Seismically detected cratering on Mars: Enhanced recent impact flux?

Seismic observations of impacts on Mars indicate a higher impact flux than previously measured. Using six confirmed seismic impact detections near the NASA InSight lander and two distant large impacts, we calculate appropriate scalings to compare these rates with lunar-based chronology models. We also update the impact rate from orbital observations using the most recent catalog of new craters on Mars. The snapshot of the current impact rate at Mars recorded seismically is higher than that found using orbital detections alone. The measured rates differ between a factor of 2 and 10, depending on the diameter, although the sample size of seismically detected impacts is small. The close timing of the two largest new impacts found on Mars in the past few decades indicates either a heightened impact rate or a low-probability temporal coincidence, perhaps representing recent fragmentation of a parent body. We conclude that seismic methods of detecting current impacts offer a more complete dataset than orbital imaging.

Neurotoxicity of crack cocaine exposure: evidence from a systematic review of in vitro and in vivo studies.

Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use. Nevertheless, few experimental studies attempted to verify the neurotoxicity after crack cocaine exposure, especially when compared with other routes of cocaine administration. This systematic review aimed to verify whether in vitro and/or in vivo crack cocaine exposure is more neurotoxic than cocaine exposure (snorted or injected). A search was performed in the PubMed, EMBASE, Scopus, Web of Science, and LILACS databases for in vitro and in vivo toxicological studies conducted with either rats or mice, with no distinction with regard to sex or age. Other methods including BioRxiv, BDTD, Academic Google, citation searching, and specialist consultation were also adopted. Two independent investigators screened the titles and abstracts of retrieved studies and subsequently performed full-text reading and data extraction. The quality of the included studies was assessed by the Toxicological data Reliability assessment Tool (ToxRTool). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022332250). Of the twelve studies included, three were in vitro and nine were in vivo studies. According to the ToxRTool, most studies were considered reliable either with or without restrictions, with no one being considered as not reliable. The studies found neuroteratogenic effects, decreased threshold for epileptic seizures, schizophrenic-like symptoms, and cognitive deficits to be associated with crack cocaine exposure. Moreover, both in vitro and in vivo studies reported a worsening in cocaine neurotoxic effect caused by the anhydroecgonine methyl ester (AEME), a cocaine main pyrolysis product, which is in line with the more aggressive pattern of crack cocaine use. This systematic review suggests that crack cocaine exposure is more neurotoxic than other routes of cocaine administration. However, before the scarcity of studies on this topic, further toxicological studies are necessary.

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine.

Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine-induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.

Prenatal caffeine consumption and neurobehavioral disorders - A systematic review.

Studies have suggested associations between gestational exposure to caffeine and adverse outcomes, however the evidence is still limited. Therefore, a systematic review was conducted to investigate the association between prenatal caffeine exposure and neurobehavioral disorders. The MEDLINE (PubMed), EMBASE, Scopus, Web of Science, and LILACS databases were searched. Observational studies involving women with documented caffeine consumption during pregnancy were eligible for inclusion. The outcomes evaluated were behavioral and intellectual development, Attention Deficit Hyperactivity Disorder, and related behaviors. The data were analyzed by qualitative synthesis. The ROBINS-I tool was employed to assess the risk of bias, and the certainty of evidence was evaluated using GRADE (PROSPERO: CRD42023421164). The search yielded fourteen studies that met the inclusion/exclusion criteria. The sample size among pregnant women ranged from 173 to 64,189, and among children ranged from 88 to 49,190. Maternal caffeine consumption during pregnancy ranged from 0 to 1000 mg/day, with the highest levels observed during mid-pregnancy. Seven studies indicated a potential association between prenatal caffeine exposure and neurobehavioral/neurodevelopment deficits, one study showed that prenatal caffeine exposure improved peer problems, and six studies did not show a significant effect of prenatal caffeine consumption on neurobehavioral disorders. The included studies were classified as moderate for the risk of bias and with very low certainty of evidence. Thus, the evidence is insufficient to confirm with certainty that the prenatal caffeine exposure leads to neurobehavioral disorders. Studies heterogenicity, as well as their variable quality and the presence of several confounding factors, generate uncertainty.

Geophysical evidence for an enriched molten silicate layer above Mars's core.

