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Crocodiles and alligators: Antiamoebic and antitumor compounds of crocodiles

Siddiqui R, Jeyamogan S, Ali SM, Abbas F, Sagathevan KA, Khan NA

Exp Parasitol, 2017 Dec;183:194-200.
PMID: 28917711 DOI: 10.1016/j.exppara.2017.09.008

Crocodiles exist in unsanitary environments, feed on rotten meat, are often exposed to heavy metals such as arsenic, cadmium, cobalt, chromium, mercury, nickel, lead, selenium, tolerate high levels of radiation, and are amid the very few species to survive the catastrophic Cretaceous-Tertiary extinction event, nonetheless they can live for up to a 100 years. Moreover, as they live in unhygienic conditions, they regularly come across pathogens. Logically, we postulate that crocodiles possess mechanisms to defend themselves from noxious agents as well as protecting themselves from pathogens. To test this hypothesis, various organ lysates and serum of Crocodylus palustris were prepared. Amoebicidal assays were performed using Acanthamoeba castellanii belonging to the T4 genotype. Cytotoxicity assays were performed using Prostate cancer cells culture by measuring lactate dehydrogenase release as a marker for cell death. Growth inhibition assays were performed to determine the growth inhibitory effects of various organ lysates. Serum and heart lysates of Crocodylus palustris exhibited powerful anti-tumor activity exhibiting more than 70% Prostate cancer cell death (P brain showed partial cytotoxicity. Both sera and heart lysates of Crocodylus palustris abolished Prostate cells growth. Moreover, serum completely abolished A. castellanii viability. For the first time, these findings showed that the organ lysates of Crocodylus palustris exhibit potent anti-amoebic and anti-tumor activity. The discovery of antimicrobial and antitumor activity in crocodile will stimulate research in finding therapeutic molecules from unusual sources, and has potential for the development of novel antitumor/antimicrobial compound(s) that may also overcome drug resistance. Nevertheless, rigorous research in the next few years will be necessary to realize these expectations.

Matched MeSH terms: Brain Chemistry
Fulltext Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations

Jha NK, Ojha S, Jha SK, Dureja H, Singh SK, Shukla SD, et al.

J Mol Neurosci, 2021 Nov;71(11):2192-2209.
PMID: 33464535 DOI: 10.1007/s12031-020-01767-6

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.

Matched MeSH terms: Blood-Brain Barrier
Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro

Choong PF, Mok PL, Cheong SK, Leong CF, Then KY

Cytotherapy, 2007;9(2):170-83.
PMID: 17453969

The multipotency of stromal cells has been studied extensively. It has been reported that mesenchymal stromal cells (MSC) are capable of differentiating into cells of multilineage. Different methods and reagents have been used to induce the differentiation of MSC. We investigated the efficacy of different growth factors in inducing MSC differentiation into neurons.

Matched MeSH terms: Brain-Derived Neurotrophic Factor/pharmacology
Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion

Gorain B, Choudhury H, Tekade RK, Karan S, Jaisankar P, Pal TK

Regul Toxicol Pharmacol, 2016 Dec;82:20-31.
PMID: 27815174 DOI: 10.1016/j.yrtph.2016.10.020

Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients.

Matched MeSH terms: Brain/metabolism
Formulation optimization of palm kernel oil esters nanoemulsion-loaded with chloramphenicol suitable for meningitis treatment

Musa SH, Basri M, Masoumi HR, Karjiban RA, Malek EA, Basri H, et al.

Colloids Surf B Biointerfaces, 2013 Dec 1;112:113-9.
PMID: 23974000 DOI: 10.1016/j.colsurfb.2013.07.043

Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.

Matched MeSH terms: Blood-Brain Barrier
Effects of early age feed restriction and heat conditioning on heat shock protein 70 expression, resistance to infectious bursal disease, and growth in male broiler chickens subjected to heat stress

