RESUMO
As an academic department, we sought to identify effective strategies to engage our faculty and staff in diversity, equity, and inclusion initiatives and programs to build an inclusive department that would address our needs and those of our community and partners. Over a 4-year period, our faculty and staff have participated in town hall meetings, focus group discussions, surveys, and community-building activities to foster stakeholder engagement that will build a leading academic department for the future. We noted that our faculty and staff were committed to building diversity, equity, and inclusion, and our mission and vision were reflective of this. However, communication and transparency may be improved to help support a more inclusive department for all. In the future, we hope to continue with the integration of diversity, equity, and inclusion into our department's business processes to achieve meaningful, sustained change and impact through continued focus on recruitment, selection, retention, development, and wellness of faculty and staff-in addition to the continued recruitment of faculty and staff from underrepresented minority groups. Our findings should serve as a call to action for other academic obstetrics and gynecology departments to improve the health and well-being of the individuals we serve.
Assuntos
Diversidade Cultural , Docentes de Medicina , Grupos Minoritários , Unidade Hospitalar de Ginecologia e Obstetrícia/organização & administração , Relações Médico-Paciente , Ginecologia/educação , Humanos , Obstetrícia/educação , Seleção de Pessoal , Reorganização de Recursos Humanos , Desenvolvimento de Pessoal , Participação dos Interessados , Visitas de Preceptoria , Local de TrabalhoRESUMO
Using ultraviolet spectrophotometry and 1H-NMR high-resolution spectroscopy, it has been demonstrated that the formation of alpha-tocopherol complexes with free fatty acids occurs via two types of interaction, namely formation of a hydrogen bond between the alpha-tocopherol chromanol nucleus hydroxyl and the carboxyl group of a fatty acid, and interaction of the fatty acid acyl chains with the chromanol nucleus methyl groups. The second interaction is significantly enhanced by an increase in the number of double bonds in the fatty acid molecule, which results in restriction of the molecular mobility of alpha-tocopherol. The proposed structural model of alpha-tocopherol-fatty acid complexes has been confirmed by the use of molecular models. It has been assumed that the efficiency of complex formation of natural tocopherols with fatty acids is correlated with their biological activity.
Assuntos
Ácidos Graxos , Vitamina E , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Espectrofotometria Ultravioleta , TemperaturaRESUMO
The formation of alpha-tocopherol complexes with saturated and unsaturated fatty acids in ethanol has been demonstrated. The values of equilibrium constants for alpha-tocopherol interactions with fatty acids have been determined. These values do not depend in practice on the number of carbon atoms in saturated fatty acid molecules (from 7:0 to 24:0) and are equal to about 40-50 M-1. For unsaturated fatty acids the values of equilibrium constants are increased exponentially with an increase in the number of double bonds in the fatty acid molecule (1.25 X 10(4) M-1 for arachidonic acid). alpha-Tocopherol can form complexes with free fatty acids incorporated into phosphatidylcholine liposomes or into skeletal muscle sarcoplasmic reticulum membranes. The formation of alpha-tocopherol complexes with free fatty acids is regarded as a molecular mechanism of membrane stabilization by vitamin E against the damaging action of free fatty acids.
Assuntos
Ácidos Graxos , Lipídeos de Membrana , Vitamina E , Animais , Cinética , Lipossomos , Modelos Biológicos , Coelhos , Retículo Sarcoplasmático , Espectrometria de Fluorescência , Espectrofotometria UltravioletaRESUMO
The effects of alpha-tocopherol and its homologues with different chain lengths (6-hydroxy-chromanes: C1, C6, C11) on lipid peroxidation in natural membranes (liver microsomes and mitochondria, brain synaptosomes) and liposomes were studied. It was shown that the antioxidant activity of alpha-tocopherol homologues decreased in the order: C1 greater than C6 greater than C11 greater than alpha-tocopherol (C16). Using fluorescent measurements, the possible reasons underlying these differences were investigated: (i) the distribution between the aqueous media and nonpolar phase of the membrane, which predetermines the binding of alpha-tocopherol homologues to membranes; (ii) the incorporation of alpha-tocopherol homologues into lipid bilayer; (iii) non-uniform distribution (formation of the clusters) of tocopherol homologues in the lipid bilayer; and (iv) transbilayer mobility of alpha-tocopherol homologues and accessibility of the inhibitors for radical-generating centres under enzymically and non-enzymically induced lipid peroxidation. It was demonstrated that: (i) binding of C1 with membranes was less efficient than that of longer-chain homologues (C6, C11, C16); (ii) the level of incorporation of alpha-tocopherol homologues into membranes decreased in a succession alpha-tocopherol C11 greater than C6 greater than C1; (iii) all alpha-tocopherol homologues existed in the lipid bilayer not only in a monomeric form but also associated in clusters thus decreasing the efficiency of radical scavenging; (iv) the short-chain alpha-tocopherol homologue, C1, exhibited a high transbilayer mobility whereas the long-chain one, C16, underwent no transbilayer migration within tens of minutes. The inhibiting effect of alpha-tocopherol esters and C1-acetate was predetermined by their hydrolysis in biomembranes; a strong correlation exists between the rate of the ester hydrolysis and their antioxidant activity in the membrane. In liposomes, in which the esterase activity was absent, alpha-tocopherol esters and C1-acetate exhibited very low lipid peroxidation inhibition.
