RESUMO
BACKGROUND: Doxorubicin (DOX) may cause various neurological side effects in the brain. Lercanidipine (LRD) has antioxidant, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the potential benefits of. METHODS AND RESULTS: Lercanidipine in reducing doxorubicin-induced neuroinflammation and maintaining the expressions of choline acetyltransferase. Thirty-two adult Wistar albino female rats were divided into four groups as Control, DOX (20 mg/kg intraperitoneally), DOX + LRD 0.5 (0.5 mg/kg orally), and DOX + LRD2(2 mg/kg orally). Twenty-four hours after the last drug administration (9th day), brain tissues were taken for histopathological, immunohistochemical (choline acetyltransferase [CHAT], interleukin-10 [IL-10], and caspase-3 [Cas-3] staining), biochemical (total antioxidant status [TAS], total oxidant status [TOS], and oxidative stress index [OSI]), and genetic analyzes (PI3K/AKT/HIF1-α and IL-6 gene expressions). Histopathological analyses revealed hyperemia, slight hemorrhage, degeneration, neuronal loss, gliosis in the cerebellum, and neuronal loss in the brain cortex and hippocampus in the DOX group. According to other analyzes, decreased CHAT, PI3K, AKT, HIF1-α and increased IL-6, IL-10, Cas-3 expression were observed in the DOX group. CONCLUSIONS: Both LRD doses reversed all these findings, but LRD2 was observed to be more effective. In conclusion, we determined that LRD has potential therapeutic effect by reducing DOX-induced neuroinflammation, oxidative stress and apoptosis in brain tissues.
Assuntos
Colina O-Acetiltransferase , Di-Hidropiridinas , Interleucina-10 , Animais , Ratos , Ratos Wistar , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Antioxidantes/farmacologia , Interleucina-6 , Doenças Neuroinflamatórias , Doxorrubicina/efeitos adversosRESUMO
Methotrexate (MTX) is an antineoplastic agent and has neurotoxic effects. It exerts its toxic effect on the brain by triggering inflammation and apoptosis. Cannabidiol (CBD) is an agent known for its antioxidant, anti-inflammatory effects in various tissues. The aim of this study is to examine the protective effects of CBD treatment in various brain structures from MTX damage and to evaluate the effect of intracellular pathways involved in apoptosis. Thirty-two adult Wistar Albino female rats were divided into four groups as control, MTX (20 mg/kg intraperitoneally [i.p.]), MTX + CBD (0.1 mL of 5 mg/kg i.p.), and CBD (for 7 days, i.p.). At the end of the experiment, brain tissues collected for biochemical analyses as total oxidant status (TOS), total antioxidant status, oxidative stress index (OSI), histopathological and immunohistochemical analyses as tumor necrosis factor-α (TNF-α), serotonin, mammalian target of rapamycin (mTOR) staining, genetic analyses as caspase-9 (Cas-9), caspase-12 (Cas-12), C/EBP homologous protein (CHOP), and cytochrome-c (Cyt-c) gene expressions. In the histopathological and immunohistochemical evaluation, hyperemia, microhemorrhage, neuronal loss, and significant decreasing expressions of seratonin were observed in the cortex, hippocampus, and cerebellum regions in the MTX group. mTOR, TNF-α, Cas-9, Cas-12, CHOP, and Cyt-c expressions with TOS and OSI levels were increased in the cortex. It was observed that these findings were reversed after CBD application in all regions. MTX triggers neuronal apoptosis via endoplasmic reticulum and mitochondrial stress while destroying serotonergic neurons. The reversal of the pathological changes with CBD treatment proves that it has anti-inflammatory and antiapoptotic activity in brain.
