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1.
Spinal Cord Ser Cases ; 10(1): 48, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009566

ABSTRACT

INTRODUCTION: Pure epidural spinal cavernous hemangiomas are rare, benign vascular tumors that account for approximately 4% of all spinal epidural tumors. Due to their dumbbell shape and propensity for foraminal invasion, they are often misdiagnosed and inadequately treated. We present a case of a 58-year-old male with extra-osseous cavernous hemangioma to better aid in diagnosis and management of these lesions. CASE PRESENTATION: A 58-year-old male presented with chronic lower back pain, progressive lower extremity weakness, T10 sensory level, absent lower extremity proprioception, hyperreflexia, and an episode of bowel incontinence. Imaging demonstrated T7-T10 homogenous dorsal epidural mass causing cord signal change. He underwent resection with histopathologic exam revealing a pure epidural cavernous hemangioma. CONCLUSION: Spinal epidural cavernous hemangiomas are exceedingly rare lesions that are often misdiagnosed as nerve sheath tumors and meningiomas. Common features include chronic pain and myelopathy as well as T1 isodensity, T2 hyperintensity, and homogenous enhancement. Uniquely, they present as a lobulated, spindled shape with tapered ends in the dorsal epidural space. Both gross and subtotal resection result in favorable neurologic outcomes.


Subject(s)
Hemangioma, Cavernous , Spinal Cord Diseases , Thoracic Vertebrae , Humans , Male , Middle Aged , Thoracic Vertebrae/diagnostic imaging , Hemangioma, Cavernous/surgery , Hemangioma, Cavernous/diagnosis , Hemangioma, Cavernous/diagnostic imaging , Spinal Cord Diseases/surgery , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/diagnosis , Spinal Cord Diseases/pathology , Epidural Neoplasms/surgery , Epidural Neoplasms/diagnosis , Epidural Neoplasms/pathology , Epidural Neoplasms/complications , Magnetic Resonance Imaging
2.
Eur Radiol Exp ; 8(1): 25, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38361025

ABSTRACT

BACKGROUND: Digital subtraction angiography (DSA) yields high cumulative radiation dosages (RD) delivered to patients. We present a temporal interpolation of low frame rate angiograms as a method to reduce cumulative RDs. METHODS: Patients undergoing interventional evaluation and treatment of cerebrovascular vasospasm following subarachnoid hemorrhage were retrospectively identified. DSAs containing pre- and post-intervention runs capturing the full arterial, capillary, and venous phases with at least 16 frames each were selected. Frame rate reduction (FRR) of the original DSAs was performed to 50%, 66%, and 75% of the original frame rate. Missing frames were regenerated by sampling a gamma variate model (GVM) fit to the contrast response curves to the reduced data. A formal reader study was performed to assess the diagnostic accuracy of the "synthetic" studies (sDSA) compared to the original DSA. RESULTS: Thirty-eight studies met inclusion criteria (average RD 1,361.9 mGy). Seven were excluded for differing views, magnifications, or motion. GVMs fit to 50%, 66%, and 75% FRR studies demonstrated average voxel errors of 2.0 ± 2.5% (mean ± standard deviation), 6.5 ± 1.5%, and 27 ± 2%, respectively for anteroposterior projections, 2.0 ± 2.2%, 15.0 ± 3.1%, and 14.8 ± 13.0% for lateral projections, respectively. Reconstructions took 0.51 s/study. Reader studies demonstrated an average rating of 12.8 (95% CI 12.3-13.3) for 75% FRR, 12.7 (12.2-13.2) for 66% FRR and 12.0 (11.5-12.5) for 50% FRR using Subjective Image Grading Scale. Kendall's coefficient of concordance resulted in W = 0.506. CONCLUSION: FRR by 75% combined with GVM reconstruction does not compromise diagnostic quality for the assessment of cerebral vasculature. RELEVANCE STATEMENT: Using this novel algorithm, it is possible to reduce the frame rate of DSA by as much as 75%, with a proportional reduction in radiation exposure, without degrading imaging quality. KEY POINTS: • DSA delivers some of the highest doses of radiation to patients. • Frame rate reduction (FRR) was combined with bolus tracking to interpolate intermediate frames. • This technique provided a 75% FRR with preservation of diagnostic utility as graded by a formal reader study for cerebral angiography performed for the evaluation of cerebral vasospasm. • This approach can be applied to other types of angiography studies.


