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Vincristine-induced peripheral neuropathy in survivors of childhood acute lymphoblastic leukaemia

Tay CG, Lee VWM, Ong LC, Goh KJ, Ariffin H, Fong CY

Pediatr Blood Cancer, 2017 Aug;64(8).
PMID: 28139029 DOI: 10.1002/pbc.26471

BACKGROUND: Vincristine, an essential component of childhood acute lymphoblastic leukaemia (ALL) therapeutic protocols, is associated with dose-dependent neurotoxicity, but its long-term morbidity in treated children has not been clearly elucidated. The aim of this study is to determine the prevalence of vincristine-induced peripheral neuropathy (VIPN) among Malaysian childhood ALL survivors and its impact on motor function and quality of life.
PROCEDURE: Survivors of childhood ALL aged 4-18 years who had completed chemotherapy for 2 years or more were evaluated for VIPN using both the clinical Total Neuropathy Score (cTNS) and nerve conduction studies. Motor function and quality of life of the survivors were assessed via the Bruininks-Oseretsky Test of Motor Proficiency Brief Form, Second Edition (BOT-2 Brief Form) and the Paediatric Quality of Life version 4.0 Generic Core Scales (PedsQL4.0) questionnaire, respectively.
RESULTS: One hundred and one survivors with a duration of follow-up ranging from 2.0 to 10.3 years were recruited. Twenty-seven (26.7%) had abnormal cTNS scores and 69 (68.3%) had electrophysiological evidence of neuropathy. Of these, 16 (15.8%) had combined clinical and electrophysiological neuropathy (VIPN). Those previously treated on the intermediate- or high-risk treatment stratification arms had a higher risk of developing VIPN (67.3 vs. 32.7%; odds ratio [OR]: 9.06, 95% confidence interval [CI]: 1.14-71.86; P = 0.014). Survivors with VIPN had significantly lower quality of life scores in the physical (P = 0.024) and social domains (P = 0.039) compared with peers without VIPN, but no association with poorer motor function was observed.
CONCLUSIONS: Sixteen percent of ALL survivors had VIPN. VIPN should be increasingly recognised as a late effect of chemotherapy, as it significantly affects physical and social function quality of life.

Matched MeSH terms: Peripheral Nervous System Diseases/chemically induced*; Peripheral Nervous System Diseases/epidemiology
The Use of Methylphenidate for Physical and Psychological Symptoms in Cancer Patients: A Review

Andrew BN, Guan NC, Jaafar NRN

Curr Drug Targets, 2018;19(8):877-887.
PMID: 28322161 DOI: 10.2174/1389450118666170317162603

BACKGROUND: One of the goals of cancer treatment is symptoms management especially at the end stage. The common symptoms in cancer include pain, fatigue, depression and cognitive dysfunction. The available treatment options for symptom management are limited. Methylphenidate, a psychostimulant, may be of benefit for these patients. In this report, we review the use of methylphenidate for symptoms control in cancer patients.
METHOD: Electronic literature search on PubMed was conducted using the following keywords: methylphenidate, cancer, carcinoma, oncology, oncological and tumour. We identified forty two relevant studies and publications on the use of methylphenidate in cancer patients to be included in this review.
RESULTS: Methylphenidate was found to have some evidence in reducing opioid-induced sedation, improving cognitive symptoms and reduction of fatigue in cancer patients. Nevertheless, the results were inconsistent due to variations in the study populations, study design and outcome measures, among others. There was minimal evidence on its use in treating depression. Otherwise, methylphenidate was generally well-tolerated by patients.
CONCLUSION: This review potentially supports the use of methylphenidate for opioid-induced sedation, cognitive decline and fatigue in cancer patients. Further placebo-controlled trials would help in strengthening the evidence for this treatment.

Matched MeSH terms: Central Nervous System Stimulants/adverse effects; Central Nervous System Stimulants/therapeutic use*
Hypersexuality As a Neuropsychiatric Disorder: The Neurobiology and Treatment Options

Asiff M, Sidi H, Masiran R, Kumar J, Das S, Hatta NH, et al.

