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Bioanalysis 2024Validate a method to quantify 1-(5-fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-indole-3-carboxamide (5F-CUMYL-PICA) and methyl 2-[[1-(5-fluoropentyl) indole-3-carbonyl]...
Validate a method to quantify 1-(5-fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-indole-3-carboxamide (5F-CUMYL-PICA) and methyl 2-[[1-(5-fluoropentyl) indole-3-carbonyl] amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA) in blood samples using GC-MS/MS. A solid-phase extraction (SPE) method has been developed to quantify 5F-MDMB-PICA and 5F-CUMYL-PICA in authentic human blood samples. The limit of detection (LOD) was 0.1 and 0.11 ng/ml for 5F-CUMYL-PICA and 5F-MDMB-PICA, respectively, while the limit of quantification (LOQ) was 0.50 ng/ml for both two compounds. Recovery was 91.40, 82.54 and 85.10% for SPE, supported liquid extraction (SLE) and ISOLUTE C18; matrix effects 15, 24 and 22.5% for SPE, SLE and ISOLUTE C18; accuracy was 2.4-5.5 and 3.9-7.3% for SPE, SLE and ISOLUTE C18, while precision was 4.6-7.7 and 6.4-8.3% for SPE, SLE and ISOLUTE C18, respectively. The concentrations of 5F-CUMYL-PICA and 5F-MDMB-PICA in the authentic human blood samples were 2.18 and 3.07 ng/ml, respectively. The validated method was successfully used in supporting the quantification of analytes in blood.
Topics: Humans; Gas Chromatography-Mass Spectrometry; Cannabinoids; Tandem Mass Spectrometry; Limit of Detection; Solid Phase Extraction; Indoles
PubMed: 38466892
DOI: 10.4155/bio-2023-0185 -
Anatomical Record (Hoboken, N.J. : 2007) Jan 2024To date, several studies describe post-hatching ontogenetic variation in birds; however, none of these studies document and compare ontogenetic variation of the entire...
To date, several studies describe post-hatching ontogenetic variation in birds; however, none of these studies document and compare ontogenetic variation of the entire skull in multiple avian species. Therefore, we studied ontogenetic skull variation of two bird species with very different ecologies, Pica pica, and Struthio camelus, using μCT based 3D reconstructions. For each specimen, we performed bone-by-bone segmentation in order to visualize and describe the morphological variation of each bone during ontogeny and estimated the average sutural closure of the skulls to identify different ontogenetic stages. Although bone fusion of P. pica occurs more rapidly than that of S. camelus the general sequence of bone fusion follows a similar trend from posterior to anterior, but a more detailed analysis reveals some interspecific variation in the fusion patterns. Although growth persists over a longer period in S. camelus than in P. pica and adults of the former species are significantly larger, the skull of the most mature S. camelus is still less fused than that of P. pica. Different growth and fusion patterns of the two species indicate that the interspecific ontogenetic variation could be related to heterochronic developments. Nevertheless, this hypothesis needs to be tested in a broader phylogenetic framework in order to detect the evolutionary direction of the potential heterochronic transformations.
Topics: Animals; Cranial Sutures; Phylogeny; Struthioniformes; Pica; Skull; Biological Evolution
PubMed: 37338258
DOI: 10.1002/ar.25275 -
Neurosurgical Focus: Video Oct 2022A 47-year-old female with a history of a ruptured left posterior inferior cerebellar artery (PICA) aneurysm, status post coil embolization and retreatment for...
A 47-year-old female with a history of a ruptured left posterior inferior cerebellar artery (PICA) aneurysm, status post coil embolization and retreatment for recurrence, presented with evidence of a recurrent dissecting PICA aneurysm. Given that these aneurysms are considered high risk and have a greater propensity for rupture than anterior circulation aneurysms, retreatment was recommended. With the patient's strong preference for endovascular therapy, flow diversion with a Silk Vista Baby was performed. Given the low-profile design of the device, a radial artery approach and coaxial technique were used to deploy the flow diverter. The device was successfully placed, with complete obliteration of the aneurysm after 1 year. The video can be found here: https://stream.cadmore.media/r10.3171/2022.7.FOCVID2247.