Subject(s)
Radiation Exposure , Humans , Angiography, Digital Subtraction/methods , Retrospective Studies , Cerebral Angiography/methods , Radiation Dosage
3.
J Neurosurg Case Lessons ; 7(5)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38285975

ABSTRACT

BACKGROUND: Neuromuscular choristomas (NMCs) are rare tumors involving aberrant intercalation of muscle fibers into peripheral nerves, most commonly the sciatic nerve. Although benign, these lesions risk developing into NMCs with desmoid-type fibrosis (NMC-DTFs), aggressive lesions potentially requiring amputation. Currently, information on NMCs and the link between NMCs and NMC-DTFs is limited in adults, with the majority of cases reported in children. We present the case of a 66-year-old male with a sciatic NMC alongside a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-based systematic review of similar cases to better characterize this lesion in the adult population. OBSERVATIONS: A male presented with 10 years of progressive left lower-extremity weakness and paresthesia, and a mildly enlarged proximal sciatic nerve was discovered on magnetic resonance imaging. He underwent left sciatic fascicular nerve biopsy, with histopathological examination identifying the lesion as an NMC. The literature review revealed that our case, alongside other cases of adults with NMCs, shared characteristics similar to NMCs in the pediatric population. LESSONS: More comprehensive studies of adults with NMCs are needed, as the current literature contains limited information concerning disease course, diagnostic characteristics, and treatment. Furthermore, NMCs in adults should be handled with care because of the increased likelihood of transformation to NMC-DTF after surgical intervention.

4.
J Neurosurg Spine ; 38(4): 417-424, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36681945

ABSTRACT

OBJECTIVE: Knowledge of the manufacturer of the previously implanted pedicle screw systems prior to revision spinal surgery may facilitate faster and safer surgery. Often, this information is unavailable because patients are referred by other centers or because of missing information in the patients' records. Recently, machine learning and computer vision have gained wider use in clinical applications. The authors propose a computer vision approach to classify posterior thoracolumbar instrumentation systems. METHODS: Lateral and anteroposterior (AP) radiographs obtained in patients undergoing posterior thoracolumbar pedicle screw implantation for any indication at the authors' institution (2015-2021) were obtained. DICOM images were cropped to include both the pedicle screws and rods. Images were labeled with the manufacturer according to the operative record. Multiple feature detection methods were tested (SURF, MESR, and Minimum Eigenvalues); however, the bag-of-visual-words technique with KAZE feature detection was ultimately used to construct a computer vision support vector machine (SVM) classifier for lateral, AP, and fused lateral and AP images. Accuracy was tested using an 80%/20% training/testing pseudorandom split over 100 iterations. Using a reader study, the authors compared the model performance with the current practice of surgeons and manufacturer representatives identifying spinal hardware by visual inspection. RESULTS: Among the three image types, 355 lateral, 379 AP, and 338 fused radiographs were obtained. The five pedicle screw implants included in this study were the Globus Medical Creo, Medtronic Solera, NuVasive Reline, Stryker Xia, and DePuy Expedium. When the two most common manufacturers used at the authors' institution were binarily classified (Globus Medical and Medtronic), the accuracy rates for lateral, AP, and fused images were 93.15% ± 4.06%, 88.98% ± 4.08%, and 91.08% ± 5.30%, respectively. Classification accuracy decreased by approximately 10% with each additional manufacturer added. The multilevel five-way classification accuracy rates for lateral, AP, and fused images were 64.27% ± 5.13%, 60.95% ± 5.52%, and 65.90% ± 5.14%, respectively. In the reader study, the model performed five-way classification on 100 test images with 79% accuracy in 14 seconds, compared with an average of 44% accuracy in 20 minutes for two surgeons and three manufacturer representatives. CONCLUSIONS: The authors developed a KAZE feature detector with an SVM classifier that successfully identified posterior thoracolumbar hardware at five-level classification. The model performed more accurately and efficiently than the method currently used in clinical practice. The relative computational simplicity of this model, from input to output, may facilitate future prospective studies in the clinical setting.