Curr Drug Targets, 2018;19(12):1391-1401.
PMID: 28325146 DOI: 10.2174/1389450118666170321144931

Hypersexuality refers to abnormally increased or extreme involvement in any sexual activity. It is clinically challenging, presents trans-diagnostically and there is extensive medical literature addressing the nosology, pathogenesis and neuropsychiatric aspects in this clinical syndrome. Classification includes deviant behaviours, diagnosable entities related to impulsivity, and obsessional phenomena. Some clinicians view an increase in sexual desire as 'normal' i.e. psychodynamic theorists consider it as egodefensive at times alleviating unconscious anxiety rooted in intrapsychic conflicts. We highlight hypersexuality as multi-dimensional involving an increase in sexual activity that is associated with distress and functional impairment. The aetiology of hypersexuality is multi-factorial with differential diagnoses that include major psychiatric disorders (e.g. bipolar disorder), adverse effects of treatments (e.g. levodopatreatment), substance-induced disorders (e.g. amphetamine substance use), neuropathological disorders (e.g. frontal lobe syndrome), among others. Numerous neurotransmitters are implicated in its pathogenesis, with dopamine and noradrenaline playing a crucial role in the neural reward pathways and emotionally- regulated limbic system neural circuits. The management of hypersexuality is determined by the principle of de causa effectu evanescent, if the causes are treated, the effect may disappear. We aim to review the role of pharmacological agents causing hypersexuality and centrally acting agents treating the associated underlying medical conditions. Bio-psycho-social determinants are pivotal in embracing the understanding and guiding management of this complex and multi-determined clinical syndrome.

Matched MeSH terms: Nervous System Diseases/diagnosis; Nervous System Diseases/drug therapy*
Anterior spinal cord syndrome as a rare complication of acute bacterial meningitis in an adult

Ng KS, Abdul Halim S

BMJ Case Rep, 2018 Oct 24;2018.
PMID: 30361450 DOI: 10.1136/bcr-2018-226082

Acute bacterial meningitis is not an uncommon central nervous system infection. In severe cases, it can be associated with various neurological or systemic complications. However, acute spinal cord dysfunction rarely occurs. We report a case of bacterial meningitis complicated with spinal cord infarction despite adequate treatment with antibiotics and corticosteroid therapy. He had residual paraplegia and was fully dependent in the activity of daily living.

Matched MeSH terms: Central Nervous System Bacterial Infections/diagnosis*; Central Nervous System Bacterial Infections/drug therapy
Cardiorespiratory findings in epilepsy: A recent review on outcomes and pathophysiology

Akyüz E, Üner AK, Köklü B, Arulsamy A, Shaikh MF

J Neurosci Res, 2021 09;99(9):2059-2073.
PMID: 34109651 DOI: 10.1002/jnr.24861

Epilepsy is a debilitating disorder of uncontrollable recurrent seizures that occurs as a result of imbalances in the brain excitatory and inhibitory neuronal signals, that could stem from a range of functional and structural neuronal impairments. Globally, nearly 70 million people are negatively impacted by epilepsy and its comorbidities. One such comorbidity is the effect epilepsy has on the autonomic nervous system (ANS), which plays a role in the control of blood circulation, respiration and gastrointestinal function. These epilepsy-induced impairments in the circulatory and respiratory systems may contribute toward sudden unexpected death in epilepsy (SUDEP). Although, various hypotheses have been proposed regarding the role of epilepsy on ANS, the linking pathological mechanism still remains unclear. Channelopathies and seizure-induced damages in ANS-control brain structures were some of the causal/pathological candidates of cardiorespiratory comorbidities in epilepsy patients, especially in those who were drug resistant. However, emerging preclinical research suggest that neurotransmitter/receptor dysfunction and synaptic changes in the ANS may also contribute to the epilepsy-related autonomic disorders. Thus, pathological mechanisms of cardiorespiratory dysfunction should be elucidated by considering the modifications in anatomy and physiology of the autonomic system caused by seizures. In this regard, we present a comprehensive review of the current literature, both clinical and preclinical animal studies, on the cardiorespiratory findings in epilepsy and elucidate the possible pathological mechanisms of these findings, in hopes to prevent SUDEP especially in patients who are drug resistant.