Liew PK, Zulkifli I, Hair-Bejo M, Omar AR, Israf DA

Poult Sci, 2003 Dec;82(12):1879-85.
PMID: 14717545

The effects of early age feed restriction and heat conditioning on heat shock protein (HSP) 70 expression, antibody production, resistance to infectious bursal disease (IBD), and growth of heat-stressed male broiler chickens were investigated. Chicks were divided into 4 groups: 60% feed restriction on d 4,5, and 6 (FR); exposure to 36 +/- 1 degrees C for 1 h from d 1 to 21 (HT); combination of FR and HT (FRHT); and control. From d 35 to 50, heat stress was induced by exposing birds to 38 +/- 1 degrees C and 80% RH for 2 h/d. On d 36, each bird was administered 10 times the normal dose of live IBD vaccine. After heat exposure, the FRHT birds had higher HSP 70 density (d 41) and weight gain (from d 35 to 49) and lower bursal histological score (BHS) (d 51) than their HT and control counterparts. The HSP 70 expression and BHS of FR birds were not significantly different from those of the other 3 groups during the heat exposure period. Heat shock protein 70 and BHS data were negatively correlated (r = -0.33, P = 0.0008). We concluded that FRHT could improve weight gain and resistance to IBD in male broiler chickens under heat stress conditions. The improved heat tolerance and disease resistance in FRHT birds could be attributed to better HSP 70 response.

Matched MeSH terms: Brain Chemistry
Fulltext Leptomeningeal Carcinomatosis With Optic Nerve Metastasis Secondary to Breast Cancer

Chew C, Wan Hitam WH, Ahmad Tajudin LS

Cureus, 2021 Mar 31;13(3):e14200.
PMID: 33936906 DOI: 10.7759/cureus.14200

Leptomeningeal carcinomatosis (LC) and optic nerve metastasis are uncommon occurrences in breast cancer. We report a rare case of LC with optic nerve infiltration secondary to breast cancer. A 45-year-old lady who was a known case of treated right breast carcinoma six years ago presented with a blurring of vision in both eyes, floaters, and diplopia for one month. She also had recurrent attacks of seizure-like episodes, headache, and vomiting. Examination revealed high blood pressure with tachycardia. Her right eye visual acuity was counting fingers at two feet and 6/36 in the left eye. She had right abducens nerve palsy. Fundoscopy showed bilateral optic disc swelling with pre-retinal, flame-shaped haemorrhages and macular oedema. CT scan of brain and orbit was normal. She was admitted for further investigations. While in the ward, her vision deteriorated further. Her visual acuity in both eyes was at the level of no perception to light. She also developed bilateral abducens nerve palsy and right facial nerve palsy. Subsequently, she started having bilateral hearing loss. There were few episodes of fluctuations in conscious awareness. MRI brain showed mild hydrocephalus. Both optic nerves were thickened and enhanced on T1-weighted and post-gadolinium. Lumbar puncture was performed. There was high opening pressure. Cerebrospinal fluid cytology showed the presence of malignant cells. Family members opted for palliative care in view of poor prognosis. Unfortunately, she succumbed after a month's stay in hospital. Diagnosis of LC and optic nerve infiltration presents a formidable challenge to clinicians especially in the early stages where neuroimaging appears normal and lumbar puncture has high false negatives. Multiple high-volume taps are advised if clinical suspicion of LC is high.

Matched MeSH terms: Brain
Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation

Tan SZK, Temel Y, Chan AY, Mok ATC, Perucho JAU, Blokland A, et al.

Brain Struct Funct, 2020 Sep;225(7):1957-1966.
PMID: 32594260 DOI: 10.1007/s00429-020-02102-w

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful as an unconditioned stimulus for modelling anticipatory fear and agoraphobia in a contextual fear conditioning paradigm. In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then attempted to unravel some of the interactions with dopamine signalling using tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons. We showed that acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, while chronic administrations of both drugs were effective. We found that the dlPAG stimulation induced increase number of dopaminergic neurons in the ventral tegmental area (VTA) which was reversed in both chronic buspirone and escitalopram groups. We further found a strong positive correlation between the number of dopaminergic neurons and freezing in the VTA and showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta (SNpc) in escitalopram and buspirone groups, respectively. Overall, we showed that chronic treatment with an SSRI and a 5-HT1A agonist reduced anticipatory freezing behaviour which seems to be associated, through correlative studies, with a reversal of dlPAG stimulation induced increase in number of dopaminergic neurons in the VTA and/or SNpc.

