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Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes. Resumen: Introducción: La identificación temprana de los neonatos expuestos a drogas de abuso permite realizar un manejo clínico más preciso. Objetivos: Describir las características clínicas e identificar factores de riesgo asociados a la detección precoz de neonatos expuestos a drogas de abuso en una Unidad de Cuidados Intensivos e Intermedios Neonatales. Métodos: Estudio observacional prospectivo de neonatos con y sin sospecha clínica de exposición prenatal a drogas de abuso. Se analizó meconio empleando técnicas cromatográficas estandarizadas. Se realizaron análisis estadísticos univariante y multivariante. Resultados: Se incluyeron 372 neonatos. En 49 (13,2%) casos se detectó exposición a alguna droga de abuso; en 41 (83,7%) a una, y en ocho (16,3%) a más de una. La somatometría al nacimiento objetivó: a) menor percentil de longitud en expuestos a alguna droga, a más de una y a cannabis; b) menor percentil de peso en expuestos a cannabis, y de éstos en comparación con los expuestos a alcohol. En mayores de 34 semanas de gestación (SG): a) menor percentil de longitud en expuestos a alguna droga; b) menor percentil de longitud y peso en expuestos a más de una. Los factores de riesgo independientes clínicamente útiles para detectar casos de exposición prenatal a drogas de abuso fueron (odds ratio [IC 95%]): motivo de ingreso distinto a prematuridad (5,52 [2,55-1,93]), percentil de longitud menor a 33 (1,95 [1,05-3,60]) y (2,14 [1,04-3,40]) en mayores de 34 SG y distocia social/embarazo no controlado en mayores a 34SG (4,47 [1,03-19,29]). Conclusiones: Existen alteraciones somatométricas y factores de riesgo que pueden ayudar a detectar precozmente a los neonatos expuestos a drogas de abuso. Las alteraciones somatométricas identificadas pueden servir para ampliar su diagnóstico diferencial y el estudio de sus causas.

Resumen: Introducción: La identificación temprana de los neonatos expuestos a drogas de abuso permite realizar un manejo clínico más preciso. Objetivos: Describir las características clínicas e identificar factores de riesgo asociados a la detección precoz de neonatos expuestos a drogas de abuso en una Unidad de Cuidados Intensivos e Intermedios Neonatales. Métodos: Estudio observacional prospectivo de neonatos con y sin sospecha clínica de exposición prenatal a drogas de abuso. Se analizó meconio empleando técnicas cromatográficas estandarizadas. Se realizaron análisis estadísticos univariante y multivariante. Resultados: Se incluyeron 372 neonatos. En 49 (13,2%) casos se detectó exposición a alguna droga de abuso; en 41 (83,7%) a una, y en ocho (16,3%) a más de una. La somatometría al nacimiento objetivó: a) menor percentil de longitud en expuestos a alguna droga, a más de una y a cannabis; b) menor percentil de peso en expuestos a cannabis, y de éstos en comparación con los expuestos a alcohol. En mayores de 34 semanas de gestación (SG): a) menor percentil de longitud en expuestos a alguna droga; b) menor percentil de longitud y peso en expuestos a más de una. Los factores de riesgo independientes clínicamente útiles para detectar casos de exposición prenatal a drogas de abuso fueron (odds ratio [IC 95%]): motivo de ingreso distinto a prematuridad (5,52 [2,55-1,93]), percentil de longitud menor a 33 (1,95 [1,05-3,60]) y (2,14 [1,04-3,40]) en mayores de 34 SG y distocia social/embarazo no controlado en mayores a 34SG (4,47 [1,03-19,29]). Conclusiones: Existen alteraciones somatométricas y factores de riesgo que pueden ayudar a detectar precozmente a los neonatos expuestos a drogas de abuso. Las alteraciones somatométricas identificadas pueden servir para ampliar su diagnóstico diferencial y el estudio de sus causas. Abstract: Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

