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BACKGROUND: Amide proton transfer (APT) imaging has been proposed as a technique to assess tumor metabolism. However, the relationship between APT imaging and other quantitative modalities including positron emission tomography (PET) has not been investigated in detail. This study aimed to evaluate the clinical usefulness of APT imaging in determining the metabolic status of malignant glioma and to compare findings with those from 11C-methionine (Met)-PET. METHODS: This research analyzed APT imaging data from 20 consecutive patients with malignant glioma treated between January 2022 and July 2023. Patients underwent tumor resection and correlations between tumor activity and intensity of APT signal were investigated. We also compared 11C-Met-PET and APT imaging for the same regions of the perifocal tumor invasion area. RESULTS: Clear, diagnostic APT images were obtained from all 20 cases. Mean APT intensity (APTmean) was significantly higher in the glioblastoma (GBM), IDH wild type group (27.2 ± 12.8%) than in other gliomas (6.0 ± 4.7%; p < 0.001). The cut-off APTmean to optimally distinguish between GBM and other malignant gliomas was 12.8%, offering 100% sensitivity and 83.3% specificity. These values for APTmean broadly matched the tumor-to-contralateral normal brain tissue ratio from 11C-Met-PET analysis (r = 0.66). The APT signal was also observed in the gadolinium non-contrast region on T1-weighted imaging, appearing to reflect the surrounding tumor-infiltrated area. CONCLUSIONS: APT imaging can be used to evaluate the area of tumor invasion, similar to 11C-Met-PET. APT imaging revealed low invasiveness in patients and was useful in preoperative planning for tumor resection, facilitating maximum tumor resection including the tumor invasive area.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Prótons , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/metabolismo , Metionina , Amidas/metabolismo , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/metabolismo , Tomografia por Emissão de Pósitrons/métodos , RacemetioninaRESUMO
BACKGROUND: Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS). METHODS: Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated. RESULTS: In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p < 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were > 1.25, > 1.09, and > 0.88, respectively. CONCLUSIONS: Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.
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Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Glioblastoma , Humanos , Ácido Glutâmico/metabolismo , Creatina/metabolismo , Glioblastoma/complicações , Glioblastoma/diagnóstico por imagem , Ácido Láctico/metabolismo , Ácido Aspártico/metabolismo , Espectroscopia de Ressonância MagnéticaRESUMO
Medulloepithelioma is a rare and highly malignant primitive neuroectodermal tumor that usually occurs in childhood. The diagnosis of this entity required only morphological analysis until the World Health Organization classification of central nervous system (CNS) tumors was revised, and now genetic analysis is necessary. We report a case of medulloepithelioma in the posterior cranial fossa that was diagnosed by both morphological and genetic analyses based on this classification. A 10-month-old girl was admitted to our hospital with consciousness disturbance and vomiting. Neuroimaging revealed a partially calcified mass and cyst formation in the posterior cranial fossa. Partial resection of the tumor was performed and histological findings revealed multilayered rosettes with LIN28A staining, but genetic analysis showed no amplification of the C19MC microRNA cluster at 19q14.32. Therefore, we diagnosed the tumor as medulloepithelioma belonging to other CNS embryonal tumors. The patient was immediately treated with systemic high-dose chemotherapy. Follow-up neuroimaging 10 months later showed no signs of recurrence. Medulloepitheliomas are difficult to diagnose by routine HE staining and require combined morphological, immunohistochemical and genetic analyses to provide an accurate diagnosis.