Assuntos
Canabidiol , Metotrexato , Ratos , Animais , Metotrexato/toxicidade , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos Wistar , Canabidiol/farmacologia , Doenças Neuroinflamatórias , Fator de Necrose Tumoral alfa/metabolismo , Estresse Oxidativo , Apoptose , Anti-Inflamatórios/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Estresse do Retículo Endoplasmático , Mamíferos/metabolismoRESUMO
Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the central nervous system that causes functional disability in young people. The aim of this study was to investigate the neutrophil-to-lymphocyte ratio (NLR) in patients with MS and the relationship between the NLR and the severity of the disease. One hundred and two MS patients (31 patients were in relapse; 71 patients were in remission) and 56 healthy controls were included. Complete blood counts as well as demographic and clinical data from MS patients were evaluated retrospectively. The NLRs were calculated for all participants and were compared; the cut-off value was also determined for the NLR and Expanded Disability Status Scale (EDSS). MS patients had a significantly higher NLR (p < 0.001) than the control group. The NLR levels were significantly higher in patients who were in relapse than patients in remission (p = 0.039). The cut-off value for the NLR to predict an MS diagnosis and activity were determined to be 2.04 and 3.90, respectively. The NLRs were directly correlated with erythrocyte sedimentation rate levels (r = 0.795, p < 0.001). Logistic regression analysis with dichotomous EDSS score showed that a high NLR was an independent predictor of the progression of disability. The NLR may be a biomarker that has simple, quick, inexpensive and reproducible properties in MS to predict patient's prognosis.
Assuntos
Progressão da Doença , Linfócitos , Esclerose Múltipla Recidivante-Remitente/sangue , Neutrófilos , Adulto , Biomarcadores/sangue , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , PrognósticoRESUMO
CONTEXT: Migraine is a frequent and disabling chronic neurological condition with complex pathophysiology. Both cigarette smoking and migraine may cause damage to the optic nerve. OBJECTIVE: The primary objective of this study was to investigate the effect of cigarette smoking on retinal nerve fiber layer (RNFL) thickness in patients with migraine. MATERIALS AND METHODS: Eighty-four consecutive patients diagnosed with migraine (34 smokers and 50 nonsmokers) and 66 age- and gender-matched healthy non-smoker controls were enrolled for this observational cross-sectional study. RNFL thickness was measured using spectral-domain optical coherence tomography (OCT) and then RNFL thickness in patients with migraine who smoke was compared to nonsmoking patients with migraine and healthy subjects. RESULTS: The average, superior, nasal and inferior RNFL thicknesses were significantly thinner in patients with migraine compared to the control group (p < 0.001, p = 0.02, p < 0.001 and p = 0.04, respectively). The average and inferior RNFL thicknesses were significantly reduced in smoker patients with migraine compared to the nonsmokers (p = 0.011, p = 0.045, respectively). Nonsmoker patients with migraine had significantly thinner average and nasal RNFL thicknesses than the control group (p = 0.001, p = 0.001, respectively). CONCLUSION: Cigarette smoking may cause significant RNFL thinning in patients with migraine. OCT may be a feasible technique for determination of smoking-induced ocular damage in patients with migraine.
Assuntos
Transtornos de Enxaqueca/patologia , Fibras Nervosas/efeitos dos fármacos , Retina/efeitos dos fármacos , Fumar/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Fibras Nervosas/patologia , Retina/patologia , Tomografia de Coerência ÓpticaRESUMO
The essential use of riboflavin is the prevention of migraine headaches, although its effect on migraines is considered to be associated with the increased mitochondrial energy metabolism. Oxidative stress is also important in migraine pathophysiology. Vitamin E is a strong antioxidant in nature and its analgesic effect is not completely clear in migraines. The current study aimed to investigate the effects of glyceryl trinitrate (GTN)-sourced exogen nitric oxide (NO), in particular, and also riboflavin and/or vitamin E on involved in the headache model induced via GTN-sourced exogen NO on oxidative stress, total brain calcium levels, and microsomal membrane Ca(2+)-ATPase levels. GTN infusion is a reliable method to provoke migraine-like headaches in experimental animals and humans. GTN resulted in a significant increase in brain cortex and microsomal lipid peroxidation levels although brain calcium, vitamin A, vitamin C, and vitamin E, and brain microsomal-reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and plasma-membrane Ca(2+)-ATPase values decreased through GTN. The lipid peroxidation, GSH, vitamin A, ß-carotene, vitamin C, and vitamin E, and calcium concentrations, GSH-Px, and the Ca(2+)-ATPase activities were increased both by riboflavin and vitamin E treatments. Brain calcium and vitamin A concentrations increased through riboflavin only. In conclusion, riboflavin and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system. However, the effects of vitamin E on the values seem more important than in riboflavin.