The detection of deep reflected S waves on Mars inferred a core size of 1,830 ± 40 km (ref. 1), requiring light-element contents that are incompatible with experimental petrological constraints. This estimate assumes a compositionally homogeneous Martian mantle, at odds with recent measurements of anomalously slow propagating P waves diffracted along the core-mantle boundary2. An alternative hypothesis is that Mars's mantle is heterogeneous as a consequence of an early magma ocean that solidified to form a basal layer enriched in iron and heat-producing elements. Such enrichment results in the formation of a molten silicate layer above the core, overlain by a partially molten layer3. Here we show that this structure is compatible with all geophysical data, notably (1) deep reflected and diffracted mantle seismic phases, (2) weak shear attenuation at seismic frequency and (3) Mars's dissipative nature at Phobos tides. The core size in this scenario is 1,650 ± 20 km, implying a density of 6.5 g cm-3, 5-8% larger than previous seismic estimates, and can be explained by fewer, and less abundant, alloying light elements than previously required, in amounts compatible with experimental and cosmochemical constraints. Finally, the layered mantle structure requires external sources to generate the magnetic signatures recorded in Mars's crust.

First observations of core-transiting seismic phases on Mars.

We present the first observations of seismic waves propagating through the core of Mars. These observations, made using seismic data collected by the InSight geophysical mission, have allowed us to construct the first seismically constrained models for the elastic properties of Mars' core. We observe core-transiting seismic phase SKS from two farside seismic events detected on Mars and measure the travel times of SKS relative to mantle traversing body waves. SKS travels through the core as a compressional wave, providing information about bulk modulus and density. We perform probabilistic inversions using the core-sensitive relative travel times together with gross geophysical data and travel times from other, more proximal, seismic events to seek the equation of state parameters that best describe the liquid iron-alloy core. Our inversions provide constraints on the velocities in Mars' core and are used to develop the first seismically based estimates of its composition. We show that models informed by our SKS data favor a somewhat smaller (median core radius = 1,780 to 1,810 km) and denser (core density = 6.2 to 6.3 g/cm3) core compared to previous estimates, with a P-wave velocity of 4.9 to 5.0 km/s at the core-mantle boundary, with the composition and structure of the mantle as a dominant source of uncertainty. We infer from our models that Mars' core contains a median of 20 to 22 wt% light alloying elements when we consider sulfur, oxygen, carbon, and hydrogen. These data can be used to inform models of planetary accretion, composition, and evolution.

Gestational lead exposure and its effects on fetal/infant development - A systematic review.

Studies suggest that gestational exposure to lead (Pb) is related to spontaneous abortions, preterm birth, lower infant birth weight and length, and neurological dysfunctions. However, the evidence about its effects during pregnancy exposure on fetal and child development is still poor. Thus, the aim of this systematic review was to verify the association between prenatal exposure to Pb and the occurrence of neurobehavioral deficits, miscarriages, and child mortality. Observational studies with pregnant women exposed to Pb during pregnancy were included, without gender or ethnicity restrictions. The MEDLINE, Cochrane Library, EMBASE, Scopus, Web of Science, and LILACS databases were searched. The reading of titles and abstracts was conducted, followed by reading in full format and data extraction, that were performed independently by two reviewers. The included studies were evaluated by Downs and Black tool and qualitatively synthesized. Certainty of evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluations (GRADE). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022296750). Among twenty-one studies included, sixteen were classified as prospective cohort, two case-control, one nested case-control, one cohort, and one longitudinal study. No study that evaluated child mortality associated with gestational Pb exposure was found. There is a very low certainty of evidence in the association of gestational Pb exposure and neurobehavioral deficits or miscarriages. This systematic review reflects the poor evidence and the challenges of human toxicology studies, since it was not possible to associate gestational Pb exposure to neurobehavioral deficits, miscarriages, and child mortality.

Neurotoxicity Assessment of 1-[(2,3-Dihydro-1-Benzofuran-2-yl)Methyl]Piperazine (LINS01 Series) Derivatives and their Protective Effect on Cocaine-Induced Neurotoxicity Model in SH-SY5Y Cell Culture.