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Neoplasias Encefálicas/diagnóstico , Fossa Craniana Posterior , Tumores Neuroectodérmicos Primitivos/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Fossa Craniana Posterior/diagnóstico por imagem , Fossa Craniana Posterior/patologia , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Imuno-Histoquímica , Lactente , Antígeno Ki-67/metabolismo , MicroRNAs/metabolismo , Tumores Neuroectodérmicos Primitivos/diagnóstico por imagem , Tumores Neuroectodérmicos Primitivos/genética , Tumores Neuroectodérmicos Primitivos/patologia , Proteínas de Ligação a RNA/metabolismoRESUMO
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rapidly growing malignant tumor that typically shows sensitivity to high-dose methotrexate-based chemotherapy. Rapid diagnosis and early chemotherapy are thus essential to obtain the best outcome. To accomplish this, we have performed intraoperative rapid immunohistochemistry (IHC) as an examination method for obtaining accurate diagnosis during surgery. Here, to markedly enhance the accuracy of intraoperative rapid IHC, the utility of adding intraoperative rapid examinations of cytology and flow cytometry (FCM) in addition to rapid IHC was investigated. METHODS: From April 2020 to January 2024, we performed intraoperative rapid IHC in 35 patients with intracranial lesions, including PCNSL. In the last 17 of these cases, intraoperative cytology and FCM were also performed simultaneously. We examined the utility of examination methods in determining treatment strategies for brain tumors, particularly early therapeutic intervention for PCNSL. RESULTS: Postoperative final pathological diagnoses from paraffin-embedded sections were as follows: 20 PCNSLs, 9 glioblastomas, 4 diffuse gliomas, 1 meningioma, and 1 inflammatory disorder. In all cases, results from intraoperative rapid IHC were consistent with final pathological diagnoses from paraffin-embedded sections. In two cases, results from conventional intraoperative rapid pathological diagnoses based on morphological assessments using frozen sections changed with the addition of intraoperative rapid IHC. Further, the time from surgery to initiation of chemotherapy for PCNSL was significantly reduced by adding cytology and FCM to rapid IHC alone (only rapid IHC group: 7.3 days, combination group: 1.6 days; p = 0.015). CONCLUSIONS: The combination of rapid intraoperative IHC, cytology, and FCM contributes to deciding appropriate treatment strategies and facilitating early initiation of chemotherapy for PCNSL. These examination methods may allow new therapeutic strategies for not only PCNSL, but also other brain tumors.
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A rapid preparation method for the analysis of the urine from a cannabis user was established. Generally, 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH), which is one of the main metabolites of ∆9-tetrahydorocannabinol (THC), must be detected from a user's urine to verify cannabis use. However, existing preparation methods are usually multistep and time-consuming processes. Before the analysis by liquid-chromatography tandem mass spectrometry (LC-MS/MS), deconjugation by treatment with ß-glucuronidase or alkaline solution, liquid-liquid extraction or solid-phase extraction (SPE), and evaporation are generally performed. In addition, subsequent derivatization (silylation or methylation) are certainly necessary for gas-chromatography mass spectrometry (GC/MS) analysis. Here, we focused on the phenylboronic-acid (PBA) SPE, which selectively binds compounds with a cis-diol moiety. THC-COOH is metabolized as a glucuronide conjugate (THC-COOGlu) which has cis-diol moieties, therefore, we investigated the conditions of its retention and elution to reduce the operating time. We developed four elution conditions, which afford the following derivatives: acidic elution for THC-COOGlu, alkaline elution for THC-COOH, methanolysis elution for the THC-COOH methyl ester (THC-COOMe), and methanolysis elution and following methyl etherification for O-methyl-THC-COOMe (O-Me-THC-COOMe). All repeatability and recovery rates were evaluated by LC-MS/MS in this study. As a result, these four pathways required short times (within 10-25 min) and exhibited good repeatability and recovery rates. Detection limits of pathway I-IV were 10.8, 1.7, 18.9, and 13.8 ng mL-1, respectively. Lower limits of quantification were 62.5, 31.25, 57.3, and 62.5 ng mL-1, respectively. When proof of cannabis use is required, any elution condition can be selected to match the possessing reference standards and analytical instruments. To our knowledge, this is the first report of using PBA SPE for the preparation of the urine samples containing cannabis and achieving partial derivatization when eluting from a PBA carrier. Our method can provide a new and practical solution for the preparation of the urine samples from cannabis users. Although the PBA SPE method cannot recover THC-COOH in urine because of its lack of a 1,2-diol moiety, this method has technological advantages for simplifying the process and reducing the operating time, thereby avoiding human errors.
