1,556 results on '"Jacob RG"'
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2. Synthesis of 4-(Phenylchalcogenyl)tetrazolo[1,5- a ]quinolines by Bicyclization of 2-Azidobenzaldehydes with Phenylchalcogenylacetonitrile.
- Author
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Monzon LI, Rocha NCM, Quadros GT, Nunes PPP, Cargnelutti R, Jacob RG, Lenardão EJ, Perin G, and Hartwig D
- Subjects
- Water, Solvents, Catalysis, Dimethyl Sulfoxide, Quinolines chemistry
- Abstract
A general methodology to access valuable 4-(phenylchalcogenyl)tetrazolo[1,5- a ]quinolines was developed by the reaction of 2-azidobenzaldehyde with phenylchalcogenylacetonitriles (sulfur and selenium) in the presence of potassium carbonate (20 mol%) as a catalyst. The reactions were conducted using a mixture of dimethylsulfoxide and water (7:3) as solvent at 80 °C for 4 h. This new methodology presents a good functional group tolerance to electron-deficient and electron-rich substituents, affording a total of twelve different 4-(phenylchalcogenyl)tetrazolo[1,5- a ]quinolines selectively in moderate to excellent yields. The structure of the synthesized 4-(phenylselanyl)tetrazolo[1,5- a ]quinoline was confirmed by X-ray analysis.
- Published
- 2023
- Full Text
- View/download PDF
3. Antinociceptive and anti-inflammatory effects of 4-(arylchalcogenyl)-1H-pyrazoles containing selenium or sulfur.
- Author
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Oliveira DH, Sousa FSS, Birmann PT, Alves D, Jacob RG, and Savegnago L
- Subjects
- Analgesics administration & dosage, Analgesics chemistry, Animals, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents chemistry, Celecoxib pharmacology, Disease Models, Animal, Dose-Response Relationship, Drug, Edema drug therapy, Inflammation drug therapy, Male, Mice, Nociception drug effects, Pain drug therapy, Pyrazoles administration & dosage, Pyrazoles chemistry, Selenium chemistry, Sulfur chemistry, Analgesics pharmacology, Anti-Inflammatory Agents pharmacology, Pyrazoles pharmacology
- Abstract
Background/objectives: 4-(Arylchalcogenyl)-1H-pyrazoles containing selenium or sulfur (0.001-50 mg/kg) were investigated regarding the intragastric route effect (ig) administration on nociception in mice. In this study, nociception and inflammation were induced by chemical agents such as formalin (0.92%), sodium L-glutamate 1-hydrate (20 μmol), croton oil (2.5%), acetic acid (1.6%) and thermic model with a hot plate test., Results: Compounds 1a-c had the ability to reduce licking time in both phases (neurogenic and inflammatory) of the formalin test and glutamate. Only compounds 1a and 1b had the ability to reduce the number of abdominal writhes caused by acetic acid. The same was observed with the positive control celecoxib. To evaluate the possible anti-inflammatory activity of compounds 1a-c, the induction of paw edema by formalin and ear edema by croton oil was performed. For the inflammation induced by formalin, significant effects were observed from the dose of 0.1 mg/kg (1a-b) and 10 mg/kg (1c). In the ear edema test, it can be observed that only compound 1a had a significant effect. In the hotplate test, all the compounds had the ability to reduce the latency time., Conclusion: The results demonstrated that acute antinociceptive and anti-inflammatory effects of 4-(arylchalcogenyl)-1H-pyrazoles 1a is better than compared with the compound 1b and 1c in mice. This resulted in these molecules attracting the interest of researchers to perform future studies to develop new drugs to treat pain and inflammatory clinical conditions.
- Published
- 2020
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4. Synthesis, characterization, antioxidant potential, and cytotoxicity screening of new Cu(II) complexes with 4-(arylchalcogenyl)-1H-pyrazoles ligands.
- Author
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Pinheiro AC, Busatto FF, Schaefer BT, Tomasini PP, Nunes IJ, Machado TDS, Cargnelutti R, de Aquino TFB, Ferreira KQ, Casaril AM, Jacob RG, Savegnago L, Hartwig D, and Saffi J
- Subjects
- Humans, Ligands, Antioxidants pharmacology, Copper chemistry, Pyrazoles pharmacology, Sulfur, Selenium, Coordination Complexes chemistry
- Abstract
Two new Cu(II) complexes based on 4-(arylchalcogenyl)-1H-pyrazoles monodentate bis(ligand) containing selenium or sulfur groups (2a and 2b) have been synthesized and characterized by IR spectroscopy, high-resolution mass spectrometry (HRMS), and by X-ray crystallography. In the effort to propose new applications for the biomedical area, we evaluated the antioxidant activity and cytotoxicity of the newly synthesized complexes. The antioxidant activity of the Cu(II) complexes (2a - 2b) were assessed through their ability to inhibit the formation of reactive species (RS) induced by sodium azide and to scavenge the synthetic radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS
+ ). Both copper complexes containing selenium (2a) and sulfur (2b) presented in vitro antioxidant activity. The (1a - 1b and 2a - 2b) compounds did not show cytotoxicity in V79 cells at low concentrations. Furthermore, the antiproliferative activity of free ligands (1a - 1b) and their complexes (2a - 2b) were tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and HepG2 (hepatocarcinoma). Also, 2a was tested against U2OS (osteosarcoma). Our results demonstrated that 1a and 1b show little or no growth inhibition activities on human cell lines.The 2a compound exhibited good cytotoxic activity toward human tumor cell lines. However, 2a showed no selectivity, with a selectivity index of 1.12-1.40. Complex 2b was selective for the MCF-7 human tumor cell lines with IC50 of 59 ± 2 μM. This study demonstrates that the Cu(II) complexes 2a and 2b represent promising antitumoral compounds, and further studies are necessary to understand the molecular mechanisms of these effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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5. Radical cyclization of alkynyl aryl ketones for the synthesis of 3-seleno-substituted thiochromones and chromones.
- Author
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Bartz RH, Silva KB, Peglow TJ, Barcellos AM, Jacob RG, Lenardão EJ, and Perin G
- Subjects
- Cyclization, Catalysis, Ketones, Chromones
- Abstract
We report a strategy for the direct synthesis of 3-organylselanylthiochromones and 3-organylselanylchromones via the radical cyclization reaction between alkynyl aryl ketones containing an ortho -thiopropyl/methoxy group and diorganyl diselenides promoted by Oxone®. This method allows the construction and seleno -functionalization of thiochromones and chromones using Oxone® as a stable and non-hazardous oxidizing agent in the presence of CH
3 CN at 82 °C. These reactions tolerate a variety of substituents, and allowed the synthesis of twenty-one new 3-organylselanylthiochromones and selanylchromones in good to excellent yields (55-95%). Additionally, the developed method proved to be suitable for scale up (3.0 mmol, 80%), and the synthetic usefulness of the prepared compounds was demonstrated in the oxidation of 2-phenyl-3-(phenylselanyl)-4 H -thiochromen-4-one.- Published
- 2022
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6. Flower essential oil of Tagetes minuta mitigates oxidative stress and restores BDNF-Akt/ERK2 signaling attenuating inflammation- and stress-induced depressive-like behavior in mice.
- Author
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Birmann PT, Casaril AM, Zugno GP, Acosta GG, Severo Sabedra Sousa F, Collares T, Seixas FK, Jacob RG, Brüning CA, Savegnago L, and Hartwig D
- Subjects
- Animals, Behavior, Animal, Brain-Derived Neurotrophic Factor metabolism, Depression drug therapy, Depression metabolism, Disease Models, Animal, Flowers metabolism, Hippocampus metabolism, Inflammation drug therapy, Inflammation metabolism, Mice, Mitogen-Activated Protein Kinase 1 metabolism, Oxidative Stress, Proto-Oncogene Proteins c-akt metabolism, Depressive Disorder, Major metabolism, Oils, Volatile metabolism, Oils, Volatile pharmacology, Oils, Volatile therapeutic use, Tagetes metabolism
- Abstract
Essential oils (EO) are plant extracts widely used for various pharmacological applications and their antioxidant and anti-inflammatory effects have received a lot of attention because they hold the potential to reduce oxidative stress, and neuroinflammation, alterations involved in the pathophysiology of major depressive disorder. This study examined the benefits of administration of flower EO of the Tagetes minuta (10 and 50 mg/kg, intragastric route) in attenuating behavioral, neurochemical, and neuroendocrine changes in animal models of depressive-like behavior induced by acute restraint stress and lipopolysaccharide (0.83 mg/kg, intraperitoneally). We demonstrated that the treatment of mice with flower EO of the T. minuta reversed the depressive-like behavior induced by stress or inflammatory challenge in mice. This effect is most likely due to the reversal of oxidative stress in the hippocampus of mice, the decrease in plasma corticosterone levels, and restoration of the mRNA levels of brain-derived neurotrophic factor, phosphatidylinositol-3-kinase, protein kinase B, and extracellular signal-regulated kinase 2. As an outcome, flower EO of the T. minuta has promising antidepressant properties and could be considered for new therapeutic strategies for major depressive disorder., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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7. Synthesis of Seleno-Dibenzocycloheptenones/Spiro[5.5]Trienones by Radical Cyclization of Biaryl Ynones.
