonina Quinasas TOR , Amnesia/inducido químicamente , Amnesia/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico , Transducción de Señal , Cognición
13.
Biomed Pharmacother ; 165: 115144, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37437376

RESUMEN

The current study aims to quantify HPLC-DAD polyphenolics in the crude extracts of Desmodium elegans, evaluating its cholinesterase inhibitory, antioxidant, molecular docking and protective effects against scopolamine-induced amnesia in mice. A total of 16 compounds were identified which include gallic acid (239 mg g-1), p-hydroxybenzoic acid (11.2 mg g-1), coumaric acid (10.0 mg g-1), chlorogenic acid (10.88 mg g-1), caffeic acid (13.9 mg g-1), p-coumaroylhexose (41.2 mg g-1), 3-O-caffeoylquinic acid (22.4 mg g-1), 4-O-caffeoylquinic acid (6.16 mg g-1), (+)-catechin (71.34 mg g-1), (-)-catechin (211.79 mg g-1), quercetin-3-O-glucuronide (17.9 mg g-1), kaempferol-7-O-glucuronide (13.2 mg g-1), kaempferol-7-O-rutinoside (53.67 mg g-1), quercetin-3-rutinoside (12.4 mg g-1), isorhamnetin-7-O-glucuronide (17.6 mg g-1) and isorhamnetin-3-O-rutinoside (15.0 mg g-1). In a DPPH free radical scavenging assay, the chloroform fraction showed the highest antioxidant activity, with an IC50 value of 31.43 µg mL-1. In an AChE inhibitory assay, the methanolic and chloroform fractions showed high inhibitory activities causing 89% and 86.5% inhibitions with IC50 values of 62.34 and 47.32 µg mL-1 respectively. In a BChE inhibition assay, the chloroform fraction exhibited 84.36% inhibition with IC50 values of 45.98 µg mL-1. Furthermore, molecular docking studies revealed that quercetin-3-rutinoside and quercetin-3-O-glucuronide fit perfectly in the active sites of AChE and BChE respectively. Overall, the polyphenols identified exhibited good efficacy, which is likely as a result of the compounds' electron-donating hydroxyl groups (-OH) and electron cloud density. The administration of methanolic extract improved cognitive performance and demonstrated anxiolytic behavior among tested animals.


Asunto(s)
Enfermedad de Alzheimer , Escopolamina , Ratones , Animales , Quempferoles/farmacología , Quempferoles/uso terapéutico , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Polifenoles/efectos adversos , Cloroformo/efectos adversos , Quercetina/efectos adversos , Simulación del Acoplamiento Molecular , Glucurónidos , Extractos Vegetales/efectos adversos , Inhibidores de la Colinesterasa/efectos adversos , Amnesia/inducido químicamente , Amnesia/tratamiento farmacológico , Antioxidantes/efectos adversos , Metanol/química , Modelos Animales , Rutina
14.
Hippocampus ; 33(10): 1113-1122, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37483092

RESUMEN

The prevailing view in human cognitive neuroscience associates the medial temporal lobes (MTLs) with declarative memory. Compelling experimental evidence has, however, demonstrated that these regions are specialized according to the representations processed, irrespective of the cognitive domain assessed. This account was supported by the study of patients with bilateral medial temporal amnesia, who exhibit impairments in perceptual tasks involving complex visual stimuli. Yet, little is known regarding the impact of unilateral MTL damage on complex visual abilities. To address this issue, we administered a visual matching task to 20 patients who underwent left (N = 12) or right (N = 8) anterior temporal lobectomy for drug-resistant epilepsy and to 38 healthy controls. Presentation viewpoint was manipulated to increase feature ambiguity, as this is critical to reveal impairments in perceptual tasks. Similar to control participants, patients with left-sided damage succeeded in all task conditions. In contrast, patients with right-sided damage had decreased accuracy compared with that of the other two groups, as well as increased response time. Notably, the accuracy of those with right-sided damage did not exceed chance level when feature ambiguity was high (i.e., when stimuli were presented from different viewpoints) for the most complex classes of stimuli (i.e., scenes and buildings, compared with single objects). The pattern reported in bilateral patients in previous studies was therefore reproduced in patients with right, but not left, resection. These results suggest that the complex visual-representation functions supported by the MTL are right-lateralized, and raise the question as to how the representational account of these regions applies to representations supported by left MTL regions.