Matched MeSH terms: Deep Brain Stimulation
Factors contributing to hearing impairment in patients with cleft lip/palate in Malaysia: A prospective study of 346 ears

Cheong JP, Soo SS, Manuel AM

Int J Pediatr Otorhinolaryngol, 2016 Sep;88:94-7.
PMID: 27497393 DOI: 10.1016/j.ijporl.2016.06.045

OBJECTIVE: To determine the factors contributing towards hearing impairment in patients with cleft lip/palate.
METHOD: A prospective analysis was conducted on 173 patients (346 ears) with cleft lip and palate (CL/P) who presented to the combined cleft clinic at University Malaya Medical Centre (UMMC) over 12 months. The patients' hearing status was determined using otoacoustic emission (OAE), pure tone audiometry (PTA) and auditory brainstem response (ABR). These results were analysed against several parameters, which included age, gender, race, types of cleft pathology, impact and timing of repair surgery.
RESULTS: The patients' age ranged from 1-26 years old. They comprised 30% with unilateral cleft lip and palate (UCLP), 28% with bilateral cleft lip and palate (BCLP), 28% with isolated cleft palate (ICP) and 14% with isolated cleft lip (ICL). Majority of the patients (68.2%) had normal otoscopic findings. Out of the 346 ears, 241 ears (70%) ears had passed the hearing tests. There was no significant relationship between patients' gender and ethnicity with their hearing status. The types of cleft pathology significantly influenced the outcome of PTA and ABR screening results (p

Matched MeSH terms: Evoked Potentials, Auditory, Brain Stem
Anti-depressant activity of Erythrina variegata bark extract and regulation of monoamine oxidase activities in mice

Martins J, Brijesh S

J Ethnopharmacol, 2019 Oct 07.
PMID: 31600560 DOI: 10.1016/j.jep.2019.112280

ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina variegata, commonly referred to as 'tiger's claw' or 'Indian coral tree' and 'Parijata' in Sanskrit, belongs to the Fabaceae family. It is a plant native to the coast of India, China, Malaysia, East Africa, Northern Australia and distributed in tropical and subtropical regions worldwide. In traditional medicine, 'Paribhadra' an Indian preparation, makes use of the leaves and bark of E. variegata to destroy pathogenic parasites and relieve joint pains. E. variegata is known to exhibit anxiolytic and anti-convulsant activities. Folkore medicine also suggests that E. variegata barks act on the central nervous system. However, there is a lack of data demonstrating this. The anti-depressant activity of E. variegata bark has not been reported in literature.
AIM OF THE STUDY: Our study focuses on previously unreported anti-depressant activity of E. variegata bark ethanolic extract (EBE) and determination of its mechanism of action possibly through regulation of monoamine oxidase activity in mouse brain homogenates.
MATERIALS AND METHODS: EBE was characterized using standard protocols for phytochemical analysis, followed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) analysis. Anti-depressant activity of EBE (50, 100, 200 and 500 mg/kg) was evaluated in Swiss white albino mice using acute and chronic forced swim test (FST) models. Furthermore, the potential use of the extract as an adjunct to selective serotonin reuptake inhibitor (SSRI), escitalopram, was evaluated using the chronic unpredictable mild stress test model wherein inhibitory effects on monoamine oxidase (MAO) A and B were assessed by spectrophotometric-chemical analysis in mouse whole brain homogenates.
RESULTS: The extract showed significant reduction in immobility time periods in both acute (200 mg/kg) and chronic (100, 200 and 500 mg/kg) FST models. When used as an adjunct with escitalopram (15 mg/kg), the extract (100, 200 and 500 mg/kg) showed significantly greater inhibition of MAO-A and B activities when compared to escitalopram alone (30 mg/kg). Phytochemical analysis of EBE revealed presence of sugars, steroids, glycosides, alkaloids and tannins. LC-MS and GC-MS analysis identified components such as 2-amino-3-methyl-1-butanol, phenylethylamine, eriodictyol, daidzein and pomiferin, N-ethyl arachidonoyl amine, inosine diphosphate, trimipramine, granisetron, 3,4-dihydroxymandelic acid, ethyl ester, tri-TMS and dodecane, previously reported for their anti-depressant activity.
CONCLUSIONS: The study thus demonstrated potential for use of the E. variegata bark ethanolic extract as an adjunct to currently available SSRI treatment. The study also identified components present in E. variegata bark ethanolic extract that may be responsible for its anti-depressant activity. Furthermore, the study thus confirms the traditional use of E. variegata barks in improving CNS function through its anti-depressant like activity.

Matched MeSH terms: Brain
Fulltext Negative correlation of cortical thickness with the severity and duration of abdominal pain in Asian women with irritable bowel syndrome

Chua CS, Bai CH, Shiao CY, Hsu CY, Cheng CW, Yang KC, et al.

PLoS One, 2017;12(8):e0183960.
PMID: 28859146 DOI: 10.1371/journal.pone.0183960

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain-gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS.
METHODS: Thirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics.
RESULTS: The left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain.
CONCLUSIONS: Some of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.