- Author
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Goulart HA, Bartz RH, Peglow TJ, Barcellos AM, Cervo R, Cargnelutti R, Jacob RG, Lenardão EJ, and Perin G
- Subjects
- Cyclization, Oxidation-Reduction, Solvents, Spiro Compounds
- Abstract
We report herein an alternative method for the synthesis of seleno-dibenzocycloheptenones and seleno-spiro[5.5]trienones through the radical cyclization of biaryl ynones in the presence of diorganyl diselenides, using Oxone as a green oxidizing agent. The reactions were conducted using acetonitrile as the solvent in a sealed tube at 100 °C. The protocol is operationally simple and scalable, exhibits high regioselectivity, and allows the synthesis of 24 dibenzocycloheptenones/spiro[5.5]trienones in yields of up to 99%, 17 of which are unpublished compounds. Additionally, synthetic transformations of the prepared compounds, such as oxidation and reduction reactions, are demonstrated.
- Published
- 2022
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8. Recent Advances in the Oxone-Mediated Synthesis of Heterocyclic Compounds.
- Author
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Goulart HA, Araujo DR, Penteado F, Jacob RG, Perin G, and Lenardão EJ
- Abstract
Oxone is a commercially available oxidant, composed of a mixture of three inorganic species, being the potassium peroxymonosulfate (KHSO
5 ) the reactive one. Over the past few decades, this cheap and environmentally friendly oxidant has become a powerful tool in organic synthesis, being extensively employed to mediate the construction of a plethora of important compounds. This review summarizes the recent advances in the Oxone-mediated synthesis of N-, O- and chalcogen-containing heterocyclic compounds, through a wide diversity of reactions, starting from several kinds of substrate, highlighting the main synthetic differences, advantages, the scope and limitations.- Published
- 2021
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9. Organoselenium-chitosan derivative: Synthesis via "click" reaction, characterization and antioxidant activity.
- Author
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Nornberg AB, de Aquino TFB, Martins CC, Luchese C, Wilhelm EA, Jacob RG, Hartwig D, and Fajardo AR
- Subjects
- Triazoles chemistry, Antioxidants chemical synthesis, Chitosan analogs & derivatives, Click Chemistry methods, Organoselenium Compounds chemistry
- Abstract
The derivatization of chitosan (CS) is widely exploited to endow this polysaccharide with enhanced physicochemical and biological properties. Beyond the synthetic route, the nature of the compounds used to functionalize the CS-derivatives exerts a pivotal role in their final properties. Making use of a simple "click" reaction, we synthesized for the first time an organoselenium-CS derivative through a 1,2,3-triazole formation. The product (CS-TSe) was characterized in detail by FTIR, NMR (
1 H,13 C, and77 Se) and UV-Vis techniques, and SEM microscopy. The antioxidant activity of CS-TSe was examined by ABTS+ and DPPH (free radical-scavenging) assays. Experimentally, it was demonstrated that CS-TSe has superior antioxidant activity compared with raw CS and "free" organoselenium compound, suggesting a benign and synergistic effect due to the derivatization. In short, the antioxidant property of CS-TSe combined with the other attractive properties of CS and selenium could be useful in the formulation of advanced materials for biomedical and packaging applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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10. Synthesis of 4-Selanyl- and 4-Tellanyl-1 H -isochromen-1-ones Promoted by Diorganyl Dichalcogenides and Oxone.
- Author
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Goulart HA, Neto JSS, Barcellos AM, Silva KB, de Moraes MC, Jacob RG, Lenardão EJ, Barcellos T, and Perin G
- Subjects
- Catalysis, Cyclization, Solvents, Sulfuric Acids, Molecular Structure
- Abstract
A new method was developed for the synthesis of 4-chalcogenyl-1 H -isochromen-1-ones through the 6- endo - dig electrophilic cyclization of 2-alkynylaryl esters and diorganyl dichalcogenides under ultrasound irradiation. The reactions were performed under mild conditions, using Oxone as a green oxidant to promote the cleavage of the chalcogen-chalcogen bond in diorganyl diselenides and ditellurides to generate electrophilic species in situ . A total of 25 compounds were selectively obtained after 30-70 min, in good to excellent yields (74-95%). This procedure was extended to prepare 5 H -selenopheno[3,2- c ]isochromen-5-ones. Additionally, for the first time, the 4-chalcogenyl-1 H -isochromen-1-ones were used as substrates in the thionation reaction, using Lawesson's reagent and microwave irradiation under solvent-free conditions, obtaining the thio derivatives in yields of up to 99% in only 15 min.
- Published
- 2021
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11. Synthesis of benzo[ b ]chalcogenophenes fused to selenophenes via intramolecular electrophilic cyclization of 1,3-diynes.
- Author
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Hellwig PS, Guedes JS, Barcellos AM, Jacob RG, Silveira CC, Lenardão EJ, and Perin G
- Abstract
We describe herein an alternative and transition-metal-free procedure for the access of benzo[b]chalcogenophenes fused to selenophenes via intramolecular cyclization of 1,3-diynes. This efficient protocol involves a double cyclization of 1,3-diynyl chalcogen derivatives promoted by the electrophilic species of organoselenium generated in situ by the oxidative cleavage of the Se-Se bond of dibutyl diselenide using Oxone® in acetonitrile as solvent in an open-flask at 80 °C. In this study, 15 selenophenes with broad substrate scope were prepared in moderate to excellent yields (55-98%) with short reaction times (0.5-3.0 h).
- Published
- 2021
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12. A pyrazole-containing selenium compound modulates neuroendocrine, oxidative stress, and behavioral responses to acute restraint stress in mice.
- Author
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Birmann PT, Domingues M, Casaril AM, Smaniotto TÂ, Hartwig D, Jacob RG, and Savegnago L
- Subjects
- Animals, Anti-Anxiety Agents administration & dosage, Corticosterone blood, Male, Mice, Pyrazoles, Restraint, Physical, Selenium, Anti-Anxiety Agents pharmacology, Anxiety drug therapy, Behavior, Animal drug effects, Hippocampus drug effects, Hyperalgesia drug therapy, Neurosecretory Systems drug effects, Nociception drug effects, Oxidative Stress drug effects, Prefrontal Cortex drug effects, Stress, Psychological drug therapy, Stress, Psychological metabolism
- Abstract
The contribution of oxidative stress has been described in numerous studies as one of the main pathways involved in the pathophysiology of anxiety and its comorbidities, such as chronic pain. Therefore, in this study, we investigated the anxiolytic-like, antiallodynic, and anti-hyperalgesic effects of 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) in response to acute restraint stress (ARS) in mice through the modulation of oxidative stress and neuroendocrine responses. Mice were restrained for 2 h followed by SePy (1 or 10 mg/kg, intragastrically) treatment. Behavioral, and biochemical tests were performed after further 30 min. The treatment with SePy reversed (i) the decreased time spent and the number of entries in the open arms of the elevated plus-maze apparatus, (ii) the decreased time spent in the central zone of the open field test and the increased number of grooming, (iii) the increased number of marbles buried, (iv) the increased response frequency of Von Frey Hair stimulation, and (v) the decreased latency time to nociceptive response in the hot plate test stress induced by ARS. Biochemically, SePy reversed ARS-induced increased levels of plasma corticosterone, and reversed the ARS-induced alterations in the levels of reactive species, lipid peroxidation, and superoxide dismutase and catalase activities in the prefrontal cortices and hippocampi of mice. Moreover, a molecular docking approach suggested that SePy may interact with the active site of the glucocorticoid receptor. Altogether, these results indicate that SePy attenuated anxiolytic-like behavior, hyperalgesia, and mechanical allodynia while modulating oxidative stress and neuroendocrine responses in stressed mice., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
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13. A novel pyrazole-containing selenium compound modulates the oxidative and nitrergic pathways to reverse the depression-pain syndrome in mice.
- Author
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Birmann PT, Casaril AM, Hartwig D, Jacob RG, Seixas FK, Collares T, and Savegnago L
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- Animals, Depression chemically induced, Depression metabolism, Glycogen Synthase Kinase 3 beta chemistry, Glycogen Synthase Kinase 3 beta metabolism, Injections, Intraventricular, Male, Mice, Nitric Oxide Synthase Type II chemistry, Nitric Oxide Synthase Type II metabolism, Nitrosative Stress physiology, Oxidative Stress physiology, Pain chemically induced, Pain metabolism, Pain Measurement drug effects, Pain Measurement methods, Protein Structure, Secondary, Streptozocin administration & dosage, Streptozocin toxicity, Depression drug therapy, Nitrosative Stress drug effects, Oxidative Stress drug effects, Pain drug therapy, Pyrazoles administration & dosage, Selenium administration & dosage
- Abstract
Bearing in mind that pain and major depressive disorder (MDD) often share biological pathways, this condition is classified as depression-pain syndrome. Mounting evidence suggests that oxidative stress is implicated in the pathophysiology of this syndrome. The development of effective pharmacological interventions for the depression-pain syndrome is of particular importance as clinical treatments for this comorbidity have shown limited efficacy. Therefore, the present study aimed to evaluate whether the 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) was able to reverse the depression-pain syndrome induced by intracerebroventricular (i.c.v) streptozotocin (STZ) in mice and the possible modulation of oxidative and nitrergic pathways in its effect. The treatment with SePy (1 and 10 mg/kg) administered intragastrically (i.g.) reversed the increased immobility time in the tail suspension test, decreased grooming time in the splash test, latency time to nociceptive response in the hot plate test, and the response frequency of Von Frey hair (VFH) stimulation induced by STZ (0.2 mg/4 μl/per mouse). Additionally, SePy (10 mg/kg, i.g.) reversed STZ-induced alterations in the levels of reactive oxygen species, nitric oxide, and lipid peroxidation and the superoxide dismutase and catalase activities in the prefrontal cortices (PFC) and hippocampi (HC) of mice. Treatment with SePy (10 mg/kg, i.g.) also reversed the STZ-induced increased expression of inducible nitric oxide synthase (iNOS) and glycogen synthase kinase 3 beta (GSK3β) in the PFC and HC. An additional molecular docking investigation found that SePy binds to the active site of iNOS and GSK3β. Altogether, these results indicate that the antidepressant-like effect of SePy is accompanied by decreased hyperalgesia and mechanical allodynia, which were associated with its antioxidant effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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14. Evaluation of antioxidant activity and toxicity of sulfur- or selenium-containing 4-(arylchalcogenyl)-1 H -pyrazoles.
