Kinetic profile of N,N-dimethyltryptamine and ß-carbolines in saliva and serum after oral administration of ayahuasca in a religious context.

Ayahuasca is a beverage obtained from Banisteriopsis caapi plus Psychotria viridis. B. caapi contains the ß-carbolines harmine, harmaline, and tetrahydroharmine that are monoamine oxidase inhibitors and P. viridis contains N,N-dimethyltryptamine (DMT) that is responsible for the visionary effects of the beverage. Ayahuasca use is becoming a global phenomenon, and the recreational use of DMT and similar alkaloids has also increased in recent years; such uncontrolled use can lead to severe intoxications. In this investigation, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study the kinetics of alkaloids over a 24 h period in saliva and serum of 14 volunteers who consumed ayahuasca twice a month in a religious context. We compared the area under the curve (AUC), maximum concentration (Cmax ), time to reach Cmax (Tmax ), mean residence time (MRT), and half-life (t1/2 ), as well as the serum/saliva ratios of these parameters. DMT and ß-carboline concentrations (Cmax ) and AUC were higher in saliva than in serum and the MRT was 1.5-3.0 times higher in serum. A generalized estimation equations (GEEs) model suggested that serum concentrations could be predicted by saliva concentrations, despite large individual variability in the saliva and serum alkaloid concentrations. The possibility of using saliva as a biological matrix to detect DMT, ß-carbolines, and their derivatives is very interesting because it allows fast noninvasive sample collection and could be useful for detecting similar alkaloids used recreationally that have considerable potential for intoxication.

Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users.

Ayahuasca is a beverage obtained from decoctions of the liana Banisteriopsis caapi plus the shrub Psychotria viridis. 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 ritualistic use of ayahuasca is becoming a global phenomenon. Most members of ayahuasca churches consume this beverage throughout their life, and many reports have discussed the therapeutic potential of this beverage. Ayahuasca is consumed orally, and the liver, as the major organ for the metabolism and detoxification of xenobiotics absorbed from the alimentary tract, may be susceptible to injury by compounds present in the ayahuasca decoction. In this study, we evaluated biochemical parameters related to hepatic damage in the serum of 22 volunteers who consumed ayahuasca twice a month or more for at least one year. There was no significant alteration in the following parameters: alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, and gamma glutamyl transferase. These findings indicate that chronic ayahuasca consumption in a religious context apparently does not affect hepatic function.

Poisoning by illegal rodenticides containing acetylcholinesterase inhibitors (chumbinho): a prospective case series.

OBJECTIVE: To describe a prospective case series of poisonings caused by ingestion of illegal rodenticides containing acetylcholinesterase inhibitors, mainly "chumbinho," followed-up by the Campinas PCC for a period of 1 year. CASE SERIES: Seventy-six cases were included, of which 53.9% were males. Age ranged from 2 to 74 years (median = 36 years). The main circumstances leading to poisoning were intentional (suicide attempts 92.1%; homicide attempts 5.3%), and 65.8% were admitted less than 2 hours after ingestion. Most of the patients (96.1%) showed cholinergic muscarinic manifestations, particularly salivation (86.8%), myosis (77.6%), sweating (50%), and bronchorrhea (35.5%). Atropine was used in 82.9% of patients (median = 2 days), intubation and mechanical ventilation in 46.1% (median = 3 days), and the median length of the hospital stay was 4 days. Plasma samples obtained upon admission in 59 cases revealed (LC-MS/MS): aldicarb (55), carbofuran (2), aldicarb and carbofuran (1), no active component (1). In most of the plasma and urine samples collected upon admission, the highest concentrations (ng/mL) obtained were for the active metabolite aldicarb sulphoxide (plasma, median = 831, IIQ = 99.2-2885; urine, median = 9800, IIQ = 2000-15000) than aldicarb (plasma, median = 237, IIQ = 35.7-851; urine, median = 584, IIQ = 166-1230), indicating rapid metabolism. The excretion of aldicarb and its metabolites was rapid since these compounds were rarely detected in plasma samples 48 hours after admission. Sequential cholinesterase analysis in 14 patients revealed almost complete reactivation in the first 48 hours post-admission, compatible for poisoning by carbamates. Based on the Poisoning Severity Score, the cases were classified as asymptomatic (5.3%), minor (11.8%), moderate (35.5%), severe (43.4%), and fatal (3.9%). CONCLUSIONS: Most poisonings involved aldicarb and resulted from suicide attempts; the poisonings were generally severe, with a mortality of 3.9%. Aldicarb was rapidly absorbed, metabolized, and excreted.