Subject(s)
Pedicle Screws , Spinal Fusion , Surgery, Computer-Assisted , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Prospective Studies , Surgery, Computer-Assisted/methods , Spinal Fusion/methods , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery
5.
Anat Histol Embryol ; 52(1): 73-84, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36148518

ABSTRACT

Undergraduate student engagement in research increases retention and degree completion, especially for students who are underrepresented in science. Several approaches have been adopted to increase research opportunities including curriculum based undergraduate research opportunities (CUREs), in which research is embedded into course content. Here we report on efforts to tackle a different challenge: providing research opportunities to students engaged in remote learning or who are learning at satellite campuses or community colleges with limited research infrastructure. In our project we engaged students learning remotely or at regional centers to map gene expression in the mouse brain. In this project we mapped expression of the Down syndrome cell adhesion molecule like 1 (Dscaml1) gene in mouse brain using a LacZ expression reporter line. Identifying where Dscaml1 is expressed in the brain is an important next step in determining if its roles in development and function in the retina are conserved in the rest of the brain. Students working remotely reconstruct brain montages and annotated Dscaml1 expression in the brain of mice carrying one or two copies of the gene trap. We built on these findings by further characterizing Dscaml1 expression in inhibitory neurons of the visual pathway. These results build on and extend previous findings and demonstrate the utility of including distance learners in an active research group for both the student learners and the research team. We conclude with best practices we have developed based on this and other distance learner focused projects.


Subject(s)
Neurons , Students , Animals , Mice , Humans , Lac Operon , Neurons/metabolism , Retina , Brain , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism
6.
IUCrdata ; 8(Pt 11): x231020, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38313070

ABSTRACT

The reaction between a racemic mixture of (R,S)-fixolide and 4-methyl-thio-semicarbazide in ethanol with a 1:1 stoichiometric ratio and catalysed with HCl, yielded the title compound, C20H31N3S [common name: (R,S)-fixolide 4-methyl-thio-semicarbazone]. There is one crystallographically independent mol-ecule in the asymmetric unit, which is disordered over the aliphatic ring [site-occupancy ratio = 0.667 (13):0.333 (13)]. The disorder includes the chiral C atom, the neighbouring methyl-ene group and the methyl H atoms of the methyl group bonded to the chiral C atom. The maximum deviations from the mean plane through the disordered aliphatic ring amount to 0.328 (6) and -0.334 (6) Š[r.m.s.d. = 0.2061 Å], and -0.3677 (12) and 0.3380 (12) Š[r.m.s.d. = 0.2198 Å] for the two different sites. Both fragments show a half-chair conformation. Additionally, the N-N-C(=S)-N entity is approximately planar, with the maximum deviation from the mean plane through the selected atoms being 0.0135 (18) Š[r.m.s.d. = 0.0100 Å]. The mol-ecule is not planar due to the dihedral angle between the thio-semicarbazone entity and the aromatic ring, which amounts to 51.8 (1)°, and due to the sp 3-hybridized carbon atoms of the fixolide fragment. In the crystal, the mol-ecules are connected by H⋯S inter-actions with graph-set motif C(4), forming a mono-periodic hydrogen-bonded ribbon along [100]. The Hirshfeld surface analysis suggests that the major contributions for the crystal cohesion are [(R,S)-isomers considered separately] H⋯H (75.7%), H⋯S/S⋯H (11.6%), H⋯C/C⋯H (8.3% and H⋯N/N⋯H (4.4% for both of them).

7.
Neurospine ; 20(4): 1112-1123, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38171281

ABSTRACT

Osteoporotic vertebral fractures (OVFs) are a significant health concern linked to increased morbidity, mortality, and diminished quality of life. Traditional OVF risk assessment tools like bone mineral density (BMD) only capture a fraction of the risk profile. Artificial intelligence, specifically computer vision, has revolutionized other fields of medicine through analysis of videos, histopathology slides and radiological scans. In this review, we provide an overview of computer vision algorithms and current computer vision models used in predicting OVF risk. We highlight the clinical applications, future directions and limitations of computer vision in OVF risk prediction.