To detect the presence of unsuspected and/or undeclared cathinone and piperazine-type designer drugs in methamphetamine (METH) and amphetamine users treated in emergency departments, and to compare clinical and toxicologic profiles.Retrospective observational study of emergency department patients treated for confirmed acute intoxication by recreational drugs (METH and amphetamines) between March 2019 and December 2020. We ordered high-performance liquid chromatography with tandem mass spectrometry to detect cathinones (methylone, fluoromethcathinone, mexedrone, fluoromethamphetamine, mephedrone, methylenedioxypyrovalerone) and synthetic piperazines (meta-chlorophenylpiperazine and trifluoromethylphenylpiperazine). Demographic, clinical, and toxicologic variables were analyzed with SPSS software (version 23).Thirty-nine patients were included: 24 (61.5%) had used METH and 15 (38.5%) an amphetamine. Synthetic cathinones were detected in samples from 11 patients (28.2%), 10 (90.9%) in the METH group and 1 (9.1%) in the amphetamine group (P = .028). The METH users had taken mephedrone (8 patients) or methylone (2 patients); the amphetamine user had taken mephedrone. None of the patients had declared use of a cathinone; nor was use suspected. The mean (SD) number of substances involved was higher among users of cathinones (3.5 [1.13] vs 2.5 [1.40] in those who took no cathinones; P = .036). Among the cathinone users, 90.9% were men, 90.9% had used METH, and 45.5% had practiced chemsex. HIV positivity was significantly associated with cathinone use (in 45.5% vs 10.7% of those not using cathinones; P = .028). All 5 of the patients who had taken cathinones and also practiced chemsex were HIV positive. Significantly more patients who had taken cathinones presented with anxiety (72.7% vs 21.43%; P = .007). No differences in clinical management were found.Detection of METH in intoxicated patients should raise suspicion of probable use of a synthetic cathinone. Patients in whom new psychoactive substances are detected should be kept under observation, and clinical protocols should include referring them to addiction treatment centers.Determinar la incidencia de catinonas y piperazinas, no sospechadas y/o declaradas en consumidores de metanfetamina (MANF) y anfetamina (ANF) atendidos en servicios de urgencias hospitalarios (SUH) y comparar los perfiles clínicos y toxicológicos.Estudio retrospectivo de pacientes con intoxicación aguda por drogas recreativas con MANF y ANF confirmadas analíticamente atendidos en 3 SUH entre marzo de 2019 y diciembre de 2020. Se detectaron por HPLC-MS/MS las catinonas [metilona, fluorometcatinona, mecedrona, fluorometanfetamina, mefedrona, metilendioxipirovalerona (MDPV)] y las piperazinas sintéticas [meta-clorofenilpiperazina (mCPP), trifluorometilfenilpiperazina (TFMPP)].Se incluyeron 39 pacientes: 24 (61,5%) en el grupo MANF y 15 (38,5%) en el ANF. En 11 (28,2%), se detectaron catinonas sintéticas (grupo CAT), 10 en el grupo MANF (8 mefedrona, 2 metilona) y 1 en el grupo ANF (1 mefedrona) (90,9% vs 9,1%; p = 0,028). Ninguno de los pacientes declaró consumo de catinonas. El número de drogas implicadas en la intoxicación fue superior en el grupo CAT (3,5 [1,13] vs 2,5 [1,40]; p = 0,036). El perfil clínico del grupo CAT fue: varón (90,9%), consumidor de MANF (90,9%) y usuario de chemsex (45,5%). El diagnóstico de VIH se asoció significativamente al grupo CAT (45,5% vs 10,7%; p = 0,028). Los pacientes del grupo CAT presentaron mayor ansiedad (72,7% vs 21,4%; p = 0,007). No se hallaron diferencias en su manejo clínico.La detección de MANF debería considerarse un dato de sospecha de consumo de catinonas sintéticas, y en esos casos debería contemplarse la detección de nuevas sustancias psicoactivas de abuso.

Scopolamine is used clinically, but it is also used as a recreational drug and as an incapacitating drug, in sexual crimes and robberies. In this paper, the authors report the case of a woman with a diminished consciousness following an unsuspected overdose with scopolamine and review published articles on scopolamine poisoning that included concentrations in biological samples. Scopolamine was identified in the patient’s serum and urine samples collected 1 h post-admission to intensive care unit at concentrations of 8.4 ng/mL and 62,560 ng/mL (169,539 ng/mg creatinine), respectively. In non-fatal cases, the median [interquartile range] of serum scopolamine levels was 1.9 [2.1] ng/mL. The serum concentration found in our case would explain the abrupt clinical presentation suffered by the patient. Scopolamine in urine could be detected up to 48 h after admission. This report illustrates that broad toxicology screening, including scopolamine, should be considered when patients with diminished consciousness are attended after ruling out infection or cerebrovascular disease. This can play an important role in identifying this potentially life-threatening etiology.