Assuntos
Membrana Celular/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Bicamadas Lipídicas/metabolismo , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Vitamina E/metabolismoRESUMO
Using fluorescent and ESR-spin probes, the effects of phospholipases A2, C and D on rat brain synaptosomal membranes were investigated. It was shown that the exposure of synaptosomal membranes to phospholipases A2, C and D results in their depolarization and an increase of the negative surface potential. In the case of phospholipases A2 and C, these changes are associated with a decrease of the microviscosity of the membrane lipid bilayer. alpha-Tocopherol stabilizes synaptosomal membranes against the damaging action of the phospholipases. This stabilization consists in the reconstitution of the transmembrane potential and an increase of microviscosity of the phospholipase-treated membranes. The stabilizing effect of alpha-tocopherol is due to the binding of phospholipid hydrolysis products, but not to the inhibition of phospholipases. The observed stabilization of synaptosomal membranes by alpha-tocopherol is regarded as a possible mechanism of biological action of vitamin E on biomembranes.
Assuntos
Encéfalo/ultraestrutura , Fosfolipases/farmacologia , Membranas Sinápticas/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Lipídeos de Membrana/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Fosfolipase D/farmacologia , Fosfolipases A/farmacologia , Ratos , Ratos Endogâmicos , Membranas Sinápticas/metabolismo , Membranas Sinápticas/fisiologia , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Temperatura , Fosfolipases Tipo C/farmacologiaRESUMO
Unscheduled DNA synthesis (UDS) and lipid peroxidation (LPO) were measured in human peripheral lymphocytes from healthy volunteers. These processes were induced by the catalytic system Fe2+-sodium ascorbate. The degree of induced LPO was measured spectrophotometrically by the thiobarbituric acid assay. UDS was detected by scintillometric measurement of the incorporation of 3H-thymidine into DNA. The protective action by fat-soluble vitamin E (D,L-alpha-tocopherol) and the artificial antioxidant pyritinol on UDS and LPO was also investigated. The system Fe2+ (2 mumole/l)-sodium ascorbate (30 mumole/l) increased the LPO level in healthy volunteers approximately 2.5 times and the incorporation of 3H-thymidine by 60-70%. alpha-Tocopherol (0.2 mmole/l) very efficiently suppressed LPO processes (p less than 0.01) and the oxidative damage of DNA measured as UDS was also significantly diminished (p less than 0.05). Pyritinol had no effect on LPO and UDS under our experimental conditions.
Assuntos
Peróxidos Lipídicos/metabolismo , Linfócitos/fisiologia , Piridinas/farmacologia , Piritioxina/farmacologia , Vitamina E/farmacologia , Ácido Ascórbico/farmacologia , Reparo do DNA , Humanos , Técnicas In VitroRESUMO
The effects of lipid peroxidation (LPO) on the physical state (fluidity) of the rat brain synaptosomal lipid bilayer matrix and the annular lipid domains were investigated using the fluorescent probe pyrene. The parameters of pyrene fluorescence intensity alpha = IE/IM were measured at excitation wavelengths 280 nm and 340 nm (alpha 280 and alpha 340), reflecting fluidity of lipid bilayer matrix and annular lipids, respectively. LPO induction was shown to result in changes of fluidity of both the bilayer and annular lipids. Upon reducing formation of LPO products by carnosine, fluidity changes of both the lipid bilayer matrix and annular lipids were diminished. Conformational changes of the annular lipid domain by LPO may therefore be considered as a possible cause of the functional changes in the receptor mediated responses and of the inactivation of membrane-bound enzymes by oxidative stress.