Excessive levels of dopamine in the synaptic cleft, induced by cocaine for example, activates dopaminergic receptors, mainly D1R, D2R, and D3R subtypes, contributing to neurotoxic effects. New synthetic 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine derivatives (the LINS01 compounds), designed as histaminergic receptor (H3R) ligands, are also dopaminergic receptor ligands, mainly D2R and D3R. This study aims to evaluate the neurotoxicity of these new synthetic LINS01 compounds (LINS01003, LINS01004, LINS01011, and LINS01018), as well as to investigate their protective potential on a cocaine model of dopamine-induced neurotoxicity using SH-SY5Y cell line culture. Neurotoxicity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and automated cell counting with fluorescent dyes (acridyl orange and propidium iodide) assays. Concentration-response curves (CRCs) were performed for all LINS compounds and cocaine using MTT assay. The results show that LINS series did not decrease cell viability after 48h of exposure-except for 100 µM LINS01018, which was discontinued from the study. Likewise, MTT, LDH, and fluorescent dyes staining showed no difference is cell viability for LINS compounds at 10 µM. When incubated with 2.5 mM cocaine (lethal concentration 50) for 48h, 10 µM of each LINS compound, metoclopramide (D2R antagonist) and haloperidol (D2R/D3R antagonist), ameliorated cocaine-induced neurotoxicity. However, only metoclopramide, haloperidol, and LINS01011 compound significantly decreased LDH released in the culture medium, suggesting that this new synthetic compound presents a more robust effect. This preliminary in vitro neurotoxicity study suggests that LINS01 compounds are not neurotoxic, and that they play a promising role in preventing cocaine-induced neurotoxicity.

Nicotine exposure through breastfeeding affects brain-derived neurotrophic factor and synaptic proteins levels in the brain of stressed adult female mice.

Nicotine has been used during pregnancy and lactation as a tobacco harm reduction strategy. However, it is unclear whether nicotine exposure during a critical development period negatively impacts stress responses in adulthood. This study investigated how nicotine, administered via breastfeeding, affects the brain-derived neurotrophic factor (BDNF), synaptic proteins levels, and anxiety-like behavior in adult female mice subjected to stress. Female Swiss mice were exposed to saline or nicotine (8 mg/kg/day) through breastfeeding between their fourth and 17th postnatal days (P) via implanted osmotic mini pumps. The unpredictable chronic mild stress (UCMS) protocol was performed during their adulthood (P65) for 10 consecutive days, followed by the elevated plus maze (EPM) test 1 day after the protocol. Animals were euthanized and their blood, collected for plasma corticosterone measurements and their brain structures, dissected for BDNF and synaptic proteins analyses. We found no significant differences in corticosterone levels between groups (Saline/Non-stress, Nicotine/Non-stress, Saline/Stress, and Nicotine/Stress). The UCMS protocol hindered weight gain. Mice exposed to nicotine through breastfeeding with or without the UCMS protocol in adulthood showed higher grooming and head dipping frequency; decreased BDNF levels in cerebellum and striatum; increased postsynaptic density protein 95 (PSD-95), synapsin I, and synaptophysin levels in cerebellum; and decreased PSD-95 and synapsin I levels in brainstem. Our results indicate that nicotine exposure through breastfeeding leads to long-lasting behavioral effects and synaptic protein changes, most of which were independent of the UCMS protocol, even after a long nicotine-free period, highlighting the importance of further studies on nicotine exposure during development.

Chronic escalating-dose and acute binge cocaine treatments change the hippocampal cholinergic muscarinic system on drug presence and after withdrawal.

Cocaine addiction is a relapsing disorder with loss of control in limiting drug intake. Considering the involvement of acetylcholine in the neurobiology of the disease, our aim was to evaluate whether cocaine induces plastic changes in the hippocampal cholinergic muscarinic system. Male Swiss-Webster mice received saline or cocaine (ip) three times daily (60-min intervals) either acutely or in an escalating-dose binge paradigm for 14 days. Locomotor activity was measured in all treatment days. Dopaminergic and cholinergic muscarinic receptors (D1R, D2R, M1-M5, mAChRs), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) were quantified in the hippocampus by immunoblotting one hour after the last injection (on drug) or after 14 days of abstinence (withdrawal). Escalating-dose group showed cocaine-induced locomotor sensitization from day 2. M3 mAChR and ChAT significantly increased after the on-drug acute binge treatment. Escalating-dose on-drug group showed increased ChAT, M1, M5 mAChR and D2R; and decreased D1R. Acute-binge withdrawal group showed increased VAChT, M2 mAChR, D1R, and D2R; and decreased M1 mAChR. Escalating-dose withdrawal group presented increased D1R and VAChT and decreased M1 mAChR and D2R. Locomotor activity was negatively correlated with M1 mAChR and AChE in on-drug group and positively correlated with VAChT in withdrawal group. M1 mAChR was positively correlated with M2 mAChR and ChAT in on-drug group, whereas ChAT was positively correlated with M5 mAChR in withdrawal group. The results indicate that cocaine induced an increase in the hippocampal cholinergic tone in the presence of the drug, whereas withdrawal causes a resetting in the system.