Assuntos
Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Cálcio/metabolismo , Microssomos/metabolismo , Riboflavina/farmacologia , Vitamina E/farmacologia , Animais , Ácido Ascórbico/metabolismo , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Glutationa , Glutationa Peroxidase , Cefaleia/induzido quimicamente , Cefaleia/metabolismo , Peroxidação de Lipídeos , Nitroglicerina/efeitos adversos , Estresse Oxidativo , Ratos , Vitamina A/metabolismo , beta Caroteno/metabolismoRESUMO
CONTEXT: In Turkey, Veronica species (Plantaginaceae) have been used as a diuretic and for wound healing in traditional medicine. OBJECTIVE: To examine the fatty acid and essential oil profiles, the antioxidant, anticholinesterase, antimicrobial, and DNA damage effects of Veronica thymoides P.H. Davis subsp. pseudocinerea M.A. Fischer as a potential source of natural active compounds. MATERIALS AND METHODS: GC/MS was used to analyze essential oil and fatty acid obtained from whole plant. The antioxidant activity was evaluated by the ß-carotene-linoleic acid test system, DPPH-free and ABTS cation radicals scavenging, and cupric reducing antioxidant capacity assays. The anticholinesterase and antimicrobial activities were determined by Ellman and broth macrodillution methods, respectively. The effect of the methanol extract on DNA cleavage was investigated. RESULTS: Hexatriacontene (21.0%) was found to be the main constituent in essential oil, and linoleic acid (25.2%) and palmitic acid (20.6%) in fatty acid. Methanol extract demonstrated the best IC50 values in lipid peroxidation (49.81 ± 0.31 µg/ml) and DPPH-free radical scavenging activity (15.32 ± 0.17 µg/ml). Methanol and water extracts possessed strong ABTS cation radical scavenging activity with IC50 values 9.15 ± 0.28 and 8.90 ± 0.1 µg/ml, respectively. The acetone extract exhibited moderate butyrylcholinesterase inhibitory activity. The highest antimicrobial activity was determined in methanol extract against Escherichia coli with 31.25 µg/ml MIC value. Inhibition of methanol extract on plasmid DNA cleavage by OH radicals was found to be 93.32% at 500 µg/ml. CONCLUSION: The methanol extract having strong antioxidant and DNA damage effects could be investigated phytochemically to find natural active compounds.
Assuntos
Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Veronica , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologiaRESUMO
6-Substituted amino-penicillanic acid esters were synthesized starting with 6-apa. The compounds containing a 1,3-thiazole- or 1,3-thiazolidinone nucleus linked to the penicillanic acid skeleton via a hydrazino linkage were obtained from 6-apa. The treatment of carbonylamino and carbonothioylamino compounds with 4-chlorophenacyl bromide or ethyl bromoacetate gave 6-bis{4-[1,3-thiazol(idinone)amino]benzoyl}amino derivatives of 6-apa. Benzyl derivatives were synthesized in several steps, starting with 4-aminobenzoyl chloride. The treatment of 4-{[3-benzyl-4-oxo-1,3-thia(oxa)zolidin-2-ylidene]amino}benzoyl chlorides with 6-apa in ethanolic solution produced the 6-[bis(4-{[3-benzyl-4-oxo-1,3-thiazolidin-2-ylidene]amino}benzoyl)amino] derivative of penicillanic acid, while the reaction of the same intermediates in DMF gave the mono-substituted amino derivative of 6-apa. The synthesized compounds were screened for their biological activities, and some of them were found to possess good to moderate antimicrobial activity. Moreover, some of the compounds displayed antiurease, anti-ß-lactamase, and/or antilipase activities.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Ácido Penicilânico/síntese química , Ácido Penicilânico/farmacologia , Relação Dose-Resposta a Droga , Lipase/antagonistas & inibidores , Lipase/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácido Penicilânico/análogos & derivados , Relação Estrutura-Atividade , Urease/antagonistas & inibidores , Urease/metabolismo , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/farmacologiaRESUMO
Neuroinflammation is a process associated with degeneration and loss of neurons in different parts of the brain. The most important damage mechanisms in its formation are oxidative stress and inflammation. This study aimed to investigate the protective effects of cannabidiol (CBD) against neuroinflammation through various mechanisms. Thirtytwo female rats were randomly divided into 4 groups as control, lipopolysaccharide (LPS), LPS + CBD and CBD groups. After six hours following LPS administration, rats were sacrificed, brain and cerebellum tissues were obtained. Tissues were stained with hematoxylineosin for histopathological analysis. Apelin and tyrosine hydroxylase synthesis were determined immunohistochemically. Total oxidant status and total antioxidant status levels were measured, and an oxidative stress index was calculated. Protein kinase B (AKT), brain-derived neurotrophic factor (BDNF), cyclicAMP response elementbinding protein (CREB) and nuclear factor erythroid 2related factor 2 (NRF2) mRNA expression levels were also determined. In the LPS group, hyperemia, degeneration, loss of neurons and gliosis were seen in all three tissues. Additionally, Purkinje cell loss in the cerebellum, as well as neuronal loss in the cerebral cortex and hippocampus, were found throughout the LPS group. The expressions of AKT, BDNF, CREB and NRF2, apelin and tyrosine hydroxylase synthesis all decreased significantly. CBD treatment reversed these changes and ameliorated oxidative stress parameters. CBD showed protective effects against neuroinflammation via regulating AKT, CREB, BDNF expressions, NRF2 signaling, apelin and tyrosine hydroxylase synthesis.