Assuntos
Peroxidação de Lipídeos/fisiologia , Lipídeos de Membrana/metabolismo , Sinaptossomos/metabolismo , Animais , Fenômenos Químicos , Físico-Química , Corantes Fluorescentes , Membranas Intracelulares/metabolismo , Membranas Intracelulares/ultraestrutura , Masculino , Pirenos , Ratos , Ratos Endogâmicos , Sinaptossomos/ultraestruturaRESUMO
We studied effects of gangliosides on the level of lipid peroxides and microviscosity of membrane lipid bilayer in primary dissociated cultures of cerebellar granule cells prepared from 8 day-old rats under conditions of neurotoxic effect of glutamate. It was found that glutamate (100 mkM) treatment of primary cultures activated the processes of lipid peroxidation and decreased microviscosity of neuronal membranes determined as a degree of pyrene excimerization. It was also shown that preincubation of granule cells with gangliosides did not prevent the accumulation of TBA-reactive products induced by glutamate. At the same time gangliosides significantly decreased the membrane-fluidizing effect caused by glutamate.
Assuntos
Gangliosídeos/farmacologia , Ácido Glutâmico/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Cerebelo/citologia , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Bicamadas Lipídicas , Neurônios/metabolismo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Using gas chromatography the authors have studied the time course of lipid peroxidation (LPO) in patients with manic depressive psychosis (a depressive phase) during a course of antidepressive therapy. The results indicate that the levels of LPO in young patients (up to 30 years) with a disease standing of up to 5 years are significantly higher than in age-matched controls whereas with increasing duration of the disease the levels of this parameter decrease and in elderly patients (over 50 years) with a longer duration of the disease (over 15 years) this parameter is significantly lower than in age-matched controls. A decrease of LPO is particularly pronounced in a bipolar course of manic depressive psychosis.
Assuntos
Transtorno Bipolar/metabolismo , Peróxidos Lipídicos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Bipolar/terapia , Testes Respiratórios , Cromatografia Gasosa , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Oxirredução , Pentanos/análiseRESUMO
The intensity of lipid peroxidation was studied in schizophrenic and manic-depressive patients. Peroxidation was found to be activated in these diseases as assessed by the content of peroxidation products in the lipid fraction of blood plasma. Manic-depressive patients showed a significant decrease in the intensity of peroxidation processes with improvement in the clinical symptoms of the disease.
Assuntos
Transtorno Bipolar/sangue , Peróxidos Lipídicos/sangue , Bases de Schiff/sangue , Esquizofrenia/sangue , Adolescente , Adulto , Feminino , Fluorometria , Humanos , Masculino , Pessoa de Meia-Idade , PolarografiaAssuntos
Fagócitos/imunologia , Fagocitose , Animais , Bactérias/imunologia , Atividade Bactericida do Sangue , Candida/imunologia , Cobaias , Peróxido de Hidrogênio/metabolismo , Imunidade Inata , Cinética , Ativação Linfocitária , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Oxirredução , Consumo de Oxigênio , Fagócitos/metabolismoAssuntos
Ativação de Macrófagos , Absorção , Animais , Cálcio/metabolismo , Membrana Celular/imunologia , Membrana Celular/metabolismo , Complemento C3b/imunologia , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Fagocitose , Prostaglandinas/imunologia , Prostaglandinas/metabolismo , Receptores de Complemento/imunologia , Receptores de Complemento 3b , Receptores Fc/imunologia , Superóxidos/metabolismoRESUMO
It was shown by the methods of luminol- and lucigenin-dependent chemiluminescence that 6-hydroxydopamine 6-ONDA autooxidation is accompanied by generation of superoxide anion-radical which can further react with next 6-ONDA molecule. This fact is based on the observations that intensities of luminol- and lucigenin-dependent chemiluminescence during 6-ONDA autooxidation was increased in aprotonic aqueous solutions (with the decreasing of pH) and was extremely depended on 6-ONDA concentration. The obtained data allows to suggest that one of the possible mechanisms of 6-ONDA neurotoxic action includes the generation of superoxide, whose dismutation to hydrogen peroxide in the presence of transient valency ions gives rise to HO.