Ayahuasca, a psychedelic beverage, modulates neuroplasticity induced by ethanol in mice.

Alcohol use disorder needs more effective treatments because relapse rates remain high. Psychedelics, such as ayahuasca, have been used to treat substance use disorders. Our study aimed to evaluate the effects of ayahuasca on ethanol-induced behavioral sensitization (EIBS). Swiss mice received 2.2 g/kg ethanol or saline IP injections every other day across nine days (D1, D3, D5, D7, and D9), and locomotor activity was evaluated 10 min after each injection. Then, animals were treated daily with ayahuasca (corresponding to 1.76 mg/kg of N,N-dimethyltryptamine, DMT) or water by oral gavage for eight consecutive days. On the seventh day, mice were evaluated in the elevated plus maze. Then, mice were challenged with a single dose of ethanol to measure their locomotor activity. Dopamine receptors, serotonin receptors, dynorphin, and prodynorphin levels were quantified in the striatum and hippocampus by blot analysis. Repeated ethanol administration resulted in EIBS. However, those animals treated with ayahuasca had an attenuated EIBS. Moreover, ayahuasca reduced the anxiogenic response to ethanol withdrawal and prevented the ethanol-induced changes on 5-HT1a receptor and prodynorphin levels in the hippocampus and reduced ethanol effects in the dynorphin/prodynorphin ratio levels in the striatum. These results suggest a potential application of ayahuasca to modulate the neuroplastic changes induced by ethanol.

Marsquake Locations and 1-D Seismic Models for Mars From InSight Data.

We present inversions for the structure of Mars using the first Martian seismic record collected by the InSight lander. We identified and used arrival times of direct, multiples, and depth phases of body waves, for 17 marsquakes to constrain the quake locations and the one-dimensional average interior structure of Mars. We found the marsquake hypocenters to be shallower than 40 km depth, most of them being located in the Cerberus Fossae graben system, which could be a source of marsquakes. Our results show a significant velocity jump between the upper and the lower part of the crust, interpreted as the transition between intrusive and extrusive rocks. The lower crust makes up a significant fraction of the crust, with seismic velocities compatible with those of mafic to ultramafic rocks. Additional constraints on the crustal thickness from previous seismic analyses, combined with modeling relying on gravity and topography measurements, yield constraints on the present-day thermochemical state of Mars and on its long-term history. Our most constrained inversion results indicate a present-day surface heat flux of 22 ± 1 mW/m2, a relatively hot mantle (potential temperature: 1740 ± 90 K) and a thick lithosphere (540 ± 120 km), associated with a lithospheric thermal gradient of 1.9 ± 0.3 K/km. These results are compatible with recent seismic studies using a reduced data set and different inversion approaches, confirming that Mars' potential mantle temperature was initially relatively cold (1780 ± 50 K) compared to that of its present-day state, and that its crust contains 10-12 times more heat-producing elements than the primitive mantle.

A Reconstruction Algorithm for Temporally Aliased Seismic Signals Recorded by the InSight Mars Lander.