Asunto(s)
Lobectomía Temporal Anterior , Epilepsia del Lóbulo Temporal , Humanos , Percepción Visual/fisiología , Lóbulo Temporal/cirugía , Lóbulo Temporal/fisiología , Amnesia , Tiempo de Reacción , Imagen por Resonancia Magnética , Epilepsia del Lóbulo Temporal/cirugía , Pruebas Neuropsicológicas
15.
Mol Psychiatry ; 28(8): 3332-3342, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37369719

RESUMEN

Alzheimer's Disease (AD) is a prevalent neurodegenerative disease characterized by tau hyperphosphorylation, Aß1-42 aggregation and cognitive dysfunction. Therapeutic agents directed at mitigating tau aggregation and clearing Aß1-42, and delivery of growth factor genes (BDNF, FGF2), have ameliorated cognitive deficits, but these approaches did not prevent or stop AD progression. Here we report that viral-(AAV) delivery of Neurotrophic Factor-α1/Carboxypeptidase E (NF-α1/CPE) gene in hippocampus at an early age prevented later development of cognitive deficits as assessed by Morris water maze and novel object recognition assays, neurodegeneration, and tau hyperphosphorylation in male 3xTg-AD mice. Additionally, amyloid precursor protein (APP) expression was reduced to near non-AD levels, and insoluble Aß1-42 was reduced significantly. Pro-survival proteins: mitochondrial Bcl2 and Serpina3g were increased; and mitophagy inhibitor Plin4 and pro-inflammatory protein Card14 were decreased in AAV-NF-α1/CPE treated versus untreated AD mice. Thus NF-α1/CPE gene therapy targets many regulatory components to prevent cognitive deficits in 3xTg-AD mice and has implications as a new therapy to prevent AD progression by promoting cell survival, inhibiting APP overexpression and tau hyperphosphorylation.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Enfermedades Neurodegenerativas , Ratones , Masculino , Animales , Enfermedad de Alzheimer/metabolismo , Carboxipeptidasa H/genética , Carboxipeptidasa H/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Péptidos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Trastornos de la Memoria/genética , Trastornos de la Memoria/prevención & control , Trastornos de la Memoria/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Amiloidosis/genética , Amiloidosis/metabolismo , Amnesia/metabolismo , Ratones Transgénicos , Modelos Animales de Enfermedad , Proteínas tau/genética , Proteínas tau/metabolismo
16.
Medisan ; 27(3)jun. 2023. tab
Artículo en Español | LILACS, CUMED | ID: biblio-1514544

RESUMEN

Introducción: La edad es el factor de riesgo más importante asociado al deterioro cognitivo. Al respecto, la pérdida de la memoria resulta un motivo frecuente y creciente de atención en las consultas médicas del nivel primario. Sin embargo, la disfunción cognitiva en los ancianos suele ser una de las afecciones que transcurren usualmente sin un diagnóstico oportuno. Objetivo: Determinar la prevalencia del deterioro cognitivo leve de tipo amnésico en ancianos de un área de salud. Métodos: Se realizó un estudio observacional, descriptivo y transversal de 203 ancianos pertenecientes al área de salud del Policlínico Docente Ramón López Peña de Santiago de Cuba, desde junio hasta diciembre de 2022. Para diagnosticar a los pacientes con disfunción cognitiva leve se utilizaron los criterios de Petersen. Resultados: Se halló que 36,9 % de los ancianos presentaron deterioro cognitivo leve de tipo amnésico, con predominio del sexo masculino (43,6 %) y del nivel de escolaridad primario (50,0 %), seguido del medio (40,3 %). Conclusiones: El deterioro cognitivo leve de tipo amnésico prevaleció en más de un tercio de la muestra estudiada; frecuencia que aumentó según la edad. Asimismo, se detectó una mayor incidencia del sexo masculino y de los ancianos con escolaridad primaria y media finalizadas.


Introduction: Age is the most important risk factor associated with cognitive deterioration. In this regard, loss of memory is a frequent and growing reason for attention in medical consultations of primary care. However, cognitive dysfunction in the elderly is one of the affections that usually go without an opportune diagnosis. Objective: To determine the prevalence of the amnestic mild cognitive impairment in elderly of a health area. Methods: An observational, descriptive and cross-sectional study of 203 elderly, belonging to the health area of Ramón López Peña Teaching Polyclinic was carried out in Santiago de Cuba, from June to December, 2022. To diagnose the patients with light cognitive dysfunction the Petersen approaches were used. Results: It was found that 36.9% of the elderly presented amnestic mild cognitive impairment, with a prevalence of male sex (43.6%) and the primary school level (50.0%), followed by the middle level (40.3%). Conclusions: Amnestic mild cognitive impairment prevailed in more than a third of the studied sample; frequency that increased according to the age. Likewise, a higher incidence of male sex and the elderly with concluded primary and middle schooling was detected.