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Cannabis , Alucinógenos , Humanos , Dronabinol/análise , Cromatografia Líquida , Espectrometria de Massas em Tandem , Cromatografia Gasosa-Espectrometria de Massas/métodos , Alucinógenos/análise , Extração em Fase Sólida/métodosRESUMO
Various synthetic drugs have appeared over the past years across the world, and phenethylamine derivatives are among them; indeed, aromatic fluoro analogs of methamphetamine and amphetamine have been in the illicit drug market since the early 2000s. Although they are currently widely abused across the world, little information is available on their metabolism and toxicology. Recently, we came across an alleged 2-fluoromethamphetamine (2-FMA) drug abuse case. The urine obtained from the alleged abuser was analyzed as part of a criminal investigation. 2-FMA, 2-fluoroamphetamine (2-FAP) and some related compounds were detected by liquid chromatography-tandem mass spectrometry. In forensic science, both an "unchanged" drug and its metabolite(s) need to be detected in urine to verify the illicit drug use. Notably, the detection of 2-FAP, which is a plausible 2-FMA metabolite, is insufficient as evidence of 2-FMA use because 2-FAP is widely available and may be present as such in taken liquids. In this study, we synthesized analytical standards for N-hydroxy 2-FMA (N-OH-2-FMA) and two diastereomers of 2-fluoroephedrine, which are plausible metabolites of 2-FMA. Using these standards, the urine specimen was found to contain N-OH-2FMA and one diastereomer of 2-fluoroephedrine; moreover, the concentrations of these compounds were successfully determined. The results of our study suggest that N-hydroxylation and aliphatic hydroxylation are the characteristic metabolic pathways of 2-FMA compared with that of methamphetamine. This evidence indicates that both N-OH-2-FMA and 2-fluoroephedrine are plausible candidates as analytical targets for drug-use certification in forensic science.
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Drogas Ilícitas , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Humanos , Anfetamina/urina , Espectrometria de Massas , Drogas Ilícitas/urina , Detecção do Abuso de Substâncias/métodosRESUMO
High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels of CD44 are highly invasive and resistant to radio-chemotherapy. CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways reciprocally activate invasion and proliferation under different hypoxic conditions. Severe hypoxia (0.5-2.5% O2) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-ß, and cMET, all of which are related to tumor migration and invasion. In contrast, moderate hypoxia (2.5-5% O2) upregulates HIF-2α, which activates target genes, such as vascular endothelial growth factor (VEGF)/VEGFR2, cMYC, and cyclin D1. All these genes are related to tumor proliferation. Oxygen environments around GBM can change before and after tumor resection. Before resection, the oxygen concentration at the tumor periphery is severely hypoxic. In the reparative stage after resection, the resection cavity shows moderate hypoxia. These observations suggest that upregulated CD44 under severe hypoxia may promote the migration and invasion of tumor cells. Conversely, when tumor resection leads to moderate hypoxia, upregulated HIF-2α activates HIF-2α target genes. The phenotypic transition regulated by CD44, leading to a dichotomy between invasion and proliferation according to hypoxic conditions, may play a crucial role in GBM recurrence.
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Background: The efficacy of perioperative prophylactic antiepileptic drug therapy in "seizure-naïve" patients with brain tumor, including glioblastoma (GBM), remains controversial. This study investigated whether perampanel (PER) is effective and safe for preventing perioperative onset of epileptic seizures, so-called early seizure, in patients with brain tumors. Methods: Forty-five patients underwent tumor resection through craniotomy for a primary supratentorial brain tumor at Ehime University Hospital between April 2021 and July 2022. PER was administered from the 1st to the 6th day after surgery for seizure prophylaxis. Occurrence of early seizure, hematological toxicities, and various side effects were recorded on postoperative days 7 and 14. In addition, the clinical course of these patients was compared with 42 brain tumor patients under the same treatment protocol who received levetiracetam (LEV) for seizure prophylaxis between April 2017 and October 2018. Results: In 45 patients with brain tumor, including GBM, who received PER administration, no early seizures were identified within 7 days postoperatively. No adverse drug reactions such as hematological toxicity, liver or kidney dysfunction, or exanthematous drug eruption were observed in any cases. As side effects, somnolence was reported in 14 patients (31.1%), vertigo in 3 patients (6.7%), and headache in 3 patients (6.7%). Although somnolence and vertigo were difficult to assess in the case of intraparenchymal tumors, particularly GBM, these side effects were not identified in patients with extraparenchymal tumors such as meningiomas, epidermoid cysts, and pituitary adenomas. In addition, no significant differences were identified compared to patients who received LEV. Conclusion: The efficacy and safety of PER in preventing early seizures among patients with brain tumors were retrospectively evaluated. Perioperative administration of PER to patients with brain tumors may reduce the risk of early seizures without incurring serious side effects, showing no significant differences compared to patients who received LEV.