Assuntos
Canabidiol , Fármacos Neuroprotetores , Feminino , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Canabidiol/farmacologia , Canabidiol/metabolismo , Fármacos Neuroprotetores/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Dopamina/farmacologia , Apelina/metabolismo , Apelina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doenças Neuroinflamatórias , Lipopolissacarídeos/toxicidade , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/farmacologia , Hipocampo/metabolismo , Expressão GênicaRESUMO
Background: Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. Aims: To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Study Design: Multicenter, retrospective, observational study. Methods: Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayis University's Faculty of Medicine were included in the study. Results: Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. Conclusion: For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.
Assuntos
Glicoproteína Mielina-Oligodendrócito , Humanos , Masculino , Feminino , Glicoproteína Mielina-Oligodendrócito/imunologia , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Neurite Óptica/sangue , Neurite Óptica/imunologia , Neurite Óptica/diagnóstico por imagem , Neuromielite Óptica/sangue , Neuromielite Óptica/imunologia , Neuromielite Óptica/diagnóstico por imagem , Autoanticorpos/sangue , Autoanticorpos/análise , Idoso , Adolescente , Imunoglobulina G/sangue , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologiaRESUMO
Three new 1,3,4-oxadiazole, 1,3-thiazolidine and 1,2,4-triazole derivatives were obtained starting from furan-2-carbohydrazide. Then, 1,2,4-triazole compound was converted to the corresponding Mannich bases using several secondary amines including piperidine, piperazine, morpholine or thiomorpholine moiety. The synthesis of 5-(furan-2-yl)-4-{[(4-methoxyphenyl)methylidene]amino}-4H-1,2,4-triazole-3-thiol (XIII) was performed starting from furan-2-carbohydrazide by three steps. The structures of the synthesized compounds were well characterized by elemental analyses, IR, 1H NMR, 13C NMR and mass spectral studies. Newly synthesized compounds were screened for their antimicrobial activities and some of them displayed activity against the tested microorganisms.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Azóis/síntese química , Azóis/farmacologia , Bactérias/efeitos dos fármacos , Desenho de Fármacos , Bactérias/crescimento & desenvolvimento , Espectroscopia de Ressonância Magnética , Bases de Mannich/síntese química , Bases de Mannich/farmacologia , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-AtividadeRESUMO
The tyrosinase enzyme, which is widely found in microorganisms, animals and plants, has a significant position in melanogenesis, plays an important role in undesirable browning of fruits and vegetables, antibiotic resistance, skin pigment formation, sclerotization of cuticle, neurodegeneration, etc. Therefore, with the wide potential application fields of tyrosinase in food, agriculture, cosmetics and pharmaceutical industries, which has become the target enzyme for the development of therapeutic agents such as antibrowning, anticancer, antibacterial, skin whitening, insecticides, etc., a large number of synthetic tyrosinase inhibitors have been widely reported in recent years. The triazole ring, which has a broad spectrum of biological action, is of increasing interest in the synthesis of new tyrosinase inhibitors. In this review, tyrosinase inhibition effects, structure-activity relationships, enzyme inhibition kinetics and mechanisms of action of 1,2,3- or 1,2,4-triazole derivatives were investigated. The data gathered is anticipated to supply rational guidance and an influential strategy for the development of novel, potent and safe tyrosinase inhibitors for better practical application in the future.