Matched MeSH terms: Autonomic Nervous System/physiology; Autonomic Nervous System/physiopathology*
Fulltext In Silico and In Vitro Analysis of Bacoside A Aglycones and Its Derivatives as the Constituents Responsible for the Cognitive Effects of Bacopa monnieri

Ramasamy S, Chin SP, Sukumaran SD, Buckle MJ, Kiew LV, Chung LY

PLoS One, 2015;10(5):e0126565.
PMID: 25965066 DOI: 10.1371/journal.pone.0126565

Bacopa monnieri has been used in Ayurvedic medicine to improve memory and cognition. The active constituent responsible for its pharmacological effects is bacoside A, a mixture of dammarane-type triterpenoid saponins containing sugar chains linked to a steroid aglycone skeleton. Triterpenoid saponins have been reported to be transformed in vivo to metabolites that give better biological activity and pharmacokinetic characteristics. Thus, the activities of the parent compounds (bacosides), aglycones (jujubogenin and pseudojujubogenin) and their derivatives (ebelin lactone and bacogenin A1) were compared using a combination of in silico and in vitro screening methods. The compounds were docked into 5-HT1A, 5-HT2A, D1, D2, M1 receptors and acetylcholinesterase (AChE) using AutoDock and their central nervous system (CNS) drug-like properties were determined using Discovery Studio molecular properties and ADMET descriptors. The compounds were screened in vitro using radioligand receptor binding and AChE inhibition assays. In silico studies showed that the parent bacosides were not able to dock into the chosen CNS targets and had poor molecular properties as a CNS drug. In contrast, the aglycones and their derivatives showed better binding affinity and good CNS drug-like properties, were well absorbed through the intestines and had good blood brain barrier (BBB) penetration. Among the compounds tested in vitro, ebelin lactone showed binding affinity towards M1 (Ki = 0.45 μM) and 5-HT2A (4.21 μM) receptors. Bacoside A and bacopaside X (9.06 μM) showed binding affinity towards the D1 receptor. None of the compounds showed any inhibitory activity against AChE. Since the stimulation of M1 and 5-HT2A receptors has been implicated in memory and cognition and ebelin lactone was shown to have the strongest binding energy, highest BBB penetration and binding affinity towards M1 and 5-HT2A receptors, we suggest that B. monnieri constituents may be transformed in vivo to the active form before exerting their pharmacological activity.

Matched MeSH terms: Central Nervous System/drug effects; Central Nervous System/chemistry
Fulltext Factors associated with vascular and neurological complications of hand-arm vibration syndrome among tire shop workers in Kelantan, Malaysia

Qamruddin AA, Nik Husain NR, Sidek MY, Hanafi MH, Mohd Ripin Z

J Occup Health, 2021 Jan;63(1):e12220.
PMID: 33942440 DOI: 10.1002/1348-9585.12220

OBJECTIVE: Prolonged exposure to hand-arm vibration (HAV) at the workplace is associated with hand-arm vascular syndrome (HAVS). This study aimed to determine the prevalence and the factors associated with the vascular and neurological complications of HAVS among tire shop workers in Kelantan, Malaysia.
METHODS: A cross-sectional study involving 200 tire shop workers from two districts in Kelantan was conducted. Data were collected at the field using Malay Translated HAVS questionnaire, and hand-arm vibration was measured. Multiple logistic regression analysis was used to determine the associated factors.
RESULTS: The prevalence of vascular and neurological complications of HAVS among the tire shop workers was 12.5% (95% CI: 10.16, 14.84) and 37.0% (95% CI: 30.31, 43.69), respectively. From multiple logistic regression analysis, only A(8) of HAV exposure was significantly associated with the development of vascular complications and A(8) of HAV exposure, age. and body mass index were significantly associated with the development of neurological complications of HAVS.
CONCLUSION: This study has identified that HAVS is a significant problem among workers exposed to HAV in a warm environment. A(8) of HAV exposure is significantly associated with the development of both vascular and neurological complications. Therefore, there is a need for better control of vibration exposure in Malaysia.