- Author
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Hartwig de Oliveira D, Sousa FSS, Birmann PT, Pesarico AP, Alves D, Jacob RG, and Savegnago L
- Subjects
- Administration, Oral, Animals, Cerebral Cortex metabolism, Cerebral Cortex pathology, Drug Evaluation, Preclinical, Free Radical Scavengers chemistry, Kidney drug effects, Kidney pathology, Liver drug effects, Liver pathology, Male, Mice, Models, Animal, Pyrazoles chemistry, Reactive Oxygen Species metabolism, Selenium chemistry, Sulfur chemistry, Toxicity Tests, Acute, Cerebral Cortex drug effects, Free Radical Scavengers pharmacology, Lipid Peroxidation drug effects, Pyrazoles pharmacology
- Abstract
Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1 H -pyrazol ( 1a ), 3,5-dimethyl-4-(phenylselanyl)-1 H -pyrazole ( 2a ), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 3a ), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 4a ), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1 H -pyrazole ( 1b ), 3,5-dimethyl-4-(phenylthio)-1 H -pyrazole ( 2b ), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 3b ), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1 H -pyrazole ( 4b ), and 3,5-dimethyl-1-phenyl-1 H -pyrazole ( 1c ). In vitro, 4-(arylcalcogenyl)-1 H -pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a , 1b , and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a , 1b , and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a , 1b , and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.
- Published
- 2020
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15. Synthesis, Molecular Docking, and Preliminary Evaluation of 2-(1,2,3-Triazoyl)benzaldehydes As Multifunctional Agents for the Treatment of Alzheimer's Disease.
- Author
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Costa GP, Baldinotti RSM, Fronza MG, Nascimento JER, Dias ÍFC, Sonego MS, Seixas FK, Collares T, Perin G, Jacob RG, Savegnago L, and Alves D
- Subjects
- Acetylcholinesterase metabolism, Alzheimer Disease chemically induced, Alzheimer Disease metabolism, Animals, Behavior, Animal drug effects, Benzaldehydes chemical synthesis, Benzaldehydes chemistry, Cholinesterase Inhibitors chemical synthesis, Cholinesterase Inhibitors chemistry, Disease Models, Animal, Male, Mice, Neuroprotective Agents chemical synthesis, Neuroprotective Agents chemistry, Streptozocin, Alzheimer Disease drug therapy, Benzaldehydes pharmacology, Cholinesterase Inhibitors pharmacology, Molecular Docking Simulation, Neuroprotective Agents pharmacology
- Abstract
We described here our results on the use of thiourea as a ligand in the copper catalysed azide-alkyne cycloaddition (CuAAC) of 2-azidobenzaldehyde with alkynes. Reactions were performed reacting 2-azidobenzaldehyde with a range of terminal alkynes using 10 mol % of copper iodide as a catalyst, 20 mol % of thiourea as a ligand, triethylamine as base, DMSO as solvent at 100 °C under nitrogen atmosphere. The corresponding 2-(1H-1,2,3-triazoyl)-benzaldehydes (2-TBH) were obtained in moderated to excellent yields and according our experiments, the use of thiourea decreases the formation of side products. The obtained compounds were screened for their binding affinity with multiple therapeutic targets of AD by molecular docking: β-secretase (BACE), glycogen synthase kinase (GSK-3β) and acetylcholinesterase (AChE). The three compounds with highest affinity, 5 a (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzaldehyde), 5 b (2-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzaldehyde), and 5 d (2-(4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzaldehyde) were selected and evaluated on its antioxidant effect, in view of select the most promising one to perform the in vivo validation. Due the antioxidant potential ally to the affinity with BACE, GSK-3β and AChE, compound 5 b was evaluated in a mouse model of AD induced by intracerebroventricular injection of streptozotocin (STZ). Our results indicate that 5 b (1 mg/kg) treatment during 20 days is able to reverse the cognitive and memory impairment induced by STZ trough the modulation of AChE activity, amyloid cascade and GSK-3β expression., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2020
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16. α-Keto Acids: Acylating Agents in Organic Synthesis.
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Penteado F, Lopes EF, Alves D, Perin G, Jacob RG, and Lenardão EJ
- Abstract
A significant number of important acyl-transfer reactions, such as direct acylation, ortho acylation, heteroatom acylation, and a diversity of cyclization reactions using the title compound as a key starting material, have been described in recent years. Just like a sleeping beauty, α-oxocarboxylic acids were awakened from a 17-year sleep to become important reagents in classical and new acylation reactions. The greener characteristic of the coproduct formed in reactions using α-keto acid (only CO
2 ), together with its versatility as a building block in catalytic organic synthesis, accredit it as a candidate to green acylating agent, an alternative to acyl chloride, and other acyl-transfer reagents. This review presents the impressive breakthroughs achieved mainly in the past decade in the development of new catalytic reactions for the formation of C-C, C-N, and C-S bonds using α-keto acids.- Published
- 2019
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17. NMR chiral discrimination of chalcogen containing secondary alcohols.
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Marques NBG, Jacob RG, Perin G, Lenardão EJ, Alves D, and Silva MS
- Abstract
Here, we report the general strategies by which NMR spectroscopy can be used to determine the enantiopurity and absolute configuration of chalcogen containing secondary alcohols, including the evaluation of the use of chiral solvating and chiral derivatizing agents. The BINOL/DMAP ternary complex demonstrated a simple and fast protocol for determining enantiopurity. The drug Naproxen afforded a stable, nonhygroscopic, and readily available chiral derivatizing agent (CDA) for NMR chiral discrimination of chalcogen containing secondary alcohols. The chiral recognition by CDA and chiral solvating agent (CSA) was assessed using
1 H,77 Se-{1H}, and125 Te-{1H} NMR spectroscopy. A simple model for the assignment of the absolute configuration from NMR data is presented., (© 2018 Wiley Periodicals, Inc.)- Published
- 2019
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18. Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1 H -pyrazoles.
- Author
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Pires CS, de Oliveira DH, Pontel MRB, Kazmierczak JC, Cargnelutti R, Alves D, Jacob RG, and Schumacher RF
- Abstract
A one-pot iodine-catalyzed multicomponent reaction has been developed for the selective preparation of 5-amino-4-(arylselanyl)-1 H -pyrazoles from a diverse array of benzoylacetonitriles, arylhydrazines and diaryl diselenides. The reactions were conducted in MeCN as solvent at reflux temperature under air. The methodology presents a large functional group tolerance to electron-deficient, electron-rich, and bulky substituents and gave the expected products in good to excellent yields. The synthesized 1,3-diphenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine was submitted to an oxidative dehydrogenative coupling to produce a diazo compound confirmed by X-ray analysis.
- Published
- 2018
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19. Ultrasound-promoted synthesis of 2-organoselanyl-naphthalenes using Oxone ® in aqueous medium as an oxidizing agent.
- Author
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Perin G, Araujo DR, Nobre PC, Lenardao EJ, Jacob RG, Silva MS, and Roehrs JA
- Abstract
A green methodology to synthesize 2-organoselanyl-naphthalenes based on the reaction of alkynols with diaryl diselenides is described. The electrophilic species of selenium were generated in situ, by the oxidative cleavage of the Se-Se bond of diaryl diselenides by Oxone
® using water as the solvent. The reactions proceeded efficiently under ultrasonic irradiation as an alternative energy source, using a range of alkynols and diorganyl diselenides as starting materials. Through this methodology, the corresponding 2-organoselanyl-naphthalenes were obtained in moderate to good yields (56-94%) and in short reaction times (0.25-2.3 h)., Competing Interests: Eder J Lenardao is an Academic Editor for PeerJ.- Published
- 2018
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20. Synthesis, Antimicrobial, and Antioxidant Activities of Chalcogen-Containing Nitrone Derivatives from (R)-citronellal.
