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Neuropsychopharmacology : Official... Mar 2022Synthetic cannabinoid receptor agonists (SCRAs) are an evolving class of new psychoactive substances found on recreational drug markets worldwide. The indole-containing...
Synthetic cannabinoid receptor agonists (SCRAs) are an evolving class of new psychoactive substances found on recreational drug markets worldwide. The indole-containing compound, 5F-MDMB-PICA, is a popular SCRA associated with serious medical consequences, including overdose and hospitalizations. In vitro studies reveal that 5F-MDMB-PICA is a potent agonist at cannabinoid type 1 receptors (CB), but little information exists regarding in vivo pharmacology of the drug. To this end, we examined the in vitro and in vivo cannabinoid-like effects produced by 5F-MDMB-PICA and related 5F-pentylindole analogs with differing composition of the head group moiety (i.e., 5F-NNEI, 5F-SDB-006, 5F-CUMYL-PICA, 5F-MMB-PICA). In mouse brain membranes, 5F-MDMB-PICA and its analogs inhibited binding to [H]rimonabant-labeled CB and displayed agonist actions in [S]GTPγS functional assays. 5F-MDMB-PICA exhibited the highest CB affinity (K = 1.24 nM) and functional potency (EC = 1.46 nM), but head group composition markedly influenced activity in both assays. For example, the 3,3-dimethylbutanoate (5F-MDMB-PICA) and cumyl (5F-CUMYL-PICA) head groups engendered high CB affinity and potency, whereas a benzyl (5F-SDB-006) head group did not. In C57BL/6J mice, all 5F-pentylindole SCRAs produced dose- and time-dependent hypothermia, catalepsy, and analgesia that were reversed by rimonabant, indicating CB involvement. In vitro K and EC values were positively correlated with in vivo ED potency estimates. Our findings demonstrate that 5F-MDMB-PICA is a potent SCRA, and subtle alterations to head group composition can have profound influence on pharmacological effects at CB. Importantly, measures of CB binding and efficacy in mouse brain tissue seem to accurately predict in vivo drug potency in this species.
Topics: Animals; Cannabinoid Receptor Agonists; Cannabinoids; Indazoles; Mice; Mice, Inbred C57BL; Receptor, Cannabinoid, CB1; Structure-Activity Relationship
PubMed: 34802041
DOI: 10.1038/s41386-021-01227-8 -
Cureus Jul 2020Pica is an unusual condition in which patients crave and chew substances with no nutritional value. Ice pica (pagophagia) is commonly seen in patient with iron...
Pica is an unusual condition in which patients crave and chew substances with no nutritional value. Ice pica (pagophagia) is commonly seen in patient with iron deficiency. People chew ice cubes or add ice to their drinks to cool or refresh themselves, and they may not consider this as an abnormal behavior. Excessive ice chewing/eating can have significant health risks, including electrolyte abnormalities and metabolic disorders. We report a patient admitted to our hospital with severe hyponatremia and seizures due to iron deficiency-associated pagophagia. Ice pica leading to hyponatremia and seizure is not commonly seen in clinical practice. It was a challenging case and the patient was seen and investigated at outpatient clinic for polyuria, though an underlying cause was not identified. Patients may be secretive or reluctant to mention their pica habit. Studies have also shown that most physicians are unaware of pica and most cases can be easily missed.
PubMed: 32742885
DOI: 10.7759/cureus.9330 -
Journal of Ethnopharmacology Jan 2024Xiaobanxia Decoction (XBXD), a traditional antiemetic formula, is effective in preventing chemotherapy-induced nausea and vomiting (CINV), but its underlying mechanism...
ETHNOPHARMACOLOGICAL RELEVANCE
Xiaobanxia Decoction (XBXD), a traditional antiemetic formula, is effective in preventing chemotherapy-induced nausea and vomiting (CINV), but its underlying mechanism has not been fully clarified.
AIM OF THE STUDY
To investigate whether the antiemetic mechanisms of XBXD against CINV is associated with the reduction of GSDME-mediated pyroptosis and the alleviation of gastrointestinal inflammation induced by cisplatin.
