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Drug Metabolism Letters

Editor-in-Chief

ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

Research Article

Ameliorative Effect of Acetyl L-carnitine in Alzheimer's Disease via Downregulating of Homocysteine Levels in Hyperhomocysteinemia Induced Cognitive Deficit in Mouse Model

Author(s): Nisha Verma, Jeetendra Kumar Gupta, Krishna Kumar Varshney and Rajnish Srivastava*

Volume 14, Issue 3, 2021

Published on: 21 December, 2021

Page: [219 - 231] Pages: 13

DOI: 10.2174/1872312814666211209102136

Price: $65

Abstract

Aims: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD manifestations in the mouse model.

Background: Alzheimer’s disease (AD) is a neurological disorder that is marked by dementia, and degradation of cognitive abilities. There is great popularity gained by natural supplements as the treatment for AD, due to the higher toxicities of synthetic drugs. Hyperhomocysteinemia causes excitotoxicity to the cortical neurons, which brought us to the point that amino acids possibly have a role in causing cholinergic deformities, which are an important etiological parameter in AD. Acetyl L-Carnitine a methyl donor with the presence of three chemically reactive methyl groups linked to a nitrogen atom was found to possess neuroprotective activity against experimental models of AD.

Objective: The objective of the present investigation was to investigate and evaluate the pharmacological effect of Acetyl L-Carnitine against hyperhomocysteinemia induced Alzheimer’s disease (AD) in the mouse model.

Materials and Methods: The animals were divided into normal control (vehicle-treated), HHcy (dl-Homocysteine thiolactone treated) negative control, test group i.e., low dose (50mg/kg, p.o) of acetyl L-carnitine (L-ALC), high dose (100mg/kg,p.o) of acetyl L-carnitine (H-ALC), L-ALC+ SOV (Sodium orthovanadate) and H-ALC+SOV. HHcy was induced by administration of dl-Homocysteine thiolactone (dl-HCT; 1 g/kg, p.o.) on day-1 to day-15 of experimental schedule to all animals except normal control. The changes in the behaviour pattern of the animals due to neuroinflammation, and cholinergic dysfunction were examined in rotarod, novel objective recognition, passive avoidance, elevated plus maze, and morris water maze analysis. Biochemical investigation includes the estimation of total homocysteine (tHcy), Creatinine Kinase (CK), Acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and IL-6 and TNF-α.

Results: Supplementation of ALC in mouse considerably lowered the HHcy-induced AD manifestations in the experimental animals. It was found that ALC and SOV successfully diminished the behaviour abnormalities and lessened the Hcy-induced alteration in systemic Hcy levels, CK activity, and cholinergic dysfunction with improved bioenergetics in the Prefrontal cortex of the mice.

Conclusion: ALC was found to improve the HHcy-induced cognitive disabilities which was found to be associated with the decreased systemic levels of Hcy, CK, and cholinergic abnormalities. It also combats the oxidative stress-induced neuroinflammation with diminished pro-inflammatory markers in the pre frontal cortex. The outcomes collectively indicate ALC's potential to be used as a supplementation in the pharmacotherapy of AD.

Keywords: Acetyl L-carnitine, methyl donor, sodium orthovanadate, hyperhomocysteinemia, alzheimer’s disease, prefrontal cortex.

