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1.
Medicina (B.Aires) ; 83(3): 402-410, ago. 2023. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1506694

ABSTRACT

Resumen Introducción: Las encefalitis inmunomediadas son un desorden neurológico de origen autoinmune. Actual mente es escasa la descripción de las secuelas cognitivas crónicas. El objetivo del presente trabajo fue caracterizar la secuela cognitiva de diferentes tipos de encefalitis inmunomediadas en una cohorte de un centro único de Argentina. Métodos: Estudio prospectivo, observacional, trans versal, de pacientes en seguimiento en un hospital de la Ciudad de Buenos Aires, con diagnóstico de encefalitis inmunomediada probable y definitiva. Se evaluaron variables epidemiológicas, clínicas, paraclínicas y tra tamiento. Se determinó la secuela cognitiva a través de una evaluación neurocognitiva realizada a partir del año de la presentación clínica. Resultados: Fueron incluidos 15 pacientes, todos con resultado disminuido en al menos un test. La memoria fue el dominio más afectado. Aquellos que se encon traban bajo tratamiento inmunosupresor al momento de evaluarse presentaron menores resultados en el aprendizaje seriado (media -2.94; desvío estándar 1.54) versus los que se encontraban sin tratamiento (media -1.18; desvío estándar 1.40; p = 0.05) y en la prueba de reconocimiento (media -10.34; desvío estándar 8.02) ver sus sin tratamiento (media -1.39; desvío estándar 2.21; p = 0.003). Los pacientes con estatus epiléptico tuvieron resultados deficitarios en la prueba de reconocimiento (media -7.2; desvío estándar 7.91) en comparación a los que no lo tenían (media -1.47; desvío estándar 2.34; p = 0.05). Conclusión: Nuestros resultados demuestran que, a pesar del curso monofásico de la enfermedad, todos los pacientes presentan daño cognitivo persistente más allá del año del inicio del cuadro. Estudios prospectivos de mayor envergadura serían necesarios para confirmar nuestros hallazgos.


Abstract Introduction: Autoimmune encephalitis represents a group of immune-mediated neurological disorders. At present, the description of the chronic cognitive sequela is scarce. The objective of this study was to characterize the cognitive after effects of different types of autoimmune encephalitis in a cohort from a single center in Argentina. Methods: Prospective, observational, cross-sectional study of patients under follow-up at a hospital in Buenos Aires city, with a diagnosis of probable and definitive immune-mediated encephalitis. Epidemiological, clini cal, paraclinical and treatment related variables were evaluated. Cognitive sequela was determined through a neurocognitive evaluation performed at least a year after the clinical presentation. Results: Fifteen patients were included. All had di minished results in at least one test. Memory was the most affected domain. Patients who were under im munosuppressive treatment at the time of evaluation presented lower results in serial learning (mean -2.94; standard deviation 1.54) versus those who weren't under treatment (mean -1.18; standard deviation 1.40; p = 0.05). The same pattern was observed on the recognition test of treatment group (mean -10.34; standard deviation 8.02) versus treatment-free group (mean -1.39; standard deviation 2.21; p =0.003). Patients with status epilepticus had poorer results in the recognition test (mean -7.2; standard deviation 7.91) compared to those without it (mean -1.47; standard deviation 2.34; p = 0.05). Conclusion: Our results show that, despite the mo nophasic course of this disease, all patients had persis tent cognitive damage beyond the year of onset. Larger prospective studies are required to confirm our findings.

2.
Article in Chinese | WPRIM | ID: wpr-992177

ABSTRACT

OBJECTIVE Alzheimer's disease(AD)and vascular dementia(VD)are the primary causes of dementia in elderly individuals,and therapeutic options for both conditions are limited.Overactivation of N-methyl-D-aspartate(NMDA)receptors,decreased cerebral blood flow,and subsequent pathological events,play signifi-cant roles in the progression of AD and VD.METHODS In this study,we investigated the therapeutic effects and underlying mechanisms of MN-08,a novel memantine nitrate,in mouse models of AD and rats with VD.RESULTS MN-08 was found to inhibit Aβ accumulation,prevent neuronal and dendritic spine loss,and attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(following a 6-month preventative course)and in 8-month-old triple-transgenic(3×Tg-AD)mice(following a 4-month therapeutic course),as well as in rat models of VD with preventive and therapeutic treatments.In vitro,MN-08 was shown to bind to and antagonize NMDA receptors,inhibit calcium influx,and reverse dysregula-tions of the ERK and PI3K/Akt/GSK3β pathway,subse-quently preventing glutamate-induced neuronal loss.Additionally,MN-08 exhibited favorable pharmacokinet-ics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CONCLUSION These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD and VD.