Matched MeSH terms: Nervous System Diseases/etiology; Nervous System Diseases/epidemiology*
Dexamphetamine increased speech and visual unimodal illusions in healthy participants without affecting temporal binding window

Voon FL, Loffman SJ, Lim MJH, Lee JWY, Iyyalol R, Martin-Iverson MT

Hum Psychopharmacol, 2024 May;39(3):e2896.
PMID: 38353526 DOI: 10.1002/hup.2896

OBJECTIVE: Stimuli received beyond a very short timeframe, known as temporal binding windows (TBWs), are perceived as separate events. In previous audio-visual multisensory integration (McGurk effect) studies, widening of TBWs has been observed in people with schizophrenia. The present study aimed to determine if dexamphetamine could increase TBWs in unimodal auditory and unimodal visual illusions that may have some validity as experimental models for auditory and visual hallucinations in psychotic disorders.
METHODS: A double-blind, placebo-controlled, counter-balanced crossover design with permuted block randomisation for drug order was followed. Dexamphetamine (0.45 mg/kg, PO, q.d.) was administered to healthy participants. Phantom word illusion (speech illusion) and visual-induced flash illusion/VIFI (visual illusion) tests were measured to determine if TBWs were altered as a function of delay between stimuli presentations. Word emotional content for phantom word illusions was also analysed.
RESULTS: Dexamphetamine significantly increased the total number of phantom words/speech illusions (p

Matched MeSH terms: Central Nervous System Stimulants/administration & dosage; Central Nervous System Stimulants/pharmacology
Fulltext Following "the Roots" of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries

Cinosi E, Martinotti G, Simonato P, Singh D, Demetrovics Z, Roman-Urrestarazu A, et al.

Biomed Res Int, 2015;2015:968786.
PMID: 26640804 DOI: 10.1155/2015/968786

The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.

Matched MeSH terms: Central Nervous System Stimulants
Fulltext Tryptophan-catabolizing enzymes - party of three

Ball HJ, Jusof FF, Bakmiwewa SM, Hunt NH, Yuasa HJ

Front Immunol, 2014;5:485.
PMID: 25346733 DOI: 10.3389/fimmu.2014.00485

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that have independently evolved to catalyze the first step in tryptophan catabolism via the kynurenine pathway (KP). The depletion of tryptophan and formation of KP metabolites modulates the activity of the mammalian immune, reproductive, and central nervous systems. IDO and TDO enzymes can have overlapping or distinct functions depending on their expression patterns. The expression of TDO and IDO enzymes in mammals differs not only by tissue/cellular localization but also by their induction by distinct stimuli. To add to the complexity, these genes also have undergone duplications in some organisms leading to multiple isoforms of IDO or TDO. For example, many vertebrates, including all mammals, have acquired two IDO genes via gene duplication, although the IDO1-like gene has been lost in some lower vertebrate lineages. Gene duplications can allow the homologs to diverge and acquire different properties to the original gene. There is evidence for IDO enzymes having differing enzymatic characteristics, signaling properties, and biological functions. This review analyzes the evolutionary convergence of IDO and TDO enzymes as tryptophan-catabolizing enzymes and the divergent evolution of IDO homologs to generate an enzyme family with diverse characteristics not possessed by TDO enzymes, with an emphasis on the immune system.

Matched MeSH terms: Central Nervous System
Fulltext Electrocution induced symptomatic bradycardia necessitating pacemaker implantation

Yew KL

Heart Views, 2014 Apr;15(2):49-50.
PMID: 25104983 DOI: 10.4103/1995-705X.137497

Electrical or electrocution injury is a common accidental occurrence and mostly workplace related. Fatal arrhythmias, skin injury and sudden death may ensue. However, it is rare for electrocution to result in permanent low rate sinus bradycardia, incompatible with an active lifestyle. The probable mechanisms for this pathological sinus bradycardia are sinus node dysfunction and autonomic dysfunction with vagal predominance. We describe a young patient who suffered a non fatal electrocution with resultant low rate sinus bradycardia and its successful treatment with a dual chamber rate responsive pacemaker.