Graphical Abstract

[1]
Kelley, B.J.; Petersen, R.C. Alzheimer’s disease and mild cognitive impairment. Neurol. Clin., 2007, 25(3), 577-609.
[http://dx.doi.org/10.1016/j.ncl.2007.03.008] [PMID: 17659182]
[2]
Varshney, K.K.; Gupta, J.K.; Mujwar, S. Homocysteine induced neurological dysfunctions: A link to neurodegenerative disorders. Int. J. Med. Res. Health Sci., 2019, 8, 135-146.
[3]
Patterson, C. World alzheimer report. 2018.
[4]
Grimm, A.; Mensah-Nyagan, A.G.; Eckert, A. Alzheimer, mitochondria and gender. Neurosci. Biobehav. Rev., 2016, 67, 89-101.
[http://dx.doi.org/10.1016/j.neubiorev.2016.04.012] [PMID: 27139022]
[5]
Lian, W.; Fang, J.; Xu, L.; Zhou, W.; Kang, D.; Xiong, W.; Jia, H.; Liu, A.L.; Du, G.H. DL0410 ameliorates memory and cognitive impairments induced by scopolamine via increasing cholinergic neurotransmission in mice. Molecules, 2017, 22(3), 410.
[http://dx.doi.org/10.3390/molecules22030410] [PMID: 28272324]
[6]
Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the cholinergic system. Curr. Neuropharmacol., 2016, 14(1), 101-115.
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[7]
Ballinger, E.C.; Ananth, M.; Talmage, D.A.; Role, L.W. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron, 2016, 91(6), 1199-1218.
[http://dx.doi.org/10.1016/j.neuron.2016.09.006] [PMID: 27657448]
[8]
Hasselmo, M.E.; Wyble, B.P.; Wallenstein, G.V. Encoding and retrieval of episodic memories: Role of cholinergic and GABAergic modulation in the hippocampus. Hippocampus, 1996, 6(6), 693-708.
[http://dx.doi.org/10.1002/(SICI)1098-1063(1996)6:6<693::AID-HIPO12>3.0.CO;2-W] [PMID: 9034856]
[9]
Maurer, S.V.; Williams, C.L. The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Front. Immunol., 2017, 8, 1489.
[http://dx.doi.org/10.3389/fimmu.2017.01489] [PMID: 29167670]
[10]
Agis-Torres, A.; Sölhuber, M.; Fernandez, M.; Sanchez-Montero, J.M. Multi-target-directed ligands and other therapeutic strategies in the search of a real solution for Alzheimer’s disease. Curr. Neuropharmacol., 2014, 12(1), 2-36.
[http://dx.doi.org/10.2174/1570159X113116660047] [PMID: 24533013]
[11]
Wang, Y.; Wang, H.; Chen, H.Z. AChE inhibition-based multi-target-directed ligands, a novel pharmacological approach for the symptomatic and disease-modifying therapy of Alzheimer’s disease. Curr. Neuropharmacol., 2016, 14(4), 364-375.
[http://dx.doi.org/10.2174/1570159X14666160119094820] [PMID: 26786145]
[12]
Abdul Manap, A.S.; Wei Tan, A.C.; Leong, W.H.; Yin Chia, A.Y.; Vijayabalan, S.; Arya, A.; Wong, E.H.; Rizwan, F.; Bindal, U.; Koshy, S.; Madhavan, P. Synergistic effects of curcumin and piperine as potent acetylcholine and amyloidogenic inhibitors with significant neuroprotective activity in SH-SY5Y cells via computational molecular modeling and in vitro assay. Front. Aging Neurosci., 2019, 11, 206.
[http://dx.doi.org/10.3389/fnagi.2019.00206] [PMID: 31507403]
[13]
Ho, P.I.; Ortiz, D.; Rogers, E.; Shea, T.B. Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage. J. Neurosci. Res., 2002, 70(5), 694-702.
[http://dx.doi.org/10.1002/jnr.10416] [PMID: 12424737]
[14]
McCaddon, A.; Davies, G.; Hudson, P.; Tandy, S.; Cattell, H. Total serum homocysteine in senile dementia of Alzheimer type. Int. J. Geriatr. Psychiatry, 1998, 13(4), 235-239.
[http://dx.doi.org/10.1002/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8] [PMID: 9646150]
[15]
Morris, M.S. Homocysteine and Alzheimer’s disease. Lancet Neurol., 2003, 2(7), 425-428.
[http://dx.doi.org/10.1016/S1474-4422(03)00438-1] [PMID: 12849121]
[16]
Xie, F.; Zhao, Y.; Ma, J.; Gong, J.B.; Wang, S.D.; Zhang, L.; Gao, X.J.; Qian, L.J. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats. Cell Stress Chaperones, 2016, 21(5), 915-926.