Asunto(s)
Amnesia , Anciano
17.
Arch Phys Med Rehabil ; 104(7): 1007-1015, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37084937

RESUMEN

OBJECTIVE: To examine the association between severity of traumatic brain injury (TBI) as measured by duration of post-traumatic amnesia (PTA) and first year hospitalization costs for service members and veterans (SMVs) treated for TBI at Polytrauma Rehabilitation Centers (PRCs) within the Veterans Health Administration (VHA). DESIGN: Multivariable models of merged datasets from the VA TBI Model Systems (VA TBIMS) national database containing TBI clinical characterization including PTA with VHA hospital cost data. SETTING: Five VA PRCs. PARTICIPANTS: VA TBIMS participants with known PTA who received inpatient rehabilitation within 1 year of their TBI at any of 5 PRCs between 2010 and 2020 (N=717). INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Total, acute care, rehabilitation, intensive care unit (ICU), and surgery costs across all VA hospitals. RESULTS: A total of 717 SMVs (mean age 36.9 years, 94.1% men, 76.8% non-Hispanic White, 7.8% active duty) met inclusion criteria for the unadjusted analyses. Unadjusted mean total hospital costs in the first-year post TBI were approximately $201,214 higher for those with PTA duration ≥24 hours ($351,157) than PTA <24 hours ($149,943). In adjusted models (n=583), each additional day of PTA duration incrementally increased total ($1453), rehabilitation ($1324), ICU ($78), and surgery ($39) costs. Other significant covariates included age, acute care length of stay, Disability Rating Scale on rehabilitation admission, penetrating violent cause of injury, and drug abuse. CONCLUSIONS: This study demonstrates that PTA as a quantitative measure of TBI severity significantly affects first-year hospitalization costs of SMVs treated at PRCs. Each additional day of PTA was associated with higher total, rehabilitation, ICU, and surgery costs. Mean first year hospital costs were also found to exceed the highest budget allocation to VHA facilities for a veteran treated at a PRC. These findings have possible implications for hospital care provision for those receiving inpatient rehabilitation in VHA settings.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Traumatismo Múltiple , Veteranos , Masculino , Humanos , Adulto , Femenino , Lesiones Traumáticas del Encéfalo/rehabilitación , Hospitalización , Hospitales , Amnesia
18.
Cogn Behav Neurol ; 36(2): 108-117, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36651853

RESUMEN

BACKGROUND: Health providers frequently probe patients' recall of current and/or remote news events to determine the extent of memory loss. Impaired memory for transient events (ie, in the news for a circumscribed time) may provide information regarding the onset of cognitive impairment. OBJECTIVE: To use the Transient News Events Test (TNET) to explore how memory changes over time in both older adults with cognitive impairment (CI) and noncognitively impaired (NCI) older adults. We also investigated the role of episodic and semantic memory on TNET performance. METHOD: Sixty-seven older adults completed the TNET as part of a comprehensive neuropsychological assessment. Analyses included t tests to evaluate group differences for TNET score and correlations between TNET and neuropsychological measures, including episodic and semantic memory tests. RESULTS: NCI adults demonstrated better memory for TNET items than adults with CI. The NCI and CI groups did not differ regarding memory for remote events; however, the CI group exhibited worse memory for recent events. There was a significant association between TNET score and the capacity for episodic and semantic memory in the CI group. In the NCI group, TNET score was significantly associated with episodic memory. CONCLUSION: Findings support the use of transient news events to assess remote memories in older adults. Novel remote memory measures broaden the scope of memory assessment far beyond what is feasible with traditional neuropsychological assessment and may provide insight into the onset of memory changes.


