Criminalistic Institute of Sao Paulo

São Paulo, Brazil

Criminalistic Institute of Sao Paulo

São Paulo, Brazil
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Garcia R.C.T.,University of Sao Paulo | Garcia R.C.T.,Federal University of São Paulo | Garcia R.C.T.,Federal University of Alfenas | Garcia R.C.T.,Criminalistic Institute of Sao Paulo | And 7 more authors.
Toxicology | Year: 2017

Crack cocaine has a high potential to induce cocaine addiction and its smoke contains cocaine's pyrolysis product anhydroecgonine methyl ester (AEME), a partial agonist at M1- and M3-muscarinic acetylcholine receptor and an antagonist at the remaining subtypes. No reports have assessed AEME's role in addiction. Adult male Wistar rats were intraperitoneally administered with saline, 3 mg/kg AEME, 15 mg/kg cocaine, or a cocaine-AEME combination on every other day during a period of 9 days. After a 7-days withdrawal period, a challenge injection of the respective drugs was performed on the 17th day. The locomotor activity was evaluated on days 1, 3, 5, 7, 9 and 17, as well as dopamine levels (9th day) and dopaminergic receptors proteins (D1R and D2R on the 17th day) in the caudate-putamen (CPu) and nucleus accumbens (NAc). AEME was not able to induce the expression of behavioral sensitization, but it substantially potentiates cocaine-effects, with cocaine-AEME combination presenting higher expression than cocaine alone. An increase in the dopamine levels in the CPu in all non-saline groups was observed, with the highest levels in the cocaine-AEME group. There was a decrease in D1R protein level in this brain region only for cocaine and cocaine-AEME groups. In the NAc, an increase in the dopamine levels was only observed for cocaine and cocaine-AEME groups, with no changes in both D1R and D2R protein levels. These behavioral and neurochemical data indicate that AEME alone does not elicit behavioral sensitization but it significantly potentiates cocaine effects when co-administered, resulting in dopamine increase in CPu and NAc, brain regions where dopamine release is mediated by cholinergic activity. © 2016 Elsevier Ireland Ltd


Garcia R.C.T.,University of Sao Paulo | Dati L.M.M.,University of Sao Paulo | Fukuda S.,University of Sao Paulo | Torres L.H.L.,University of Sao Paulo | And 11 more authors.
Toxicological Sciences | Year: 2012

Smoking crack cocaine involves the inhalation of cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). Although there is evidence that cocaine is neurotoxic, the neurotoxicity of AEME has never been evaluated. AEME seems to have cholinergic agonist properties in the cardiovascular system; however, there are no reports on its effects in the central nervous system. The aim of this study was to investigate the neurotoxicity of AEME and its possible cholinergic effects in rat primary hippocampal cell cultures that were exposed to different concentrations of AEME, cocaine, and a cocaine-AEME combination. We also evaluated the involvement of muscarinic cholinergic receptors in the neuronal death induced by these treatments using concomitant incubation of the cells with atropine. Neuronal injury was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The results of the viability assays showed that AEME is a neurotoxic agent that has greater neurotoxic potential than cocaine after 24 and 48 h of exposure. We also showed that incubation for 48 h with a combination of both compounds in equipotent concentrations had an additive neurotoxic effect. Although both substances decreased cell viability in the MTT assay, only cocaine increased LDH release. Caspase-3 activity was increased after 3 and 6 h of incubation with 1mM cocaine and after 6 h of 0.1 and 1.0mM AEME exposure. Atropine prevented the AEME-induced neurotoxicity, which suggests that muscarinic cholinergic receptors are involved in AEME's effects. In addition, binding experiments confirmed that AEME has an affinity for muscarinic cholinergic receptors. Nevertheless, atropine was not able to prevent the neurotoxicity produced by cocaine and the cocaine-AEME combination, suggesting that these treatments activated other neuronal death pathways. Our results suggest a higher risk for neurotoxicity after smoking crack cocaine than after cocaine use alone. The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.


Lanaro R.,University of Campinas | Calemi D.B.A.,Criminalistic Institute of Sao Paulo | Togni L.R.,Criminalistic Institute of Sao Paulo | Costa J.L.,University of Campinas | And 3 more authors.
Journal of Psychoactive Drugs | Year: 2015