[http://dx.doi.org/10.1007/s12192-016-0718-0] [PMID: 27435080]
[17]
Mahaman, Y.A.R.; Huang, F.; Wu, M.; Wang, Y.; Wei, Z.; Bao, J.; Salissou, M.T.M.; Ke, D.; Wang, Q.; Liu, R.; Wang, J.Z.; Zhang, B.; Chen, D.; Wang, X. Moringa oleifera alleviates homocysteine-induced Alzheimer’s disease-like pathology and cognitive impairments. J. Alzheimers Dis., 2018, 63(3), 1141-1159.
[http://dx.doi.org/10.3233/JAD-180091] [PMID: 29710724]
[18]
Zeng, P.; Shi, Y.; Wang, X.M.; Lin, L.; Du, Y.J.; Tang, N.; Wang, Q.; Fang, Y.Y.; Wang, J.Z.; Zhou, X.W.; Lu, Y.; Tian, Q. Emodin rescued hyperhomocysteinemia-induced dementia and alzheimer’s disease-like features in rats. Int. J. Neuropsychopharmacol., 2019, 22(1), 57-70.
[http://dx.doi.org/10.1093/ijnp/pyy090] [PMID: 30407508]
[19]
Aureli, T.; Miccheli, A.; Ricciolini, R.; Di Cocco, M.E.; Ramacci, M.T.; Angelucci, L.; Ghirardi, O.; Conti, F. Aging brain: Effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy. Brain Res., 1990, 526(1), 108-112.
[http://dx.doi.org/10.1016/0006-8993(90)90255-A] [PMID: 2078811]
[20]
Goo, M.J.; Choi, S.M.; Kim, S.H.; Ahn, B.O. Protective effects of acetyl-L-carnitine on neurodegenarative changes in chronic cerebral ischemia models and learning-memory impairment in aged rats. Arch. Pharm. Res., 2012, 35(1), 145-154.
[http://dx.doi.org/10.1007/s12272-012-0116-9] [PMID: 22297753]
[21]
Onger, M.E.; Kaplan, S.; Deniz, O.G.; Altun, G.; Altunkaynak, B.Z.; Balcı, K.; Raimondo, S.; Geuna, S. Possible promoting effects of melatonin, leptin and alcar on regeneration of the sciatic nerve. J. Chem. Neuroanat., 2017, 81, 34-41.
[http://dx.doi.org/10.1016/j.jchemneu.2017.02.003] [PMID: 28163216]
[22]
Barhwal, K.; Hota, S.K.; Prasad, D.; Singh, S.B.; Ilavazhagan, G. Hypoxia-induced deactivation of NGF-mediated ERK1/2 signaling in hippocampal cells: Neuroprotection by acetyl-L-carnitine. J. Neurosci. Res., 2008, 86(12), 2705-2721.
[http://dx.doi.org/10.1002/jnr.21722] [PMID: 18500755]
[23]
Hota, K.B.; Hota, S.K.; Chaurasia, O.P.; Singh, S.B. Acetyl-L-carnitine-mediated neuroprotection during hypoxia is attributed to ERK1/2-Nrf2-regulated mitochondrial biosynthesis. Hippocampus, 2012, 22(4), 723-736.
[http://dx.doi.org/10.1002/hipo.20934] [PMID: 21542052]
[24]
White, H.L.; Scates, P.W. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem. Res., 1990, 15(6), 597-601.
[http://dx.doi.org/10.1007/BF00973749] [PMID: 2215852]
[25]
Obeid, R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients, 2013, 5(9), 3481-3495.
[http://dx.doi.org/10.3390/nu5093481] [PMID: 24022817]
[26]
Resstel, L.B.; de Andrade, C.R.; Haddad, R.; Eberlin, M.N.; de Oliveira, A.M.; Corrêa, F.M. Hyperhomocysteinaemia-induced cardiovascular changes in rats. Clin. Exp. Pharmacol. Physiol., 2008, 35(8), 949-956.
[http://dx.doi.org/10.1111/j.1440-1681.2008.04940.x] [PMID: 18430058]
[27]
Celotto, A.C.; Fukada, S.Y.; Laurindo, F.R.; Haddad, R.; Eberlin, M.N.; de Oliveira, A.M. Chronic hyperhomocysteinemia impairs vascular function in ovariectomized rat carotid arteries. Amino Acids, 2010, 38(5), 1515-1522.
[http://dx.doi.org/10.1007/s00726-009-0368-y] [PMID: 19876715]
[28]
Jakubowski, H. Metabolism of homocysteine thiolactone in human cell cultures. Possible mechanism for pathological consequences of elevated homocysteine levels. J. Biol. Chem., 1997, 272(3), 1935-1942.
[http://dx.doi.org/10.1016/S0021-9258(19)67504-6] [PMID: 8999883]
[29]
Kumar, S.; Ivanov, S.; Lagunin, A.; Goel, R.K. Attenuation of hyperhomocysteinemia induced vascular dementia by sodium orthovanadate perhaps via PTP1B: Pertinent downstream outcomes. Behav. Brain Res., 2019, 364, 29-40.