3.
Article in Chinese | WPRIM | ID: wpr-989089

ABSTRACT

In the past decade, significant progress has been made in the study of epilepsy-causing genetic mutations and the molecular mechanisms of epilepsy clinical manifestations.A growing number of studies have shown that the mechanism of action of pathogenic genes related to clinical symptoms shows significant correlation.In the selection of antiepileptic drugs for patients with different gene mutation, early identification of pathogenic genes has guiding significance for the selection of antiepileptic drugs.This review summairzes common epilepsy pathogenic genes, including ion channels genes, cellular metabolism related genes and cell signaling pathway related genes, and research progress on therapeutic targets corresponding to pathogenic genes in recent years.As research deepens, specific gene defects and their machanisms of action provide a basis for studying new treatment methods.

4.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 44(1): 61-73, Jan.-Feb. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360177

ABSTRACT

Rapid antidepressant effects associated with ketamine have shifted the landscape for the development of therapeutics to treat major depressive disorder (MDD) from a monoaminergic to glutamatergic model. Treatment with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be effective, but has many non-glutamatergic targets, and clinical and logistical problems are potential challenges. These factors underscore the importance of manipulations of binding mechanics to produce antidepressant effects without concomitant clinical side effects. This will require identification of efficient biomarkers to monitor target engagement. The mismatch negativity (MMN) is a widely used electrophysiological signature linked to the activity of NMDA receptors (NMDAR) in humans and animals and validated in pre-clinical and clinical studies of ketamine. In this review, we explore the flexibility of the MMN and its capabilities for reliable use in drug development for NMDAR antagonists in MDD. We supplement this with findings from our own research with three distinct NMDAR antagonists. The research described illustrates that there are important distinctions between the mechanisms of NMDAR antagonism, which are further crystallized when considering the paradigm used to study the MMN. We conclude that the lack of standardized methodology currently prevents MMN from being ready for common use in drug discovery. Clinical trial registration: This manuscript describes data collected from the following National Institutes of Health (NIH) and Veterans Affairs (VA) studies: AV-101, NCT03583554; lanicemine, NCT03166501; ketamine, NCT02556606.

5.
Chinese Journal of Biotechnology ; (12): 1149-1158, 2022.
Article in Chinese | WPRIM | ID: wpr-927770

ABSTRACT

The α2δ-1 protein coded by Cacna2d1 is dramatically up-regulated in dorsal root ganglion (DRG) neurons and spinal dorsal horn following sensory nerve injury in various animal models of neuropathic pain. Cacna2d1 overexpression potentiates presynaptic and postsynaptic NMDAR activity of spinal dorsal horn neurons to cause pain hypersensitivity. The α2δ-1-NMDAR interaction promotes surface trafficking and synaptic targeting of NMDARs in neuropathic pain caused by chemotherapeutic agents and peripheral nerve injury, as well as in other pathological conditions such as in the paraventricular nucleus (PVN) with neurogenic hypertension and in the brain with ischemic stroke. The lentiviral transfection method was used to construct a human embryonic kidney HEK293T cell line that could stably express α2δ-1-NMDAR complex. A stably transfected cell line was observed by florescence microscope, and identified by RT-qPCR and Western blotting. The results showed that the HEK293T cell line was successfully transfected and the genes could be stably expressed. Subsequently, the transfected cell line was successfully developed into a target drug screening system using patch clamp techniques. It provides a promising cell model for further research on the interaction mechanism of α2δ-1-NMDAR complex and drug screening for chronic pain and related diseases with low side effects.