- Author
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Ferraz MC, Mano RA, Oliveira DH, Maia DSV, Silva WP, Savegnago L, Lenardão EJ, and Jacob RG
- Abstract
Background: The main constituents of Cymbopogonnardus (L) Rendle and C. citratus (DC) Stapfessential oils are ( R )-citronellal and citral, respectively. Organochalcogen compounds can boost the biological activities of natural products. Methods: Several chalcogen-containing nitrones derived from ( R )-citronellal and citral were prepared and evaluated for their antimicrobial and antioxidant activities. The antimicrobial activity was evaluated by the disc diffusion test and the antioxidant properties were evaluated in vitro by DPPH (1,1-diphenyl-2-picryl-hydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and FRAP (ferric ion reducing antioxidant power) assays. Results: In the antimicrobial assay, ( E )- N ,3,7-trimethyl-3-(phenylthio)oct-6-en-1-imine oxide 5c exhibited halos between 21.5 mm ( Escherichia coli O157:H7) and 26.0 mm ( Listeria monocytogenes ), while ( E )- N ,3,7-trimethyloct-6-en-1-imine oxide 5d presented halos between 22.5 mm ( E. coli O157:H7) and 31.0 mm ( L. monocytogenes ). ( E )- N ,3,7-Trimethyl-2-(phenylthio)oct-6-en-1-imine oxide 5a showed the lowest minimal inhibitory concentration (MIC) value against Bacillus cereus (0.48 mM), and 5c was the most potent bactericide, with a minimal bactericidal concentration (MBC) of 0.52 mM for E. coli O157:H7. In the antioxidant assays, 5c , 5d , and 10 (( E )-3,7-dimethyl-2-(phenylselanyl)oct-6-enal oxime) were the most actives in the DPPH, ABTS, and FRAP assays, respectively. Conclusions: The presence of a phenylthio group in the nitrone increases its antimicrobial activity against Gram-positive and Gram-negative foodborne pathogens in the disk diffusion test and the antioxidant activity in vitro.
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- 2017
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21. Ultrasound-promoted organocatalytic enamine-azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1 H -1,2,3-triazol-4-yl)ketones.
- Author
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Costa GP, Seus N, Roehrs JA, Jacob RG, Schumacher RF, Barcellos T, Luque R, and Alves D
- Abstract
The use of sonochemistry is described in the organocatalytic enamine-azide [3 + 2] cycloaddition between 1,3-diketones and aryl azidophenyl selenides. These sonochemically promoted reactions were found to be amenable to a range of 1,3-diketones or aryl azidophenyl selenides, providing an efficient access to new ((arylselanyl)phenyl-1 H -1,2,3-triazol-4-yl)ketones in good to excellent yields and short reaction times. In addition, this protocol was extended to β-keto esters, β-keto amides and α-cyano ketones. Selanyltriazoyl carboxylates, carboxamides and carbonitriles were synthesized in high yields at short times of reaction under very mild reaction conditions.
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- 2017
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22. Green Hydroselenation of Aryl Alkynes: Divinyl Selenides as a Precursor of Resveratrol.
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Perin G, Barcellos AM, Luz EQ, Borges EL, Jacob RG, Lenardão EJ, Sancineto L, and Santi C
- Subjects
- Alkynes chemical synthesis, Catalysis, Chemistry Techniques, Synthetic, Organoselenium Compounds chemical synthesis, Organoselenium Compounds chemistry, Resveratrol, Stilbenes chemical synthesis, Stilbenes chemistry, Tellurium chemistry, Alkynes chemistry, Selenium chemistry
- Abstract
A simple and efficient protocol to prepare divinyl selenides has been developed by the regio- and stereoselective addition of sodium selenide species to aryl alkynes. The nucleophilic species was generates in situ , from the reaction of elemental selenium with NaBH₄, utilizing PEG-400 as the solvent. Several divinyl selenides were obtained in moderate to excellent yields with selectivity for the ( Z , Z )-isomer by a one-step procedure that was carried out at 60 °C in short reaction times. The methodology was extended to tellurium, giving the desired divinyl tellurides in good yields. Furthermore, the Fe-catalyzed cross-coupling reaction of bis(3,5-dimethoxystyryl) selenide 3f with (4-methoxyphenyl)magnesium bromide 5 afforded resveratrol trimethyl ether 6 in 57% yield.
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- 2017
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23. Sonochemistry in organocatalytic enamine-azide [3+2] cycloadditions: A rapid alternative for the synthesis of 1,2,3-triazoyl carboxamides.
- Author
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Xavier DM, Goldani BS, Seus N, Jacob RG, Barcellos T, Paixão MW, Luque R, and Alves D
- Abstract
We described herein the use of sonochemistry in the organocatalytic enamine-azide [3+2] cycloadditions of β-oxo-amides with a range of substituted aryl azides. These sonochemical promoted reactions were found to be amenable to a range of β-oxo amides or aryl azides, providing an efficient access to new N-aryl-1,2,3-triazoyl carboxamides in good to excellent yields and short times of reaction., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2017
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24. Water and Aqueous Mixtures as Convenient Alternative Media for Organoselenium Chemistry.
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Santi C, Jacob RG, Monti B, Bagnoli L, Sancineto L, and Lenardão EJ
- Subjects
- Catalysis, Chemistry, Organic methods, Organoselenium Compounds chemistry, Water chemistry
- Abstract
Even if water is the natural environment for bioorganic reactions, its use in organic chemistry is often severely limited by the high insolubility of the organic derivatives. In this review, we introduce some examples of the use of water to perform organoselenium chemistry. We mainly discuss the advantages of this medium when the recyclability is demonstrated and when the water can control the selectivity of a reaction or enhance the reaction rate.
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- 2016
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25. Acute thermogenic effects of nicotine combined with caffeine during light physical activity in male and female smokers
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Perkins, KA, primary, Sexton, JE, additional, Epstein, LH, additional, DiMarco, A, additional, Fonte, C, additional, Stiller, RL, additional, Scierka, A, additional, and Jacob, RG, additional
- Published
- 1994
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26. Association of Benign Paroxysmal Positional Vertigo with Depression and Anxiety-A Systematic Review and Meta-Analysis.
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Yeo BSY, Toh EMS, Lim NE, Lee RS, Ho RCM, Tam WWS, and Ngo RYS
- Subjects
- Adult, Humans, Adolescent, Anxiety complications, Anxiety epidemiology, Anxiety Disorders, Databases, Factual, Benign Paroxysmal Positional Vertigo complications, Benign Paroxysmal Positional Vertigo diagnosis, Depression complications, Depression epidemiology
- Abstract
Objective: To evaluate the extent to which Benign Paroxysmal Positional Vertigo (BPPV) is associated with a higher prevalence of depression and anxiety in patients., Data Sources: Three databases including PubMed, Embase, and The Cochrane Library were searched by two independent authors from inception to June 12, 2022 for observational studies and randomized controlled trials investigating the association between BPPV and depression and anxiety. We included studies published as full-length articles in peer-reviewed journals with an adult population aged at least 18 years who have BPPV, detected through validated clinical methods like clinical diagnosis, interview and Dix-Hallpike test., Results: A total of 23 articles met the final inclusion criteria and 19 articles were included in the meta-analysis. BPPV was associated with a 3.19 increased risk of anxiety compared to controls, and 27% (17%-39%) of BPPV patients suffered from anxiety. Furthermore, the weighted average Beck's Anxiety Inventory score was 18.38 (12.57; 24.18), while the weighted average State-Trait Anxiety Index score was 43.08 (37.57; 48.60)., Conclusion: There appears to be some association between BPPV and anxiety, but further studies are required to confirm these associations. Laryngoscope, 134:526-534, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)
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- 2024
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27. Metabolic effects of nicotine after consumption of a meal in smokers and nonsmokers
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Perkins, KA, primary, Epstein, LH, additional, Stiller, RL, additional, Sexton, JE, additional, Fernstrom, MH, additional, Jacob, RG, additional, and Solberg, R, additional
- Published
- 1990
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28. Migraine-anxiety related dizziness (MARD): a new disorder?
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Furman JM, Balaban CD, Jacob RG, Marcus DA, Furman, J M, Balaban, C D, Jacob, R G, and Marcus, D A
- Published
- 2005
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29. Validation of a brief nurse-administered migraine assessment tool.
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Marcus DA, Kapelewski C, Jacob RG, Rudy TE, and Furman JM
- Abstract
OBJECTIVE: To validate a brief tool for screening migraine. BACKGROUND: Migraine is a common, but underdiagnosed condition. Effective utilization of nonphysician personnel to reliably screen patients for migraine may improve identification of migraineurs for clinical treatment and research. METHODS: An 8-question Migraine Assessment Tool (based on International Headache Society criteria) was designed for administration by a nurse with no specialized headache training as a pre-assessment for the diagnosis of migraine for use in either a research or clinical environment. A community sample of 80 adults (71 women, 9 men; mean age, 33.7 years; 80% white, 14% African American, 2.5% Asian American) with self-reported headache was recruited through advertisements. A headache specialist independently diagnosed subjects using clinical assessment, and a nurse who works in a balance disorder clinic used the Migraine Assessment Tool. Agreement between physician and nurse-administered Migraine Assessment Tool diagnoses was determined. Each subject returned in 2 to 4 weeks for a second assessment, administered by the same nurse. Agreement between the 2 diagnoses from the Migraine Assessment Tool was calculated. RESULTS: Comparison between diagnosis by the physician versus the Migraine Assessment Tool revealed a positive predictive value of 0.85; negative predictive value, 0.84; sensitivity, 0.89; specificity, 0.79; and observed agreement, 0.85. Cohen's kappa reliability measure was 0.69, indicating good test reliability. Interestingly, in 8 of the 12 cases of disagreement, the examiner diagnosing nonmigraine diagnosed analgesic overuse headache. Comparing diagnoses assigned by the 2 separate administrations of the Migraine Assessment Tool revealed a Cohen's kappa of 0.69. Notably, 9 of the 12 cases of nonagreement on the 2 assessments were due to subjects endorsing analgesic overuse in only 1 of the 2 testing sessions. CONCLUSIONS: This study showed good reliability and stability of a new, brief, nurse-administered migraine questionnaire. In addition, the study also showed that consistency in self-reporting analgesic overuse within individuals with headache is poor. This suggests the need for repeat questioning about analgesic overuse on subsequent appointments to ensure absence of analgesic overuse headache. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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30. Sonochemistry: An efficient alternative to the synthesis of 3-selanylindoles using CuI as catalyst.