[http://dx.doi.org/10.1016/j.bbr.2019.01.039] [PMID: 30721761]
[30]
Yu, H.; Zhang, Z.L.; Chen, J.; Pei, A.; Hua, F.; Qian, X.; He, J.; Liu, C.F.; Xu, X. Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PLoS One, 2012, 7(3), e33584.
[http://dx.doi.org/10.1371/journal.pone.0033584] [PMID: 22438954]
[31]
Willebrords, J.; Maes, M.; Crespo Yanguas, S.; Vinken, M. Inhibitors of connexin and pannexin channels as potential therapeutics. Pharmacol. Ther., 2017, 180, 144-160.
[http://dx.doi.org/10.1016/j.pharmthera.2017.07.001] [PMID: 28720428]
[32]
Shibata, M.; Yamasaki, N.; Miyakawa, T.; Kalaria, R.N.; Fujita, Y.; Ohtani, R.; Ihara, M.; Takahashi, R.; Tomimoto, H. Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke, 2007, 38(10), 2826-2832.
[http://dx.doi.org/10.1161/STROKEAHA.107.490151] [PMID: 17761909]
[33]
Hattori, Y.; Enmi, J.; Kitamura, A.; Yamamoto, Y.; Saito, S.; Takahashi, Y.; Iguchi, S.; Tsuji, M.; Yamahara, K.; Nagatsuka, K.; Iida, H.; Ihara, M. A novel mouse model of subcortical infarcts with dementia. J. Neurosci., 2015, 35(9), 3915-3928.
[http://dx.doi.org/10.1523/JNEUROSCI.3970-14.2015] [PMID: 25740520]
[34]
Broadbent, N.J.; Gaskin, S.; Squire, L.R.; Clark, R.E. Object recognition memory and the rodent hippocampus. Learn. Mem., 2009, 17(1), 5-11.
[http://dx.doi.org/10.1101/lm.1650110] [PMID: 20028732]
[35]
Kolling, J.; Longoni, A.; Siebert, C.; Dos Santos, T.M.; Marques, E.P.; Carletti, J.; Pereira, L.O.; Wyse, A.T.S. Severe hyperhomocysteinemia decreases creatine kinase activity and causes memory impairment: Neuroprotective role of creatine. Neurotox. Res., 2017, 32(4), 585-593.
[http://dx.doi.org/10.1007/s12640-017-9767-0] [PMID: 28656547]
[36]
Hosseini, N.; Alaei, H.; Reisi, P.; Radahmadi, M. The effect of treadmill running on passive avoidance learning in animal model of Alzheimer disease. Int. J. Prev. Med., 2013, 4(2), 187-192.
[PMID: 23543475]
[37]
Choi, S.J.; Kim, M.J.; Heo, H.J.; Hong, B.; Cho, H.Y.; Kim, Y.J.; Kim, H.K.; Lim, S.T.; Jun, W.J.; Kim, E.K.; Shin, D.H. Ameliorating effect of Gardenia jasminoides extract on amyloid beta peptide-induced neuronal cell deficit. Mol. Cells, 2007, 24(1), 113-118.
[PMID: 17846505]
[38]
Itoh, J.; Nabeshima, T.; Kameyama, T. Utility of an elevated plus- maze for the evaluation of memory in mice: Effects of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology (Berl.), 1990, 101(1), 27-33.
[http://dx.doi.org/10.1007/BF02253713] [PMID: 2343073]
[39]
Dhingra, D.; Parle, M.; Kulkarni, S.K. Memory enhancing activity of Glycyrrhiza glabra in mice. J. Ethnopharmacol., 2004, 91(2-3), 361-365.
[http://dx.doi.org/10.1016/j.jep.2004.01.016] [PMID: 15120462]
[40]
Dhingra, D.; Kumar, V. Memory-enhancing activity of palmatine in mice using elevated plus maze and morris water maze. Adv. Pharmacol. Sci., 2012, 2012, 357368.
[http://dx.doi.org/10.1155/2012/357368] [PMID: 23193393]
[41]
Higaki, A.; Mogi, M.; Iwanami, J.; Min, L.J.; Bai, H.Y.; Shan, B.S.; Kukida, M.; Kan-No, H.; Ikeda, S.; Higaki, J.; Horiuchi, M. Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning. PLoS One, 2018, 13(2), e0191708.
[http://dx.doi.org/10.1371/journal.pone.0191708] [PMID: 29415035]
[42]
Pahwa, P.; Goel, R.K. Antidepressant-like effect of a standardized hydroethanolic extract of Asparagus adscendens in mice. Indian J. Pharmacol., 2019, 51(2), 98-108.
[http://dx.doi.org/10.4103/ijp.IJP_116_17] [PMID: 31142945]
[43]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[44]
Esterbauer, H.; Cheeseman, K.H. Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal. Methods Enzymol., 1990, 186, 407-421.
[http://dx.doi.org/10.1016/0076-6879(90)86134-H] [PMID: 2233308]
[45]