Subject(s)
Animals , Humans , Analgesics/therapeutic use , Drug Discovery , HEK293 Cells , Neuralgia/metabolism , Receptors, N-Methyl-D-Aspartate/genetics
6.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 43(5): 484-493, Sept.-Oct. 2021. tab, graf
Article in English | LILACS | ID: biblio-1345467

ABSTRACT

Objective: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of augmenting antidepressant treatment with N2O. Methods: This double blind, placebo-controlled randomized parallel pilot trial was conducted from June 2016 to June 2018 at the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Twenty-three subjects with MDD (aged 18 to 65, on antidepressants, with a score > 17 on the 17-item-Hamilton Depression Rating Scale [HAM-D17]) received 50% N2O (n=12; 37.17±13.59 years) or placebo (100% oxygen) (n=11; 37.18±12.77 years) for 60 minutes twice a week for 4 weeks. The primary outcome was changes in HAM-D17 from baseline to week 4. Results: Depressive symptoms improved significantly in the N2O group (N2O: from 22.58±3.83 to 5.92±4.08; placebo: from 22.44±3.54 to 12.89±5.39, p < 0.005). A total of 91.7% and 75% of the N2O group subjects achieved response (≥ 50% reduction in HAM-D17 score) and remission (HAM-D17 < 7), respectively. The predominant adverse effects of N2O treatment were nausea, vomiting, and headache. Conclusion: N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo. Clinical trial registration: Brazilian Register of Clinical Trials, RBR-5rz5ch


Subject(s)
Depressive Disorder, Major/drug therapy , Brazil , Pilot Projects , Double-Blind Method , Treatment Outcome , Antidepressive Agents/therapeutic use , Nitrous Oxide/therapeutic use
7.
Article in English | WPRIM | ID: wpr-876433

ABSTRACT

@#Introduction: The amino acids that function as co-agonists at the N-methyl-D-aspartate (NMDA) receptor have been investigated in bipolar disorder (BD). However, studies comparing amino acid levels in the plasma of BD patients with healthy controls have yielded inconsistent results. We, therefore, conducted a study in Hospital Universiti Sains Malaysia to determine the plasma levels of glutamate, glycine, and alanine in BD patients and compared them with the healthy controls. Materials and Methods: An overnight fast of 10-hour plasma levels of glutamate, glycine, alanine, and tryptophan were measured in 83 bipolar patients, and were compared to a group of 82 healthy controls. Results: The mean (SD) age of bipolar patients was 40.9 (12.1), while the mean (SD) age for control groups was 35.6 (7.7) years. The median (25th, 75th percentile) of glutamate and alanine levels in bipolar patients was 111.0 (65.0,176.0) and 530.0 (446.0,629.0), respectively, while the mean (SD) of glycine level in bipolar patients was 304.0 (98.1). Significant higher glutamate, glycine, and alanine levels were found in bipolar disorder patients in the manic episode as compared to the healthy controls. Conclusion: Although the exact relationship between peripheral NMDA receptor co-agonist levels in the pathogenesis of BD is not well understood, these findings should be explored and may enlighten some new paths for BD therapy which could reward the patients also clinicians.

8.
Neuroscience Bulletin ; (6): 905-920, 2021.
Article in Chinese | WPRIM | ID: wpr-951968

ABSTRACT

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.

9.
Article | IMSEAR | ID: sea-204692

ABSTRACT

Anti NMDA receptor encephalitis is autoimmune encephalitis where antibodies are directed against NMDA receptor subunit. It represents a new category of immune-mediated disorder that is often paraneoplastic, presenting with neuropsychiatric symptoms, which is treatable and can be diagnosed serologically affecting both children and adults. Patient can have variable clinical presentation ranging from prodromal illness, neuropsychiatric symptoms, seizures, autonomic instability, hyperkinesias, catatonia, hypoventilation and with or without an associated teratoma. A positive serum or CSF sample screening for antibodies to the NMDA receptor subunit is confirmative. Supportive findings include CSF study, EEG and MRI Brain. The first-line therapies includes IVIG, corticosteroids or plasma exchange. Second line immunotherapy is rituximab or cyclophosphamide or both. Given the high mortality rate (up to 25%), the likelihood of presentation across the age range and the potential for treatment, a high index of suspicion is warranted by clinicians. Authors report a case of a 5 year old child with anti NMDA receptor encephalitis who responded well to IVIG therapy.