In December 2018, the NASA InSight lander successfully placed a seismometer on the surface of Mars. Alongside, a hammering device was deployed at the landing site that penetrated into the ground to attempt the first measurements of the planetary heat flow of Mars. The hammering of the heat probe generated repeated seismic signals that were registered by the seismometer and can potentially be used to image the shallow subsurface just below the lander. However, the broad frequency content of the seismic signals generated by the hammering extends beyond the Nyquist frequency governed by the seismometer's sampling rate of 100 samples per second. Here, we propose an algorithm to reconstruct the seismic signals beyond the classical sampling limits. We exploit the structure in the data due to thousands of repeated, only gradually varying hammering signals as the heat probe slowly penetrates into the ground. In addition, we make use of the fact that repeated hammering signals are sub-sampled differently due to the unsynchronized timing between the hammer strikes and the seismometer recordings. This allows us to reconstruct signals beyond the classical Nyquist frequency limit by enforcing a sparsity constraint on the signal in a modified Radon transform domain. In addition, the proposed method reduces uncorrelated noise in the recorded data. Using both synthetic data and actual data recorded on Mars, we show how the proposed algorithm can be used to reconstruct the high-frequency hammering signal at very high resolution.

Thickness and structure of the martian crust from InSight seismic data.

A planet's crust bears witness to the history of planetary formation and evolution, but for Mars, no absolute measurement of crustal thickness has been available. Here, we determine the structure of the crust beneath the InSight landing site on Mars using both marsquake recordings and the ambient wavefield. By analyzing seismic phases that are reflected and converted at subsurface interfaces, we find that the observations are consistent with models with at least two and possibly three interfaces. If the second interface is the boundary of the crust, the thickness is 20 ± 5 kilometers, whereas if the third interface is the boundary, the thickness is 39 ± 8 kilometers. Global maps of gravity and topography allow extrapolation of this point measurement to the whole planet, showing that the average thickness of the martian crust lies between 24 and 72 kilometers. Independent bulk composition and geodynamic constraints show that the thicker model is consistent with the abundances of crustal heat-producing elements observed for the shallow surface, whereas the thinner model requires greater concentration at depth.

Seismic detection of the martian core.

Clues to a planet's geologic history are contained in its interior structure, particularly its core. We detected reflections of seismic waves from the core-mantle boundary of Mars using InSight seismic data and inverted these together with geodetic data to constrain the radius of the liquid metal core to 1830 ± 40 kilometers. The large core implies a martian mantle mineralogically similar to the terrestrial upper mantle and transition zone but differing from Earth by not having a bridgmanite-dominated lower mantle. We inferred a mean core density of 5.7 to 6.3 grams per cubic centimeter, which requires a substantial complement of light elements dissolved in the iron-nickel core. The seismic core shadow as seen from InSight's location covers half the surface of Mars, including the majority of potentially active regions-e.g., Tharsis-possibly limiting the number of detectable marsquakes.

Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner.

Crack cocaine users are simultaneously exposed to volatilized cocaine and to its main pyrolysis product, anhydroecgonine methyl ester (AEME). Although the neurotoxic effects of cocaine have been extensively studied, little is known about AEME or its combination. We investigated cell death processes using rat primary hippocampal cells exposed to cocaine (2 mM), AEME (1 mM) and their combination (C + A), after 1, 3, 6 and 12 h. Cocaine increased LC3 I after 6 h and LC3 II after 12 h, but reduced the percentage of cells with acid vesicles, suggesting failure in the autophagic flux, which activated the extrinsic apoptotic pathway after 12 h. AEME neurotoxicity did not involve the autophagic process; rather, it activated caspase-9 after 6 h and caspase-8 after 12 h leading to a high percentage of cells in early apoptosis. C + A progressively reduced the percentage of undamaged cells, starting after 3 h; it activated both apoptotic pathways after 6 h, and was more neurotoxic than cocaine and AEME alone. Also, C + A increased the phosphorylation of p62 after 12 h, but there was little difference in LC3 I or II, and a small percentage of cells with acid vesicles at all time points investigated. In summary, the present study provides new evidence for the neurotoxic mechanism and timing response of each substance alone and in combination, indicating that AEME is more than just a biological marker for crack cocaine consumption, as it may intensify and hasten cocaine neurotoxicity.

Protective effects of luteolin on the venous endothelium.