MATERIALS AND METHODS
We established the in vivo pica rat model and the in vitro small intestinal epithelial cell (IEC-6 cell) injury model by cisplatin challenge. The levels of ROS, IL-1β, IL-18, HMGB1 were measured by ELISA. The histopathological changes of gastrointestinal (GI) tissues were examined by HE staining. The expression and localization of GSDME in GI tissues were determined by IHC. The GSDME mRNA expression in GI tissues was determined by RT-PCR. The IEC-6 cell viability was detected by CCK-8. The morphology of IEC-6 cells was observed by optical microscope and scanning electron microscopy. Pyroptosis was examined using Hoechst33342/PI staining. The intracellular ROS levels were measured with the fluorescent probe DCFH-DA. The expression levels of JNK, p-JNK, Bax, Bcl-2, caspase-9, caspase-3 and GSDME in GI tissues and IEC-6 cells were determined by WB.
RESULTS
We found that the cumulative kaolin intake (pica behavior, analogous to emesis) significantly increased in cisplatin-treated rats, accompanied by significant inflammatory pathological changes of GI tissues. XBXD decreased the cumulative kaolin intake and alleviated GI inflammation in cisplatin-treated rats by inhibiting the activation of the ROS/JNK/Bax signaling pathway and by reducing GSDME-mediated pyroptosis. Additionally, cisplatin damaged IEC-6 cells by activating GSDME-dependent pyroptosis. XBXD reduced GSDME-mediated IEC-6 cell pyroptotic death by regulating the ROS/JNK/Bax signaling pathway.
CONCLUSIONS
This study suggested that GSDME-mediated pyroptosis greatly contributes to the occurrence of CINV, and suppressing GSDME-mediated pyroptosis is the important antiemetic mechanism of XBXD.
Topics: Rats; Animals; Pyroptosis; Cisplatin; Antiemetics; bcl-2-Associated X Protein; Reactive Oxygen Species; Kaolin; Pica; Antineoplastic Agents; Vomiting; Nausea; Inflammation; Caspase 3
PubMed: 37516392
DOI: 10.1016/j.jep.2023.116970 -
Maternal and Child Health Journal Mar 2016To describe and determine the association between the occurrence of pica and eating attitudes in women with high-risk pregnancies and to determine the prevalence of pica...
OBJECTIVE
To describe and determine the association between the occurrence of pica and eating attitudes in women with high-risk pregnancies and to determine the prevalence of pica during pregnancy.
METHODS
A cross-sectional and prospective 24-month study was conducted with 913 women with high-risk pregnancies. Structured interviews were carried out and the Eating Attitudes Test was applied.
RESULTS
Pica was diagnosed in 5.7 % of the pregnant women, and its most commonly practiced type was geophagia (57.7 %). The association between pica and signs related to the eating attitudes: "to be considered too thin by others" (p < 0.02), and "to spend too much time thinking about food" (p = 0.05); and the association between pica and the risk of both anorexia nervosa and bulimia nervosa (p < 0.01) were statistically significant.
CONCLUSIONS
The absence of validated instruments in the literature for assessing pica reinforces the difficulty of investigating this practice and the need for further studies. Moreover, additional efforts need to focus in the improvement of screening for other eating disorders with obstetric consequences associated with pica and be incorporated into the routine of healthcare professionals.
Topics: Adult; Cross-Sectional Studies; Feeding and Eating Disorders; Female; Humans; Interviews as Topic; Pica; Pregnancy; Pregnancy Complications; Pregnancy, High-Risk; Prevalence; Prospective Studies; Socioeconomic Factors; Young Adult
PubMed: 26558792
DOI: 10.1007/s10995-015-1856-1 -
Cureus Sep 2021Although pica is commonly associated with nutritional deficiencies, it is also observed in psychiatric disorders such as obsessive-compulsive disorder and less commonly...
Although pica is commonly associated with nutritional deficiencies, it is also observed in psychiatric disorders such as obsessive-compulsive disorder and less commonly in schizophrenia. We describe a case of pica in a 34-year-old male with decompensated schizophrenia. Emergency medical services brought the patient from a state facility as he was scavenging and eating foreign objects. Upon initial evaluation, no notable nutritional deficiencies were noted. After surgical removal of foreign objects, he was started on antipsychotics. His pica was determined to be due to his active psychosis involving delusions, disorganized thought processes, and loosening of associations. His psychosis improved on paliperidone intramuscular injection and oral olanzapine, which coincided with reduction and resolution of pica. Our case highlights the need to understand further the exact psychopathology of pica that may not be limited to nutritional deficiencies.