- Author
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Vieira BM, Thurow S, Brito JS, Perin G, Alves D, Jacob RG, Santi C, and Lenardão EJ
- Abstract
Ultrasonic (US) irradiation was successfully used as an alternative energy source to prepare 3-selanylindoles through the direct selanylation of indoles with diorganyl diselenides using CuI (20 mol%) as catalyst and DMSO as the solvent. By using this US-promoted reaction, eleven 3-organylselanylindoles were prepared selectively and in good yields. A comparative study between the reactions under conventional heating, microwave and ultrasound irradiations was performed, and it was observed advantage in using US over the other heating systems., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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31. In vitro susceptibility of Brazilian Pythium insidiosum isolates to essential oils of some Lamiaceae family species.
- Author
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Fonseca AO, Pereira DI, Jacob RG, Maia Filho FS, Oliveira DH, Maroneze BP, Valente JS, Osório LG, Botton SA, and Meireles MC
- Subjects
- Anti-Infective Agents chemistry, Anti-Infective Agents isolation & purification, Brazil, Microbial Sensitivity Tests, Oils, Volatile chemistry, Oils, Volatile isolation & purification, Plant Oils chemistry, Plant Oils isolation & purification, Pythium growth & development, Anti-Infective Agents pharmacology, Lamiaceae chemistry, Oils, Volatile pharmacology, Plant Oils pharmacology, Pythium drug effects
- Abstract
The present study aimed to evaluate the in vitro antimicrobial action of Origanum vulgare, Origanum majorana, Mentha piperita and Rosmarinus officinalis on Pythium insidiosum oomycete zoospores. The antimicrobial activity evaluation was performed by the broth microdilution method according to CSLI M38-A2 documentation adapted to phytopharmaceuticals. Twenty-two P. insidiosum isolates were evaluated, and the minimum inhibitory concentration was determined at 100% growth inhibition. All P. insidiosum isolates evaluated showed a minimum inhibitory concentration ranging from 0.05 to 1.75 mg/mL when O. vulgare oil was used and from 0.11 to 3.5 mg/mL for O. majorana, M. piperita and R. officinalis oils. The results obtained indicate that the essential oils tested showed antimicrobial activity on P. insidiosum, with O. vulgare essential oil showing the best performance. These findings emphasize the potential use of plant essential oils as control agents in P. insidiosum infections; further research, however, is needed so as the in vivo activity of these oils can also be evaluated.
- Published
- 2015
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32. Essential oil of Psidium cattleianum leaves: antioxidant and antifungal activity.
- Author
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Castro MR, Victoria FN, Oliveira DH, Jacob RG, Savegnago L, and Alves D
- Subjects
- Animals, Antifungal Agents chemistry, Antifungal Agents isolation & purification, Antifungal Agents toxicity, Antioxidants chemistry, Antioxidants isolation & purification, Antioxidants toxicity, Biphenyl Compounds chemistry, Brain drug effects, Brain metabolism, Candida drug effects, Dose-Response Relationship, Drug, Free Radicals chemistry, Kidney drug effects, Kidney metabolism, Lipid Peroxidation drug effects, Liver drug effects, Liver metabolism, Male, Mice, Microbial Sensitivity Tests, Molecular Structure, Oils, Volatile chemistry, Oils, Volatile pharmacology, Oils, Volatile toxicity, Picrates chemistry, Plant Leaves chemistry, Toxicity Tests, Acute, Trichosporon drug effects, Antifungal Agents pharmacology, Antioxidants pharmacology, Oils, Volatile isolation & purification, Psidium chemistry
- Abstract
Context: Psidium cattleianum Sabine (Myrtacea) is rich in vitamin C and phenolic compounds, including epicatechin and gallic acid as the main components., Objective: To evaluate the antifungal and antioxidant capacity in vitro of the essential oil of araçá (EOA). The acute toxicity of the EOA also was evaluated in mice., Materials and Methods: The leaves of the P. cattleianum were extracted by steam distillation. The antioxidant capacity was evaluated by in vitro tests [1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric ion reducing antioxidant power (FRAP), linoleic acid oxidation, thiobarbituric acid reactive species (TBARS)], and ex vivo analysis [TBARS, δ-aminulevunilate dehydratase (δ-Ala-D) and catalase activity, non-protein thiols (NPSH), and ascorbic acid levels]. The toxicity was studied in mice by a single oral administration of EOA; and the antifungal activity was performed with five strains of fungi., Results: The EOA exhibited antioxidant activity in the FRAP assay and reduced lipid peroxidation in the cortex (Imax = 32.90 ± 2.62%), hippocampus (IC50 = 48.00 ± 3.00 µg/ml and Imax = 32.90 ± 2.62%), and cerebellum (Imax = 45.40 ± 14.04%) of mice. Acute administration of the EOA by the oral route did not cause toxicological effects in mice (LD50 > 500 µg/ml). The EOA also showed antifungal activity through of the determination minimum inhibitory concentration (MIC) values ranging from 41.67 ± 18.04 to 166.70 ± 72.17 µg/ml for tested strains., Conclusion: The results of present study indicate that EOA possess antioxidant properties, antifungal and not cause toxicity at tested doses.
- Published
- 2015
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33. Selenium-containing azoles: synthesis and possibilities of application.
- Author
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Akhmadiev, Nail S., Ameta, Keshav L., and Akhmetova, Vnira R.
- Subjects
SUSTAINABLE chemistry ,DRUG design ,AZOLES ,POSSIBILITY - Abstract
The review summarizes and analyzes data published over the last twenty years on the synthesis of functionalized selanyl azoles containing two pharmacophore centers responsible for different pharmacological activities. The design of such molecules with multipurpose action is effected by the improvement and development of new synthesis methods, including those that consider the fundamental principles of green chemistry. The material is systematized according to the methods of synthesis of the claimed selanyl azaheterocycles. The possibilities of practical application of selanyl azoles as a framework for the design of new drugs are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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34. Evaluation and diagnosis of pediatric patients with dizziness.
- Author
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Doerfer, Karl W., Harvey, Erin, and LaPrade, Samantha
- Published
- 2024
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35. Psychometric properties of the Turkish version of the Vestibular Migraine Patient Assessment Tool and Handicap Inventory.
- Author
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CENGİZ, Deniz Uğur, İNCEOĞLU, Feyza, KARABABA, Ercan, SATAR, Bülent, ERBEK, Hatice Seyra, BAYINDIR, Tuba, KURTCU, Büşra, ÇOLAK, Sanem Can, ERCAN, Mehmet Kadir, SÖYLEMEZ, Emre, AKYILDIZ, Metin Yüksel, İSLAMOĞLU, Yüce, ARSLAN, Bengi, DEMİREL BİRİŞİK, Sümeyye, ÖZDEMİR, Emre Akgün, DEMİR, İsmail, and ADIGÜZEL, Ahmet
- Subjects
EXPLORATORY factor analysis ,CONFIRMATORY factor analysis ,CRONBACH'S alpha ,PSYCHOMETRICS ,MEDICAL needs assessment - Abstract
Background/aim: There are insufficient tools to assist in the diagnosis and treatment of vestibular migraine. Hence, the aim of this study was to perform the Turkish adaptation of the Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI). Materials and methods: After the language and content validity was completed, a pilot study was conducted. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to test construct validity, and as a result of the validity analyses, Cronbach's alpha internal consistency coefficient and test-retest analyses were conducted for reliability. Results: In the study, in which 289 participants were evaluated, the Kaiser-Meyer-Olkin coefficient was calculated as 0.903. The percentage of variance explained by the EFA was 67.246% and the range of factor load change was 0.433-0.828. The scale structure was tested with CFA and the model was confirmed with adequate goodness of fit index values. The Cronbach's alpha internal consistency coefficient of the scale was 0.931. Conclusion: The VM-PATHI is a valid and reliable tool for the subjective evaluation of vestibular migraine in Türkiye. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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36. In vitro and in vivo acaricide action of juvenoid analogs produced from the chemical modification of Cymbopogon spp. and Corymbia citriodora essential oil on the cattle tick Rhipicephalus (Boophilus) microplus.
