Determinations of new psychoactive substances in biological matrices with focus on microextraction techniques: a review of fundamentals and state-of-the-art extraction methods

Purpose

This review article provides a detailed discussion of studies in which microextraction techniques are applied for the determination of new psychoactive substances (NPS) in biological samples. Definitions and classifications of NPS are highlighted as well as the fundamentals of the microextraction techniques used in their analyses.

Methods

A complete literature search was carried out with PubMed, Scopus and the World Wide Web using relevant keywords, e.g., NPS, microextraction and biological fluids.

Results

The determinations of NPS in biological samples remain a challenge for analytical laboratories due to its wide diversity of compounds. The utilization of microextraction techniques in this context is still not many. However, the 96 deep well plate for microextraction and microextraction by packed sorbent (MEPS) can be highlighted as the most explored configurations. Microextraction approaches have the potential to be further improved and optimized to provide rapid and low-cost analyses with reliable results.

Conclusions

There is a wide scope of microextraction techniques to be explored in the field of toxicology and NPS determinations. These techniques are compatible with recent trends of automation and miniaturization, which can enable a straightforward workflow for NPS analyses.

     

Impairment of the septal cholinergic neurons in MPTP-treated A30P α-synuclein mice

Dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) are characterized by loss of acetylcholine (ACh) from cortical areas. Clinical studies report positive effects of acetylcholine esterase (AChE) inhibitors in PDD and dementia with Lewy bodies. We here report that the number of neurons expressing a cholinergic marker in the medial septum-diagonal band of Broca complex decreases in A30P α-synuclein-expressing mice during aging, paralleled by a lower AChE fiber density in the dentate gyrus and in the hippocampal CA1 field. After inducing dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), no acute but a delayed loss of cholinergic neurons and AChE-positive fibers was observed, which was attenuated by L-3,4-dihydroxyphenylalanine (DOPA) treatment. Expression of nerve growth factor (NGF) and tyrosine receptor kinase A (TrkA) genes was upregulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride-treated wild type mice, but not in A30P α-synuclein expressing animals. In contrast, upregulation of sortilin and p75^NTR genes was found in the A30P α-synuclein-expressing mice. These results suggest that dopamine deficiency may contribute to the impairment of the septohippocampal system in patients with PDD and that L-3,4-dihydroxyphenylalanine may not only result in symptomatic treatment of the akinetic-rigid syndrome but may also alleviate the degeneration of basal forebrain cholinergic system and the cognitive decline.     

From iPS Cells to Rodents and Nonhuman Primates: Filling Gaps in Modeling Parkinson's Disease

Parkinson's disease (PD) is primarily known as a movement disorder because of typical clinical manifestations associated with the loss of dopaminergic neurons in the substantia nigra. However, it is now widely recognized that PD is a much more complex condition, with multiple and severe nonmotor features implicating additional brain areas and organs in the disease process. Pathologically, typical forms of PD are characterized by the accumulation of α-synuclein-rich protein inclusions known as Lewy bodies and Lewy neurites, although other types of protein inclusions are also often present in the brain. Familial forms of PD have provided a wealth of information about molecular pathways leading to neurodegeneration, but only to add to the complexity of the problem and uncover new knowledge gaps. Therefore, modeling PD in the laboratory has become increasingly challenging. Here, we discuss knowledge gaps and challenges in the use of laboratory models for the study of a disease that is clinically heterogeneous and multifactorial. We propose that the combined use of patient-derived cells and animal models, along with current technological tools, will not only expand our molecular and pathophysiological understanding of PD, but also assist in the identification of therapeutic strategies targeting relevant pathogenic pathways. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.     

Ventricular remodeling in growing rats with experimental diabetes: The impact of swimming training

Diabetic cardiomyopathy is associated with cardiac muscle remodeling, resulting in myocardial dysfunction, whereas exercise training (ET) is a useful nonpharmacological strategy for the therapy of cardiac diseases. This study tested the effects of low-intensity swimming-training on the structural remodeling of the left ventricle (LV) in growing rats with unmanaged experimental diabetes. Thirty-day-old male Wistar rats were divided into four groups (n = 5/group): sedentary-control (SC), exercised-control (EC), sedentary-diabetic (SD), and exercised-diabetic (ED). Swimming-training rats exercised 5 days/week, 90 min/day, with a load of 5% BW during 8 weeks. Sections of LV were stained with Periodic acid-Schiff, Sirius Red, and Gomori's reticulin. Seven days and 8 weeks after streptozotocin (STZ) induction (60 mg kg⁻¹ BW), blood glucose (BG) in the diabetic groups (SD = 581.40 ± 40.48; ED = 558.00 ± 48.89) was greater (p < 0.05) than in their controls (SC = 88.80 ± 21.70; EC = 85.60 ± 11.55). Swimming-training reduced BG by 23 mg/dL in the diabetics (p > 0.05). The LV of diabetic rats had increased interstitial collagen and reticular fibers on the extracellular matrix and presented glycogen accumulation. More importantly, all these adverse tissue changes induced by STZ were attenuated by ET. Together, these findings support the idea of a beneficial role of exercise in the LV remodeling in rats with unmanaged type-1 diabetes mellitus.     