To determine whether clinical and toxicologic findings differed between cases of amphetamine (AMP) and methamphetamine (mAMP) poisoning attended in 2 Balearic Island hospital emergency departments.Retrospective observational study of AMP and mAMP cases with laboratory confirmation between 2013 and 2018. We compared clinical and toxicologic variables as well as clinical management between groups.1) A total of 120 cases were found: 86 (71.7%) with AMP poisoning and 34 (28.3%) with mAMP poisoning. 2) Drug poisoning was confirmed by gas chromatography associated with mass spectrometry (GC-MS) in 787 urine samples found to be positive during screening. One hundred fifty-four (19.6%) were confirmed by GC-MS. Thirtyfour of them did not meet the inclusion criteria. 3) Significant differences between AMP and mAMP cases were found for age (32.3 vs 28.4 y, respectively); sex (72.1% vs 94.1% men); and Spanish nationality (64.0% vs 29.4%). Reasons for admission and clinical features also differed: the reasons were aberrant behavior (15.1% in the AMP group vs 0% in the mAMP group) and palpitations (1.2% vs 20.6%); agitation was observed in 27.9% and 8.8%, respectively. Clinical management was similar in the 2 groups. Multiple drug poisoning was detected in 76.6% patients and was more common in patients in the AMP group (82.6% vs 61.8%). The additional drugs in these cases were mainly cocaine (63.0%), cannabis (48.9%), 3,4-methylenedioxy-N-methamphetamine (MDMA) (38.0%), and alcohol (35.9%). Cannabis was detected in a significantly higher proportion in the AMP group (45.3%) than in the mAMP group (17.6%). False positives were found in 78.7% of the samples. The culprit drug was most often MDMA (71.2%).AMP poisonings were associated with age over 30 years, Spanish nationality, aberrant behavior, agitation, multiple drug findings, and the use of cannabis. Poisonings caused by mAMP abuse were associated with age under 30 years, non-Spanish nationality, palpitations, and single-drug use.Investigar si existen diferencias clínicas y toxicológicas en pacientes intoxicados por anfetamina (ANF) y metanfetamina (MANF) atendidos en servicios de urgencias.Estudio observacional retrospectivo de intoxicaciones por ANF y MANF con confirmación analítica en Baleares (2013-2018). Se compararon variables clínicas, toxicológicas y de manejo clínico entre grupos.1) Se incluyeron 120 pacientes, 86 (71,7%) grupo ANF y 34 (28,3%) grupo MANF. 2) La confirmación de derivados anfetamínicos se realizó por cromatografía de gases-espectrometría de masas en 787 muestras de orina previamente positivas mediante un método de cribado cualitativo. Se confirmaron 154 (19,6%) muestras. De ellas, 34 fueron excluidas. 3) Se encontraron diferencias significativas entre ANF y MANF en: edad (32,3 vs 28,4 años); sexo (72,1 vs 94,1% hombres); nacionalidad española (64,0 vs 29,4%); en motivos de admisión: alteración de conducta (15,1 vs 0%) y palpitaciones (1,2 vs 20,6%); y en características clínicas: agitación (27,9 vs 8,8%). No hubo diferencias de manejo clínico. El 76,6% de casos fueron polintoxicaciones, más comunes en ANF (82,6 vs 61,8%). En estos casos se detectó principalmente cocaína (63,0%), cannabis (48,9%), MDMA (38,0%) y alcohol (35,9%). La mayor asociación del cannabis con el grupo de ANF fue estadísticamente significativa (45,3 vs 17,6%). La causa de los falsos positivos se identificó en el 78,7% de muestras, siendo el MDMA (71,2%) la principal.Se observaron diferencias entre ANF y MANF en cuanto a variables demográficas y motivo de asistencia; no obstante en esta serie hubo un alto porcentaje de polintoxicaciones.

Objective To evaluate the clinical utility of glycolic acid (GA) determination in the diagnosis and prognosis of ethylene glycol (EG) intoxications. Method Systematic review of serum and/or urine GA concentrations available in the literature in cases of EG poisoning. Present a clinical case in which the determination of the GA was decisive. Results In total, 137 patients were included. Serum GA concentrations (but not EG) of patients who survive are different from those who die. The optimal cut-off of serum GA to predict mortality was 990.5 mg/L (sensitivity 85.2%, specificity 54.3%) with an Odds Ratio of 6.838 (2.868–16.302). In our clinical case, serum EG was negative; however, urine GA was positive (1230.7 mg/L). Conclusions In all suspected cases of EG poisoning, it is advisable to carry out the simultaneous analysis of EG and GA.