10.
Med. leg. Costa Rica ; 37(1): 39-44, ene.-mar. 2020.
Article in Spanish | LILACS | ID: biblio-1098370

ABSTRACT

Resumen La intoxicación con alcohol está frecuentemente asociada con trauma craneoencefálico (TCE), pero el impacto del alcohol en la patogénesis y el pronóstico del TCE sigue siendo poco clara. La literatura actual provee evidencia en términos de datos clínicos y experimentales que respaldan los efectos neuroprotectores del alcohol en pacientes con TCE. Para establecer de manera significativa esta relación es necesario el desarrollo de estudios prospectivos observacionales fuertes, con el fin de comprender los efectos del alcohol en los resultados clínicos a largo plazo (incluyendo el resultado neurológico) en pacientes con TCE con una apropiada selección y ajuste del riesgo basal.


Abstract Alcohol intoxication is often associated with traumatic brain injuries (TBIs), but the impact of alcohol on the pathogenesis and prognosis of TBIs remains unclear. Current literature provides evidence in terms of experimental and clinical data supporting alcohol's neuroprotective effects in patients with TBIs. To establish in a significative way this association, there lies a need for strong prospective observational studies, in order to comprehend the effects of alcohol on the long-term outcomes (including the neurological outcome) in patients with TBI with proper selection and baseline risk adjustment.


Subject(s)
Apoptosis , Alcoholic Intoxication/complications , Craniocerebral Trauma/complications , Indicators of Morbidity and Mortality , Ethanol/adverse effects , Alcoholism/complications
11.
Article in Chinese | WPRIM | ID: wpr-837700

ABSTRACT

@#Objective    To analyze the protective mechanism of spinal cord ischemia-reperfusion injury mediated by N-methyl-D-aspartate (NMDA) receptor. Methods    A total of 42 SD rats were randomly assigned to 4 groups: a non-blocking group (n=6), a saline group (n=12), a NMDA receptor blocker K-1024 (25 mg/kg) group (n=12) and a voltage-gated Ca2+ channel blocker nimodipine (0.5 mg/kg) group (n=12). The medications were injected intraperitoneally 30 min before ischemia. The neural function was evaluated. The neuronal histologic change of spinal cord lumbar region, the release of neurotransmitter amino acids and expression of spinal cord neuronal nitric oxide synthase (nNOS) were compared. Results    At 8 h after reperfusion, the behavioral score of the K-1024 group was 2.00±0.00 points, which was statistically different from those of the saline group (5.83±0.41 points) and the nimodipine group (5.00±1.00 points, P<0.05). Compared with the saline group and nimodipine group, K-1024 group had more normal motor neurons (P<0.05). There was no significant difference in glutamic acid concentration in each group at 10 min after ischemia (P=0.731). The nNOS protein expression in the K-1024 group was significantly down-regulated compared with the saline group (P<0.01). After 8 h of reperfusion, the expression of nNOS protein in the K-1024 group was significantly up-regulated compared with the saline group (P<0.05). Conclusion    K-1024 plays a protective role in spinal cord ischemia by inhibiting NMDA receptor and down-regulating nNOS protein expression; during the reperfusion, K-1024 has a satisfactory protective effect on spinal cord function, structure and biological activity of nerve cells.

12.
Article in English | WPRIM | ID: wpr-739800

ABSTRACT

BACKGROUND: This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli. METHODS: Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed. RESULTS: DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B. CONCLUSION: We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.


Subject(s)
Animals , Humans , Male , Rats , Diabetes Mellitus , Diabetic Neuropathies , Formaldehyde , Hyperalgesia , N-Methylaspartate , Pain Measurement , Pain Threshold , Phosphorylation , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate , Spinal Cord , Streptozocin
13.
Article in Chinese | WPRIM | ID: wpr-843469

ABSTRACT

Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. △9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.

14.
Article in Chinese | WPRIM | ID: wpr-743441

ABSTRACT

Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. Δ9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.

