- Prognostic Utility of Initial Lactate in Patients With Acute Drug Overdose: A Validation Cohort. [Journal Article]
- AEAnn Emerg Med 2018 Apr 06
- CONCLUSIONS: Initial lactate concentration is a useful biomarker for early clinical decisionmaking in ED patients with acute drug overdose. Studies of lactate-tailored management for these patient populations are warranted.
- Lactulose attenuates METH-induced neurotoxicity by alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum. [Journal Article]
- TLToxicol Lett 2018 Jun 01; 289:107-113
- Methamphetamine (METH) is a widely abused psychostimulant. Lactulose is a non-absorbable sugar, which effectively decreases METH-induced neurotoxicity in rat. However, the exact mechanisms need furth...
Methamphetamine (METH) is a widely abused psychostimulant. Lactulose is a non-absorbable sugar, which effectively decreases METH-induced neurotoxicity in rat. However, the exact mechanisms need further investigation. In this study, 5-week-old male Sprague Dawley rats received METH (15 mg/kg, 8 intraperitoneal injections, 12-h interval) or saline and received lactulose (5.3 g/kg, oral gavage, 12-h interval) or vehicle 2 days prior to the METH administration. Compared to the control group, in the METH alone group, cytoplasmic vacuolar degeneration in hepatocytes, higher levels of alanine transaminase, aspartate transaminase and ammonia, overproduction of reactive oxygen species (ROS) and increase of superoxide dismutase activity in the blood were observed. Moreover, in rat striatum, expressions of nuclear factor erythroid 2-relatted factor-2 (Nrf2) and heme oxygenase-1 were suppressed in the nucleus, although over-expression of Nrf2 were observed in cytoplasm. Over-expressions of BECN1 and LC3-II indicated initiation of autophagy, while overproduction of p62 might suggest deficient autophagic vesicle turnover and impaired autophagy. Furthermore, accumulation of p62 cloud interact with Keap1 and then aggravate cytoplasmic accumulation of Nrf2. Consistently, over-expressions of cleaved caspase 3 and poly(ADP-ribose) polymerase-1 suggested the activation of apoptosis. The pretreatment with lactulose significantly decreased rat hepatic injury, suppressed hyperammonemia and ROS generation, alleviated the impaired autophagy in striatum, rescued the antioxidant system and repressed apoptosis. Taken together, with decreased blood ammonia, lactulose pretreatment reduced METH-induced neurotoxicity through alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum.
- Effects of Mitochondrial Antioxidant SkQ1 on Biochemical and Behavioral Parameters in a Parkinsonism Model in Mice. [Journal Article]
- BBiochemistry (Mosc) 2017; 82(12):1513-1520
- According to one hypothesis, Parkinson's disease pathogenesis is largely caused by dopamine catabolism that is catalyzed on mitochondrial membranes by monoamine oxidase. Reactive oxygen species are f...
According to one hypothesis, Parkinson's disease pathogenesis is largely caused by dopamine catabolism that is catalyzed on mitochondrial membranes by monoamine oxidase. Reactive oxygen species are formed as a byproduct of these reactions, which can lead to mitochondrial damage followed by cell degeneration and death. In this study, we investigated the effects of administration of the mitochondrial antioxidant SkQ1 on biochemical, immunohistochemical, and behavioral parameters in a Parkinson-like condition caused by protoxin MPTP injections in C57BL/6 mice. SkQ1 administration increased dopamine quantity and decreased signs of sensory-motor deficiency as well as destruction of dopaminergic neurons in the substantia nigra and ventral tegmental area in mice with the Parkinson-like condition.
- Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity. [Journal Article]
- BCBMC Complement Altern Med 2018 Feb 23; 18(1):76
- CONCLUSIONS: Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.
- Alterations in the nigrostriatal dopamine system after acute systemic PhIP exposure. [Journal Article]
- TLToxicol Lett 2018 May 01; 287:31-41
- Heterocyclic amines (HCAs) are primarily formed during cooking of meat at high temperature. HCAs have been extensively studied as mutagens and possible carcinogens. Emerging data suggest that HCAs ar...
Heterocyclic amines (HCAs) are primarily formed during cooking of meat at high temperature. HCAs have been extensively studied as mutagens and possible carcinogens. Emerging data suggest that HCAs are neurotoxic and may be relevant to Parkinson's disease (PD) etiology. However, the majority of HCAs have not been evaluated for in vivo neurotoxicity. Here, we investigated acute in vivo neurotoxicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). PhIP is the most prevalent genotoxin in many types of meats. Adult, male Sprague-Dawley rats were subjected to acute, systemic PhIP at doses and time-points that have been extensively utilized in cancer studies (100 and 200 mg/kg for 8, 24 h) and evaluated for changes in dopaminergic, serotoninergic, GABAergic, and glutamatergic neurotransmission. PhIP exposure resulted in decreased striatal dopamine metabolite levels and dopamine turnover in the absence of changes to vesicular monoamine transporter 2 levels; other neurotransmitter systems were unaffected. Quantification of intracellular nitrotyrosine revealed higher levels of oxidative damage in dopaminergic neurons in the substantia nigra after PhIP exposure, while other neuronal populations were less sensitive. These changes occurred in the absence of an overt lesion to the nigrostriatal dopamine system. Collectively, our study suggests that acute PhIP treatment in vivo targets the nigrostriatal dopaminergic system and that PhIP should be further examined in chronic, low-dose studies for PD relevance.
- Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia. [Review]
- CDCochrane Database Syst Rev 2018 01 18; 1:CD000458
- CONCLUSIONS: Although there has been a large amount of research in this area, many studies were excluded due to inherent problems in the nature of their cross-over designs. Usually data are not reported before the cross-over and the nature of TD and its likely response to treatments make it imprudent to use this data. The review provides little usable information for service users or providers and more well-designed and well-reported studies are indicated.
- Comprehensive characterization of neurochemicals in three zebrafish chemical models of human acute organophosphorus poisoning using liquid chromatography-tandem mass spectrometry. [Journal Article]
- ABAnal Bioanal Chem 2018; 410(6):1735-1748
- There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of d...
There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of development. Zebrafish, a vertebrate model increasingly used in neurobiology and neurotoxicology, shares the common neurotransmitter systems with mammals, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin, acetylcholine, and histamine. In this study, we have evaluated the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the multiresidue determination of neurotransmitters and related metabolites. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined to optimize two selected reaction monitoring (SRM) transitions. Chromatographic conditions were optimized considering the chemical structure and chromatographic behavior of the analyzed compounds. The best performance was obtained with a Synergy Polar-RP column, which allowed the separation of the 38 compounds in 30 min. In addition, the performance of LC-MS/MS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method was able to quantify 27 of these neurochemicals in zebrafish chemical models for mild (P1), moderate (P2), and severe (P3) acute organophosphorus poisoning (OPP). The results show a general depression of synaptic-related neurochemicals, including the excitatory and inhibitory amino acids, as well as altered phospholipid metabolism, with specific neurochemical profiles associated to the different grades of severity. These results confirmed that the developed analytical method is a new tool for neurotoxicology research using the zebrafish model.
- Understanding the role of glycogen synthase kinase-3 in L-DOPA-induced dyskinesia in Parkinson's disease. [Review]
- EOExpert Opin Drug Metab Toxicol 2018; 14(1):83-90
- Levodopa (L-DOPA) is the most commonly used drug for Parkinson's disease (PD), but its long-term use is associated with various complications, including L-DOPA-induced dyskinesia (LID). Many studies ...
Levodopa (L-DOPA) is the most commonly used drug for Parkinson's disease (PD), but its long-term use is associated with various complications, including L-DOPA-induced dyskinesia (LID). Many studies have suggested that L-DOPA neurotoxicity and LID are associated with glycogen synthase kinase-3 (GSK-3) activation. Areas covered: LID is caused by striatal dopamine (DA) denervation in PD and pulsatile L-DOPA treatment. These factors lead to dysregulated DA transmission, abnormal intracellular signaling and transcription factors in striatal neurons, and altered gene expression and plasticity at corticostriatal synapses. The mechanisms of L-DOPA toxicity involve oxidative stress, L-DOPA oxidation to quinone, mitochondrial dysfunction, and α-synuclein. GSK-3 has been suggested to play key roles in all the mechanisms associated of L-DOPA toxicity and LID in PD. Expert opinion: GSK-3 plays critical roles in L-DOPA-induced neurotoxicity, and the development of specific methods to inhibit GSK-3 function may help prevent L-DOPA neurotoxicity and LID in PD. However, balanced GSK-3 inhibition and less β-catenin degradation is essential for preventing LID, because too much GSK-3 inhibition increases β-catenin levels, which is related to cancers.
- Potential diagnostic markers of olanzapine efficiency for acute psychosis: a focus on peripheral biogenic amines. [Randomized Controlled Trial]
- BPBMC Psychiatry 2017 Dec 08; 17(1):394
- CONCLUSIONS: The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.
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- A Stinging Suspicion Something Was Just Not Right: Methamphetamine Toxicity in Infant Mimics Scorpion Envenomation. [Case Reports]
- PEPediatr Emerg Care 2017; 33(11):e124-e125
- The sting from Centuroides sculpturatus, commonly known as the bark scorpion, is a serious medical problem and can be potentially fatal to young children. Centuroides sculpturatus envenomation can ca...
The sting from Centuroides sculpturatus, commonly known as the bark scorpion, is a serious medical problem and can be potentially fatal to young children. Centuroides sculpturatus envenomation can cause a wide spectrum of symptoms, often including autonomic dysfunction, cranial nerve abnormalities, and somatic motor abnormalities. We discuss a 6-month-old male infant who presented with signs and symptoms consistent with bark scorpion envenomation, later found to be secondary to methamphetamine toxicity. Emergency pediatricians should be aware of the strong similarities between scorpion envenomation and methamphetamine toxicity in pediatric patients residing in or having visited the southwestern region of the United States. Methamphetamine toxicity should be considered in their differential diagnosis.