Determination of Traditional and Designer Benzodiazepines in Urine through LC-MS/MS.

Background: The detection of new designer benzodiazepines in biological fluids and tissues, together with the traditional ones, could represent an important analytical update for laboratories performing clinical and forensic toxicological analysis.

Objective: A liquid chromatography tandem mass spectrometry method (LC-MS/MS) has been developed, fully validated, and applied to a cohort of real urine samples collected from patients under withdrawal treatment and from intoxication cases.

Methods: 100 μL urines were added to a buffer solution containing deuterated internal standards; the samples were then extracted through a liquid/liquid procedure, dried under a nitrogen stream, and reconstituted in mobile phase.

Ethyl glucuronide in hair: A 5-year retrospective cohort study in subjects sanctioned for driving under the influence of alcohol and psychoactive substances.

The evaluation of drinking behaviors can help in limiting high-risk situation, such as driving under the influence (DUI). We investigate ethyl glucuronide in hair (hEtG) levels to evaluate alcohol consumption behavior in subjects followed up after having been charged for DUI of psychoactive substances and/or alcohol. We performed a retrospective observational cohort study on 4328 subjects over 18 years old who underwent hEtG analysis in the period 2015-2019 in the Italian Province of Pavia.

Comparison of Two Immunoassay Screening Methods and a LC-MS/MS in Detecting Traditional and Designer Benzodiazepines in Urine.

Sensitive and specific immunoassay screening methods for the detection of benzodiazepines in urine represent an important prerequisite for routine analysis in clinical and forensic toxicology. Moreover, emerging designer benzodiazepines force labs to keep their methodologies updated, in order to evaluate the reliability of the immunochemical techniques. This study aimed at evaluating the sensitivity and specificity of two different immunoassay methods for the detection of benzodiazepines in urine, through a comparison with the results obtained by a newly developed liquid chromatographic tandem mass spectrometric (LC-MS/MS) procedure.

New Synthetic Cathinones and Phenylethylamine Derivatives Analysis in Hair: A Review.

The analysis of psychoactive substances in hair is of great importance for both clinical and forensic toxicologists since it allows one to evaluate past and continuative exposure to xenobiotics. In particular, a new challenge is represented by new psychoactive substances: Among this new class of drugs of abuse, synthetic cathinone and phenethylamine derivatives are often detected in biological samples. Hence, there is a growing need to develop new analytical procedures or improve old ones in order to conduct evaluations of these emerging substances.

Analysis of Cannabinoids and Metabolites in Dried Urine Spots (DUS).

Dried urine spots (DUS) represent a potential alternative sample storage for forensic toxicological analysis. The aim of the current study was to develop and validate a liquid chromatographic tandem mass spectrometric procedure for the detection and quantitative determination of cannabinoids and metabolites in DUS. A two-step extraction was performed on DUS and urine samples.

Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome.

Study Objectives: To carry out an analysis of leg movement activity during sleep in a polysomnography dataset of patients with multiple sclerosis (MS) in comparison to idiopathic restless legs syndrome (iRLS) and healthy controls.

Methods: In this cross-sectional, observational, instrumental study, 57 patients (males/females: 11/46; mean age 46.2 ± 10.

A case report on fatal intoxication by tapentadol: Study of distribution and metabolism.

We report a case in which a tapentadol acute intoxication was suspected as the cause of death of a 39-year-old man: approximately two days after death, cardiac and femoral blood, as well as urine, bile, gastric content and chest hair, were collected during the autopsy. Tapentadol was detected before and after hydrolysis in femoral (530 ng/mL unconjugated and 1570 ng/mL conjugated) and cardiac (680 ng/mL unconjugated and 3440 ng/mL conjugated) blood, and additionally in bile (3200 ng/mL), urine (9300 ng/mL), chest hair (2850 pg/mg) and gastric content. LC-QTOF screening analysis confirmed the presence of five different tapentadol metabolites (tapentadol-O-glucuronide, tapentadol-O-sulfate, N-desmethyltapentadol, N-desmethyltapentadol-glucuronide and N-desmethyltapentadol-O-sulfate), in urine, bile, cardiac and femoral blood.

New insights on fibrodysplasia ossificans progressiva: discussion of an autoptic case report and brief literature review.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition with soft tissue progressive ossification, leading to severe disability. We describe a 27-years-old female affected by FOP who died after a fall. An autopsy was performed.