15.
Article in Chinese | WPRIM | ID: wpr-743421

ABSTRACT

Ovarian teratoma is agynecological disease,which has been found to be closely related to antiNMDA receptor encephalitis in recent years.Anti-NMDA receptor encephalitis is a kind of autoimmune encephalitis.Its etiology,pathogenesis,diagnosis and treatment are still not clear,and the disease has various clinical manifestations and special test methods,which are often ignored by clinicians.The prognosis is poor if the best treatment timing is missed,so early treatment is very important.At present,the main treatment methods include surgical treatment and immunotherapy.Most people can be cured,but the disease has a certain recurrence rate.The recurrence mechanism and treatment need further investigation.Reports on maternal anti-NMDAR encephalitis are rare,but we need to pay lots of attention to it as it is related to maternal and fetal outcomes.

16.
Article in Chinese | WPRIM | ID: wpr-753937

ABSTRACT

Objective To investigate the effects of low dose of gamma knife irradiation on the expression of N-methyl-D-aspartate (NMDA) receptor subunits in cortex and hippocampus of epileptic rats. Methods The rats were randomly divided into 4 groups: control group, GK group, pentylenetetrazole (PTZ) group and GK+ PTZ group. The rats were injected intraperitoneally with PTZ to establish the epileptic models. Gamma knife irradiation was performed on bilateral frontal cortex of rats at a peripheral dose of 15Gy. After irradiation, the changes of the seizure and behaviors were observed and recorded. The rats were killed on the 12th week after irradiation, Immunohistochemstry and western blotting were used to detect the relative expression levels of NMDAR subunits (NR1, NR2A, and NR2B) in the cortex and hippocampus. Results There were no epileptic seizures in the control group and the GK group. Compared with the PTZ group, the epileptic seizures of rats in the GK+PTZ group were significantly reduced after low dose gamma knife irradiation (P<0.05). Compared with control group, the protein expression levels of NR1, NR2A and NR2B in the PTZ group increased significantly in the cortex and hippocampus, and so were the positive neurons and their average absorbance value (P<0.05). Compared with PTZ group, the protein expression levels of NR1, NR2A and NR2B of the GK+PTZ group decreased remarkably in the cortex and hippocampus (P<0.05). Protein expression levels of NR1, NR2A and NR2B were not significantly different between control group and GK group (P>0.05). Conclusion Epileptic rats exhibited an increase in the protein expression levels of NR1, NR2A and NR2B in the cortex and hippocampus while low dose of gamma knife irradiation can decrease expression levels of NMDA receptor subunits in the cortex and hippocampus of epileptic rats, which might represent a possible mechanism underlying the therapeutic effects of gamma knife irradiation on epileptic seizure.

17.
Singapore medical journal ; : 154-160, 2019.
Article in English | WPRIM | ID: wpr-777550

ABSTRACT

INTRODUCTION@#Singapore has a rapidly ageing population and an increasing prevalence of Alzheimer's disease (AD). Compliance to AD medications is associated with treatment effectiveness. We investigated compliance to acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonist and treatment persistence among patients seen at the General Memory Clinic of National University Hospital, Singapore. We also identified the reasons for non-compliance.@*METHODS@#Patients seen at the General Memory Clinic between 1 January 2013 and 31 December 2014, who were prescribed AChEIs and NMDA receptor antagonist, were included in this retrospective cohort study. Non-compliance to medications was indirectly measured by failure to renew prescription within 60 days of the last day of medication supplied by the previous prescription. The reasons for non-compliance were identified.@*RESULTS@#A total of 144 patients were included. At one year, 107 patients were compliant to AD medications, while 37 patients were non-compliant. Around 60% of the non-compliant patients discontinued the use of AD medications within the first six months, and the mean persistent treatment period among this group of patients was 10.3 ± 3.5 months. The main reason for non-compliance was patients' and caregivers' perception that memory loss was of lower priority than other coexisting illnesses. Other reasons for non-compliance included side effects of medications (18.9%), perceived ineffectiveness of treatment (16.2%), inability to attend clinic (5.4%) and high cost of medications (2.7%).@*CONCLUSION@#Our findings suggest that the reasons for medication non-compliance can be identified early. Better compliance may be achieved through a multidisciplinary approach to patient education.