- Author
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Chagas AC, Domingues LF, Fantatto RR, Giglioti R, Oliveira MC, Oliveira DH, Mano RA, and Jacob RG
- Subjects
- Acaricides chemistry, Animals, Cattle, Cattle Diseases parasitology, Cattle Diseases prevention & control, Female, Larva drug effects, Tick Infestations prevention & control, Tick Infestations veterinary, Acaricides pharmacology, Cymbopogon chemistry, Myrtaceae chemistry, Oils, Volatile pharmacology, Plant Oils pharmacology, Rhipicephalus drug effects
- Abstract
The present study aimed to evaluate the acaricidal action of the chemically modified essential oil of Cymbopogon spp. and Corymbia citriodora on Rhipicephalus (Boophilus) microplus. Citronellal was converted into N-butylcitronellylamine and in N-prop-2-inylcitronellylamine, analogs of juvenoids, by reductive amination using butylamine (N1 to N3) and propargylamine (N4 to N7). In vitro assays included the adult immersion, and larval packet tests. Engorged females were weighed in groups of 10 and tested in three replicates for six concentrations. They were immersed in the modified oils or control solution and incubated. In the larval packet test, the same substances and concentrations were evaluated in three replicates. In the in vivo test, six pastured heifers naturally infested with R. (B.) microplus were used per treatment: negative control, positive control (amitraz, Triatox(®)), original oil of C. citriodora at 1.5%, and modified oil containing 0.9% N-prop-2-inylcitronellylamine (N7). Ticks were counted in the right side of the body in 24 animals from day D-3 to D21. LC50 and LC90 were obtained by Probit analysis, while the in vivo results were log transformed and compared using the Tukey test. Among the nitrocellylamines tested in vitro, N6 was most effective on the engorged females (100% efficacy at 50mg/mL) and N7 on the larvae (100% efficacy at 6.25mg/mL). In the test with larvae, the original oil of C. citriodora was less effective than the counterpart modified oil (N7), proving that the chemical modification optimized its effect. In the in vivo test, no significant difference was observed between N7 and the negative control. The average numbers of ticks on the animals' right side were 32.8, 8.1, 37.9 and 35.4 for the negative control, positive control, original oil and N7, respectively. The chemical modification improved the efficacy in vitro, but it was not observed in vivo, perhaps due to the low stability of the amines under field conditions. The evaluation carried out here has not been previously studied, so this concept expands the horizon for research into chemically modified substances for parasite control and shed light on the challenges to find effective formulations and application methods., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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37. A selenium-based ionic liquid as a recyclable solvent for the catalyst-free synthesis of 3-selenylindoles.
- Author
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Zimmermann EG, Thurow S, Freitas CS, Mendes SR, Perin G, Alves D, Jacob RG, and Lenardão EJ
- Subjects
- Catalysis, Imidazoles chemistry, Recycling, Selenium chemistry, Selenium Compounds chemistry, Solvents, Imidazoles analysis, Indoles chemical synthesis, Ionic Liquids chemistry, Selenium analysis, Selenium Compounds chemical synthesis
- Abstract
The ionic liquid 1-butyl-3-methylimidazolium methylselenite, [bmim][SeO2(OCH3)], was successfully used as solvent in the catalyst-free preparation of 3-arylselenylindoles by the reaction of indole with ArSeCl at room temperature. The products were obtained selectively in good yields without the need of any additive and the solvent was easily reused for several cycles with good results.
- Published
- 2013
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38. Essential oil of the leaves of Eugenia uniflora L.: antioxidant and antimicrobial properties.
- Author
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Victoria FN, Lenardão EJ, Savegnago L, Perin G, Jacob RG, Alves D, da Silva WP, da Motta Ade S, and Nascente Pda S
- Subjects
- Animals, Candida drug effects, Lethal Dose 50, Listeria monocytogenes drug effects, Mice, Microbial Sensitivity Tests, Staphylococcus aureus drug effects, Anti-Infective Agents pharmacology, Antioxidants pharmacology, Oils, Volatile pharmacology, Plant Extracts pharmacology, Plant Leaves chemistry, Syzygium chemistry
- Abstract
Essential oil (EO) of the leaves of Eugenia uniflora L. (Brazilian cherry tree) was evaluated for its antioxidant, antibacterial and antifungal properties. The acute toxicity of the EO administered by oral route was also evaluated in mice. The EO exhibited antioxidant activity in the DPPH, ABTS and FRAP assays and reduced lipid peroxidation in the kidney of mice. The EO also showed antimicrobial activity against two important pathogenic bacteria, Staphylococcus aureus and Listeria monocytogenes, and against two fungi of the Candida species, C. lipolytica and C. guilliermondii. Acute administration of the EO by the oral route did not cause lethality or toxicological effects in mice. These findings suggest that the EO of the leaves of E. uniflora may have the potential for use in the pharmaceutical industry., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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39. In vitro antioxidant activity and in vivo antidepressant-like effect of α-(phenylselanyl) acetophenone in mice.
- Author
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Gerzson MF, Victoria FN, Radatz CS, de Gomes MG, Boeira SP, Jacob RG, Alves D, Jesse CR, and Savegnago L
- Subjects
- Acetophenones administration & dosage, Animals, Antidepressive Agents administration & dosage, Antioxidants therapeutic use, Depression drug therapy, Depression metabolism, Lipid Peroxidation drug effects, Lipid Peroxidation physiology, Male, Mice, Organoselenium Compounds administration & dosage, Random Allocation, Treatment Outcome, Acetophenones chemistry, Acetophenones therapeutic use, Antidepressive Agents chemistry, Antidepressive Agents therapeutic use, Antioxidants chemistry, Antioxidants pharmacology, Organoselenium Compounds chemistry, Organoselenium Compounds therapeutic use
- Abstract
In this study, the antioxidant and antidepressant-like effects of α-(phenylselanyl) acetophenone (PSAP), an organoselenium compound, were investigated. To assess the in vitro antioxidant properties, PSAP was evaluated in four test systems (DPPH, ABTS, FRAP and inhibition of lipid peroxidation). PSAP (100-500 μM) showed potent antioxidant activity and protected against lipid peroxidation. Additionally, we investigated whether PSAP, when administered in mice (100, 200 and 400mg/kg, per oral, p.o.), could cause acute toxicity. Our results demonstrated that PSAP did not cause the death of any animal, significantly reduce body weight or cause any oxidative tissue stress following treatment. This study also evaluated the effect of PSAP (0.1-10 mg/kg, p.o) on mice in a forced swim test (FST) and tail suspension test (TST), assays that are predictive of depressant activity and motor activity in the open-field. PSAP (5-10 mg/kg) significantly reduced immobility time in the FST and TST without affecting motor activity. In addition, the antidepressant-like effect caused by PSAP (5m/kg, p.o) in mice during the TST was dependent on an interaction with the serotonergic system (5-HT(1A) receptors), but not with the noradrenergic, dopaminergic or adenosinergic system. Together, these results suggest that PSAP possesses antioxidant and antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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- View/download PDF
40. [Validation of the French version of the situational characteristics questionnaire in the measurement of space and motion discomfort].
- Author
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Vaillancourt L, Bélanger C, Léger-Bélanger MP, and Jacob RG
- Subjects
- Adult, Agoraphobia diagnosis, Female, Humans, Language, Male, Middle Aged, Motion Sickness diagnosis, Panic Disorder diagnosis, Psychometrics statistics & numerical data, Quebec, Reference Values, Reproducibility of Results, Risk Factors, Translating, Agoraphobia psychology, Kinesthesis, Motion Sickness psychology, Orientation, Panic Disorder psychology, Space Perception, Surveys and Questionnaires
- Abstract
Introduction: Space and motion discomfort (SMD) refers to various symptoms that occur in environments with unreliable visual and kinesthetic information that do not permit adequate spatial orientation. Some studies have demonstrated that there is a stable and predictable relationship between vestibular dysfunction and anxiety disorders. Further, vestibular dysfunction can predispose or trigger the development of panic disorder with or without agoraphobia (PD/A) or reinforce phobic avoidance. It therefore seems clinically useful to develop and validate instruments for evaluating SMD in various populations. Measuring SMD could facilitate identification of individuals with PD/A who present comorbid vestibular dysfunction. Jacob et al. developed and validated such a questionnaire: the Situational characteristics questionnaire (SitQ). This questionnaire evaluates the presence of symptoms such as dizziness, vertigo, and instability under specific conditions. The SitQ comprises two subscales that measure SMD and one subscale (agoraphobia) that measures agoraphobic avoidance behaviours. The instrument has two sections. The first section is composed of the SMD-I and agoraphobia subscales, containing 19 and seven items, respectively. Each item consists of two contrasting descriptors of a specific situation or environment. The respondent is required to indicate to what extent the two described situations or environments cause discomfort. Each item includes a "criterion" descriptor for the situation (i.e., a descriptor that is presumed to engender SMD) and an alternative (non-criterion) descriptor. The second section comprises the SMD-II scale; this scale is composed of nine criterion situations, for which non-criterion situations are not supplied. The instrument takes approximately 20 minutes to complete., Objective: The present study focuses on the validation of the French-language version of the SitQ: the questionnaire des caractéristiques situationnelles (QCS)., Method: The sample was composed of French Canadians recruited across Quebec from an anxiety disorders treatment clinic, general psychiatric care clinics, a community organization for individuals with anxiety disorders, advertisements in local newspapers, and ads posted in various public locations. The sample included 141 participants who met the criteria for lifetime PD/A. Participants reported current PD/A (n=73) or PD/A in remission (n=68). The control sample was recruited from undergraduate courses in various disciplines. Two hundred and thirty-five (n=235) students completed the questionnaires. Data from 63 (26.8%) participants were excluded from the analyses due to failure to complete all of the research questionnaires., Results: Analysis of the global descriptive data and the descriptive data for each dependent variable revealed that the data were independent of sociodemographic variables and respected the assumptions of normal distribution (skewness and kurtosis). Parametric tests were subsequently conducted. Using the combined data from the control and clinical groups, the internal consistency of the scales was analyzed using Cronbach's alpha. The SMD-I and SMD-II scales demonstrated good homogeneity. The results were comparable or superior to those obtained with the English-language version of the questionnaire. The agoraphobia scale demonstrated weaker internal consistency and corresponding weaker homogeneity. This result was consistent with that of the original version of the agoraphobia scale; this scale was eliminated for the subsequent analyses. Construct validity was analyzed via t-tests comparing clinical and control groups. Effect sizes were estimated using percentage of variance explained. The SMD-I scale demonstrated weak construct validity and was also eliminated from subsequent analyses. The SMD-II scale demonstrated good construct validity and provided an adequate measure of the theoretical construct of SMD. This scale permitted discrimination of participants according to the presence or absence of PD/A. It is therefore possible to identify participants with PD/A by their level of SMD. This result is comparable to that of Jacob et al., Conclusion: The results of the present study are generally consistent with the results of the validation of the original version of the questionnaire. However, the SMD-I and agoraphobia scales in the French-language version of the measure did not achieve a level of significance sufficient to definitively establish validity., (Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2012
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41. Neurologic bases for comorbidity of balance disorders, anxiety disorders and migraine: neurotherapeutic implications.