PubMed: 34540508
DOI: 10.7759/cureus.17964 -
Transfusion Apr 2017Pica, the compulsive consumption of ice or other nonnutritious substances, is associated with iron deficiency, a common negative consequence of frequent blood donation.... (Clinical Trial)
Clinical Trial
BACKGROUND
Pica, the compulsive consumption of ice or other nonnutritious substances, is associated with iron deficiency, a common negative consequence of frequent blood donation. Because of this, blood donors, such as those participating in the Strategies to Reduce Iron Deficiency (STRIDE) study, are an ideal population to explore pica and iron deficiency.
STUDY DESIGN AND METHODS
STRIDE was a 2-year intervention trial to assess the effectiveness of iron supplementation for mitigating iron deficiency in frequent blood donors. Subjects completed baseline and follow-up questionnaires that included questions about pica symptoms. In-depth telephone interviews were conducted with 14 of these subjects reporting pica symptoms and eight presumed controls (casual ice chewers) to gain a deeper understanding of pica symptoms and their impact on daily life and to make a final determination on the presence of pica.
RESULTS
Pica was confirmed in five of the 14 subjects reporting symptoms and in two of eight controls. Outcome misclassification based on the questionnaire was attributed to inadequate assessment of several pica symptoms identified during the interview. Comparison of subjects' repeated quantitative iron measurements taken throughout STRIDE with subjects' final adjudicated pica status revealed a positive relationship between development of pica and worsening iron status; the opposite was found in those whose pica symptoms resolved.
CONCLUSION
Continued refinement of pica symptom questions will allow for rapid and accurate detection of pica in frequent blood donors and confirmation of successful treatment with iron supplements.
Topics: Blood Donors; Cohort Studies; Dietary Supplements; Female; Humans; Ice; Iron; Male; Pica; Time Factors
PubMed: 28164344
DOI: 10.1111/trf.13981 -
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 -
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 -
Forensic Toxicology 2017CUMYL-PICA [1-pentyl--(2-phenylpropan-2-yl)-1-indole-3-carboxamide] and 5F-CUMYL-PICA [1-(5-fluoropentyl)--(2-phenylpropan-2-yl)-1-indole-3-carboxamide] are recently...
CUMYL-PICA [1-pentyl--(2-phenylpropan-2-yl)-1-indole-3-carboxamide] and 5F-CUMYL-PICA [1-(5-fluoropentyl)--(2-phenylpropan-2-yl)-1-indole-3-carboxamide] are recently identified recreationally used/abused synthetic cannabinoids, but have uncharacterized pharmacokinetic profiles and metabolic processes. This study characterized clearance and metabolism of these compounds by human and rat liver microsomes and hepatocytes, and then compared these parameters with in vivo rat plasma and urine sampling. It also evaluated hypothermia, a characteristic cannabimimetic effect. Incubation of CUMYL-PICA and 5F-CUMYL-PICA with rat and human liver microsomes suggested rapid metabolic clearance, but in vivo metabolism was prolonged, such that parent compounds remained detectable in rat plasma 24 h post-dosing. At 3 mg/kg (intraperitoneally), both compounds produced moderate hypothermic effects. Twenty-eight metabolites were tentatively identified for CUMYL-PICA and, coincidentally, 28 metabolites for 5F-CUMYL-PICA, primarily consisting of phase I oxidative transformations and phase II glucuronidation. The primary metabolic pathways for both compounds resulted in the formation of identical metabolites following terminal hydroxylation or dealkylation of the -pentyl chain for CUMYL-PICA or of the 5-fluoropentyl chain for 5F-CUMYL-PICA. These data provide evidence that in vivo elimination of CUMYL-PICA, 5F-CUMYL-PICA and other synthetic cannabinoids is delayed compared to in vitro modeling, possibly due to sequestration into adipose tissue. Additionally, the present data underscore the need for careful selection of metabolites as analytical targets to distinguish between closely related synthetic cannabinoids in forensic settings.
PubMed: 28824730
DOI: 10.1007/s11419-017-0361-1