Compartment syndrome after Bothrops jararaca snakebite: monitoring, treatment, and outcome.

OBJECTIVE: To report the outcome of a patient who developed compartment syndrome after Bothrops jararaca snakebite. CASE REPORT: A 39-year-old male was admitted 5 h after being bitten on the lower right leg. Physical examination revealed tense swelling, ecchymosis, hypoesthesia, and intense local pain that worsened after passive stretching, limited right foot dorsiflexion, and gingival bleeding. The case was classified as moderate/severe and eight vials of bothropic antivenom (AV) were infused 1 h postadmission. The main laboratory findings upon admission were incoagulable blood (incoagulable PT, aPTT, and INR), thrombocytopenia, serum creatine kinase (CK) of 580 U/L (reference value < 170 U/L), and a serum venom level of 33.7 ng/mL (ELISA; cutoff = 2.3 ng/mL). High anterior compartment pressure (60 mmHg) was identified 8 h post bite, with progressively lower pressures after AV administration and limb elevation (36 mmHg; 19 h post bite). However, moderate pain and limited foot dorsiflexion persisted. In addition, there was a progressive increase in serum CK (6,729 U/L; 45 h post bite), as well as marked edema and hemorrhage of the anterior compartment detected by magnetic resonance imaging (MRI) at 48 h post bite. A fasciotomy done after a further increase in intracompartmental pressure (66 mmHg, 57 h post bite) revealed hemorrhage/necrosis of the anterior tibial muscle that subsequently required partial resection. The patient developed a local infection (day 15 post bite) and a permanent fibular palsy. CONCLUSION: Compartment syndrome is an unusual but severe complication of snakebites. MRI, in conjunction with subfascial pressure measurements, may be useful in the diagnosis of compartment syndrome after snakebites.

Serotonin syndrome following sibutramine poisoning in a child, with sequential quantification of sibutramine and its primary and secondary amine metabolites in plasma.

OBJECTIVE: To report a case of serotonin syndrome (SS) after sibutramine overdose in a child. CASE REPORT: A 4-year-old girl was admitted 25 h after accidentally ingesting approximately 27 pills of sibutramine (15 mg, approximately 23 mg/kg). The child developed clinical features suggestive of SS, including diaphoresis, tachycardia, hypertension, agitation, insomnia, incoordination, hypertonia (lower limbs >> upper limbs), and hallucinations. Serum creatine phosphokinase levels reached a peak on day 3 (2,577 U/L, reference value <145), suggesting mild rhabdomyolysis. No relevant changes were detected in other laboratory examinations or in the electrocardiogram throughout the period of hospitalization. The quantification of sibutramine and the active metabolites, M1 (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine), by liquid chromatography/electrospray ionization tandem mass spectrometry in six sequential samples collected from 25 to 147 h post-ingestion revealed a nonlinear decrease in the log-scale plasma concentrations. Treatment was only supportive and involved prolonged sedation to control the agitation, sleeplessness, and hypertension; no cyproheptadine was used. The patient was discharged on day 6 and follow-up revealed no sequelae. CONCLUSION: To our knowledge, this is the first report of SS after sibutramine overdose in a child, with sequential monitoring of the plasma levels of the drug and its two active metabolites. The growing consumption of weight reducing pills may increase the risk of unintentional acute toxic exposures in children.