Background Methamphetamine misuse represents an increasing global public health problem. Its consumption during pregnancy becomes a relevant issue, since it has clinical consequences for the child's health and the pregnant woman. Despite this, there are only few data in the literature that include analytical results in the matrices used to detect prenatal exposure. Objectives 1) Present a case report of prenatal methamphetamine exposure with toxicological analytical confirmation in biological matrices; and 2) Perform a compilation of prenatal methamphetamine exposure studies and case reports which include toxicological analytical results. Methods Prenatal methamphetamine exposure was confirmed using a traditional "screen with reflex" approach. Methamphetamine and amphetamine were quantified in urine, meconium and hair samples of the neonate and mother by gas chromatography-mass spectrometry. Also, a detailed revision of the existent literature that provides information on the analytical toxicology results has been included. Results In the neonatal biological matrices test results of methamphetamine/amphetamine were: urine 2,966.43/1,638.71 ng/mL, meconium 1,450/l0.1 ng/g and hair 36.54/9.66 ng/mg. In the maternal biological matrices, test results were: urine 13,393.89/3,074.95 ng/mL and hair 11.29/3.37 ng/mg (0-3 cm), 4.68/2.58 (3-6 cm), 6.43/3.13 ng/mg (6-9 cm) and 4.72/2.49 ng/mg (9-12 cm). These results confirm a recent and continued regular substance use throughout pregnancy including delivery. Conclusion The data provided will be useful for clinical purposes to improve the diagnostic and follow- up of acute and chronic intoxications. Additionally, results will be used to support interpretations in the field of forensic and legal medicine.

Aim: The aim of this study was to perform a cross-reactivity investigation of six benzofurans with immunoassays (IAs) screening tests for amphetamines and ecstasy in urine samples. Methods: The following benzofuranes were investigated: 5-(2-Methylaminopropyl)Benzofuran (5-MAPB), 5-(2-methylaminopropyl)-2,3-dihydrobenzofuran (5-MAPDB), 5-(2-Aminopropyl)-Benzofuran (5-APB), 5-(2-Aminopropyl)-2,3-dihydrobenzofuran (5-APDB), 5-(2-Ethylaminopropyl)Benzofuran (5-EAPB) and 5-(2-Aminoethyl)-2,3-dihydrobenzofuran (5-AEDB). The study was performed with urine-free spiked samples and authentic urine samples using eight different IAs for amphetamines and ecstasy. Results: All evaluated benzofurans showed cross-reactivity in some of the IAs tested, except for 5-AEDB. Urine samples of an intoxication case involving 5-MAPB, 5-APB and 5-EAPB were also positives in the IAs tested. Conclusion: There is an important variability in the cross-reactivity of the IAs for amphetamine and ecstasy caused by benzofurans depending on the immunoassay employed and the tested compounds.

Synthetic cannabinoids are relatively new substances of abuse. Recently, abuse of synthetic cannabinoids has been increasingly reported in the lay press and medical literature. When new compounds are introduced, their use is initially not restricted by prohibition therefore their consumption cannot be verified by standard drug tests. The use of these compounds among adolescents and young adults is constantly growing, making it important for emergency services to be familiar with the signs and symptoms of intoxication present. Overdose and chronic use of these substances can cause adverse effects including altered mental status, tachycardia, and loss of consciousness. Here, we report five cases of acute intoxication by synthetic cannabinoids 5F-ADB and MMB-2201 with analytical confirmation.

Methoxetamine (MXE) and the arylcyclohexylamines 3-methoxy-PCP (3-MeO-PCP) and 4-methoxy-PCP (4-MeO-PCP) are substituted analogs of the dissociative psychoactive substances ketamine and phencyclidine (PCP), respectively. They have emerged on the new psychoactive substances (NPS) market as legal alternatives to these classically banned dissociatives. Little data has been published regarding the cross-reactivity of these NPS in PCP immunoassays (IAs). The aim of this work was to explore the possibilities of detecting 3-MeO-PCP, 4-MeO-PCP, MXE and ketamine in commercial IAs for PCP. The cross-reactivity study was performed in five different PCP IAs using urine-free, spiked samples and urine samples obtained from two 3-MeO-PCP overdose cases. 3-MeO-PCP and 4-MeO-PCP showed cross-reactivity (ranging from 1–143%) in all PCP IAs evaluated. MXE only showed very weak cross-reactivity (ranged from 0.04 to 0.25%) and ketamine was not detected in any PCP IA evaluated. Urine samples from the two overdose cases were positive for PCP in all IAs evaluated. The commercial PCP IAs evaluated exhibited utility as rapid, preliminary screening techniques for 3-MeO-PCP and 4-MeO-PCP, but not for ketamine. The low reactivity of MXE limits its detectability in the PCP IAs evaluated.

Background High-dose methotrexate (HDMTX) therapy is a key component of many chemotherapy protocols. However, some patients develop HDMTX-induced nephrotoxicity. Carboxypeptidase-G2 (CPDG2) hydrolyses MTX into 2,4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid, and is used as a rescue agent in patients with nephrotoxicity and delayed elimination. Despite the frequency of HDMTX-induced renal injury, crystalluria is uncommon. Furthermore, crystals are rarely identified by conventional chemical methods. Objective To determine the composition of crystalluria in a patient with osteosarcoma who was treated with CPDG2. Methods Crystalluria was evaluated by optical microscopy, and chemical identification was performed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and Orbitrap™ high-resolution mass spectrometry (HRMS). Results The HRMS spectra of the patient's urine sediment showed a main peak at m/z 326.13, corresponding to the molecular mass of DAMPA [(C15H15O2N7) + H+]. The FT-IR spectral patterns of the sediment and DAMPA were not identical. SEM was unable to identify the crystal. Conclusion DAMPA crystalluria was identified by Orbitrap™ HRMS in a patient treated with CPDG2 after HDMTX nephrotoxicity. This case reinforces the need to implement adequate measures to prevent nephrotoxicity. In cases of HDMTX-induced nephrotoxicity, urine sediment analysis should be requested.