Matched MeSH terms: Brain Mapping
Comparative effects of alpha-tocopherol and gamma-tocotrienol against hydrogen peroxide induced apoptosis on primary-cultured astrocytes

Mazlan M, Sue Mian T, Mat Top G, Zurinah Wan Ngah W

J Neurol Sci, 2006 Apr 15;243(1-2):5-12.
PMID: 16442562

Oxidative stress is thought to be one of the factors that cause neurodegeneration and that this can be inhibited by antioxidants. Since astrocytes support the survival of central nervous system (CNS) neurons, we compared the effect of alpha-tocopherol and gamma-tocotrienol in minimizing the cytotoxic damage induced by H(2)O(2), a pro-oxidant. Primary astrocyte cultures were pretreated with either alpha-tocopherol or gamma-tocotrienol for 1 h before incubation with 100 microM H(2)O(2) for 24 h. Cell viability was then assessed using the MTS assay while apoptosis was determined using a commercial ELISA kit as well as by fluorescent staining of live and apoptotic cells. The uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes were also determined using HPLC. Results showed that gamma-tocotrienol is toxic at concentrations >200 microM but protects against H(2)O(2) induced cell loss and apoptosis in a dose dependent manner up to 100 microM. alpha-Tocopherol was not cytotoxic in the concentration range tested (up to 750 microM), reduced apoptosis to the same degree as that of gamma-tocotrienol but was less effective in maintaining the viable cell number. Since the uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes is similar, this may reflect the roles of these 2 vitamin E subfamilies in inhibiting apoptosis and stimulating proliferation in astrocytes.

Matched MeSH terms: Brain/drug effects*; Brain/metabolism
Infectious cDNA clone of attenuated Langat tick-borne flavivirus (strain E5) and a 3' deletion mutant constructed from it exhibit decreased neuroinvasiveness in immunodeficient mice

Pletnev AG

Virology, 2001 Apr 10;282(2):288-300.
PMID: 11289811

Forty-five years ago a naturally attenuated tick-borne flavivirus, Langat (LGT) strain TP21, was recovered from ticks in Malaysia. Subsequently, it was tested as a live attenuated vaccine for virulent tick-borne encephalitis viruses. In a large clinical trial its attenuation was confirmed but there was evidence of a low level of residual virulence. Thirty-five years ago further attenuation of LGT TP21 was achieved by multiple passages in eggs to yield mutant E5. To study the genetic determinants of the further attenuation exhibited by E5 and to allow us to manipulate the genome of this virus for the purpose of developing a satisfactory live attenuated tick-borne flavivirus vaccine, we recovered infectious E5 virus from a full-length cDNA clone. The recombinant E5 virus (clone 651) recovered from a full-length infectious cDNA clone was more attenuated in immunodeficient mice than that of its biologically derived E5 parent. Increase in attenuation was associated with three amino acid substitutions, two located in the structural protein E and one in nonstructural protein NS4B. Subsequently an even greater degree of attenuation was achieved by creating a viable 320 nucleotide deletion in the 3'-noncoding region of infectious full-length E5 cDNA. This deletion mutant was not cytopathic in simian Vero cells and it replicated to lower titer than its E5-651 parent. In addition, the E5 3' deletion mutant was less neuroinvasive in SCID mice than its E5-651 parent. Significantly, the deletion mutant proved to be 119,750 times less neuroinvasive in SCID mice than its progenitor, LGT strain TP21. Despite its high level of attenuation, the E5 3' deletion mutant remained highly immunogenic and intraperitoneal (ip) inoculation of 10 PFU induced complete protection in Swiss mice against subsequent challenge with 2000 ip LD50 of the wild-type LGT TP21.

Matched MeSH terms: Brain/pathology; Brain/virology*
Butyrylcholinesterase: A Multifaceted Pharmacological Target and Tool

Ha ZY, Mathew S, Yeong KY

Curr Protein Pept Sci, 2020;21(1):99-109.
PMID: 31702488 DOI: 10.2174/1389203720666191107094949