Asunto(s)
Disfunción Cognitiva , Memoria Episódica , Humanos , Anciano , Trastornos de la Memoria , Amnesia/complicaciones , Recuerdo Mental , Pruebas Neuropsicológicas , Disfunción Cognitiva/complicaciones
19.
Niger J Physiol Sci ; 38(1): 91-99, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38243363

RESUMEN

Decline in cholinergic function and oxidative/nitrosative stress play a central role in Alzheimer's disease (AD). Previous quantitative HPLC profiling analysis has revealed the presence of Pinostrobin, formononetin, vitexin and other neuroprotective flavonoids in Cajanus cajan seed extract. This study was designed to investigate the protective action of Cajanus cajan ethanol seed extract (CC) on learning and memory functions using scopolamine mouse model of amnesia. Materials and methods: Adult mice were pretreated with CC (50, 100, or 200mg/kg, p.o) or vehicle (10ml/kg, p.o) for 16 days consecutively. Scopolamine, a competitive muscarinic cholinergic receptor antagonist (1mg/kg, i.p.) was given an hour after CC pretreatment from days 3 to 16.  The mice were subjected to behavioural tests from day 11 (open field test (OFT)/ Y-maze test (YMT) and Morris water maze task (MWM) from days 12-16. Animals were euthanized 1h after behavioral test on day 16 and discrete brain regions isolated for markers of oxidative stress and cholinergic signaling. Molecular docking analysis was undertaken to predict the possible mechanism(s) of CC-induced anti-amnesic action.  pre-administration of CC significantly reversed working memory and learning deficits caused by scopolamine in YMT and MWM tests, respectively. Moreover, CC prevented scopolamine-induced oxidative and nitrosative stress radicals in the hippocampus evidenced in significant increase in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities with a marked decrease in malondialdehyde (MDA) production, as well as significant inhibition of hippocampal scopolamine-induced increase in acetylcholinesterase activity by CC. The molecular docking analysis showed that out of the 19 compounds, the following had the highest binding affinity; Pinostrobin (-8.7 Kcal/mol), friedeline (-7.5kCal/mol), and lupeol (-8.2 Kcal/mol), respectively, to neuronal muscarinic M1 acetylcholine receptor, α7 nicotinic acetylcholine receptor and amyloid beta peptide binding pockets, which further supports the ability of CC to enhance neuronal cholinergic signaling and possible inhibition of amyloid beta aggregation. This study showed that Cajanus cajan seeds extract improved working memory and learning through enhancement of cholinergic signaling, antioxidant capacity and reduction in amyloidogenesis.


Asunto(s)
Antioxidantes , Cajanus , Ratones , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Escopolamina/farmacología , Cajanus/metabolismo , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/farmacología , Péptidos beta-Amiloides/efectos adversos , Péptidos beta-Amiloides/metabolismo , Simulación del Acoplamiento Molecular , Aprendizaje por Laberinto , Amnesia/inducido químicamente , Amnesia/tratamiento farmacológico , Amnesia/prevención & control , Estrés Oxidativo , Glutatión/metabolismo , Transmisión Sináptica , Hipocampo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Colinérgicos/efectos adversos , Colinérgicos/metabolismo , Mecanismos de Defensa , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo
20.
Neurocase ; 28(4): 410-414, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36260764

RESUMEN

A 52-year-old male patient with a background of adaptive personality disorder was admitted for mitral valve repair and cardiac ablation for atrial fibrillation. He suffered intraoperative complications with severe mitral insufficiency that suffered ischemia.. Post-operatively, he demonstrated acute loss of retrograde autobiographical memory, prosopagnosia and a loss of public semantic memory. His CT scan was normal and MRI was not possible due to intra-cardiac leads. An initial diagnosis of hypoxic-ischemic encephalopathy was considered. A neuropsychological examination undertaken 20 days after his surgery showed a severe alteration of retrograde autobiographical memory, marked alteration of semantic knowledge and prosopagnosia. He demonstrated an average performance in tasks measuring constructional praxis, visuospatial ability, and executive functions. 34 days after surgery, and after a short nap, the patient "returns" to the day before admission and consequently recovers his memory. Repeat neuropsychological assessment demonstrated performance within the normal range across all previously tested domains. This sudden recovery of memory, together with a normal MRI, led to a rethinking of the diagnosis of dissociative amnesia. This case illustrates the long-standing discussion about the organic or functional origin of some memory disorders, in which, despite advances in neuroimaging techniques, it is still difficult to know their etiology .


Asunto(s)
Memoria Episódica , Prosopagnosia , Masculino , Humanos , Persona de Mediana Edad , Películas Cinematográficas , Prosopagnosia/complicaciones , Amnesia/etiología , Pruebas Neuropsicológicas , Amnesia Retrógrada/diagnóstico , Amnesia Retrógrada/etiología
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