Restless legs syndrome and periodic limb movements in 86 patients with multiple sclerosis.

Study Objectives: To assess the frequency of restless legs syndrome (RLS), periodic limb movements during sleep (PLMS), and their overlap in a large sample of patients with multiple sclerosis (MS). To compare clinical and paraclinical findings among four subgroups of patients: RLS-/PLMS- (patients without RLS and PLMS), RLS+/PLMS- (patients with RLS and without PLMS), RLS-/PLMS (patients without RLS and with PLMS), and RLS+/PLMS+ (patients with both RLS and PLMS).

Methods: In this cross-sectional, observational, instrumental study, 86 patients (M/F: 27/59; mean age 48.

A comparison between two different dried blood substrates in determination of psychoactive substances in postmortem samples.

Purpose: Whatman™ 903 cards represent a valid type of support for collection, storage, and analysis of dried blood spots (DBS). Whatman™ FTA (Flinders Technology Associates) are a type of cards soaked in chemicals that cause denaturation of proteins, while preserving DNA and ensuring the safe handling of DBS; to date, these cards are still rarely employed in forensic toxicology. The aim of this study was to analyze several psychoactive substances on not-dried blood on the two different cards and to compare the qualitative and quantitative results.

Importance of segmental hair analysis in a suspected case of attempted homicide by flocoumafen and difenacoum.

The 4-hydroxycoumarin derivatives are the most used rodenticides and act as classical anticoagulants, interfering with the production of clotting factors in liver by antagonizing the action of vitamin K reductase, thereby inhibiting recycling of vitamin K1, involved in activation of blood clotting factors, resulting in massive bleeding. In this paper, we present the case of a 72-year old man providing abnormal coagulation parameters (PT-INR between 16.1 and 19.

Determination of fentanyl and 19 derivatives in hair: Application to an Italian population.

Nowadays fentanyl and its analogs represent the most numerous group among synthetic opioid and, due to their higher potency in comparison to traditionl opioids, the main cause of the critical increase of fatal intoxications opioids-intake related in the USA. We developed an LC-MS/MS method for the detection and quantification of fentanyl and its analogs in hair, then applied to 117 real samples, 97 collected from drugs users and 20 from postmortem cases of drugs addicts. The ionization and MRM parameters have been optimized for 27 molecules: 20 reached the acceptance criteria for identification and quantification.

REG-O3 chimeric peptide combining growth hormone and somatostatin sequences improves joint function and prevents cartilage degradation in rat model of traumatic knee osteoarthritis.

Objective: REG-O3 is a 24-aminoacid chimeric peptide combining a sequence derived from growth hormone (GH) and an analog of somatostatin (SST), molecules displaying cartilage repair and anti-inflammatory properties, respectively. This study aimed to investigate the disease-modifying osteoarthritis drug (DMOAD) potential of REG-O3 by analyzing its effect on pain, joint function and structure, upon injection into osteoarthritic rat knee joint.

Design: Osteoarthritis was induced in the right knee of mature male Lewis rats (n = 12/group) by surgical transection of the anterior cruciate ligament (ACLT) combined with partial medial meniscectomy (pMMx).

Ethyl glucuronide hair testing: A review.

Ethyl glucuronide (EtG) is a minor, non-oxidative ethanol metabolite that can be detected in several matrices (e.g. blood, urine, hair, meconium) for variable periods of time.

From CT scanning to 3D printing technology: a new method for the preoperative planning of a transcutaneous bone-conduction hearing device.

The aim of the present study was to assess the feasibility and utility of 3D printing technology in surgical planning of a transcutaneous bone-conduction hearing device (Bonebridge) (BB), focusing on the identification of the proper location and placement of the transducer. 3D printed (3DP) models of three human cadaveric temporal bones, previously submitted to CT scan, were created with the representation of a topographic bone thickness map and the sinus pathway on the outer surface. The 3DP model was used to detect the most suitable location for the BB.

Low concentration structural dynamics of lanreotide and somatostatin-14.

Lanreotide, a synthetic cyclic octapeptide, analogue of the peptide hormone somatostatin-14 (SST-14), is routinely used as a long-acting medication in the management of neuroendocrine tumors. Despite its therapeutic importance, low concentration structural data is still lacking for lanreotide. In fact, the major part of the previous structural investigations were focused on the remarkable aggregation properties of this peptide, appearing at high concentrations (>5 mM).