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BACKGROUND: The role of surgery in primary central nervous system lymphoma (PCNSL) is to allow pathological diagnosis from tumor biopsy. However, PCNSL is often difficult to distinguish from other tumors, particularly glioblastoma multiforme (GBM). Quantitative evaluations to facilitate differentiation between PCNSL and GBM would be useful. Here, we investigated the best examinations for exact differentiation of PCNSL from GBM among preoperative examinations, including imaging studies and tumor markers. METHODS: Various examinations were performed for 68 patients with PCNSL , including serum soluble interleukin 2 receptor, ß2-microglobulin (MG) in cerebrospinal fluid (CSF), diffusion-weighted imaging, 11C-methionine-positron emission tomography (PET), and 18F-fluorodeoxyglucose (FDG)-PET. These results were compared with findings from 28 patients with consecutive GBM who underwent the same examinations to evaluate the utility and accuracy of different investigations. RESULTS: CSF ß2-MG ≥2.0 mg/L was relatively specific for PCNSL, offering 95.0% sensitivity and 85.7% specificity. Tumor-to-contralateral normal brain tissue ratio ≥2.4 on 18F-FDG-PET was also quite specific for PCNSL, offering 83.8% sensitivity and 95.2% specificity. No other examinations displayed any significant differences in quantitative differential markers between PCNSL and GBM. CONCLUSIONS: Both ß2-MG ≥2.0 mg/dL in CSF and tumor-to-contralateral normal brain tissue ratio ≥2.4 from 18F-FDG-PET allow quantitative differentiation of PCNSL from GBM, potentially representing clinically useful indicators. These findings could lead to innovative methods for differentiating PCNSL from GBM as well as new treatment strategies for other brain tumors.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioblastoma , Linfoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Linfoma/cirurgia , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/cirurgiaRESUMO
Recurrent glioblastoma multiforme (GBM) is largely attributed to peritumoral infiltration of tumor cells. As higher CD44 expression in the tumor periphery correlates with higher risk of GBM invasion, the present study analyzed the relationship between CD44 expression and magnetic resonance imaging (MRI)-based invasiveness of GBM on a large scale. We also quantitatively evaluated GBM invasion using 5-aminolevulinic acid (5-ALA) spectroscopy to investigate the relationship between CD44 expression and tumor invasiveness as evaluated by intraoperative 5-ALA intensity. Based on MRI, GBM was classified as high-invasive type in 28 patients and low-invasive type in 22 patients. High-invasive type expressed CD44 at a significantly higher level than low-invasive type and was associated with worse survival. To quantitatively analyze GBM invasiveness, the relationship between tumor density in the peritumoral area and the spectroscopic intensity of 5-ALA was investigated. Spectroscopy showed that the 5-ALA intensity of infiltrating tumor cells correlated with tumor density as represented by the Ki-67 staining index. No significant correlation between CD44 and degree of 5-ALA-based invasiveness of GBM was found, but invasiveness of GBM as evaluated by 5-ALA matched the classification from MRI in all except one case, indicating that CD44 expression at the GBM periphery could provide a reliable biomarker for invasiveness in GBM.
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Background: Hemangioblastoma originates in the central nervous system (CNS), usually in the cerebellum, and sporadic cases in the supratentorial region are extremely rare. In addition, there have been no previous reports of cases showing hyperintensity on diffusion weighted image (DWI) on magnetic resonance imaging (MRI) and negative immunostaining for inhibin-alpha. Here, we report a rare case of sporadic supratentorial hemangioblastoma arising in the parasagittal region and suggest a useful indicator for the exact diagnosis and pitfalls for surgical procedures. Case Description: A 66-year-old woman was admitted to our hospital with a 6-month history of progressive numbness in the right lower extremities and gait disturbance. Neurological findings on admission revealed mild right-sided hemiparesis of the lower limbs (manual muscle test: 4/V). Neuroimaging demonstrated an abnormal lesion with clear boundaries in the left frontal lobe appearing hypointense on T1-weighted image (WI), hyperintense on T2-WI, and hyperintense on DWI, with strong enhancement on gadolinium (Gd)-enhanced T1-WI. Computed tomography (CT) showed no calcification, and cerebral angiography revealed strong staining from bilateral middle meningeal arteries and the left anterior cerebral artery (ACA). Surgical excision of the lesion was performed and gross total resection was achieved. Histological findings revealed a marked increase in vascular structures, and the round stroma contained tumor cells. Silver impregnation stains demonstrated abundant reticulin fibers. In addition, immunohistochemistry revealed that most tumor cells stained negatively for epithelial membrane antigen (EMA) and inhibin-alpha, and positively stained for podoplanin (D2-40), and the tumor was diagnosed as hemangioblastoma. The postoperative course was uneventful and follow-up neuroimaging after one year revealed no signs of recurrence. Conclusions: Supratentorial hemangioblastomas are extremely rare and display a strong infiltrative and aggressive nature. Careful identification from preoperative image and histopathological study for appropriate treatment selection are warranted for supratentorial hemangioblastoma.