Butyrylcholinesterase is a serine hydrolase that catalyzes the hydrolysis of esters in the body. Unlike its sister enzyme acetylcholinesterase, butyrylcholinesterase has a broad substrate scope and lower acetylcholine catalytic efficiency. The difference in tissue distribution and inhibitor sensitivity also points to its involvement external to cholinergic neurotransmission. Initial studies on butyrylcholinesterase showed that the inhibition of the enzyme led to the increment of brain acetylcholine levels. Further gene knockout studies suggested its involvement in the regulation of amyloid-beta, a brain pathogenic protein. Thus, it is an interesting target for neurological disorders such as Alzheimer's disease. The substrate scope of butyrylcholinesterase was recently found to include cocaine, as well as ghrelin, the "hunger hormone". These findings led to the development of recombinant butyrylcholinesterase mutants and viral gene therapy to combat cocaine addiction, along with in-depth studies on the significance of butyrylcholinesterase in obesity. It is observed that the pharmacological impact of butyrylcholinesterase increased in tandem with each reported finding. Not only is the enzyme now considered an important pharmacological target, it is also becoming an important tool to study the biological pathways in various diseases. Here, we review and summarize the biochemical properties of butyrylcholinesterase and its roles, as a cholinergic neurotransmitter, in various diseases, particularly neurodegenerative disorders.

Matched MeSH terms: Brain/drug effects; Brain/metabolism
Neurophysiological symptoms and aspartame: What is the connection?

Choudhary AK, Lee YY

Nutr Neurosci, 2018 Jun;21(5):306-316.
PMID: 28198207 DOI: 10.1080/1028415X.2017.1288340

Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.

Matched MeSH terms: Brain/drug effects; Brain/metabolism
Emotion classification in Parkinson's disease by higher-order spectra and power spectrum features using EEG signals: a comparative study

Yuvaraj R, Murugappan M, Ibrahim NM, Omar MI, Sundaraj K, Mohamad K, et al.

J Integr Neurosci, 2014 Mar;13(1):89-120.
PMID: 24738541 DOI: 10.1142/S021963521450006X

Deficits in the ability to process emotions characterize several neuropsychiatric disorders and are traits of Parkinson's disease (PD), and there is need for a method of quantifying emotion, which is currently performed by clinical diagnosis. Electroencephalogram (EEG) signals, being an activity of central nervous system (CNS), can reflect the underlying true emotional state of a person. This study applied machine-learning algorithms to categorize EEG emotional states in PD patients that would classify six basic emotions (happiness and sadness, fear, anger, surprise and disgust) in comparison with healthy controls (HC). Emotional EEG data were recorded from 20 PD patients and 20 healthy age-, education level- and sex-matched controls using multimodal (audio-visual) stimuli. The use of nonlinear features motivated by the higher-order spectra (HOS) has been reported to be a promising approach to classify the emotional states. In this work, we made the comparative study of the performance of k-nearest neighbor (kNN) and support vector machine (SVM) classifiers using the features derived from HOS and from the power spectrum. Analysis of variance (ANOVA) showed that power spectrum and HOS based features were statistically significant among the six emotional states (p < 0.0001). Classification results shows that using the selected HOS based features instead of power spectrum based features provided comparatively better accuracy for all the six classes with an overall accuracy of 70.10% ± 2.83% and 77.29% ± 1.73% for PD patients and HC in beta (13-30 Hz) band using SVM classifier. Besides, PD patients achieved less accuracy in the processing of negative emotions (sadness, fear, anger and disgust) than in processing of positive emotions (happiness, surprise) compared with HC. These results demonstrate the effectiveness of applying machine learning techniques to the classification of emotional states in PD patients in a user independent manner using EEG signals. The accuracy of the system can be improved by investigating the other HOS based features. This study might lead to a practical system for noninvasive assessment of the emotional impairments associated with neurological disorders.

Matched MeSH terms: Brain Mapping
Fulltext In vitro and In vivo Antioxidant Evaluation and Estimation of Total Phenolic, Flavonoidal Content of Mimosa pudica L