PubMed: 36425264
DOI: 10.3171/2022.7.FOCVID2247 -
Interventional Neuroradiology : Journal... Dec 2021Flow diversion is commonly used to treat intracranial aneurysms in various regions of the cerebral vasculature, but is only approved for use in the internal carotid...
BACKGROUND AND PURPOSE
Flow diversion is commonly used to treat intracranial aneurysms in various regions of the cerebral vasculature, but is only approved for use in the internal carotid arteries. Treatment of distal PICA aneurysms with PED is sometimes performed but has not been well studied. Here, we report our experience with flow diversion of distal PICA aneurysms with PED.
MATERIALS AND METHODS
Clinical and angiographic data of eligible patients was retrospectively obtained and assessed for key demographic characteristics and clinical and angiographic outcomes. Principal outcomes included rates of aneurysm occlusion, ischemic or hemorrhagic complication, technical complication, and in-stent stenosis.
RESULTS
Three female and 2 male patients underwent placement of PED in the PICA for treatment of 5 distal PICA aneurysms. Clinical and angiographic follow-up was obtained for all patients. Complete aneurysm occlusion was observed in 100% (5/5) of treated aneurysms at 6 month and longest angiographic follow-up. While there were no ischemic or device-related complications, delayed hemorrhagic complications occurred in 20% (1/5) of patients.
CONCLUSION
Pipeline embolization of distal PICA aneurysms can be performed in select patients. Further study is necessary in larger cohorts to better define clinical scenarios in which flow diversion in the distal PICA should be considered.
Topics: Cerebral Angiography; Embolization, Therapeutic; Endovascular Procedures; Female; Humans; Intracranial Aneurysm; Male; Retrospective Studies; Treatment Outcome; Vertebral Artery
PubMed: 33892602
DOI: 10.1177/15910199211013195 -
The Journal of Craniofacial Surgery Oct 2022For the complex posterior inferior cerebellar artery (PICA) aneurysms, standard microsurgical or endovascular technical options were not feasible. To determine the...
BACKGROUND
For the complex posterior inferior cerebellar artery (PICA) aneurysms, standard microsurgical or endovascular technical options were not feasible. To determine the efficacy and outcomes of bypass surgery for complex PICA aneurysms, the authors herein review our recent surgical experience for complex PICA aneurysms.
METHODS
The authors retrospectively reviewed our experience of extracranial-intracranial bypass and intracranial-intracranial bypass surgery in treatment of proximal and distal complex PICA aneurysms at our institution from 2016 to 2020.
RESULTS
Twelve patients harboring 12 complex PICA aneurysms received bypass surgery at our institution. Seven (58.3%) patients with proximal PICA aneurysms underwent extracranial-intracranial bypass. Five (41.7%) patients with distal PICA aneurysms accepted intracranial-intracranial bypass. The postoperative symptom improvement: Of the 6 patients with preoperative hypoperfusion or ischemic of the cerebellar hemisphere, the symptom resolved in 5 patients, improved in 1 patient, of 5 patients with preoperative mass effect, the symptom resolved in 5 patients. During the follow-up period, ten patients had a modified Rankin scale (mRS) score of 0 to 1, and 1 patient had an mRS score of 2. One patient had an mRS score of 3. The long-term graft patency rate was 91.7%. All patients had no recurrence of intracranial aneurysm.
CONCLUSIONS
Base on the complexity of anatomy structure and the vascular architecture, an individualized strategy was proposed for each patient. The use of different types of bypass procedures (occipital artery-PICA end-to-end bypass, PICA-PICA end-to-end anastomosis, and/or occipital artery graft) can safely and effectively manage these complex PICA aneurysms.
Topics: Cerebellum; Cerebral Revascularization; Humans; Intracranial Aneurysm; Retrospective Studies; Vertebral Artery
PubMed: 35119411
DOI: 10.1097/SCS.0000000000008507 -
Animals : An Open Access Journal From... Apr 2021The prevalence and cooccurrence of pica towards different target materials were investigated using prospective data from three questionnaires completed by owners...