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BACKGROUND: The incidence of brain metastasis of pancreatic cancer has been reported to be approximately 0.3%. The blood-brain barrier of the central nervous system restricts the transfer of substances, including chemotherapeutic agents, from the bloodstream. It is hypothesized that brain metastasis may occur despite successful chemotherapy for the primary tumor. Herein, we report a case of brain metastases of pancreatic cancer that occurred after chemotherapy and discuss relevant literature. CASE PRESENTATION: A 64-year-old man underwent distal pancreatectomy with D2 lymph node dissection for resectable pancreatic tail cancer. Invasive ductal carcinoma of pancreas, pT3N2M0 pStageIII (TNM Classification of Malignant Tumors, UICC 8th edition) was diagnosed. S-1 adjuvant chemotherapy was initiated. Three months postoperatively, CA19-9 had increased to 619 U/mL. Additionally, contrast-enhanced computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed local recurrence in the para-aortic lymph nodes. Chemotherapy was revised to a combined regimen of gemcitabine and nab-paclitaxel. After 4 cycles, tumor markers were normalized. After 5 cycles, recurrence could not be identified on contrast-enhanced CT; therefore, the patient was adjudged to be in complete remission. However, after 29 cycles of chemotherapy, the patient had symptoms of raised intracranial pressure. Magnetic resonance imaging showed two metastatic lesions of 20 mm and 32 mm in the left frontal lobe and cerebellum, respectively. Quasi-emergency resection of the metastatic brain tumors was performed. Pathological examination revealed that the resected specimens originated from primary pancreatic cancer. The patient was discharged on postoperative day 12, without any complications. Postoperatively, a total of 53 Gy of local brain radiation therapy was added. On postoperative day 30, blood carcinoembryonic antigen level had decreased to 5.4 ng/dl and all other tumor markers were negative. Additionally, tumor markers of the cerebrospinal fluid were markedly reduced and the cytology was negative for tumor cells. These results suggested complete resection of the metastatic brain tumors. CONCLUSIONS: Aggressive resection and salvage stereotactic radiotherapy for metastatic brain tumors may lead to complete cure and a good long-term prognosis.
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Pyrrolidinophenones (PPs) are synthetic cathinones containing a pyrrolidine ring that are used recreationally worldwide. Recently, many studies on the metabolism and cytotoxicity of PPs have been published. Here, we focus on new designer drug containing an indan skeleton, 1-(2,3-dihydro-1H-inden-5-yl)-2-(pyrrolidine-1-yl)butan-1-one (5-PPDI), because there have been no reports to date regarding the metabolism of indan-type cathinones. The identification of 5-PPDI phase I metabolites in human urine enables us to determine whether a person has taken 5-PPDI. This metabolite detection approach plays a very important role in the field of forensic science. We synthesized analytical standards of 5-PPDI and four proposed metabolites. A urine sample was prepared by salting-out assisted liquid-liquid extraction with acetonitrile. Analyses of all standards and the urine sample were performed by liquid chromatography high resolution tandem mass spectrometry. As a result, we were able to detect 5-PPDI and its metabolites in the urine specimen. Two diastereomers of synthesized 1-OH metabolites were successfully separated, and only one diastereomer was observed in the urine specimen. To the best of our knowledge, this is the first report on the stereoselective reduction of PPs in humans. Further, we performed quantitative analyses of 5-PPDI and its metabolites in the urine. We identified three characteristic features of 5-PPDI phase I metabolism: (1) hydroxylation at the indan skeleton, (2) stereoselective reduction of the carbonyl group, and (3) hydroxylation of the indan skeleton possibly proceeding more preferentially than any other metabolization. In addition, several structural isomers and diastereomers of 2'-OH metabolites were detected. Based on these data, we propose phase I metabolic pathways of 5-PPDI, which will be essential in understanding the metabolism of other PPs with an indan skeleton.