Abstract: The ritualistic use of ayahuasca is becoming a global phenomenon. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The recreational use of similar alkaloids and N,N-dimethyltryptamine has increased in recent years, mainly because of their hallucinogenic effects. In the present study, the concentrations of psychoactive alkaloids in three powder samples seized by the São Paulo State Police and nine ayahuasca aqueous extracts were analyzed by HPLC-DAD in an attempt to distinguish between illicit drugs and the religious beverage. The alkaloids detected (μg/mL) in the ayahuasca aqueous extracts were N,N-dimethyltryptamine (402–2070.3), harmaline (27.5–181.3), harmine (294.5–2893.8), and tetrahydroharmine (849.5–2052.5), whereas, of the three powder samples, one contained only N,N-dimethyltryptamine (82% and 2% w/w, respectively) while the other contained only harmaline (16%, w/w) and harmine (12%, w/w). The ritualistic use of ayahuasca involves oral intake and the probability of overdose is minimized by serotonergic stimulation of vagal pathways, leading to vomiting and diarrhea. In contrast, the recreational use of N,N-dimethyltryptamine involves consumption mainly by smoking or inhalation, both of which markedly increase its bioavailability and the potential for intoxications. © , Copyright © Taylor & Francis Group, LLC.


Resende R.R.,Federal University of Minas Gerais | Resende R.R.,Institute Ensino E Pesquisa Santa Casa Of Bh Iscm Bh | Da Costa J.L.,Criminalistic Institute of Sao Paulo | Da Costa J.L.,University of Sao Paulo | And 4 more authors.
Stem Cells and Development | Year: 2010

Changes in intracellular Ca2+ concentration ([Ca 2+]i) play a central role in neuronal differentiation. However, Ca2+ signaling in this process remains poorly understood and it is unknown whether embryonic and adult stem cells share the same signaling pathways. To clarify this issue, neuronal differentiation was analyzed in two cell lines: embryonic P19 carcinoma stem cells (CSCs) and adult murine bone-marrow mesenchymal stem cells (MSC). We studied Ca2+ release from the endoplasmic reticulum via intracellular ryanodine-sensitive (RyR) and IP3-sensitive (IP3R) receptors. We observed that caffeine, a RyR agonist, induced a [Ca2+]i response that increased throughout neuronal differentiation. We also demonstrated a functional coupling between RyRs and L- but not with N-, P-, or Q-type Cav1 Ca 2+ channels, both in embryonal CSC and adult MSC. We also found that agonists of L-type channels and of RyRs increase neurogenesis and neuronal differentiation, while antagonists of these channels have the opposite effect. Thus, our data demonstrate that in both cell lines RyRs control internal Ca 2+ release following voltage-dependent Ca2+ entry via L-type Ca2+ channels. This study shows that both in embryonal CSC and adult MSC [Ca2+]i is controlled by a common pathway, indicating that coupling of L-type Ca2+ channels and RyRs may be a conserved mechanism necessary for neuronal differentiation. © Mary Ann Liebert, Inc. 2010.


Lanaro R.,University of Campinas | Costa J.L.,University of Campinas | Costa J.L.,Criminalistic Institute of Sao Paulo | Cazenave S.O.S.,Criminalistic Institute of Sao Paulo | And 4 more authors.
Journal of Forensic Sciences | Year: 2015

In this work, two methods were developed to determine herbicides paraquat, glyphosate, and aminomethylphosphonic acid (AMPA) in marijuana samples by capillary electrophoresis. For paraquat analysis, sample was extracted with aqueous acetic acid solution and analyzed by capillary zone electrophoresis with direct UV detection. The running electrolyte was 50 mmol/L phosphate buffer (pH 2.50). For glyphosate and AMPA, indirect UV/VIS detection was used, as these substances do not present chromophoric groups. Samples were extracted with 5 mmol/L hydrochloric acid. The running electrolyte was 10 mmol/L gallic acid, 6 mmol/L TRIS, and 0.1 mmol/L CTAB (pH = 4.7). The methods presented good linearity, precision, accuracy, and recovery. Paraquat was detected in 12 samples (n = 130), ranging from 0.01 to 25.1 mg/g. Three samples were positive for glyphosate (0.15-0.75 mg/g), and one sample presented AMPA as well. Experimental studies are suggested to evaluate the risks of these concentrations to marijuana user. © 2014 American Academy of Forensic Sciences.


PubMed | Criminalistic Institute of Sao Paulo, Butantan Institute, Federal University of São Paulo, University of Sao Paulo and Federal University of Alfenas
Type: | Journal: Toxicology | Year: 2016

Crack cocaine has a high potential to induce cocaine addiction and its smoke contains cocaines pyrolysis product anhydroecgonine methyl ester (AEME), a partial agonist at M


PubMed | Criminalistic Institute of Sao Paulo, Butantan Institute, Vanderbilt University, Southern Cross University of Brazil and University of Sao Paulo
Type: | Journal: Scientific reports | Year: 2015