Luteolin is a flavonoid with antioxidant properties already demonstrated in studies related to inflammation, tumor, and cardiovascular processes; however, there are no available information regarding its antioxidant effects at the venous endothelial site. We investigated the effects of luteolin (10, 20, and 50 µmol/L) in cultures of rat venous endothelial cells. Nitric oxide (NO) and reactive oxygen species (ROS) were analyzed by fluorimetry; 3-nitrotyrosine (3-NT) residues were evaluated by immunofluorescence, and prostacyclin (PGI2) release was investigated by colorimetry. Intracellular NO levels were significantly enhanced after 10 min of luteolin incubation, with a parallel decrease in ROS generation. These results were accompanied by a significant reduction in the expression of 3-NT residues and enhanced PGI2 rates. Therefore, luteolin is effective in reducing ROS thereby improving NO availability in venous endothelial cells. Besides, luteolin-induced decrease in 3-NT residues may correlate with the enhancement in endothelial PGI2 bioavailability. These findings suggest the future application of this flavonoid as a protective agent by improving endothelial function in several circulatory disorders related to venous insufficiency.

COVID-19 Pandemic - A Narrative Review of the Potential Roles of Chloroquine and Hydroxychloroquine.

BACKGROUND: Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used against malaria, rheumatism, inflammation in the joints, lupus, among others. These drugs showed positive results in preliminary scientific research for treatment of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Since the studies with CQ and HCQ are initial with small patient populations, it is not yet known whether there are adverse effects from the use of CQ and HCQ for patients infected with the coronavirus. OBJECTIVES: The aim of this study was to evaluate the evidence regarding the efficacy and safety of CQ and HCQ used against viral infection caused by SARS-CoV-2. STUDY DESIGN: This is a narrative review of the traditional prescriptions of CQ and HCQ efficacy and adverse effects as well as their employment for coronavirus disease 2019 (COVID-19). SETTING: In vitro and clinical studies comparing the antiviral efficacy and adverse effect profile of CQ and HCQ against COVID-19 in adult patients were evaluated. METHODS: A systemic search of reviews, including in vitro and clinical trial studies in English focusing on CQ and HCQ effects and adverse effects against COVID-19 in the adult patient population from PubMed was performed. It included studies reporting chloroquine and hydroxychloroquine effects and adverse effects against COVID-19. RESULTS: A total of 42 articles published between 2004 and April 2020 were reviewed for therapeutic use of CQ and HCQ. Both these drugs showed a significant in vitro potential against coronavirus. Many studies for clinical use of CQ and HCQ showed that patients presented adverse reactions on high doses. LIMITATIONS: Clinical studies have some methodology shortcomings, such as lack of information about the treatment and small number of experimental patients, leading to a misinterpretation of the data. Besides, there are few clinical studies with a limited sample size. Moreover, most of them did not present control groups, and some patients had died during these protocols. DISCUSSION: Despite both CQ and HCQ in vitro antiviral evidence, clinically, both drugs, either alone or combined with other medications, may increase the risk of cardiac arrhythmias, leading to cardiac arrest and sudden death. Besides, a lot of uncertainty still remains, such as starting administration period, dose prescribed, length of treatment, patients' condition, concomitant drug use, among others. CONCLUSION: From the studies reviewed, it is not possible to state the precise efficacy and safety of CQ and HCQ use in the treatment of COVID-19 at any time in the course of the disease. Future studies are warranted.

Anhydroecgonine methyl ester (AEME), a cocaine pyrolysis product, impairs glutathione-related enzymes response and increases lipid peroxidation in the hippocampal cell culture.

Crack cocaine smokers inhale, alongside with cocaine, its pyrolysis product, anhydroecgonine methyl ester (AEME). We have previously described AEME neurotoxic effect and its additive effect when co-incubated with cocaine. Our aim was to evaluate, the effect of AEME, cocaine and AEME-cocaine combination on glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities after 3 and 6 h of exposure, periods previous to neuronal death. Lipid peroxidation was evaluated through malonaldehyde (MDA) levels at 3, 6, 24 and 48 h of exposure. All treated groups reduced neuronal viability after 24 h of exposure. AEME and cocaine decreased GPx, GR and GST activities after 3 and 6 h, with an increase in MDA levels after 48 h. AEME-cocaine combination decreased the enzymes activities after 3 and 6 h, showing an additive effect in MDA levels after 48 h. These data show that the glutathione-related enzymes imbalance caused by AEME, cocaine or AEME-cocaine combination exposure preceded neuronal death and lipid peroxidation. Moreover, the additive effect on lipid peroxidation observed with AEME-cocaine exposure after 48 h, suggest a higher neurotoxic effect after crack cocaine use when compared to cocaine alone.