9.
PNAS Nexus ; 1(5): pgac218, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36712345

ABSTRACT

People believe they should consider how their behavior might negatively impact other people, Yet their behavior often increases others' health risks. This creates challenges for managing public health crises like the COVID-19 pandemic. We examined a procedure wherein people reflect on their personal criteria regarding how their behavior impacts others' health risks. We expected structured reflection to increase people's intentions and decisions to reduce others' health risks. Structured reflection increases attention to others' health risks and the correspondence between people's personal criteria and behavioral intentions. In four experiments during COVID-19, people (N  = 12,995) reported their personal criteria about how much specific attributes, including the impact on others' health risks, should influence their behavior. Compared with control conditions, people who engaged in structured reflection reported greater intentions to reduce business capacity (experiment 1) and avoid large social gatherings (experiments 2 and 3). They also donated more to provide vaccines to refugees (experiment 4). These effects emerged across seven countries that varied in collectivism and COVID-19 case rates (experiments 1 and 2). Structured reflection was distinct from instructions to carefully deliberate (experiment 3). Structured reflection increased the correlation between personal criteria and behavioral intentions (experiments 1 and 3). And structured reflection increased donations more among people who scored lower in cognitive reflection compared with those who scored higher in cognitive reflection (experiment 4). These findings suggest that structured reflection can effectively increase behaviors to reduce public health risks.

10.
Surg Neurol Int ; 12: 315, 2021.
Article in English | MEDLINE | ID: mdl-34345456

ABSTRACT

BACKGROUND: Intramedullary melanocytomas are exceedingly rare and their management is largely based on case reports and small clinical series. They have characteristic imaging and histologic findings that can aid in their diagnosis. Genetic testing may be required for definitive diagnosis and management guidance in ambiguous cases. CASE DESCRIPTION: We present the case of a thoracic intramedullary meningeal melanocytoma in a patient unable to undergo an MRI. CONCLUSION: This is the first reported S-100-negative case with genetic testing to support the diagnosis of a rare intramedullary melanocytoma.

11.
Bioorg Med Chem Lett ; 41: 127988, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33775838

ABSTRACT

Skin cancer is the most common type of cancer in Brazil, representing 30% of all cases. Among these, melanoma represents only 3% of malignant neoplasms; however, it is the most serious and has a high capacity for metastasis. For this reason, it is extremely important to identify more efficient compounds and treatments that stop or decrease the proliferation of melanoma, even in its more advanced stages. This work reports the synthesis and biological evaluation of two homologous series of pyrazoline fatty chain derivatives as potent antitumoral agents in the melanoma B16F10 cell line. Cells were treated with pyrazoline fatty chain compounds (3, 30, 300, and 3000 µM) for 0, 24, 48, and 72 h. Decreased cell viability was observed when using most compounds at different concentrations and times. The structure-activity relationship (SAR) between antitumoral activity and the number of carbons and lipophilicity, as well as the oxygen-sulfur bioisosteric exchange, was evaluated. Among the tested derivatives, the lipophilic compounds 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-carboxamide (2d) and 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-thiocarboxamide (3d) showed the best results in the B16F10 cell line, as they produced the best cell viability decrease effects. The presence of fatty unbranched undecyl chain in the molecular structure appears to be important for its antimelanoma properties.


