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1.
Toxicol Res ; 34(3): 267-279, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30057701

RESUMEN

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ß-N-Oxalyl-L-α,ß-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at 200 µM L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.

2.
J Photochem Photobiol B ; 141: 47-58, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25318017

RESUMEN

Three new ruthenium(II) polypyridyl complexes [Ru(phen)2BrIPC](2+) (1), [Ru(bpy)2 BrIPC](2+) (2) and [Ru(dmb)2BrIPC](2+) (3) where, BrIPC = (6-bromo-3-(1H-imidazo[4,5-f] [1,10]-phenanthroline, phen = 1,10-phenanthroline, bpy = 2,2' bipyridine, dmb = 4,4'-dimethyl 2,2' bipyridine, were synthesised and characterised. DNA-binding nature was investigated by spectroscopic titrations and mode of binding was assessed by viscosity measurements. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be in the order of 10(5). Experimental results showed that these complexes interact with CT-DNA by intercalative mode. Photocleavage and antimicrobial activities were complex concentration dependent, at high concentration, high activity and vice versa. MTT assay was performed on HeLa cell lines, IC50 values of complexes in the order of 3 > 2 > 1 > cisplatin. From comet assay, cellular uptake studies, we observed that complexes could enter into the cell membrane and accumulate inside the nucleus. Molecular docking studies support the DNA binding affinity with hydrogen bonding and van der Waals attractions between base pairs and phosphate backbone of DNA with metal complexes.


Asunto(s)
Antineoplásicos/síntesis química , Complejos de Coordinación/síntesis química , Rutenio/química , 2,2'-Dipiridil/química , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Sitios de Unión , Ensayo Cometa , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , ADN/química , ADN/metabolismo , División del ADN/efectos de los fármacos , Células HeLa , Humanos , Enlace de Hidrógeno , Cinética , Simulación del Acoplamiento Molecular , Conformación de Ácido Nucleico , Fenantrolinas/química , Electricidad Estática
3.
Iran J Psychiatry ; 9(1): 42-4, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25561948

RESUMEN

Dyke-Davidoff-Masson Syndrome (DDMS) is a syndrome associated with refractory epilepsy. DDMS is a rare syndrome characterized by seizures, facial asymmetry, contralateral hemiplegia and mental retardation. The characteristic radiologic features are cerebral hemiatrophy with homolateral hypertrophy of the skull and sinuses. The case was an 18 years old female with seizures, hemiparesis of the right side and mental retardation who was diagnosed with DDMS based on computed tomography.

4.
Eur J Med Chem ; 64: 410-21, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23665797

RESUMEN

In an endeavor toward the development of metal-based anticancer drugs, we present here the design, synthesis and characterization of three ruthenium(II) functionalized phenanthroline complexes with extended π-conjugation. These complexes have been shown to act as promising CT-DNA intercalators as evidenced by UV-visible, luminescence, emission quenching by [Fe(CN)6](4-), DNA competitive binding with ethidium bromide and salt dependent studies. All three complexes [Ru(Hdpa)2PPIP](2+) (1), [Ru(Hdpa)2PIP](2+) (2), [Ru(Hdpa)24HEPIP](2+) (3) clearly demonstrated that they can bind to DNA through the intercalation mode. Cell viability experiments indicated that all complexes showed significant dose dependent cytotoxicity in selected cell lines. The apoptosis and cell cycle arrest were also investigated. The complexes were docked into DNA-base-pairs using the 'GOLD' (Genetic Optimization for Ligand Docking), docking program.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , ADN/efectos de los fármacos , Compuestos Organometálicos/farmacología , Rutenio/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Bovinos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ADN/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Células MCF-7 , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Relación Estructura-Actividad
5.
Asian J Psychiatr ; 6(1): 29-34, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23380314

RESUMEN

INTRODUCTION: Role of l-5-hydroxytryptophan (l-5-HTP) in depression is relatively less studied but the literature has shown its robust role in depression. The present randomized double blind study was undertaken to assess the role of l-5-HTP as an antidepressant and to compare its antidepressant efficacy with fluoxetine in first depressive episode patients of Indian population. METHODS: A total of 70 patients of first depressive episode, all of whom were diagnosed with ICD-10 criteria, were recruited but only 60 patients completed the study and were randomly divided into two groups, receiving l-5-HTP and fluoxetine, respectively, for a period of 8weeks. All patients were administered Hamilton Rating Scale for Depression (HAM-D) to assess severity of depression at baseline, 2weeks, 4weeks and 8weeks. The efficacy of treatment was assessed by comparing HAM-D scores obtained at these examinations with the baseline examination; final evaluation of both efficacy and tolerance was assessed using the Clinical Global Impression (CGI) scale at the end of study. RESULTS: Both treatment groups showed significant and nearly equal reduction in HAM-D scores beginning at week two and continuing through week eight. Twenty-two patients (73.33%) in the l-5-HTP group and 24 patients (80%) in the fluoxetine group showed positive response at the end of the study. CONCLUSION: l-5-HTP has definitely got antidepressant effect in patients of depression. Antidepressant effect was seen within 2weeks of treatment and was apparent in all degrees of depression. The therapeutic efficacy of l-5-HTP was considered as equal to that of fluoxetine.


Asunto(s)
5-Hidroxitriptófano/uso terapéutico , Antidepresivos de Segunda Generación/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Fluoxetina/uso terapéutico , 5-Hidroxitriptófano/administración & dosificación , Adulto , Antidepresivos de Segunda Generación/administración & dosificación , Método Doble Ciego , Fluoxetina/administración & dosificación , Humanos , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento
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