Cadenas, S.; Rojas, C.; Pérez-Campo, R.; López-Torres, M.; Barja, G. Vitamin E protects guinea pig liver from lipid peroxidation without depressing levels of antioxidants. Int. J. Biochem. Cell Biol., 1995, 27(11), 1175-1181.
[http://dx.doi.org/10.1016/1357-2725(95)00077-3] [PMID: 7584603]
[46]
Mehta, M.; Adem, A.; Sabbagh, M. New acetylcholinesterase inhibitors for Alzheimer’s disease. Int. J. Alzheimers Dis., 2012, 2012, 728983.
[http://dx.doi.org/10.1155/2012/728983] [PMID: 22216416]
[47]
Colović, M.B.; Krstić, D.Z.; Lazarević-Pašti, T.D.; Bondžić, A.M.; Vasić, V.M. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr. Neuropharmacol., 2013, 11(3), 315-335.
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[48]
Seltzer, B. Donepezil: An update. Expert Opin. Pharmacother., 2007, 8(7), 1011-1023.
[http://dx.doi.org/10.1517/14656566.8.7.1011] [PMID: 17472546]
[49]
Farlow, M.; Veloso, F.; Moline, M.; Yardley, J.; Brand-Schieber, E.; Bibbiani, F.; Zou, H.; Hsu, T.; Satlin, A. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer’s disease. BMC Neurol., 2011, 11, 57.
[http://dx.doi.org/10.1186/1471-2377-11-57] [PMID: 21612646]
[50]
Malouf, M.; Grimley, E.J.; Areosa, S.A. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Sys. Rev., 2003, (4), CD004514.
[http://dx.doi.org/10.1002/14651858.CD004514]
[51]
de Koning, E.J.; van der Zwaluw, N.L.; van Wijngaarden, J.P.; Sohl, E.; Brouwer-Brolsma, E.M.; van Marwijk, H.W.; Enneman, A.W.; Swart, K.M.; van Dijk, S.C.; Ham, A.C.; van der Velde, N.; Uitterlinden, A.G.; Penninx, B.W.; Elders, P.J.; Lips, P.; Dhonukshe-Rutten, R.A.; van Schoor, N.M.; de Groot, L.C. Effects of two-year vitamin B12 and folic acid supplementation on depressive symptoms and quality of life in older adults with elevated homocysteine concentrations: Additional results from the B-PROOF study, an RCT. Nutrients, 2016, 8(11), 748.
[http://dx.doi.org/10.3390/nu8110748] [PMID: 27886078]
[52]
Vitamin B12 and cognitive function: An evidence-based analysis. Ont. Health Technol. Assess. Ser., 2013, 13(23), 1-45.
[PMID: 24379897]
[53]
Ford, A.H.; Almeida, O.P. Effect of homocysteine lowering treatment on cognitive function: A systematic review and meta-analysis of randomized controlled trials. J. Alzheimers Dis., 2012, 29(1), 133-149.
[http://dx.doi.org/10.3233/JAD-2012-111739] [PMID: 22232016]
[54]
van der Zwaluw, N.L.; Dhonukshe-Rutten, R.A.; van Wijngaarden, J.P.; Brouwer-Brolsma, E.M.; van de Rest, O.; In 't Veld, P.H. Results of 2-year vitamin B treatment on cognitive performance: Secondary data from an RCT. Neurology, 2014, 83(23), 2158-2166.
[55]
Ozek, C.; Kanoski, S.E.; Zhang, Z.Y.; Grill, H.J.; Bence, K.K. Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling. J. Biol. Chem., 2014, 289(46), 31682-31692.
[http://dx.doi.org/10.1074/jbc.M114.603621] [PMID: 25288805]
[56]
Sun, M.; Izumi, H.; Shinoda, Y.; Fukunaga, K. Neuroprotective effects of protein tyrosine phosphatase 1B inhibitor on cerebral ischemia/reperfusion in mice. Brain Res., 2018, 1694, 1-12.
[http://dx.doi.org/10.1016/j.brainres.2018.04.029] [PMID: 29705606]
[57]
Wilasrusmee, C.; Shah, G.; Kittur, S.; Halverson, A.; Bruch, D.; Kittur, D. Signal transduction pathway in endothelial dysfunction. Surg. Infect. (Larchmt.), 2004, 5(1), 9-14.
[http://dx.doi.org/10.1089/109629604773860255] [PMID: 15142418]
[58]
Verma, A.; Sharma, S. Beneficial effect of protein tyrosine phosphatase inhibitor and phytoestrogen in dyslipidemia-induced vascular dementia in ovariectomized rats. J. Stroke Cerebrovasc. Dis., 2015, 24(11), 2434-2446.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.02.019] [PMID: 26324516]
[59]