Assuntos
Inibidores Enzimáticos , Monofenol Mono-Oxigenase , Triazóis , Animais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Plantas/metabolismo , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologiaRESUMO
Herein, two iridoid glucosides aucubin (1) and ajugol (2), and two phenyl ethanoids, verbascoside (3) and poliumoside (4) were isolated from the methanol extract of the aerial parts of Verbascum speciosum and used to study about their anticancer activity for the first time. The structures of all compounds were elucidated using spectroscopic data (IR, 1D and 2D NMR, LC-TOF/MS). Antiproliferative activities of Aucubun (1) and Verbascoside (3) were tested against A-549 (human colon cancer), MDA-MD-453 (human breast cancer) and 3T3-L1 (mouse fibroblast)cell lines by XTT assay. In addition, the anticarcer mechanism of action of aucubin (1) was investigated on MDA-MB-453 cells for the first time. XTT result showed that both applied compounds exhibited antiproliferative effect at different dose ranges depending on the cancer type, as well as selectivity between cancer and healty cell lines. Flow cytometry analyzes revealed that aucubin (1) exerts its cytotoxic effect in MDA-MB-453 cells by directing cells to early apoptosis and inhibiting the P13K/AKT signaling pathway.
Assuntos
Verbascum , Camundongos , Animais , Humanos , Verbascum/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Glucosídeos/farmacologiaRESUMO
3-Fluoro-4-(4-phenylpiperazin-1-yl)aniline (II) prepared from 3,4-difluoro nitrobenzene was converted to the corresponding Schiff bases (III) and (IV) by treatment with 4-methoxybenzaldehyde and indol-3-carbaldehyde, respectively. Treatment of amine (II) with 4-fluorophenyl isothiocyanate affordedthe corresponding thiourea derivative (V). Compound (V) was converted to thiazolidinone and thiazoline derivatives (VI) and (VII) by cyclocondensation with ethylbromoacetate or 4-chlorophenacylbromide, respectively. The synthesis of carbothioamide derivative (X) was performed starting from compound (II) by three steps. Treatment of compound (X) with sodium hydroxide, sulfuric acid, or chlorophenacyl bromide generated the corresponding 1,2,4-triazole (XI), 1,3,4-thiadiazole (XII), and 1,3-thiazolidinone (XIII) derivatives, respectively. The structural assignments of new compounds were based on their elemental analysis and spectral (IR, 1H-NMR, 13C-NMR, and LC-MS) data. In the antimicrobial activity study all the compounds revealed high anti-Mycobacterium smegmatis activity.
Assuntos
Acetamidas , Antibacterianos , Antifúngicos , Bactérias/crescimento & desenvolvimento , Fungos/crescimento & desenvolvimento , Oxazolidinonas , Acetamidas/síntese química , Acetamidas/química , Acetamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Estrutura Molecular , Oxazolidinonas/síntese química , Oxazolidinonas/química , Oxazolidinonas/farmacologia , Especificidade da EspécieRESUMO
The targeted compounds which are Schiff base derivatives were prepared by reaction of 6-(4-phenyl-piperazin-1-yl)pyridine-3-ylamine with 2-hydroxy and 2,6-dichloro benzaldehyde. These compounds were isolated, purified and then spectrally characterized via FT-IR, 1H and 13C NMR, LC MS TOF, and TGA analysis where strong proofs confirmed the formation of the targeted product. The biological activity, which is pancreatic porcine lipase inhibition, of the compounds was investigated and Orlistat was used as standard drug. The compound 3 was found to be as potent as orlistat against PL enzyme with an IC50 value of 0.50 µM. The molecular docking studies were performed for both obtained compounds and orlistat against active side of porcine pancreatic lipase. Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analyzes were performed for pancreatic porcine lipase with compound 3, which showed potent inhibition according to the results of in vitro studies. Furthermore, The ADME and toxicity analysis of the compounds were examined using web-based online platforms, SwissADME and pkCSM. In the light of biological activity and in silico studies, the compound 3 can be a potential drug candidate with further studies.Communicated by Ramaswamy H. Sarma.