Patro G, Bhattamisra SK, Mohanty BK, Sahoo HB

Pharmacognosy Res, 2016;8(1):22-8.
PMID: 26941532 DOI: 10.4103/0974-8490.171099

OBJECTIVE: Mimosa pudica Linn. (Mimosaceae) is traditionally used as a folk medicine to treat various ailments including convulsions, alopecia, diarrhea, dysentery, insomnia, tumor, wound healing, snake bite, etc., Here, the study was aimed to evaluate the antioxidant potential of M. pudica leaves extract against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (in vitro) and its modulatory effect on rat brain enzymes.
MATERIALS AND METHODS: Total phenolic, flavonoid contents, and in vitro antioxidant potential against DPPH radical were evaluated from various extracts of M. pudica leaves. In addition, ethyl acetate extract of Mimosa pudica leaves (EAMP) in doses of 100, 200, and 400 mg/kg/day were administered orally for 7 consecutive days to albino rats and evaluated for the oxidative stress markers as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) from rat brain homogenate.
RESULTS: The ethyl acetate extract showed the highest total phenolic content and total flavonoid content among other extracts of M. pudica leaves. The percentage inhibition and IC50 value of all the extracts were followed dose-dependency and found significant (P < 0.01) as compared to standard (ascorbic acid). The oxidative stress markers as SOD, CAT, and GSH were increased significantly (P < 0.01) at 200 and 400 mg/kg of EAMP treated animals and decreased significantly the TBARS level at 400 mg/kg of EAMP as compared to control group.
CONCLUSION: These results revealed that the ethyl acetate extract of M. pudica exhibits both in vitro antioxidant activity against DPPH and in vivo antioxidant activity by modulating brain enzymes in the rat. This could be further correlated with its potential to neuroprotective activity due to the presence of flavonoids and phenolic contents in the extract.
SUMMARY: Total phenolic, flavonoid contents and in-vitro antioxidant potential were evaluated from various extracts of M. pudica leaves. Again, in-vivo antioxidant evaluation from brain homogenate on oxidative stress markers as TBARS, SOD, CAT and GSH from rat was investigated. Our findings revealed that M. pudica possesses both in-vitro and in-vivo antioxidant activity due to presence of phenolics and flavonoids.
KEYWORDS: 2; 2-diphenyl-1-picrylhydrazyl; Brain homogenate; Flavonoids; Mimosa pudica; Oxidative stress

Matched MeSH terms: Brain
2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase

Leong SW, Abas F, Lam KW, Shaari K, Lajis NH

Bioorg Med Chem, 2016 08 15;24(16):3742-51.
PMID: 27328658 DOI: 10.1016/j.bmc.2016.06.016

In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AChE and BChE activities. Compounds 39 and 40 in particular exhibited highest inhibition on both AChE and BChE with IC50 values of 1.6μM and 0.6μM, respectively. Further structure-activity relationship study suggested that presence of a long-chain heterocyclic in one of the rings played a critical role in the dual enzymes' inhibition. The Lineweaver-Burk plots and docking results suggest that both compounds could simultaneously bind to the PAS and CAS regions of the enzyme. ADMET analysis further confirmed the therapeutic potential of both compounds based upon their high BBB-penetrating. Thus, 2-benzoyl-6-benzylidenecyclohexanone containing long-chain heterocyclic amine analogs represent a new class of cholinesterase inhibitor, which deserve further investigation for their development into therapeutic agents for cognitive diseases such as Alzheimer.

Matched MeSH terms: Blood-Brain Barrier
Cadaveric organ donation at University Hospital Kuala Lumpur

Chen TP, Teo SM, Tan JC, Koh SN, Ambalavanar N, Tan SY

Transplant Proc, 2000 Nov;32(7):1809-10.
PMID: 11119946
Matched MeSH terms: Brain Injuries
Fulltext Transient Cortical Blindness After Coronary Angiography, Bypass Graft Angiography, and Coronary Angioplasty

Lee ZV, Arjan Singh RS

Cureus, 2021 Jan 07;13(1):e12542.
PMID: 33425567 DOI: 10.7759/cureus.12542

Transient cortical blindness after coronary angiography has long been reported in the literature; however, this condition remains rare until today. We report a case of transient cortical blindness after coronary angiography, bypass graft angiography, and coronary angioplasty, which was deemed to be secondary to contrast agent. A 60-year-old man who underwent prior coronary artery bypass grafting (CABG) started to experience recurrence of exertional and resting chest pain one year after CABG. In addition to coronary artery disease, he has underlying type 2 diabetes mellitus, hypertension, and dyslipidemia. Due to technical reasons, he was unable to undergo a computed tomography (CT) angiography of the coronary arteries and bypass grafts. Invasive coronary and bypass graft angiography were done, followed by stenting of the left circumflex artery. Thirty minutes after completion of the procedure, the patient had bilateral blurring of vision, which worsened drastically to only being able to perceive light bilaterally. The patient otherwise did not have any other neurological deficits. Binocular indirect ophthalmoscopy revealed no significant abnormalities apart from mild non-proliferative diabetic retinopathy of the left eye. A non-contrasted CT scan of the brain revealed acute subarachnoid bleed in both occipital lobes, but a subsequent magnetic resonance imaging scan of the brain revealed no evidence of intracranial bleed. The patient's vision gradually improved eight hours after the index event, and his vision completely normalized 12 hours later. The patient was discharged well two days later, and at one-month, three-month, and six-month follow-up, the patient remained angina-free, and his vision had remained stable bilaterally.

Matched MeSH terms: Brain

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