Ahmed, H.H. Modulatory effects of vitamin E, acetyl-L-carnitine and α-lipoic acid on new potential biomarkers for Alzheimer’s disease in rat model. Exp. Toxicol. Pathol., 2012, 64(6), 549-556.
[http://dx.doi.org/10.1016/j.etp.2010.11.012] [PMID: 21183322]
[60]
Nestor, P.J.; Fryer, T.D.; Hodges, J.R. Declarative memory impairments in Alzheimer’s disease and semantic dementia. Neuroimage, 2006, 30(3), 1010-1020.
[http://dx.doi.org/10.1016/j.neuroimage.2005.10.008] [PMID: 16300967]
[61]
Machado, S.; Cunha, M.; Minc, D.; Portella, C.E.; Velasques, B.; Basile, L.F.; Cagy, M.; Piedade, R.; Ribeiro, P. Alzheimer’s disease and implicit memory. Arq. Neuropsiquiatr., 2009, 67(2A), 334-342.
[http://dx.doi.org/10.1590/S0004-282X2009000200034] [PMID: 19547837]
[62]
Jahn, H. Memory loss in Alzheimer’s disease. Dialogues Clin. Neurosci., 2013, 15(4), 445-454.
[http://dx.doi.org/10.31887/DCNS.2013.15.4/hjahn] [PMID: 24459411]
[63]
Streck, E.L.; Bavaresco, C.S.; Netto, C.A.; Wyse, A.T. Chronic hyperhomocysteinemia provokes a memory deficit in rats in the Morris water maze task. Behav. Brain Res., 2004, 153(2), 377-381.
[http://dx.doi.org/10.1016/j.bbr.2003.12.013] [PMID: 15265632]
[64]
Chai, G.S.; Jiang, X.; Ni, Z.F.; Ma, Z.W.; Xie, A.J.; Cheng, X.S.; Wang, Q.; Wang, J.Z.; Liu, G.P. Betaine attenuates Alzheimer- like pathological changes and memory deficits induced by homocysteine. J. Neurochem., 2013, 124(3), 388-396.
[http://dx.doi.org/10.1111/jnc.12094] [PMID: 23157378]
[65]
Yang, S.P.; Yang, X.Z.; Cao, G.P. Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells. Mol. Med. Rep., 2015, 12(1), 1145-1150.
[http://dx.doi.org/10.3892/mmr.2015.3490] [PMID: 25776802]
[66]
Burbaeva, G.Sh.; Savushkina, O.K.; Dmitriev, A.D. Brain isoforms of creatine kinase in health and mental diseases: Alzheimer's disease and schizophrenia. Vestn. Ross. Akad. Med. Nauk, 1999, (1), 20-24.
[PMID: 10078058]
[67]
Pirchl, M.; Ullrich, C.; Humpel, C. Differential effects of short- and long-term hyperhomocysteinaemia on cholinergic neurons, spatial memory and microbleedings in vivo in rats. Eur. J. Neurosci., 2010, 32(9), 1516-1527.
[http://dx.doi.org/10.1111/j.1460-9568.2010.07434.x] [PMID: 21044172]
[68]
Dam, K.; Füchtemeier, M.; Farr, T.D.; Boehm-Sturm, P.; Foddis, M.; Dirnagl, U.; Malysheva, O.; Caudill, M.A.; Jadavji, N.M. Increased homocysteine levels impair reference memory and reduce cortical levels of acetylcholine in a mouse model of vascular cognitive impairment. Behav. Brain Res., 2017, 321, 201-208.
[http://dx.doi.org/10.1016/j.bbr.2016.12.041] [PMID: 28087280]
[69]
Carta, A.; Calvani, M. Acetyl-L-carnitine: A drug able to slow the progress of Alzheimer’s disease? Ann. N.Y. Acad. Sci., 1991, 640, 228-232.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb00223.x] [PMID: 1776743]
[70]
Calvani, M.; Carta, A.; Caruso, G.; Benedetti, N.; Iannuccelli, M. Action of acetyl-L-carnitine in neurodegeneration and Alzheimer’s disease. Ann. N.Y. Acad. Sci., 1992, 663, 483-486.
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb38710.x] [PMID: 1482095]
[71]
Traina, G. The neurobiology of acetyl-L-carnitine. Front. Biosci., 2016, 21, 1314-1329.
[http://dx.doi.org/10.2741/4459] [PMID: 27100509]
[72]
Streck, E.L.; Vieira, P.S.; Wannmacher, C.M.; Dutra-Filho, C.S.; Wajner, M.; Wyse, A.T. In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. Metab. Brain Dis., 2003, 18(2), 147-154.
[http://dx.doi.org/10.1023/A:1023815119931] [PMID: 12822833]
[73]
Kim, S.H.; Kim, K.; Ahn, J.H.; Chang, H.K. Increased expression of tumor necrosis factor-alpha in the rat hippocampus after acute homocysteine administration. J. Epilepsy Res., 2011, 1(1), 6-12.
[http://dx.doi.org/10.14581/jer.11002] [PMID: 24649438]