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Drogas Desenhadas/química , Pirrolidinas/urina , Humanos , Masculino , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , UrináliseRESUMO
Various new psychoactive substances, such as cathinone and its analogs, possess similar chemical structures. Accurate identification of structurally similar drugs of abuse is important in forensic drug analysis. Chromatographic differentiation is a powerful analytical technique for this purpose. In this study, we applied supercritical fluid chromatography to differentiate ring-substituted regioisomers of six synthetic cathinone analogs (fluoro-α-pyrrolidinovalerophenone, methyl-α-pyrrolidinovalerophenone, methoxy-α-pyrrolidinovalerophenone, fluoro-α-pyrrolidinooctanophenone, fluoropentedrone, and fluorooctedrone). The examined cathinone analogs were weakly retained on the stationary phase (possessing diol functional group) and eluted quickly. We optimized the conditions to retain the examined cathinone analogs to achieve sufficient separation, and found that the types of functional groups on the stationary phase greatly affected the retention and separation. Systematic examination of the chromatographic conditions showed that the two stationary phases possessing anthracene and pentafluorobenzyl groups had good separation capabilities for the examined 2-, 3-, and 4-regioisomers of six cathinone analogs, which had different skeletal structures. Interestingly, the two stationary phases showed different selectivities, and alteration of the elution order was observed. The developed method was validated and its discrimination ability was investigated by measuring mass spectra and absorption spectra. Supercritical fluid chromatography-ultraviolet absorption spectroscopy/mass spectrometry is a powerful analytical technique for differentiation of ring-substituted cathinone analogs.
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Small and broad-necked aneurysms are generally very difficult to treat using endovascular therapy. The arrival of the low-profile stent (e.g., Low-profile Visualized Intraluminal Support; LVIS) has enabled reconstructive treatment for these aneurysms. In addition, the bulging technique using LVIS is an effective and attractive technique for performing stent-assisted coiling to preserve parent arteries and achieve neck coverage. We report here a patient with a small and wide-necked ruptured basilar artery (BA) top aneurysm, in whom successful treatment was achieved by stent-assisted coiling with LVIS Jr. using the bulging technique. A 74-year-old woman with moderate hypertension consulted for treatment of subarachnoid hemorrhage with a ruptured BA top aneurysm measuring 2.7 mm in height with a 4.3 mm neck. We initially tried emergency balloon-assisted coiling, but coiling proved difficult. We therefore performed stent-assisted coiling with LVIS Jr. using the bulging technique. The postoperative course was uneventful, with no aggravation of neurological symptoms, and the patient was discharged 14 days postoperatively. This treatment strategy with LVIS Jr. using the bulging technique may be very useful for patients with a ruptured aneurysm with a small and broad neck that would otherwise require treatment with intravascular devices or open surgery.
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Aneurisma Roto/cirurgia , Artéria Basilar , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Stents Metálicos Autoexpansíveis , Hemorragia Subaracnóidea/cirurgia , Idoso , Aneurisma Roto/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Procedimentos Endovasculares/instrumentação , Desenho de Equipamento , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagemRESUMO
INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare and treatable variant of cerebral amyloid angiopathy, lacks specific imaging and clinical features, and requires invasive brain biopsy to confirm the diagnosis. We report the case of a patient with nonconvulsive status epilepticus (NCSE) caused by CAA-ri in the right occipital lobe. PRESENTATION OF CASE: A 78-year-old man with a history of hypertension and rheumatoid arthritis was admitted to our hospital following an episode of seizures. CT scan showed a low-attenuating subcortical lesion in the right occipital lobe. MRI revealed the lesion as hypointense on T1-weighted imaging (WI) and hyperintense on T2-WI, showing no enhancement on T1-WI contrast-enhanced with gadolinium. In addition, T2*-weighted gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI) revealed extensive cortical microbleeds. Biopsy to determine the exact diagnosis revealed histological findings of reactive changes and perivascular inflammatory infiltration associated with amyloid deposition in vessel walls. These findings were consistent with CAA-ri. Corticosteroid therapy with dexamethasone was initiated for a short period as a diagnostic and therapeutic maneuver, resulting in marked reductions in the lesion. DISCUSSION: CAA is generally associated with intracerebral hemorrhage, dementia, and small cerebral infarctions in the elderly population, but in a small proportion of cases is related to inflammatory responses to vascular deposits of Aß, as so-called CAA-ri. CONCLUSION: CAA-ri should be considered among the differential diagnoses for causes of unprovoked seizure onset in elderly individuals, when associated with petechial hemorrhages on T2*-GRE and SWI sequences on MRI.