- Author
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Balaban CD, Jacob RG, and Furman JM
- Subjects
- Anxiety Disorders drug therapy, Anxiety Disorders epidemiology, Comorbidity, Drug Delivery Systems, Humans, Migraine Disorders drug therapy, Migraine Disorders epidemiology, Nervous System Diseases drug therapy, Signal Transduction drug effects, Anxiety Disorders physiopathology, Migraine Disorders physiopathology, Nervous System Diseases physiopathology, Postural Balance drug effects
- Abstract
The comorbidity among balance disorders, anxiety disorders and migraine has been studied extensively from clinical and basic research perspectives. From a neurological perspective, the comorbid symptoms are viewed as the product of sensorimotor, interoceptive and cognitive adaptations that are produced by afferent interoceptive information processing, a vestibulo-parabrachial nucleus network, a cerebral cortical network (including the insula, orbitofrontal cortex, prefrontal cortex and anterior cingulate cortex), a raphe nuclear-vestibular network, a coeruleo-vestibular network and a raphe-locus coeruleus loop. As these pathways overlap extensively with pathways implicated in the generation, perception and regulation of emotions and affective states, the comorbid disorders and effective treatment modalities can be viewed within the contexts of neurological and psychopharmacological sites of action of current therapies.
- Published
- 2011
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42. Synthesis of vinyl selenides.
- Author
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Perin G, Lenardão EJ, Jacob RG, and Panatieri RB
- Published
- 2009
- Full Text
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43. Space and motion discomfort and abnormal balance control in patients with anxiety disorders.
- Author
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Jacob RG, Redfern MS, and Furman JM
- Subjects
- Adolescent, Adult, Anxiety Disorders psychology, Caloric Tests, Fear, Female, Humans, Male, Middle Aged, Panic Disorder psychology, Phobic Disorders, Posture, Prevalence, Space Perception, Vestibular Diseases diagnosis, Vestibular Diseases psychology, Young Adult, Anxiety Disorders epidemiology, Motion Perception, Panic Disorder epidemiology, Postural Balance, Vestibular Diseases epidemiology
- Abstract
Objective: Previous research suggested that panic disorder with agoraphobia is associated with abnormalities on vestibular and balance function tests. The purpose of this study was to further examine psychiatric correlates of vestibular/balance dysfunction in patients with anxiety disorders and the specific nature of the correlated vestibular abnormalities. The psychiatric variables considered included anxiety disorder versus normal control status, panic disorder versus non-panic anxiety disorder diagnosis, presence or absence of comorbid fear of heights, and degree of space and motion discomfort (SMD). The role of anxiety responses to vestibular testing was also re-examined., Methods: 104 subjects were recruited: 29 psychiatrically normal individuals and 75 psychiatric patients with anxiety disorders. Anxiety patients were assigned to four subgroups depending on whether or not they had panic disorder and comorbid fear of heights. SMD and anxiety responses were measured by questionnaires. Subjects were examined for abnormal unilateral vestibular hypofunction on caloric testing indicative of peripheral vestibular dysfunction, asymmetric responses on rotational testing as an indicator of an ongoing vestibular imbalance and balance function using Equitest dynamic posturography as an indicator of balance control. Logistic regression was used to establish the association between the psychiatric variables and vestibular or balance test abnormalities., Results: Rotational test results were not significantly related to any of the psychiatric variables. The presence of either panic attacks or fear of heights increased the probability of having caloric hypofunction in a non-additive fashion. SMD and anxiety responses were independently associated with abnormal balance. Among specific posturography conditions, the association with SMD was significant for a condition that involved the balance platform tilting codirectionally with body sway, suggesting an abnormal dependence on somatosensory cues in the control of balance., Conclusion: In patients with anxiety disorders, higher SMD is indicative of somatosensory dependence in the control of balance. The absence of both panic and fear of heights reduces the probability of having peripheral vestibular dysfunction. Future research should examine if vestibular rehabilitation can be of value for patients with anxiety disorders complicated by SMD.
- Published
- 2009
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44. Isosorbide dinitrate/hydralazine: its role in the treatment of heart failure.
- Author
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Thadani U and Jacob RG
- Subjects
- Animals, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Drug Interactions, Drug Therapy, Combination, Female, Humans, Hydralazine adverse effects, Hydralazine pharmacokinetics, Isosorbide Dinitrate adverse effects, Isosorbide Dinitrate pharmacokinetics, Male, Pregnancy, Vasodilator Agents adverse effects, Vasodilator Agents pharmacokinetics, Heart Failure drug therapy, Hydralazine therapeutic use, Isosorbide Dinitrate therapeutic use, Vasodilator Agents therapeutic use, Ventricular Dysfunction, Left drug therapy
- Abstract
Despite the advances in pharmacotherapy for heart failure due to reduced left ventricular function, mortality still remains high and many patients are hospitalized over time due to worsening heart failure symptoms. There is some experimental evidence that vasoconstriction and nitric oxide (NO) deficiency in the vasculature play a role in aggravating the symptoms of heart failure, especially in patients of African-American origin. Treatment with high doses of isosorbide dinitrate (ISDN) has been shown to increase symptom-free walking time, but tolerance to the hemodynamic effects of ISDN develops rapidly. Experimental data suggests that hydralazine, given concomitantly, attenuates the development of hemodynamic tolerance to ISDN and may increase bioavailability of NO in the vasculature. In a racially mixed population, treatment with a combination of ISDN and hydralazine reduced mortality compared to placebo to a nearly statistically significant extent in the first Vasodilator Heart Failure Trial (V-HeFT I) but was inferior to treatment with angiotensin-converting enzyme (ACE) inhibitor enalapril in the V-HeFT II study. Subgroup retrospective analysis of published data, however, suggested that ISDN/hydralazine had a substantial effect in black patients and was apparently as effective as treatment with the ACE inhibitor, enalapril, in the same population, but had a much smaller, if any, effect in white patients. A recent placebocontrolled study showed that in self-identified black patients with heart failure, ISDN/hydralazine, given in addition to current state-of-the-art pharmacotherapy for heart failure, reduces mortality and first hospitalizations due to heart failure and improves quality of life. The usefulness of ISDN/hydralazine in ethnic groups other than self-identified blacks is unknown at present and is considered off-label use. This review focuses on ISDN/hydralazine for the management of patients with heart failure due to left ventricular dysfunction and the adverse effects which may be encountered with therapy., (Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.)
- Published
- 2008
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45. Visually induced postural sway in anxiety disorders.
- Author
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Redfern MS, Furman JM, and Jacob RG
- Subjects
- Adolescent, Adult, Agoraphobia diagnosis, Agoraphobia psychology, Anxiety Disorders diagnosis, Comorbidity, Conflict, Psychological, Female, Humans, Male, Middle Aged, Motion Sickness diagnosis, Panic Disorder diagnosis, Panic Disorder psychology, Phobic Disorders diagnosis, Phobic Disorders psychology, Reference Values, Risk Factors, Rotation, Vestibular Function Tests, Anxiety Disorders psychology, Kinesthesis, Motion Perception, Motion Sickness psychology, Postural Balance, Social Environment, Visual Perception
- Abstract
Postural sensitivity to moving visual environments in patients with anxiety disorders was studied. We hypothesized that patients with anxiety disorders would have greater sway in response to a moving visual environment compared to healthy adults, especially if they have space and motion discomfort (SMD). Twenty-one patients with generalized anxiety without panic (NPA) and 38 patients with panic and agoraphobia (PAG) were compared to 22 healthy controls. SMD was evaluated in all subjects via questionnaire. Subjects stood on a force platform that was either fixed or rotating with the subject (i.e., sway referenced) during exposure to a sinusoidally moving visual surround. Center of pressure (COP) data were computed from force transducers in the platform as a measure of sway. Results showed that patients swayed significantly more in response to the moving visual scene compared to control subjects, with no differences between the NPA and PAG groups. SMD was a predictor of sway response in the patients: patients with high SMD swayed significantly more than both Controls and anxiety patients with low SMD. These results indicate that patients with anxiety disorders, particularly those with SMD, are more visually dependent for balance. This subgroup of patients may be amenable to treatment used for patients with balance disorders (i.e., vestibular rehabilitation) that focuses on sensory re-integration processes that address visual sensitivity.