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease , Drug Therapy , Epidemiology , Psychology , Caregivers , Cholinesterase Inhibitors , Therapeutic Uses , Drug Costs , Interdisciplinary Communication , Medication Adherence , Patient Compliance , Quality of Life , Receptors, N-Methyl-D-Aspartate , Retrospective Studies , Singapore , Epidemiology , Treatment Outcome
18.
Article | IMSEAR | ID: sea-199895

ABSTRACT

Background: The aim of the present study was to evaluate the potentiation of general anaesthetic activity of ketamine by NMDA receptor antagonist ‘amantadine’ in wistar albino rats.Methods: The wistar albino rats of either sex were divided into three groups of five animals in each group. Group I received ketamine 80mg/kg, group II received ketamine 40mg/kg along with amantadine 40mg/kg and group III received ketamine 80mg/kg along with amantadine 40mg/kg to evaluate the potentiation of general anaesthetic effect of ketamine. The sleep latency time and the total sleeping time were measured in all the three groups.Results: The sleep latency time of group III is significantly decreased (p <0.035) and as equal to that of group II when compared to group I. The sleeping time of group III is significantly increased (p <0.001) when compared to group I.Conclusions: Amantadine - the NMDA receptor antagonist potentiates the general anaesthetic activity of ketamine.

19.
Sci. med. (Porto Alegre, Online) ; 28(2): ID29534, abr-jun 2018.
Article in Portuguese | LILACS | ID: biblio-881479

ABSTRACT

OBJETIVOS: Relatar dois casos com apresentações diferentes de encefalite antirreceptor N-metil-D-aspartato (NMDA), uma doença autoimune recentemente identificada e caracterizada por alterações da consciência, déficit de memória, convulsões, disfunção autonômica e distúrbios do movimento. DESCRIÇÃO DOS CASOS: Criança de seis anos, sexo feminino, que se apresentou com movimentos distônicos e coreoatetósicos incapacitando a marcha. Adolescente de 17 anos, sexo masculino, com alteração do comportamento, amnésia retrógrada e convulsões. Ambos realizaram eletroencefalograma e ressonância magnética cerebral que não revelaram alterações relevantes. Os anticorpos antirreceptor NMDA foram positivos no líquido cefalorraquidiano em ambos os casos e no sangue no primeiro paciente. Foram administrados metilprednisolona, imunoglobulina e rituximab em diferentes intervalos. Ambos tiveram uma recidiva cerca de seis meses depois, com recuperação ao final de um ano e meio após o diagnóstico. CONCLUSÕES: A encefalite antirreceptor NMDA deve ser considerada quando estamos perante o início súbito de sintomas neuropsiquiátricos. O diagnóstico e terapêutica precoces são fatores prognósticos fundamentais.


AIMS: To report two cases with different presentations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, a newly identified autoimmune disease characterized by consciousness changes, memory deficit, seizures, autonomic dysfunction and movement disorders. CASES DESCRIPTION: A six-year-old female, who presented with dystonic and choreoathetoid movements with refusal to walk. A 17-yearold male, presented with behavioral changes, retrograde amnesia and seizures. Electroencephalogram and brain magnetic resonance imaging did not show any significant findings. Anti-NMDAR antibodies were positive in cerebrospinal fluid in both cases and in serum in the first patient. Methylprednisolone, immunoglobulin and rituximab were given at different intervals. Both had a recurrence about six months later, with recovery at the end of one and a half year of the diagnosis. CONCLUSIONS: Anti-NMDAR encephalitis should be considered in patients with sudden onset of neuropsychiatric symptoms. Early diagnosis and treatment are major prognostic factors.


Subject(s)
Humans , Male , Female , Child , Adolescent , Autoimmune Diseases of the Nervous System
20.
Chinese Journal of Immunology ; (12): 137-140,143, 2018.
Article in Chinese | WPRIM | ID: wpr-702689

ABSTRACT

Systemic lupus erythematosus (SLE)is an autoimmune disease,involving multiple organs and systems,and it is defined as neuropsychiatric systemic lupus erythematosus (NPSLE) when neuropsychiatric symptoms appear.The N-methyl-D-aspartate (NMDA) receptor is a kind of membrane-spanning ion channels' glutamate receptors,which mainly contains NR1 subunit and NR2 subunit.In recent years,the role of anti-NMDA-receptor antibodies in the pathogenesis of NPSLE has become a research hotspot,especially for anti-NR2 antibody.Therefore we review the research progress of the mechanism of the anti-NMDA-receptor antibodies in NPSLE in this paper.

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