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Request history8.2.27PHP Version306msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[02:55:55] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[02:55:55] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[02:55:55] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
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  • Application (172ms)time
  • 1 x Application (56.33%)
    172ms
    1 x Booting (43.67%)
    134ms
    12 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
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    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
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    app/Http/Controllers/ArticleController.php:1974-2510
    35 statements were executed, 2 of which were duplicates, 33 unique. Show only duplicated87.59ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
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      1.34msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316604151','/article/119311',1,1739847355,1739847355)
      1.05msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316604151 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316604151) limit 1
      16.53msalphaeurekaselec_live_10_06_2022UserAccess.php#784
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      • 0: 316604151
      • 1: 316604151
      • 2: 316604151
      • 3: 316604151
      • 4: 316604151
      • 5: 316604151
      • 6: 316604151
      • 7: 316604151
      • 8: 316604151
      • 9: 316604151
      • 10: 316604151
      • 11: 316604151
      • 12: 316604151
      • 13: 316604151
      • 14: 316604151
      • 15: 316604151
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=119311
      810μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 72 limit 1
      710μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 72
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=72) and sj.journal_id!=72 group by `j`.`nid`) as `aggregate_table`
      590μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=72) and sj.journal_id!=72 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      490μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=72) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      780μsalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=72) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      620μsalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '119311'
      310μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 119311
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '119311'
      2.08msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 119311
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '119311' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.16msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 119311
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      230μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      410μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 72 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      29.58msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 72 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      3.65msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 72 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      2.74msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 119311 limit 1
      190μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 119311
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 119311 and content_type = 'article' order by status desc limit 1
      200μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 198691 limit 1
      160μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 198691
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      190μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'DML' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      240μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: DML
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '119311' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      320μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '11117' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      270μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2750' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      250μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2750) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2750) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2750)
      16.77msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11117) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11117) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11117)
      600μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 119311) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 119311) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316604151 and j.to_ip >=316604151 )) and ((j.from_date <= 1739847355 and j.to_date >= 1739847355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 119311)
      540μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '219' and is_uploaded = 1 and issue_id = 11117 order by cast(first_page as SIGNED) desc limit 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 219
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '231' and is_uploaded = 1 and issue_id = 11117 order by cast(first_page as SIGNED) asc limit 1
      370μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 231
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      150μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      180μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 119311 limit 1
      2.35msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 119311
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 72 and `b`.`banner_from_date` <= 1739847355 and `b`.`banner_to_date` >= 1739847355 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.08msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 72
      • 3: 1739847355
      • 4: 1739847355
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='f3b33d45c6d2b4929ed81353c45e4dc2'
      190μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        byWdbmMTGdlWDdFd3OjWn4qZDmTBf2JuxsfJzEco
        uc_cart_id
        f3b33d45c6d2b4929ed81353c45e4dc2
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/119311" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/119311
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
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