Matched MeSH terms: Autonomic Nervous System Diseases
Ethnic variations in dementia: the contributions of cardiovascular, psychosocial and neuropsychological factors

Ng TP, Leong T, Chiam PC, Kua EH

Dement Geriatr Cogn Disord, 2010;29(2):131-8.
PMID: 20145399 DOI: 10.1159/000275668

Ethnic variations in dementia rate have been reported worldwide. Understanding these differences is vital for aetiological research, clinical care and health service planning. While age and gender have been consistently implicated, the reasons behind interethnic variation remain unclear.

Matched MeSH terms: Nervous System Diseases/complications; Nervous System Diseases/epidemiology*; Nervous System Diseases/psychology*
Inhibition of Ang II and renal sympathetic nerve influence dopamine-and isoprenaline-induced renal haemodynamic changes in normal Wistar-Kyoto and spontaneously hypertensive rats

Abdulla MH, Sattar MA, Abdullah NA, Hazim AI, Anand Swarup KR, Rathore HA, et al.

Auton Autacoid Pharmacol, 2008 Oct;28(4):95-101.
PMID: 18778332 DOI: 10.1111/j.1474-8673.2008.00422.x

1. This study was undertaken to elucidate the effects of inhibiting the renin-angiotensin system (RAS) with losartan, and acute unilateral renal denervation on renal haemodynamic responses to intrarenal administration of vasoconstrictor doses of dopamine and vasodilator doses of isoprenaline in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Acute unilateral renal denervation of the left kidney in rats was confirmed by a drop in the renal vasoconstrictor response to renal nerve stimulation (P < 0.05) along with diuresis and natriuresis. Rats were pretreated with losartan for 7 days and thereafter animals fasted overnight were anaesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and acute renal haemodynamic responses studied. 3. Dose-response curves were constructed for dopamine and isoprenaline that induced falls or increases in renal blood flow, respectively. It was observed that renal vascular responses were greater in the denervated as compared with rats with intact renal nerves (all P < 0.05). Dopamine-induced renal vasoconstrictor responses were markedly lower in losartan-treated denervated WKY and SHR compared with their untreated counterparts (all P < 0.05). It was also observed that in losartan-treated and denervated WKY rats the vasodilatory responses to isoprenaline were markedly lower compared with untreated rats (all P < 0.05). However, in SHR, under the same conditions, there was no difference in the renal response to isoprenaline whether or not rats were treated with losartan (P > 0.05). 4. The data obtained showed that the renal vasoconstrictor effect of dopamine depends on intact renal nerves and RAS in WKY and SHR. Isoprenaline responses were likewise sensitive to renal denervation and RAS inhibition in WKY rats but not SHRs. Our observations reveal a possible relationship between renal AT(1) receptors and alpha(1)-adrenoceptors in WKY and SHR. There is also evidence to suggest an interaction between renal beta-adrenoceptors and AT(1) receptors in WKY rats.

Matched MeSH terms: Sympathetic Nervous System/drug effects; Sympathetic Nervous System/physiology*; Sympathetic Nervous System/surgery
Emerging and re-emerging epidemic encephalitis: a tale of two viruses