We present a false-positive result of ecstasy (3,4-methylenedioxy-NN-methylamphetamine) screening due to the therapeutic use of fenofibrate, an antihyperlipidemic drug. Our hypothesis was that the main metabolite of fenofibrate, fenofibric acid, was responsible for this cross-reactivity on a DRI(®) Ecstasy Assay, using a cut-off of 500 ng/mL. We estimated that the addition of 225 µg/mL pure fenofibric acid to blank urine would be sufficient to result in a positive DRI(®) Ecstasy Assay. The results obtained on the urine samples analyses of the patient show that the DRI(®) Ecstasy Assay resulted negative 2 days after discontinuing fenofibrate treatment, when the urine fenofibric acid concentration corrected by creatinine and determinated by gas chromatography-mass spectrometry was 20.3 µg/mg creatinine. The cross-reactivity data for fenofibric acid would seem to indicate that there was insufficient concentration of measured compound to account for the positive immunochemical results for ecstasy. This apparent discrepancy can be explained in several ways, one of them is that the β-glucuronidase-resistent fenofibric acid isomers are responsible. This process could explain the low recovery of free fenofibric acid when we use the developed method for its quantification in urine samples. Positive results on immunoassay screening must be considered presumptive until confirmation with another method based on a different principle, preferably gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry.

Background Clinical and forensic toxicology can be defined as two disciplines involving the detection, identification and measurement of xenobiotics in biological and non-biological samples to assist in the diagnosis, treatment, prognosis and prevention of poisonings and to disclose causes and contributory causes of fatal intoxications, respectively. Objective This article explores the close connections between clinical and forensic toxicology in overlapping areas of interest. Methods An update has been carried out of the following seven areas of interest in analytical toxicology: doping control, Sudden Cardiac Death (SCD), brain death, Sudden Infant Death Syndrome (SIDS) and Munchausen Syndrome by Proxy (MSBP), prenatal exposure to drugs and Fetal Alcohol Syndrome (FAS), Drug-Facilitated Crimes (DFC) and intoxications by new psychoactive substances (NPS). Results While issues such as SCD, SIDS or doping control are investigated mainly in forensic laboratories, others such as prenatal exposure to drugs or FAS are mainly treated in clinical laboratories. On the other hand, areas such MSBP, DFC or the intoxications by NPS are of interest in both laboratories. Some of these topics are initially treated in hospital emergency departments, involving clinical laboratories and sometimes lately derived to forensic laboratories. Conversely, cases with initial medicallegal implications and fatalities are directly handled by forensic toxicology, but may trigger further studies in the clinical setting. Conclusion Many areas of common interest between clinical and forensic laboratories are building bridges between them. The increasing relationships are improving the growth, the reliability and the robustness of both kinds of laboratories.

BACKGROUND Benzofurans and benzodifurans are two groups of psychoactive substances that had originally been synthesized for research purpose. Benzofurans' structure is quite similar to the known recreational drug 3,4-methylenedioxymethamphetamine together with its active metabolite 3,4-methylenedioxyamphetamine. Benzodifurans are closely related to phenethylamines, but have more hallucinogens effects and much longer duration of action. This study aims to review the accessible evidence-based literature on benzofurans and benzodifurans pharmacology and toxicology. METHODS A literature search on benzofurans and benzodifurans has been conducted using PubMed. We reviewed articles up to February 2017 and also included data from various governmental websites and discussion groups. RESULTS This review describes the emergent literature that illustrates the chemical composition of these drugs, patterns of use, pharmacology, toxicology, desired and clinical effects, and treatments of patients. It also provides a compilation of case reports. CONCLUSION The knowledge regarding usage prevalence, pharmacokinetic and pharmacodynamic profiles, acute toxic effects, the effects desired on patients and drug related mortality attributed to these drugs is still limited. Nowadays, there are no specific guidelines available to treat benzofurans or dibenzofurans intoxications. For that reason, clinical effects should be the base of treatment. Backing exposures analytically confirmed in clinical and forensic cases and reported clinical effects need to be combined with these compounds while monitoring its prevalence.