The prevalence and cooccurrence of pica towards different target materials were investigated using prospective data from three questionnaires completed by owners participating in a longitudinal study of UK pet cats. Pica towards one or more material types was reported in 42.9% (229/534), 32.0% (171/534), and 30.9% (165/534) of cats aged approximately 6, 12, and 18 months, respectively. At all timepoints, it was most common for only one material type to be targeted. Associations between potential explanatory variables and "chronic pica" (pica exhibited at all three timepoints) were also explored. Multivariable logistic regression revealed moving to a new house when the cat was aged approximately 6-12 months, renting rather than owning a home, and living in a household without a dog(s) when the cat was aged 2-4 months increased the odds of chronic pica occurrence. This study provides novel data from a cohort of UK pet cats and it is hoped this will increase the understanding of pica and provide direction for areas for future research.
PubMed: 33921455
DOI: 10.3390/ani11041101 -
World Neurosurgery Mar 2022Vertebral artery dissection (VAD) is a rare cerebrovascular disease that can lead to permanent morbidity or mortality. Open surgery for VAD is challenging; therefore,...
BACKGROUND
Vertebral artery dissection (VAD) is a rare cerebrovascular disease that can lead to permanent morbidity or mortality. Open surgery for VAD is challenging; therefore, most cases are managed via endovascular techniques. There are several surgical methods for VAD treatment, including trapping or proximal occlusion with or without bypass; however, the standard treatment protocol is not well established. The aims of this study were to demonstrate surgical strategies, surgical outcomes, and complications of each method and to propose an algorithm to select the appropriate procedure.
METHODS
This study included 22 patients with VAD who underwent open surgical treatment between January 2015 and December 2019 and were retrospectively reviewed and evaluated for postoperative outcomes and complications.
RESULTS
Proximal occlusion, trapping, occipital artery-posterior inferior cerebellar artery (PICA) bypass with blind-alley formation, and occipital artery-PICA with trapping were performed in 13, 2, 5, and 2 patients. The surgical procedure depended on the type of VAD: pre-PICA, PICA, post-PICA, and non-PICA. All VADs were completely obliterated after surgery. Obliteration occurred immediately for 18 patients (81.8%) and within 1 week for 4 patients (18.2%). There was no postoperative bleeding or PICA infarction. Favorable outcome at 3 months after operation was achieved in 100% for good-grade patients and 86.4% overall.
CONCLUSIONS
Open surgery can be a safe and effective treatment of VAD when surgical strategies are carefully selected. Angioarchitecture and the type of VAD influence the selection of the surgical method.
Topics: Cerebellum; Endovascular Procedures; Humans; Intracranial Aneurysm; Retrospective Studies; Treatment Outcome; Vertebral Artery; Vertebral Artery Dissection
PubMed: 34954059
DOI: 10.1016/j.wneu.2021.12.057 -
Eating and Weight Disorders : EWD Aug 2020Pica is defined as a feeding and eating disorder where there is consumption of nonnutritive substances not consistent with cultural practices or social norms. Its... (Review)
Review
BACKGROUND
Pica is defined as a feeding and eating disorder where there is consumption of nonnutritive substances not consistent with cultural practices or social norms. Its aetiology is still unknown, as its prevalence and optimal treatment, which seem to vary with patients' characteristics and the specific behaviours involved.
OBJECTIVES
The authors present a case report of pica treated with copper supplementation, with further diagnostic and treatment considerations.
METHODS
Clinical records and interviews were used. A review was conducted using PubMed database.
RESULTS
A 59-year-old patient, diagnosed with paranoid schizophrenia, presented with sideroblastic anaemia secondary to zinc-induced copper deficiency in the context of pica. These behaviours ceased with copper supplementation. After 2-year remission, the patient was discontinued on oral copper. One week after, pica behaviours reoccurred, with further remission with renewed copper treatment. Based on temporal relationship, we propose that there might be an association between copper supplementation and pica, not related to its plasma levels.
CONCLUSIONS
As far as we know, this is the first case report in the literature with such a long-term follow-up of pica treatment. Our findings challenge the cause-effect relation between micronutrient deficiency and pica and prompts further research in the non-adaptive theories of this poorly understood clinical entity.
Topics: Copper; Humans; Middle Aged; Pica
PubMed: 31273687
DOI: 10.1007/s40519-019-00739-z -
Archives of Toxicology Nov 2022Synthetic cannabinoid receptor agonists (SCRAs) pose a danger to public health. This study focused on individuals experiencing recreational drug toxicity who had used...