Assuntos
Inibidores Enzimáticos , Lipase , Animais , Inibidores Enzimáticos/química , Lipase/química , Simulação de Acoplamento Molecular , Pâncreas , Espectroscopia de Infravermelho com Transformada de Fourier , SuínosRESUMO
Novel thiourea (5a, 5b) and thiazolidinone derivatives (6a, 6b) were synthesized by hybridizing molecules starting from the compound 6-(4-phenylpiperazin-1-yl)pyridin-3-amine (4) which is known to show anticancer activity. The synthesis of the leading compound was carried out by using 1-(5-nitropyridin-2-yl)-4-phenylpiperazine (3) which was obtained by a novel method of the reaction of 2-chloro-5-nitropyridine (1) and N-phenylpiperazine (2). The structures of the compounds were confirmed using FTIR, 1 H NMR, 13 C NMR, HRMS spectroscopic methods and elemental analysis. The organic molecules were tested for their anticancer activities against prostate cancer (PC) cell lines: DU 145, PC-3 and LNCaP. As the compound 5a exerted the highest cytotoxic activity, IC50 concentrations of compound 5a were further investigated in terms of morphology, colony-forming ability, RNA expression, fragmented DNA and cell cycle distributions of PC cell lines. Overall data revealed that compound 5a treatment induces apoptosis and DNA fragmentation in PC cell lines and inhibits cell cycle progression resulting in the accumulation of cells in either the G1 or the S phases.
Assuntos
Antineoplásicos/síntese química , Piperazinas/síntese química , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose , Caspases Efetoras/genética , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Fragmentação do DNA/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Regulação da Expressão Gênica/efeitos dos fármacos , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética , Humanos , Masculino , Estrutura Molecular , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/genética , RNA/metabolismo , Relação Estrutura-Atividade , Tioureia/químicaRESUMO
The authors describe a case of pheochromocytoma presenting with bithalamic infarction, dementia, and elevated intraocular pressure. The patient received glaucoma treatment to suppress high intraocular pressure in addition to antihypertensive and antidiabetic medication for his complaints. Bilateral fundus examination and visual field defects revealed glaucoma-like changes. Adrenelectomy improved all complaints and all medications were stopped. Intraocular pressure and visual field changes improved. Pheochromocytoma presenting with bithalamic infarction, dementia, and increased IOP in the same patient is unusual. Adrenelectomy can improve dementia, increased IOP, and glaucoma-like changes in such cases.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Infarto Encefálico/diagnóstico , Demência/diagnóstico , Pressão Intraocular , Hipertensão Ocular/diagnóstico , Feocromocitoma/diagnóstico , Doenças Talâmicas/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Anti-Hipertensivos/uso terapêutico , Quimioterapia Combinada , Humanos , Imageamento por Ressonância Magnética , Masculino , Hipertensão Ocular/tratamento farmacológico , Feocromocitoma/cirurgia , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico , Timolol/uso terapêuticoRESUMO
Confabulation has been defined as the falsification of memory occurring in clear consciousness in association with an organically-derived amnesia. It was first described by Korsakoff in 1889 in alcoholic amnesic patients. Later studies showed that confabulation is also seen in a variety of other pathologies, such as anterior communicating artery rupture, traumatic brain injury, Alzheimer's disease, and brain tumors. Two forms of confabulation have been described: Momentary (provoked) confabulation which is produced in response to questions, for compensating the gaps in memory; and fantastic (spontaneous) confabulation consisting of grandiose and wish-fulfilling characteristics. There is no specific localization for provoked confabulations. However spontaneous confabulations appear as a result of basal forebrain and posterior orbitofrontal cortex lesions. There are numerous hypotheses for explaining the specific nature of confabulations with reference to impairment of general executive dysfunction, temporality, and memory-control processes. Commonly, these interpretations explain memory distortion in terms of frontal network dysfunction. There is a general consensus that confabulation is primarily the result of a deficit of memory retrieval, rather than one of encoding, consolidation, or storage. The normal process of memory recall consists of the evaluation of the cues for retrieval, matching the cues with episodic memory, and reality monitoring. One possible explanation for confabulation is that these patients have lost the checking procedure in memory retrieval, i.e. reality monitoring. This article aimed to describe confabulation and to review its clinical, neuroanatomical, and neuropsychological correlates in an effort to raise clinicians' awareness of the phenomenon and the problematic areas that need to be clarified.