Subject(s)
Antineoplastic Agents/pharmacology , Pyrazoles/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Mice , Molecular Structure , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Structure-Activity Relationship
13.
Sci Rep ; 10(1): 18780, 2020 11 02.
Article in English | MEDLINE | ID: mdl-33139791

ABSTRACT

Cerebral vasospasm is a dreaded sequelae of aneurysmal subarachnoid hemorrhage (aSAH), requiring timely intervention with therapeutic goals of improving brain perfusion. There are currently no standardized real-time, objective assessments of the interventional procedures performed to treat vasospasm. Here we describe real-time techniques to quantify cerebral perfusion during interventional cerebral angiography. We retrospectively analyzed 39 consecutive cases performed to treat clinical vasospasm and quantified the changes in perfusion metrics between pre- and post- verapamil administrations. With Digital Subtraction Angiography (DSA) perfusion analysis, we are able to identify hypoperfused territories and quantify the exact changes in cerebral perfusion for each individual case and vascular territory. We demonstrate that perfusion analysis for DSA can be performed in real time. This provides clinicians with a colorized map which directly visualizes hypoperfused tissue, combined with associated perfusion statistics. Quantitative thresholds and analysis based on DSA perfusion may assist with real-time dosage estimation and help predict response to treatment, however future prospective analysis is required for validation.


Subject(s)
Vasospasm, Intracranial/diagnosis , Vasospasm, Intracranial/drug therapy , Verapamil/administration & dosage , Adolescent , Adult , Angiography, Digital Subtraction/methods , Female , Humans , Male , Middle Aged , Perfusion Imaging/methods , Retrospective Studies , Subarachnoid Hemorrhage/complications , Treatment Outcome , Vasospasm, Intracranial/diagnostic imaging , Vasospasm, Intracranial/etiology , Young Adult
14.
World Neurosurg ; 144: e389-e394, 2020 12.
Article in English | MEDLINE | ID: mdl-32890844

ABSTRACT

BACKGROUND: Sonolucent cranioplasty implants were recently introduced into clinical practice and tested for use with transcranioplasty ultrasound (TCUS). In situations where dural substitutes (DSs) are needed during closure, such as in extracranial-intracranial bypass, it is unclear if the DS influences the imaging quality of TCUS. The aim of this study was to assess the influence of DSs on imaging quality during TCUS assessment with sonolucent cranioplasty. METHODS: A tofu vascular brain model was constructed with a ClearFit implant in between 2 layers of tofu. Injection of saline solution through a 6-F Envoy DA XB endovascular catheter (6-F Envoy DA XB) inserted into the deeper tofu layer mimicked an intracranial vessel. TCUS image quality, including Doppler, with 4 different DSs (DuraGen, Durepair, DuraMatrix-Onlay, DuraMatrix Suturable) placed under the cranioplasty was compared against a control by 2 examiners. A literature search of MEDLINE and EMBASE was conducted to find previous reports of acoustic properties of DSs. RESULTS: TCUS assessment including Doppler was feasible with the model in longitudinal and axial planes, and the pulsatile particle injection was visualized in real time. DuraGen and Durepair showed Doppler quality and picture detail comparable to the control, while the DuraMatrix-Onlay and DuraMatrix Suturable were inferior to the control. The literature search yielded only 1 previous report on acoustic properties of DSs. CONCLUSIONS: DSs interfere differentially with imaging quality during TCUS assessment. However, these results are based on a benchtop model and need to be further assessed in the clinical setting.


Subject(s)
Brain/diagnostic imaging , Dura Mater , Prostheses and Implants , Ultrasonography/methods , Craniotomy , Humans , Models, Anatomic , Skull/surgery
15.
World Neurosurg ; 144: e277-e284, 2020 12.
Article in English | MEDLINE | ID: mdl-32827747

ABSTRACT

OBJECTIVE: We sought to analyze the safety and feasibility of elective sonolucent cranioplasty in the setting of extracranial-to-intracranial (EC-IC) bypass surgery to monitor bypass patency using ultrasound. METHODS: Patients who underwent direct EC-IC bypass surgery agreed to sonolucent cranioplasty at the time of surgery and received a sonolucent polymethyl methacrylate (PMMA) implant. Besides monitoring clinical outcome, all patients received transcranioplasty ultrasound (TCUS) on postoperative day 1 and at last follow-up. In addition, bypass patency was confirmed using catheter angiogram and fit of implant using computed tomography. Patient-rated outcome was assessed through phone questionnaire. RESULTS: EC-IC bypass surgery with PMMA cranioplasty was successful in all 7 patients with patent bypasses on postoperative angiogram. Direct TCUS was feasible in all patients, and bypass patency was monitored. There were no complications such as postoperative hemorrhagic/ischemic complications related to the bypass procedure in this patient population, as well as no complications related to the PMMA implant. Postoperative computed tomography showed favorable cosmetic results of the PMMA implant in both the pterional area for superficial temporal artery-middle cerebral artery bypasses and parietooccipital area for occipital artery-middle cerebral artery bypasses as confirmed by high-rated overall patient satisfaction with favorable cosmetic, pain, and sensory patient-rated outcomes. CONCLUSIONS: In this study we were able to show that this novel technique is safe, allows for patency assessment of the EC-IC bypass using bedside TCUS technique, and is cosmetically satisfying for patients.