- Published
- 2007
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46. Motion sickness whilst reading as a passenger in the car is highly predictive of vestibular migraine.
- Author
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Rova, Konstantina, Joffily, Lucia, Carvalho, Lara, Cortese, Elvira, Koohi, Nehzat, and Kaski, Diego
- Subjects
DIZZINESS ,ODDS ratio ,LOGISTIC regression analysis ,NAUSEA ,MIGRAINE ,MOTION sickness ,VERTIGO - Abstract
Background: Vestibular Migraine (VM) is a prevalent vestibular disorder, affecting up to 2.7% of the general population. Despite the establishment of diagnostic criteria by the Bárány Society and its inclusion in the International Classification of Headache Disorders, the clinical diagnosis of VM remains challenging due to its complex pathophysiology and symptom overlap with other dizziness disorders. Motion sickness is a core feature of migraine and can be interrogated through simple questionnaires. Objective: This study aims to identify to what extent motion sensitivity can predict VM compared to other causes of dizziness. Methods: We conducted a cross-sectional study involving 113 patients from the vestibular neurology clinics at University College London Hospitals. Participants were categorized into VM, Persistent Postural Perceptual Dizziness (PPPD), combined VM and PPPD, and 'other' dizziness etiologies. Data on motion sickness history and dizziness during car travel were collected through structured interviews and analyzed using logistic regression to assess the predictive value of these symptoms for VM. Results: A substantial portion of patients with VM (91.2%) reported nausea or dizziness when reading as a passenger, a symptom significantly more prevalent than in those with PPPD or other dizziness diagnoses. Logistic regression indicated that VM patients are significantly more likely to experience these symptoms compared to non-VM patients, with an odds ratio suggesting a strong predictive value for this symptom in diagnosing VM. Conclusion: The findings highlight increased motion sensitivity while reading in a moving vehicle as a promising diagnostic tool for VM, offering a practical aid in clinical settings to distinguish VM from other vestibular disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
47. Inflammo-immune perspective on the association of eight migraine risk factors with migraine: a multi-omics Mendelian randomization study.
- Author
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Jiaxi Zhao, Rong Chen, Mengqi Luo, Hongping Gong, Kaixin Li, and Qian Zhao
- Subjects
MIGRAINE ,SLEEP apnea syndromes ,SMOKING ,MULTIOMICS ,ETIOLOGY of diseases ,PSYCHONEUROIMMUNOLOGY - Abstract
Background: Migraine risk factors are associated with migraine susceptibility, yet their mechanisms are unclear. Evidence suggests a role for inflammatory proteins and immune cells in migraine pathogenesis. This study aimed to examine the inflammo-immune association between eight migraine risk factors and the disorder. Methods: This study utilized inverse variance weighted (IVW) method and colocalization analysis to explore potential causal relationships between eight migraine risk factors, migraine, 731 immune cells, and 91 circulating inflammatory proteins. Mediation Mendelian randomization (MR) was further used to confirm the mediating role of circulating inflammatory proteins and immune cells between the eight migraine risk factors and migraine. Results: Migraine risk factors are linked to 276 immune cells and inflammatory proteins, with cigarettes smoked per day strongly co-localized with CD33-HLA DR+ cells. Despite no co-localization, 23 immune cells/inflammatory proteins relate to migraine. Depression, all anxiety disorders, and sleep apnea are correlated with migraine, and all anxiety disorders are supported by strong colocalization evidence. However, the mediating effect of inflammatory proteins and immune cells between eight migraine risk factors and migraine has not been confirmed. Conclusion: We elucidate the potential causal relationships between eight migraine risk factors, migraine, immune cells, and inflammatory proteins, enhancing our understanding of the molecular etiology of migraine pathogenesis from an inflammatory-immune perspective. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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48. Management of Concussion in the Young Athlete.
- Author
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Lamothe, Meghan A., Erickson, Jillian, and Emami, Kouros
- Abstract
Sports-related concussion continues to be a rapidly growing public health concern in nearly all sports, and at all levels, in children and adolescents. Evidence-based clinical guidelines are constantly evolving but those specific to the pediatric population are less robust. There are nuances to treatment of the developing pediatric brain in the context of mild traumatic brain injury (mTBI). The purposes of this review are to (1) analyze the differences in concussion symptom presentation and recovery in children versus adults, (2) describe the role of the physical therapist in management of pediatric concussion, (3) examine current recommendations for return to participation in school and return to sport, and (4) highlight the psychological implications of concussion in the young athlete. We find that additional research is needed in nearly all aspects of concussion in the young athletic population. The current evidence stresses the importance of an active approach to recovery using a stepwise progression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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49. Nicotine exacerbates exertional heat strain in trained men: a randomized, placebo-controlled, double-blind study.
- Author
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Moyen, Nicole E., Barnes, Matthew J., Perry, Blake G., Fujii, Naoto, Amano, Tatsuro, Kondo, Narihiko, and Mündel, Toby
- Subjects
NICOTINE ,HEAT exhaustion ,THERMAL strain ,TIME trials ,BLOOD flow - Abstract
To determine whether using nicotine exacerbates exertional heat strain through an increased metabolic heat production (H
prod ) or decreased skin blood flow (SkBF), 10 nicotine-naïve trained males [37 ± 12 yr; peak oxygen consumption (V̇ o2peak ): 66 ± 10 mL·min−1 ·kg−1 ] completed four trials at 20°C and 30°C following overnight transdermal nicotine (7 mg·24 h−1 ) and placebo use in a crossover, double-blind design. They cycled for 60 min (55% V̇ o2peak ) followed by a time trial (∼75% V̇ o2peak ) during which measures of gastrointestinal (Tgi ) and mean weighted skin ( T ¯sk ) temperatures, SkBF, Hprod , and mean arterial pressure (MAP) were made. The difference in ΔTgi between nicotine and placebo trials was greater during 30°C (0.4 ± 0.5°C) than 20°C (0.1 ± 0.7°C), with T ¯sk higher during nicotine than placebo trials (0.5 ± 0.5°C, P = 0.02). SkBF became progressively lower during nicotine than placebo trials (P = 0.01) and progressively higher during 30°C than 20°C trials (P < 0.01); MAP increased from baseline (P < 0.01) and remained elevated in all trials. The difference in Hprod between 30°C and 20°C trials was lower during nicotine than placebo (P = 0.01) and became progressively higher during 30°C than 20°C trials with exercise duration (P = 0.03). Mean power output during the time trial was lower during 30°C than 20°C trials (24 ± 25 W, P = 0.02), and although no effect of nicotine was observed (P > 0.59), two participants (20%) were unable to complete their 30°C nicotine trials as one reached the ethical limit for Tgi (40.0°C), whereas the other withdrew due to "nausea and chills" (Tgi = 39.7°C). These results demonstrate that nicotine use increases thermal strain and risk of exertional heat exhaustion by reducing SkBF. NEW & NOTEWORTHY: In naïve participants, acute nicotine use exerts a hyperthermic effect that increases the risk of heat exhaustion during exertional heat strain, which is driven by a blunted skin blood flow response. This has implications for 1) populations that face exertional heat strain and demonstrate high nicotine use (e.g., athletes and military, 25%–50%) and 2) study design whereby screening and exclusion for nicotine use or standardization of prior use (e.g., overnight abstinence) is encouraged. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
50. Parenting Behaviors as Mediators of the Association Between Parental Internalizing Symptoms and Child Externalizing Symptoms.
- Author
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Klemp, Marie-Theres, Dose, Christina, Hautmann, Christopher, Jendreizik, Lea T., Mühlenmeister, Judith, Plück, Julia, Wähnke, Laura, and Döpfner, Manfred
- Subjects
INTERNALIZING behavior ,OPPOSITIONAL defiant disorder in children ,EXTERNALIZING behavior ,CHILD behavior ,ATTENTION-deficit hyperactivity disorder ,RANDOMIZED controlled trials - Abstract
This study analyzes whether the association between parental internalizing symptoms (depression, anxiety, stress) and child symptoms of attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) is mediated by positive and negative parenting behaviors. Cross-sectional data of 420 parents of children (age 6–12 years) with elevated levels of externalizing symptoms were collected in a randomized controlled trial. Measures included parent ratings of their internalizing symptoms and parenting behaviors and of their child's externalizing symptoms. Two mediation models were examined, one including ADHD symptoms and one including ODD symptoms as the dependent variable. Parental internalizing symptoms were modeled as the independent variable and positive and negative parenting behaviors were modeled as parallel mediators. Regression analyses support negative parenting behavior as a mediator of the association between parental internalizing symptoms and child ODD symptoms. For the ADHD model, no significant mediator could be found. Future studies should use prospective designs and consider reciprocal associations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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