Assuntos
Amnésia/psicologia , Lobo Frontal/patologia , Humanos , MemóriaRESUMO
INTRODUCTION: The Type D personality was reported as an important indicator of adverse clinical outcomes and quality of life in various diseases. The objective of this study was to investigate the relationships between the Type D personality and clinical features and the effect of Type D personality on quality of life in patients with multiple sclerosis (MS). METHODS: Seventy-four patients with MS participated in this study. Clinical parameters of the patients were recorded and disability was assessed using the Expanded Disability Status Scale (EDSS). Patients were examined with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Type D Scale (DS14), and 36-Item Short-Form Health Survey (SF-36). RESULTS: BDI and BAI scores were significantly higher and mental subscale of the SF-36 scores were significantly lower in Type D compared to nonType D (p<0.001, p=0.001, and p<0.001, respectively). The total DS14 scores were found to be positively correlated with EDSS, BDI, and BAI and negatively correlated with SF-36 mental subscale (p=0.02, p<0.001, p<0.001, and p<0.001, respectively). Multivariate linear regression analysis indicated that the total DS14 score was independently associated with the mental component of SF-36 (p<0.001). CONCLUSION: The Type D personality traits may worsen the quality of life, particularly the mental component, in patients with MS. Consequently, the assessment of MS patients by brief and valid DS14 may be valuable for clinical practice.
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OBJECTIVE: The present study aims to analyze the levels of resistin, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-18, and C-reactive protein (CRP) in patients with Alzheimer's disease (AD) and also investigate a potential relationship between resistin levels and TNF-α, IL-1ß, IL-6, IL-18, and CRP levels in patients with AD. METHODS: The study included fifty patients with AD and 30 healthy controls with normal cognitive functions. The serum resistin, TNF-α, IL-1ß, IL-6, IL-18, and CRP levels were assessed. We performed a Mini-Mental State Examination (MMSE) to evaluate the general cognitive performance. RESULTS: The mean serum resistin, IL-1ß, IL-18, and TNF-α levels were significantly higher in patients with AD compared with the controls (p=0.026, p=0.002, p=0.003, and p=0.038, respectively). The IL-6 and CRP levels did not differ between the groups (p=0.874 and p=0.941). The resistin levels were positively correlated with the levels of CRP and IL-18 (r=0.526, pï¼0.001; r=0.402, p=0.004, respectively). MMSE scores and inflammatory markers were not correlated (pï¼0.05 for all). CONCLUSION: Serum resistin levels were significantly increased and correlated with some inflammatory markers in AD patients, suggesting that resistin might play a role in the inflammatory process of AD.
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Cardiac autonomic dysfunction assessed by the presence of arrhythmia, by the methods, such as heart rate variability or blood pressure variability, and by the electrocardiographic abnormalities is common in Guillain-Barré syndrome (GBS). The goal of present study was to analyze the P-wave dispersion (PWD), which is the non-invasive marker of atrial arrhythmia, in GBS patients and to compare those with healthy individuals. Thirty-five patients with GBS (mean age 53.6 ± 15.5 years) and 35 healthy controls (mean age 49.2 ± 14.1 years) were included to this study. Demographic and clinical information of the patients with GBS were assessed retrospectively. A 12-lead surface electrocardiogram was acquired from all participants. Minimum and maximum P-wave duration and PWD were measured in the patients with GBS and healthy controls. Maximum P-wave duration and PWD were significantly longer, and minimum P-wave duration was significantly lower in the patients with GBS rather than the control group (p = 0.037, p < 0.001, p = 0.007, respectively). GBS disability scores were positively correlated with the maximum P-wave duration (p = 0.015, r = 0.406) and PWD (p = 0.001, r = 0.525). We found that PWD was significantly prolonged in GBS patients compared with the controls. The increased PWD which is cheap, quick, non-invasive and feasible electrocardiographic marker may be related to increased risk for atrial fibrillation in patients with GBS.