Wong KT

Neuropathol. Appl. Neurobiol., 2000 Aug;26(4):313-8.
PMID: 10931364

Two major epidemics of viral encephalitis occurred in Asia in 1997 and 1998. The first was a re-emergence of neurovirulent strains of enterovirus 71, which caused severe encephalomyelitis in children in Malaysia, Taiwan and Japan, on a background of hand, foot and mouth disease. Necropsy studies of patients who died of enterovirus 71 infection showed severe perivascular cuffing, parenchymal inflammation and neuronophagia in the spinal cord, brainstem and diencephalon, and in focal areas in the cerebellum and cerebrum. Although no viral inclusions were detected, immunohistochemistry showed viral antigen in the neuronal cytoplasm. Inflammation was often more extensive than neuronal infection, suggesting that other factors, in addition to direct viral cytolysis, may be involved in tissue damage. The second epidemic of viral encephalitis was the result of a novel paramyxovirus called Nipah, which mainly involved pig handlers in Malaysia and Singapore. Pathological evidence suggested that the endothelium of small blood vessels in the central nervous system was particularly susceptible to infection. This led to disseminated endothelial damage and syncytium formation, vasculitis, thrombosis, ischaemia and microinfarction. However, there was also evidence of neuronal infection by the virus and this may also have contributed to the neurological dysfunction in Nipah encephalitis. Some patients who seemed to recover from the acute symptoms have been re-admitted with clinical findings suggestive of relapsing encephalitis. As these two epidemics indicate, the emergence and re-emergence of viral encephalitides continue to pose considerable challenges to the neuropathologist, in establishing the diagnosis and unravelling the pathogenesis of the neurological disease.

Matched MeSH terms: Central Nervous System/blood supply; Central Nervous System/pathology; Central Nervous System/virology
Growing dural sinus malformation with associated developmental venous anomaly, multiple cavernomas and facial venous malformation in an infant. An associated disease or a disease spectrum?

Mohamed Z, Batista LL, Sachet M, Mahadevan J, Alvarez H, Lasjaunias P

Interv Neuroradiol, 2002 Dec 22;8(4):421-30.
PMID: 20594504

This is an unusual case report of an infant, who initially presented with a facial haemangioma and was later diagnosed to have a dural sinus malformation (DSM) involving the torcula. The DSM increased in size lateralising to the right transverse sinus at three months of age. Postnatal enlargement of the dural sinus has not been described before suggesting a delay in the maturation of the dural sinus which normally would occur antenatally. There was a further association with a complex developmental venous anomaly (DVA) draining the right cerebral hemisphere into the deep cerebral vein and multiple cavernous malformations. The DVA was not clearly demonstrated at age one month but was more obvious at age three months. This would be the first reported case of DSM associated with a DVA. Increasing venous hypertension probably contributed to the poor opacification of the DVA on follow-up angiography at age six months and to the haemorrhagic changes within the cavernomas on magnetic resonance imaging (MRI). The therapeutic goal was to correct venous hypertension by partially embolising the dural shunts to remodel the cerebral vasculature and preserve the patent sinus. The treatment strategy and possible link between the complex disease entities presented in this infant are discussed. Despite these attemps, the lesion continued to grow compressing the posterior fossa structures. The infant died at nine months of age.

Matched MeSH terms: Central Nervous System Venous Angioma
Toxic Elements in Food: Occurrence, Binding, and Reduction Approaches

Hajeb P, Sloth JJ, Shakibazadeh S, Mahyudin NA, Afsah-Hejri L

Compr Rev Food Sci Food Saf, 2014 Jul;13(4):457-472.
PMID: 33412705 DOI: 10.1111/1541-4337.12068

Toxic elements such as mercury, arsenic, cadmium, and lead, sometimes called heavy metals, can diminish mental and central nervous system function; elicit damage to blood composition as well as the kidneys, lungs, and liver; and reduce energy levels. Food is considered one of the main routes of their entry into the human body. Numerous studies have been performed to examine the effects of common food processing procedures on the levels of toxic elements in food. While some studies have reported negative effects of processing, several have shown that processing practices may have a positive effect on the reduction of toxic elements in foodstuffs. A number of studies have also introduced protocols and suggested chemical agents that reduce the amount of toxic elements in the final food products. In this review, the reported methods employed for the reduction of toxic elements are discussed with particular emphasis on the chemical binding of both the organic and inorganic forms of each element in various foods. The molecular groups and the ligands by which the food products bind with the metals and the types of these reactions are also presented.