Subject(s)
Cerebral Revascularization , Craniotomy/methods , Postoperative Complications/diagnostic imaging , Prostheses and Implants , Ultrasonography/methods , Adult , Cerebral Revascularization/adverse effects , Cerebral Revascularization/methods , Feasibility Studies , Female , Humans , Male , Middle Aged , Patient Reported Outcome Measures , Patient Satisfaction , Polymethyl Methacrylate , Postoperative Complications/etiology
16.
J Neurosurg Pediatr ; : 1-9, 2019 Aug 30.
Article in English | MEDLINE | ID: mdl-31470399

ABSTRACT

OBJECTIVE: Skull fractures represent a common source of morbidity in the pediatric trauma population. This study characterizes the type of follow-up that these patients receive and discusses predictive factors for follow-up. METHODS: The authors reviewed cases of nonoperative pediatric skull fractures at a single academic hospital between 2007 and 2017. Clinical patient and radiological fractures were recorded. Recommended neurosurgical follow-up, follow-up appointments, imaging studies, and fracture-related complications were recorded. Statistical analyses were performed to identify predictors for outpatient follow-up and imaging. RESULTS: The study included 414 patients, whose mean age was 5.2 years; 37.2% were female, and the median length of stay was 1 day (IQR 0.9-4 days). During 438 clinic visits and a median follow-up period of 8 weeks (IQR 4-12, range 1-144 weeks), 231 imaging studies were obtained, mostly head CT scans (55%). A total of 283 patients were given recommendations to attend follow-up in the clinic, and 86% were seen. Only 12 complications were detected, including 7 growing skull fractures, 2 traumatic encephaloceles, and 3 cases of hearing loss. Primary care physician (PCP) status and insurance status were associated with a recommendation of follow-up, actual follow-up compliance, and the decision to order outpatient imaging in patients both with and without intracranial hemorrhage. PCP status remained an independent predictor in each of these analyses. Follow-up compliance was not associated with a patient's distance from home. Among patients without intracranial hemorrhage, a follow-up recommendation and actual follow-up compliance were associated with pneumocephalus and other polytraumatic injuries, and outpatient imaging was associated with a bilateral fracture. No complications were found in patients with linear fractures above the skull base in those without an intracranial hemorrhage. CONCLUSIONS: Pediatric nonoperative skull fractures drive a large expenditure of clinic and imaging resources to detect a relatively small profile of complications. Understanding the factors underlying the decision for clinic follow-up and additional imaging can decrease future costs, resource utilization, and radiation exposure. Factors related to injury severity and socioeconomic indicators were associated with outpatient imaging, the decision to follow up patients in the clinic, and patients' subsequent attendance. Socioeconomic status (PCP and insurance) may affect access to appropriate neurosurgical follow-up and deserves future research attention. Patients with no intracranial hemorrhage and with a linear fracture above the skull base do not appear to be at risk for delayed complications and could be candidates for reduced follow-up and imaging.

18.
Mol Divers ; 21(4): 1021-1026, 2017 11.
Article in English | MEDLINE | ID: mdl-28791530

ABSTRACT

An elegant, efficient, and highly regioselective approach for the synthesis of novel methyl 5-amino-3-(methylthio)-1-differently substituted-1H-pyrazole-4-carboxylates is reported. The procedure involves the cyclocondensation of α-oxeketene S, S-dimethyl acetal building blocks with different alkyl, aryl, and heterocyclic acid hydrazides. The novel molecules were obtained in good yields and their identities confirmed by NMR and HRMS spectrometry.