The acute and chronic toxicity of several new psychoactive substances (NPS) is unknown, and only little information is available on the pharmacology and toxicology, toxicokinetics, and detectability in body samples of such new compounds. We here propose analytical methods to disclose acute and chronic use of two types of new psychostimulants: benzofurans and ethylphenidate and we applied them to a real case of a subject attending Emergency Department with signs of acute intoxication due to psychotropic drug(s). After a urinary immunoassay screening which gave a positivity to amphetamines, general unknown gas chromatography-mass spectrometry (GC-MS) urine analysis identified 5-(2-methylaminopropyl)benzofuran (5-MAPB), 5-(2-aminopropyl)benzofuran (5-APB), 5-(2-ethylaminopropyl)benzofuran (5-EAPB), ethylphenidate, and ritalinic acid. All these substances were confirmed and quantified not only in urine but also in serum samples at different times after hospitalization by GC-MS and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Two subsequent 2-cm hair segments were also analyzed and tested positive for the above reported substances, evidencing repeated use. The matching quantitative results in all the analyzed biological matrices demonstrated that both analytical methodologies were suitable to correctly quantify NPS involved in the current intoxication. The objective assessment of acute and chronic intoxication by the above reported compounds demonstrate that the development of analytical methods aiming at the detection of a broad spectrum of compounds in conventional and non-conventional biological matrices is helpful when facing the new challenging threat of intoxications caused by NPS.

Heroin-related myelopathy is an uncommon but often devastating complication of heroin intake. It is usually reported in individuals exposed to intravenous heroin after a variable drug-free period, leading to acute and complete spinal cord injury with poor long-term outcome. We describe an original case of acute longitudinally extensive transverse myelopathy following single heroin and cocaine intravenous exposure after a long period of abstinence confirmed by toxicological hair and retrospective urine drug analysis. This case could provide new insights in the understanding of this rare neurological complication.

Objective: The aim of this paper was to assess the relationships among chemical, phase and structural composition and etiopathogenic factors of non-infectious phosphate calculi formed in patients with low and high urinary phosphate concentrations, and to characterize the mechanism of their formation related on biochemical results. Material and Methods: Twelve samples of phosphate renal calculi were obtained, 4 from patients with low phosphaturia and 6 from patients with high urinary phosphate concentrations. Their chemical composition was determined qualitatively by energy dispersive X-ray analysis and quantitatively by spectrophotometric and thermal analysis; and their phase composition was determined by Fourier transform infrared transmission spectroscopy and X-ray diffraction. The structure of the calculi was assessed by scanning electron microscopy. Results: Non-infectious phosphate renal calculi of patients with low phosphaturia consist of poorly crystalline carbonate hydroxyapatite, whereas those of patients with high urinary phosphate concentrations consist of poorly crystalline hydroxyapatite with some amount of calcium oxalate crystals. Calculi of patients with high urinary phosphate concentrations are formed at urinary supersaturation with respect to hydroxyapatite and calcium oxalate about 4 times higher than in patients with low phosphaturia. Conclusion: In patients with low phosphaturia, the non-infectious phosphate renal calculi are formed in urine near pH 7 and contain only poorly crystalline carbonate hydroxyapatite. In patients with high urinary phosphate concentrations and hypercalciuria, the calculi are formed in urine near pH 6 and consist of both poorly crystalline hydroxyapatite and some amount of calcium oxalate crystals.

Serum paraoxonase 1 (PON1) has been reported to be an important contributor to the antioxidant and anti-inflammatory activities of HDL, avoiding LDL oxidation. The activity of this enzyme is reduced in patients with renal insufficiency, caused by elevated oxidative stress and disturbances of apolipoprotein metabolism. Therapeutic utilization of antioxidants to control renal oxidative stress may be an effective therapy in renal protection. The aim was to investigate the protective effects of several antioxidant compounds against the oxidative stress associated to renal failure induced by ethylene glycol (EG), focusing on the possible role of serum PON1 activity. Fifty-four male Wistar rats were randomly assigned to six groups ( n = 9): an untreated control (C) group, an EG-treated group, a catechin (CAT)-treated group, an epicatechin (EPI)-treated group, a quercetin (QUE)-treated group and a folk herbal extract (FHE)-treated group. After 16 d of treatment, calcium oxalate lithiasis was induced in the rats using EG. After eight days (treatment + EG), the animals were sacrificed. EG treatment impaired kidney composition, increased oxidative damage, and decreased serum paraoxonase and arylesterase activities. CAT, QUE and the FHE Fagolitos improved oxidative status by enhancing antioxidant defenses – superoxide dismutase and PON1 activities – and reducing oxidative damage, thus reinforcing the idea of a possible role of PON1 in the protective effects of QUE against the deleterious consequences of oxidative stress in kidney.