Evolution of endodontic medicine: a critical narrative review of the interrelationship between endodontics and systemic pathological conditions

Odontology - Endodontics has gained emphasis in the scientific community in recent years due to the increase in clinical and in animal models studies focused on endodontic medicine, which aims to...     

The influence of individual characteristics and non‐respiratory diseases on blood eosinophil count

BackgroundBlood eosinophil (B‐Eos) count is an emerging biomarker in the management of respiratory disease but determinants of B‐Eos count besides respiratory disease are poorly described. Therefore, we aimed to evaluate the influence of non‐respiratory diseases on B‐Eos count, in comparison to the effect on two other biomarkers: fraction of exhaled nitric oxide (FeNO) and C‐reactive protein (CRP), and to identify individual characteristics associated with B‐Eos count in healthy controls.MethodsChildren/adolescents (<18 years) and adults with complete B‐Eos data from the US National Health and Nutritional Examination Surveys 2005–2016 were included, and they were divided into having respiratory diseases (n = 3333 and n = 7,894, respectively) or not having respiratory disease (n = 8944 and n = 15,010, respectively). After excluding any respiratory disease, the association between B‐Eos count, FeNO or CRP, and non‐respiratory diseases was analyzed in multivariate models and multicollinearity was tested. After excluding also non‐respiratory diseases independently associated with B‐Eos count (giving healthy controls; 8944 children/adolescents and 5667 adults), the independent association between individual characteristics and B‐Eos count was analyzed.ResultsIn adults, metabolic syndrome, heart disease or stroke was independently associated with higher B‐Eos count (12%, 13%, and 15%, respectively), whereas no associations were found with FeNO or CRP. In healthy controls, male sex or being obese was associated with higher B‐Eos counts, both in children/adolescents (15% and 3% higher, respectively) and adults (14% and 19% higher, respectively) (p < 0.01 all). A significant influence of race/ethnicity was also noted, and current smokers had 17% higher B‐Eos count than never smokers (p < 0.001).ConclusionsNon‐respiratory diseases influence B‐Eos count but not FeNO or CRP. Male sex, obesity, certain races/ethnicities, and current smoking are individual characteristics or exposures that are associated with higher B‐Eos counts. All these factors should be considered when using B‐Eos count in the management of respiratory disease.     

Postpartum depression: A systematic review of the genetics involved

Postpartum depression is one of the most prevalent psychopathologies. Its prevalence is estimated to be between 10% and 15%. Despite its multifactorial etiology, it is known that genetics play an important role in the genesis of this disorder. This paper reviews epidemiological evidence supporting the role of genetics in postpartum depression (PPD). The main objectives of this review are to determine which genes and polymorphisms are associated with PPD and discuss how this association may occur. In addition, this paper explores whether these genes are somehow related to or even the same as those linked to Major Depression (MD). To identify gaps in the current knowledge that require investigation, a systematic review was conducted in the electronic databases PubMed, LILACS and SciELO using the index terms “postpartum depression” and “genetics”. Literature searches for articles in peer-reviewed journals were made until April 2014. PPD was indexed 56 times with genetics. The inclusion criteria were articles in Portuguese, Spanish or English that were available by institutional means or sent by authors upon request; this search resulted in 20 papers. Genes and polymorphisms traditionally related to MD, which are those involved in the serotonin, catecholamine, brain-derived neurotrophic factor and tryptophan metabolism, have been the most studied, and some have been related to PPD. The results are conflicting and some depend on epigenetics, which makes the data incipient. Further studies are required to determine the genes that are involved in PPD and establish the nature of the relationship between these genes and PPD.     

Adjuvant Therapy With Sodium Alendronate for the Treatment of Experimental Periodontitis in Rats

Background: This study assesses the effects of topical sodium alendronate (SA) as an adjuvant to the mechanical treatment of ligature‐induced periodontitis in rats. Methods: Ninety animals were subjected to the induction of periodontitis via the installation of a ligature around the mandibular left first molar. After 7 days, the ligature was removed, and the animals were distributed into the following groups: 1) NT group (n = 30), no treatment; 2) SRP group (n = 30), scaling and root planing (SRP) and local irrigation with physiologic saline solution; and 3) SRP/SA group (n = 30), SRP and local irrigation with SA (10^?5 M). Ten animals from each group were euthanized at 7, 15, and 30 days after treatment. Histologic and histometric analyses were performed in the furcation region. The percentage of bone in the furcation (PBF) was measured. Immunohistochemical analyses for detecting the receptor activator of nuclear factor‐κB ligand (RANKL), osteoprotegerin (OPG), tartrate‐resistant acid phosphatase (TRAP), and activated caspase‐3 were performed at the furcation region. Results: Compared with the other groups, the SRP/SA group showed less local inflammation and better tissue reparation during the entire experiment. There was more PBF in the SRP/SA group than in the other groups at days 7 and 15. Stronger OPG immunolabeling and weaker RANKL immunolabeling were observed in the SRP/SA group at 15 and 30 days. There were fewer TRAP‐positive cells in the SRP/SA group than in the NT group at all of the time points. There was no difference in the number of activated caspase‐3‐positive osteocytes among groups and time points. Conclusion: It can be concluded that topical use of SA as an adjuvant to SRP is effective in the treatment of experimental periodontitis.