Synthetic cannabinoid receptor agonists (SCRAs) pose a danger to public health. This study focused on individuals experiencing recreational drug toxicity who had used 5F-MDMB-PICA.Patient records were evaluated regarding vital signs, Glasgow Coma Scale (GCS) and clinical features. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) confirmed and quantified the presence of 5F-MDMB-PICA (and/or metabolites) as the only SCRA present in the serum of 71 patients. Cannabinoid activity was evaluated by a cannabinoid receptor (CB) bioassay, to assess the relationship between serum concentrations and ex vivo human CB activation potential. Furthermore, a link with the clinical presentation was appraised.5F-MDMB-PICA and five metabolites were pharmacologically profiled in vitro, revealing theoretically possible contributions of two active in vivo metabolites to overall cannabinoid activity. Serum concentrations of 5F-MDMB-PICA were correlated to the ex vivo cannabinoid activity, revealing a sigmoidal relationship. The latter could also be predicted based on pharmacological characterization of 5F-MDMB-PICA and its metabolites and an in-depth investigation of the bioassay outcome. Clinically, the GCS showed a significant trend (decrease) with increasing ex vivo cannabinoid activity.This is the first study to evaluate possible toxic effects of 5F-MDMB-PICA in a unique large patient cohort. It allows a better understanding of 5F-MDMB-PICA and metabolites in humans, suggesting a negligible contribution by 5F-MDMB-PICA metabolites to the overall cannabinoid activity in serum. Additionally, this work shows that in vitro pharmacological characterization allows close prediction of an individual's ex vivo CB activity, the latter showing a relationship with the level of consciousness.
Topics: Cannabinoid Receptor Agonists; Cannabinoids; Humans; Illicit Drugs; Receptor, Cannabinoid, CB1; Receptors, Cannabinoid
PubMed: 35962200
DOI: 10.1007/s00204-022-03355-6 -
Pharmacology, Biochemistry, and Behavior Oct 2022Synthetic cannabinoid receptor agonists (SCRAs) are novel psychoactive substances that bind to and activate CB receptors in the brain. The structural manipulations...
Synthetic cannabinoid receptor agonists (SCRAs) are novel psychoactive substances that bind to and activate CB receptors in the brain. The structural manipulations observed in newer SCRAs suggest that manufacturers have incorporated modern drug development techniques into their repertoire, often producing higher CB receptor affinity than Δ-tetrahydrocannabinol (Δ-THC). This study examined nine SCRAs recently detected by forensic surveillance, some of which caused fatalities: 5F-MDMB-PICA, FUB-144, 5F-MMB-PICA, MMB-4en-PICA, MMB-FUBICA, 5F-EDMB-PINACA, APP-BINACA, MDMB-4en-PINACA, and FUB-AKB48. Compounds were evaluated for CB and CB receptor binding affinity and functional activation and for their effects on body temperature, time course, and pharmacological equivalence with Δ-THC in Δ-THC drug discrimination in mice. All SCRAs bound to and activated CB and CB receptors with high affinity, with similar or greater affinity for CB than CB receptors and stimulated [S]GTPγS binding in CB and CB expressing cell membranes. All compounds produced hypothermia, with shorter latency to peak effects for SCRAs than Δ-THC. All SCRAs fully substituted for Δ-THC in drug discrimination at one or more doses. Rank order potency in producing in vivo effects mostly aligned with rank order CB receptor affinities. Potencies for Δ-THC-like discriminative stimulus effects were similar across sex except Δ-THC was more potent in females and 5F-MMB-PICA was more potent in males. In summary, 5F-EMDB-PINACA, 5F-MDMB-PICA, MDMB-4en-PINACA, FUB-144, FUB-AKB48, 5F-MMB-PICA, MMB-4en-PICA, and MMB-FUBICA are potent and efficacious SCRAs with pharmacology like that of past SCRAs that have been abused in humans. In contrast, APP-BINACA was efficacious, but had lower potency than most past SCRAs.
Topics: Animals; Cannabinoid Receptor Agonists; Cannabinoids; Dronabinol; Guanosine 5'-O-(3-Thiotriphosphate); Humans; Male; Mice; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2
PubMed: 36154844
DOI: 10.1016/j.pbb.2022.173467