Renal stone formation is a multifactorial process depending in part on urine composition. Other parameters relate to structural or pathological features of the kidney. To date, routine laboratory estimation of urolithiasis risk has been based on determination of urinary composition. This process requires collection of at least two 24 h urine samples, which is tedious for patients. The most important feature of urinary lithogenic risk is the balance between various urinary parameters, although unknown factors may be involved. The objective of this study was to compare data obtained using a commercial kit with those of a laboratory prototype, using a multicentre approach, to validate the utility of these methods in routine clinical practice.A simple new commercial test (NefroPlus®; Sarstedt AGCo., Nümbrecht, Germany) evaluating the capacity of urine to crystallize calcium salts, and thus permitting detection of patients at risk for stone development, was compared with a prototype test previously described by this group. Urine of 64 volunteers produced during the night was used in these comparisons. The commercial test was also used to evaluate urine samples of 83 subjects in one of three hospitals.Both methods were essentially in complete agreement (98%) with respect to test results. The multicentre data were: sensitivity 94.7%; specificity 76.9%; positive predictive value (lithogenic urine) 90.0%; negative predictive value (non-lithogenic urine) 87.0%; test efficacy 89.2%.The new commercial NefroPlus test offers fast and cheap evaluation of the overall risk of development of urinary calcium-containing calculi.

Chemical composition of internally non-homogeneous phosphate stones should be related to the conditions prevailing during the formation of each individual part.The object of this paper was to provide a detailed study of phosphate stone composition on the micro- and macro-scales.Fine inner structure, chemical and phase composition of 10 phosphate calculi from different patients were determined by chemical (wet) analysis, observation by scanning microscope, semi-quantitative determination of Ca, Mg, P and C by energy dispersive X-ray and by X-ray diffraction. Results. Eight calculi are formed by amorphous calcium phosphate and two by hydroxyapatite. Magnesium was inversely related to Ca/P ratio. Point chemical composition of solid phase varies in wide limits, i.e. composition of calculus interior is highly inhomogeneous on the microscale. All studied calculi contained an abundance of organic matter incorporated in their volume; the content of carbon was double the calcium content in molar quantities.Phosphate renal calculi with the low Ca/P molar ratio predominantly consist of amorphous calcium phosphate whereas those with a high Ca/P molar ratio are composed of poorly crystalline hydroxyapatite which can be partially carbonated. Magnesium may be an inhibitor of HAP formation from urine. Abundant organic matter incorporated into the calculus volume indicates its decisive role at stone formation. Variable point composition of stones implies widely varying conditions during their development.

The structures and chemical compositions of valve calcific deposits were investigated. The deposits was chosen arbitrarily and subjected to chemical analysis, observation with scanning microscope, semi-quantitative determination of Ca, Mg, Na, K, P and C elements by energy dispersive X-ray, X-ray diffraction and Fourier transform infrared spectroscopy carried out. These deposits were found to have non-uniform internal structures composed of layers of a structureless aspidinic inorganic material, substantial amounts of voluminous organic material and in a few samples small spheres were also present. Two groups of deposits with distinctly different chemical compositions were identified: one group with a low Ca/P molar ratio (1.59) and the other group with a high (1.82) Ca/P molar ratio. The deposits belonging to the group with a low Ca/P molar ratio contain higher concentration of magnesium and consist of increased amount of amorphous calcium phosphate. The deposits with a high Ca/P molar ratio contain low concentration of magnesium and consist predominantly of carbonated hydroxyapatite. The inorganic material was identified as a poorly crystalline carbonate hydroxyapatite containing molecular water of the average formula Ca9.1Mg0.4(Na,K)(PO4)5.8(CO3)0.3(OH)2. The actual chemical composition of the apatitic solid phase varies not only from deposit to deposit but also within the same deposit. The non-uniform internal structure of the deposits, the occasional presence of spherical particles and the variable point composition of the individual deposits indicate that their formation did not proceed under more or less constant conditions.

Sir,Alpha-pyrrolidinovalerophenone (α-PVP, α-pyrrolidinopentiophenone or flakka) is a synthetic stimulant drug that belongs to the cathinone family.[1] We present a non-fatal α-PVP intoxication wit...

Phytate is a natural product present in urine and biological fluids that is associated with health benefits, such as the prevention of calcium renal stone formation. The available methods for phytate analysis in urine all require elaborate instrumentation and cannot be routinely applied in clinical laboratories. Here, we describe a simple procedure for urinary phytate determination, employing colorimetric detection. Our method requires purification and preconcentration of phytate via solid-phase extraction prior to colorimetric detection employing Fe(III)–thiocyanate. The working linear range of the assay is 0–5 μM phytate. The limit of detection is 0.055 μM. The relative standard deviation obtained upon assay of samples containing 2 μM phytate was 3.5 %. Several urine samples were analyzed using an alternative method based on the detection of phosphorus; the results of the two assays were comparable. Our novel method of phytate analysis in human urine is simple, rapid (3 h for 10 samples), accurate, precise, reliable, and highly sensitive. The assay can be run in most analytical laboratories and does not require sophisticated instrumentation.