The smoke of crack cocaine contains cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). AEME possesses greater neurotoxic potential than cocaine and an additive effect when they are combined. Since atropine prevented AEME-induced neurotoxicity, it has been suggested that its toxic effects may involve the muscarinic cholinergic receptors (mAChRs). Our aim is to understand the interaction between AEME and mAChRs and how it can lead to neuronal death. Using a rat primary hippocampal cell culture, AEME was shown to cause a concentration-dependent increase on both total [(3)H]inositol phosphate and intracellular calcium, and to induce DNA fragmentation after 24hours of exposure, in line with the activation of caspase-3 previously shown. Additionally, we assessed AEME activity at rat mAChR subtypes 1-5 heterologously expressed in Chinese Hamster Ovary cells. l-[N-methyl-(3)H]scopolamine competition binding showed a preference of AEME for the M2 subtype; calcium mobilization tests revealed partial agonist effects at M1 and M3 and antagonist activity at the remaining subtypes. The selective M1 and M3 antagonists and the phospholipase C inhibitor, were able to prevent AEME-induced neurotoxicity, suggesting that the toxicity is due to the partial agonist effect at M1 and M3 mAChRs, leading to DNA fragmentation and neuronal death by apoptosis.


Resende R.R.,Federal University of Minas Gerais | Resende R.R.,Institute of Learning and Research Santa Casa of BH IEPSC BH | Resende R.R.,Federal University of Säo João del Rei | Adhikari A.,Columbia University | And 6 more authors.
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2010

Spontaneous Ca2+ events have been observed in diverse stem cell lines, including carcinoma and mesenchymal stem cells. Interestingly, during cell cycle progression, cells exhibit Ca2+ transients during the G1 to S transition, suggesting that these oscillations may play a role in cell cycle progression. We aimed to study the influence of promoting and blocking calcium oscillations in cell proliferation and cell cycle progression, both in neural progenitor and undifferentiated cells. We also identified which calcium stores are required for maintaining these oscillations. Both in neural progenitor and undifferentiated cells calcium oscillations were restricted to the G1/S transition, suggesting a role for these events in progression of the cell cycle. Maintenance of the oscillations required calcium influx only through inositol 1,4,5-triphosphate receptors (IP3Rs) and L-type channels in undifferentiated cells, while neural progenitor cells also utilized ryanodine-sensitive stores. Interestingly, promoting calcium oscillations through IP3R agonists increased both proliferation and levels of cell cycle regulators such as cyclins A and E. Conversely, blocking calcium events with IP3R antagonists had the opposite effect in both undifferentiated and neural progenitor cells. This suggests that calcium events created by IP3Rs may be involved in cell cycle progression and proliferation, possibly due to regulation of cyclin levels, both in undifferentiated cells and in neural progenitor cells.


Togni L.R.,Criminalistic Institute of Sao Paulo | Lanaro R.,University of Campinas | Resende R.R.,Federal University of Minas Gerais | Costa J.L.,Criminalistic Institute of Sao Paulo | Costa J.L.,University of Campinas
Journal of Forensic Sciences | Year: 2015

The content of ecstasy tablets has been changing over the years, and nowadays 3,4-methylenedioxymethamphetamine (MDMA) is not always present in the tablets. The aim of this study was to investigate the chemical composition in the seized tablets labeled as ecstasy. We analyzed samples from 150 different seizures made by Sao Paulo's State Police by gas chromatography-mass spectrometry. MDMA was present in 44.7% of the analyzed samples, and another twenty different active substances were identified in these tablets, such as caffeine, 2C-B, piperazines, amphetamines, phencyclidine, and others. Methamphetamine was present in 22% of these samples. The results demonstrate a huge shift in the pattern of trafficking of synthetic drugs, where MDMA has been replaced in tablets mostly by illicit psychoactive substances, in a clear attempt to bypass the law. The great variability in the tablets composition may lead to an increased risk of drug poisoning. © 2014 American Academy of Forensic Sciences.


PubMed | Criminalistic Institute of Sao Paulo
Type: Journal Article | Journal: Journal of forensic sciences | Year: 2015

The content of ecstasy tablets has been changing over the years, and nowadays 3,4-methylenedioxymethamphetamine (MDMA) is not always present in the tablets. The aim of this study was to investigate the chemical composition in the seized tablets labeled as ecstasy. We analyzed samples from 150 different seizures made by Sao Paulos State Police by gas chromatography-mass spectrometry. MDMA was present in 44.7% of the analyzed samples, and another twenty different active substances were identified in these tablets, such as caffeine, 2C-B, piperazines, amphetamines, phencyclidine, and others. Methamphetamine was present in 22% of these samples. The results demonstrate a huge shift in the pattern of trafficking of synthetic drugs, where MDMA has been replaced in tablets mostly by illicit psychoactive substances, in a clear attempt to bypass the law. The great variability in the tablets composition may lead to an increased risk of drug poisoning.

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