Systemic envenomation caused by the wandering spider Phoneutria nigriventer, with quantification of circulating venom.

INTRODUCTION: Bites by Phoneutria spp. spiders are common in Brazil, although only 0.5-1% result in severe envenomation, with most of these occurring in children. Cases of systemic envenomation in adults are very unusual, and no serum venom levels have been previously quantified in these cases. CASE REPORT: A 52-year-old man was bitten on the neck by an adult female Phoneutria nigriventer. Immediately after the bite, there was intense local pain followed by blurred vision, profuse sweating, tremors, and an episode of vomiting; 1-2 h post bite the patient showed agitation and a blood pressure of 200/130 mmHg, and was given captopril and meperidine. Upon admission to our service 4 h post bite (time zero - T0), his blood pressure was 130/80 mmHg with a heart rate of 150 beats/min, mild tachypnea, agitation, cold extremities, profuse sweating, generalized tremors, and priapism. The patient was treated with antivenom, local anesthetic, and fluid replacement. Most of the systemic manifestations disappeared within 1 h after antivenom. Laboratory blood analyses at T0, T1, T6, T24, and T48 detected circulating venom by ELISA only at T0, before antivenom infusion (47.5 ng/mL; cut-off, 17.1 ng/mL); his serum blood sugar was 163 mg/dL at T0. The patient was discharged on the second day with a normal arterial blood pressure and a follow-up evaluation revealed no sequelae. CONCLUSION: This is the first report of confirmed moderate/severe envenoming in an adult caused by P. nigriventer with the quantification of circulating venom.

Neuromuscular action of venom from the South American colubrid snake Philodryas patagoniensis.

Snakes of the opisthoglyphous genus Philodryas are widespread in South America and cause most bites by colubrids in this region. In this study, we examined the neurotoxic and myotoxic effects of venom from Philodryas patagoniensis in biventer cervicis and phrenic nerve-diaphragm preparations and we compared the biochemical activities of venoms from P. patagoniensis and Philodryas olfersii. Philodryas patagoniensis venom (40 microg/mL) had no effect on mouse phrenic nerve-diaphragm preparations but caused time-dependent neuromuscular blockade of chick biventer cervicis preparations. This blockade was not reversed by washing. The highest concentration of venom tested (40 microg/mL) significantly reduced (p<0.05) the contractures to exogenous acetylcholine (55 microM and 110 microM) and K(+) (13.4 mM) after 120 min; lower concentrations of venom had no consistent or significant effect on these responses. Venom caused a concentration- and time-dependent release of creatine kinase (CK) from biventer cervicis preparations. Histological analysis showed contracted muscle fibers at low venom concentrations and myonecrosis at high concentrations. Philodryas venoms had low esterase and phospholipase A(2) but high proteolytic activities compared to the pitviper Bothrops jararaca. SDS-PAGE showed that the Philodryas venoms had similar electrophoretic profiles, with most proteins having a molecular mass of 25-80 kDa. Both of the Philodryas venoms cross-reacted with bothropic antivenom in ELISA, indicating the presence of proteins immunologically related to Bothrops venoms. RP-HPLC of P. patagoniensis venom yielded four major peaks, each of which contained several proteins, as shown by SDS-PAGE. These results indicate that P. patagoniensis venom has neurotoxic and myotoxic components that may contribute to the effects of envenoming by this species.

Plasmatic and urinary screening for drugs that cause depressive syndrome by capillary column gas chromatography

Este trabalho descreve um procedimento para triagem de fármacos que causam síndrome depressiva do sistema nervoso central. Amostras de plasma e urina de pacientes foram extraídos com diclorometano e isopropanol 1 por cento em diclorometano, em pH ácido e básico, respectivamente. Os extratos foram analisados por cromatografia gasosa com coluna capilar CP-Sil-5-CB. O tempo de análise foi compatível com a necessidade clínica (menor que duas horas) para análise concomitante de 21 fármacos