Subject(s)
Acetals/chemistry , Ethylenes/chemistry , Hydrazines/chemistry , Ketones/chemistry , Nitrogen/chemistry , Pyrazoles/chemistry , Pyrazoles/chemical synthesis , Chemistry Techniques, Synthetic , Stereoisomerism
19.
J Am Chem Soc ; 138(2): 696-702, 2016 Jan 20.
Article in English | MEDLINE | ID: mdl-26694767

ABSTRACT

Methods for the practical, intermolecular functionalization of aliphatic C-H bonds remain a paramount goal of organic synthesis. Free radical alkane chlorination is an important industrial process for the production of small molecule chloroalkanes from simple hydrocarbons, yet applications to fine chemical synthesis are rare. Herein, we report a site-selective chlorination of aliphatic C-H bonds using readily available N-chloroamides and apply this transformation to a synthesis of chlorolissoclimide, a potently cytotoxic labdane diterpenoid. These reactions deliver alkyl chlorides in useful chemical yields with substrate as the limiting reagent. Notably, this approach tolerates substrate unsaturation that normally poses major challenges in chemoselective, aliphatic C-H functionalization. The sterically and electronically dictated site selectivities of the C-H chlorination are among the most selective alkane functionalizations known, providing a unique tool for chemical synthesis. The short synthesis of chlorolissoclimide features a high yielding, gram-scale radical C-H chlorination of sclareolide and a three-step/two-pot process for the introduction of the ß-hydroxysuccinimide that is salient to all the lissoclimides and haterumaimides. Preliminary assays indicate that chlorolissoclimide and analogues are moderately active against aggressive melanoma and prostate cancer cell lines.


Subject(s)
Chlorine/chemistry , Diterpenes/chemistry , Succinimides/chemistry , Carbon/chemistry , Hydrogen/chemistry
20.
Chem Phys Lipids ; 193: 24-35, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26453973

ABSTRACT

In this study, the interaction between soy isoflavone genistein and asolectin liposomes was investigated by monitoring the effects of isoflavone on lipidic hydration, mobility, location and order. These properties were analyzed by the following techniques: horizontal attenuated total reflection Fourier transform infrared spectroscopy (HATR-FTIR), low-field (1)H nuclear magnetic resonance (NMR), high-field (31)P NMR, zeta potential, differential scanning calorimetry (DSC) and UV-vis spectroscopy. The antioxidant and antitumoral activities of the genistein liposomal system were also studied. The genistein saturation concentration in ASO liposomes corresponded to 484 µM. HATR-FTIR results indicated that genistein influences the dynamics of the lipidic phosphate, choline, carbonyl and acyl chain methylenes groups. At the lipid polar head, HATR-FTIR and (31)P NMR results showed that the isoflavone reduces the hydration degree of the phosphate group, as well as its mobility. Genistein ordered the lipid interfacial carbonyl group, as evidenced by the HATR-FTIR bandwidth analysis. This ordering effect was also observed in the lipidic hydrophobic region, by HATR-FTIR, NMR, DSC and turbidity responses. At the saturation concentration, liposome-loaded genistein inhibits the lipid peroxidation induced by hydroxyl radical in 90.9%. ASO liposome-loaded genistein at 100 µM decreased C6 glioma cell viability by 57% after 72 h of treatment. Results showed an increase of the genistein in vitro activities after its incorporation in liposomes. The data described in this work will contribute to a better understanding of the interaction between genistein and a natural-source membrane and of its influence on isoflavone biological activities. Furthermore, the antitumoral results showed that genistein-based liposomes, which contain natural-sourced lipids, may be promising as a drug delivery system to be used in the glioma therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Genistein/pharmacology , Liposomes/chemistry , Phosphatidylcholines/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antioxidants/administration & dosage , Antioxidants/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Genistein/administration & dosage , Genistein/chemistry , Glioma/drug therapy , Humans , Lipid Peroxidation/drug effects , Magnetic Resonance Spectroscopy
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