Matched MeSH terms: Central Nervous System
Fulltext Emodin Derivatives as Multi-Target-Directed Ligands Inhibiting Monoamine Oxidase and Antagonizing Vasopressin V1A Receptors

Paudel P, Shrestha S, Park SE, Seong SH, Fauzi FM, Jung HA, et al.

ACS Omega, 2020 Oct 20;5(41):26720-26731.
PMID: 33110998 DOI: 10.1021/acsomega.0c03649

The brain neurotransmitter level is associated with the pathology of various neurodegenerative diseases, and age-dependent increase in the blood level of vasopressin, human brain monoamine oxidase (hMAO) level, oxidative stress, and imbalance in aminergic signaling are common disease-modifying factors leading to various neurodegenerative disorders. Based on the reports of emodin in hMAO inhibition and antagonist effect on the vasopressin V1A receptor, in this study we synthesized six emodin derivatives and evaluated their effects on MAO activity and G protein-coupled receptors. Among them, 4-hydroxyemodin and 5-hydroxyemodin were potent inhibitors of hMAO, and 2-hydroxyemodin and 5-hydroxyemodin were good V1AR antagonists. In silico molecular docking simulation revealed that the hydroxyl group at C2, C4, and C5 of the respective compounds interacted with prime residues, which corroborates the in vitro effect. Likewise, these three derivatives were predicted to have good drug-like properties. Overall, our study demonstrates that the hydroxyl derivatives of emodin are multi-target-directed ligands that may act as leads for the design and development of a therapy for central nervous system disorders.

Matched MeSH terms: Central Nervous System Diseases
Fulltext Examination Standards for Disabled Driver's Licensing

Citation: Examination Standards for Disabled Driver's Licensing. Putrajaya: Occupational Health Unit, Disease Control Division, Ministry of Health Malaysia; 2011

Matched MeSH terms: Nervous System Diseases
Dural arteriovenous fistula mimicking temporal arteritis

Naserrudin NS, Mohammad Raffiq MA

Clin Neurol Neurosurg, 2019 01;176:44-46.
PMID: 30504098 DOI: 10.1016/j.clineuro.2018.11.021

INTRODUCTION: Dural arteriovenous fistula (dAVF) is a very rare disease characterized by an abnormal vascular communication between arteries and veins in dural mater. It frequently presents with intracranial haemorrhage. Common presenting symptoms are headache and seizures.
CASE REPORT: Here we report a case of dAVF in which the patient's symptoms mimic a temporal arteritis in a 23-year-old woman. She presented with painful mass at forehead for 9 months with frontotemporal headache. Magnetic resonance imaging demonstrated dural arteriovenous fistula.
CONCLUSION: Since both diseases have different prognosis but similar presentation, it is important to ensure that there is no dural arteriovenous fistula in patient with suspected temporal arteritis.

Matched MeSH terms: Central Nervous System Vascular Malformations
Differentiation of Commercially Available Kratom by Purported Country of Origin using Inductively Coupled Plasma-Mass Spectrometry

Braley C, Hondrogiannis EM

J Forensic Sci, 2020 Mar;65(2):428-437.
PMID: 31560807 DOI: 10.1111/1556-4029.14201

Kratom is a plant material exhibiting both analgesic and stimulant effects and is also forensically relevant since it is abused as a "legal high." It is regulated in several countries but not scheduled in the United States at the federal level. This study used inductively coupled plasma-mass spectrometry (ICP-MS) to measure the concentrations of 13 elements in 19 kratom samples obtained from an online distributor selling kratom, from Borneo, Malaysia, Indonesia, Thailand, and Vietnam, for the purpose of using the elements to discriminate among purported country of origin, "suborigin," and strain. Analysis of variance revealed statistical differences in concentrations of elements from each group, while discriminant function analysis (using leave-one-out classification) successfully classified kratom samples by their purported country of origin (100%), "suborigin," (100%), and strain (86%). Our method illustrates the possibility of utilizing ICP-MS for determination of commercially available kratom samples by purported origin, "subororign," or by product line.

Matched MeSH terms: Central Nervous System Stimulants

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