Octreotide used for probing the type-II' β-turn CD and Raman markers.

Octreotide, a potent somatostatin (SST) analogue, is used as an antiproliferative drug in numerous endocrine tumors. Previous NMR investigations, basically performed in DMSO, had evidenced a type-II' β-turn structure for this cyclic peptide. However, apart a few incomplete studies by circular dichroism, a systematic analysis of the structural behavior of octreotide in aqueous solution as a function of concentration and ionic strength was still lacking.

Controlled sparse and percolating cross-linking in waterborne soft adhesives.

The effect of low levels of cross-linking on the adhesive and mechanical properties of waterborne pressure-sensitive adhesives was investigated. We have taken advantage of a core-shell latex particle morphology obtained by emulsion polymerization to create a heterogeneous structure of cross-links without major modification of the monomer composition. The latex particles comprise a shell containing cross-linkable diacetone acrylamide (DAAM) repeat units localized on the periphery of a slightly softer core copolymer of very similar composition.

Vibrational analysis of amino acids and short peptides in aqueous media. V. The effect of the disulfide bridge on the structural features of the peptide hormone somatostatin-14.

To emphasize the role played by the S-S bridge in the structural features of somatostatin-14 (SST-14), newly recorded CD and Raman spectra of this cyclic peptide and its open analogue obtained by Cys-->Ser substitution are presented. CD spectra of both peptides recorded in aqueous solutions in the 100-500 microM concentration range are strikingly similar. They reveal principally that random conformers constitute the major population in both peptides.

Interfaces and fluctuations in confined polymeric liquid mixtures: from immiscible to near critical systems.

In this paper the structure of the interface between polymer films is discussed to elucidate fluctuations and confinement effects in fluid polymer mixtures. The neutron reflectivity technique has been employed to investigate the dependence of the structure of the interface on the degree of immiscibility of the polymers over a wide range, as criticality is approached, and to characterize it in terms of intrinsic width, as calculated by mean field theories, and capillary fluctuations. For more immiscible systems, as the degree of incompatibility between the polymers is decreased, the width of the interface increases slowly, and it is independent of the molecular weight of the polymers.

Early-stage roughening of the polymer-polymer interface approaching the glass transition temperature by real-time neutron reflection.

The early-stage roughening of the interface between thin deuterated poly(methyl methacrylate) (d-PMMA) layers on thick polystyrene (PS) films was studied as a function of the temperature using real-time specular neutron reflectivity. By measuring the growth of the interface roughness as a precursor of the dewetting, the characteristic time constant of the early stages of the process was studied as a function of the temperature approaching the glass transition temperature (T(g)) of the two polymers from above and compared with the prediction of the growth of the interface by the spinodal process. Both solid and liquid regimes were probed, in which the viscosity of the thin film or the substrate dominates respectively.

Approaching criticality in polymer-polymer systems.

The interfacial width of polyolefins blends has been probed as a function of distance away from the critical point by using neutron reflectivity. For strongly immiscible polymer pairs, the width of the interface increases slowly when the degree of immiscibility is decreased and the interfacial width varies with the interaction parameter chi of the polymers. Closer to the critical point the dependence on the degree of miscibility becomes stronger and the way in which the interfacial width diverges, as criticality is approached, is related to both the chain length and chi.

Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination.

Progesterone (PROG) is synthesized in the brain, spinal cord and peripheral nerves. Its direct precursor pregnenolone is either derived from the circulation or from local de novo synthesis as cytochrome P450scc, which converts cholesterol to pregnenolone, is expressed in the nervous system. Pregnenolone is converted to PROG by 3beta-hydroxysteroid dehydrogenase (3beta-HSD).

Structural relaxation of spin-cast glassy polymer thin films as a possible factor in dewetting.

Reiter has recently reported a situation in which the dewetting of quasi-solid films is linked to plastic deformation--rather than viscous flow--resulting from capillary forces. Herein we propose that, in thin films of some glassy polymers--especially poly(methyl methacrylate) (PMMA)--prepared by spin-casting from solvent, structural relaxation might impart sufficient stress to cause plastic deformation. We find that PMMA films decrease in thickness by several percent, which is sufficient to create significant stress in those cases in which the film is attached to a rigid substrate.