Formation of calcium oxalate crystals, either as monohydrate or dihydrate, is apparently unrelated to urinary pH because the solubilities of these salts are practically unaltered at physiologic urinary pH values. However, a urinary pH5.5 or6.0 may induce uric acid or calcium phosphate crystals formation, respectively, which under appropriate conditions may induce the development of the calcium oxalate calculi. We assessed the relationship between the urinary pH and the formation of different types of calculi. A retrospective study in 1,478 patients was done. We determined the composition, macrostructure, and microstructure of the calculi and the urinary pH, 50.9% of calcium oxalate monohydrate unattached calculi were present in patients with urinary pH5.5. We found that 34.1 and 41.5% of calcium oxalate dihydrate calculi were present in patients with urinary pH5.5 and6.0, respectively. Infectious calculi were found primarily in patients with urinary pH6.0 (50.7%). Only calcium oxalate monohydrate papillary calculi were associated with urinary pH between 5.5 and 6.0 (43.1%). Urine of pH5.5 shows an increased capacity to develop uric acid crystals, which can act as a heterogeneous nuclei of calcium oxalate crystals. In contrast, urine of pH6.0 has an increased capacity to develop calcium phosphate crystals, which can act as a heterogeneous nuclei of calcium oxalate crystals. Oxalate monohydrate papillary calculi were associated to pH between 5.5 and 6.0 because the injured papilla acts as a heterogeneous nucleant. Consequently, measurement of urinary pH may be used to evaluate the lithogen risk of given urine.

Objectives Subepithelial hydroxyapatite calcification of renal papilla is thought to be involved in the formation of calcium oxalate monohydrate (COM) papillary calculi. To assess the mechanism of formation, we sought to correlate the fine structure of papillary renal calculi with specific pathophysiologic conditions and urinary alterations. Methods The study included 831 COM papillary renal calculi with established fine inner structures. A total of 24 patients with chronic stone formation were randomly selected, and their urine was collected and analyzed. The case history and lifestyle habits of these patients were obtained. Results The 831 papillary calculi could be classified into 1 of 4 main groups. Type I included small calculi in which COM columnar crystals begin to develop in the concave zone in close contact with papillary tissue. Type II calculi contained a hydroxyapatite core located in or near the concave zone. Type III consisted of calculi that developed on the tip of the papillae and in the concave zone, containing hydroxyapatite, calcified tissue, and calcified tubules. Type IV consisted of papillary calculi in which the core, which is situated near, but not in, the concave zone, is formed by intergrown COM crystals and organic matter. Many factors, including urinary alterations (eg, hyperoxaluria), associated diseases (eg, hypertension, diabetes), and consumption or exposure to cytotoxic substances (eg, analgesic abuse) were associated with these types of calculi. Conclusions Our findings have indicated that injury is the first cause of papillary COM calculus formation, with the location of the injury determining the morphology of the resulting calculus.

Since ancient times, various herbal preparations have been used in renal lithiasis therapy, but conclusive scientific data on their therapeutic effects and efficacy are not available. To address this issue, the present study evaluated the antilithiasic activity of a traditional Mallorcan herbal preparation, and compared its effects with those of the antioxidant flavonoids, catechin and epicatechin. Thirty-six male Wistar rats were assigned randomly to four groups (n = 9): a control group, a catechin (CAT) treatment group, an epicatechin (EPI) treatment group, and a group treated with a folk herbal extract (FHE). After 16 days of treatment, calcium oxalate lithiasis was induced in the rats using ethylene glycol. After 8 days (treatment + ethylene glycol), 24-h rat urine was collected, the animals were sacrificed and their kidneys were removed for histological and chemical analysis. The calcium concentration in kidney tissue was significantly lower in the CAT-treated (2.4 +/- 0.3 mg/g), EPI-treated (1.8 +/- 0.3 mg/g) and FHE-treated (2.1 +/- 0.3 mg/g) groups, than in the control group (5.4 +/- 1.4 mg/g). Examination of paraffin-embedded kidney sections showed that control group rats had the greatest amount of calcification. There were no significant differences between control and treated groups with respect to urinary calcium, magnesium, oxalate and citrate concentrations. These results demonstrate the ability of herbal preparations and antioxidants to prevent the development of papillary and intratubular calcification in the kidney.

We report a unique case of a melamine bladder urinary stone. A physiopathologic mechanism of formation is proposed and discussed.