Assuntos
Acridinas , Hidroxidopaminas , Medições Luminescentes , Luminol , Indicadores e Reagentes , Peroxidação de Lipídeos , OxirreduçãoRESUMO
The comparative study of the antiradical activity of carnosine and vitamin C was carried out by the means of the evaluation of quenching of ESR signals of 2,2-diphenyl-1-picrylhydrazyl (DFPH) and semiquinone radical of alpha-tocopherol. It was shown that carnosine is not able to quench the ESR signals of the stable radical of DFPH and semiquinone radical of alpha-tocopherol. It permits to conclude that: a) carnosine does not interact directly with highly active free radicals; b) carnosine is unable to regenerate the radical of alpha-tocopherol to form the antiradical synergistic couple. The data obtained are consistent with the idea that there is a difference between on the antioxidant mechanism action of vitamin C and carnosine due to the difference in the antiradical activity of these compounds.
Assuntos
Antioxidantes , Carnosina/farmacologia , Picratos , Bepridil/análogos & derivados , Bepridil/farmacologia , Compostos de Bifenilo , Sedimentação Sanguínea , Radicais Livres , Humanos , Indicadores e Reagentes , Vitamina E/farmacologiaRESUMO
The effect of synaptosomal membrane phospholipid hydrolysis by phospholipase A2 and alpha-tocopherol upon the state of beta-adrenergic receptors has been studied. The damaging action of phospholipase A2 on beta-adrenergic receptors, consisting in the decrease of specific binding of 3H-dihydroalprenolol at the expense of diminishing receptor affinity and Bmax was demonstrated. It was shown, that alpha-tocopherol protects beta-adrenergic receptors from damaging effect of phospholipase A2.
Assuntos
Encéfalo/efeitos dos fármacos , Fosfolipases A/farmacologia , Receptores Adrenérgicos beta/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Técnicas In Vitro , Masculino , Fosfolipases A2 , Ratos , Ratos EndogâmicosRESUMO
Using the fluorescent probe technique, it was shown that activation of lipid peroxidation decreases the value of transmembrane potential of rat brain synaptosomes. Depolarization of synaptosomes may be due to the impairment of the "barrier" properties of synaptosomal membranes and the decrease in Na,K-ATPase activity. alpha-Tocopherol and its model derivative devoid of the phytol chain--2,2,5,7,8-pentamethyl-6-oxychromanol--stabilize the transmembrane potential value during inhibition of lipid peroxidation. alpha-Tocopherol acetate causes no stabilizing or inhibiting effects. Unlike 2,2,5,7,8-pentamethyl-6-oxychromanol, alpha-tocopherol exerts a structuralizing action which manifests itself in the stabilization of the synaptosomal membrane potential during incomplete inhibition of lipid peroxidation. The previously established ability of alpha-tocopherol to protect synaptosomes from the damaging action of phospholipases and the experimental results of this work permit to regard vitamin E as a universal stabilizer of brain synaptosomal membranes.
Assuntos
Peróxidos Lipídicos/metabolismo , Lipídeos de Membrana/metabolismo , Sinaptossomos/metabolismo , Vitamina E/farmacologia , Animais , Corantes Fluorescentes , Técnicas In Vitro , Cinética , Potenciais da Membrana/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Membranas Sinápticas/metabolismo , Membranas Sinápticas/fisiologia , Sinaptossomos/fisiologiaRESUMO
The influence of antioxidant from hindered phenols (U-18) on a hypoxic neurodestructive effect in mouse hippocampal cell cultures was studied. Morphological and biochemical quantitative analysis of neuronal damage showed that U-18 attenuates nerve cell death resultant from 6-7-hour hypoxia and subsequent 12-hour posthypoxic reoxygenation. This antidestructive action of U-18 was observed upon its introduction in nutrient medium both before and immediately after hypoxic period. Thus, our results suggest that peroxidant reactions play a pivotal role in hypoxic neuronal injury and probably participate in this neurodestructive process mainly during posthypoxic reoxygenation period.
Assuntos
Antioxidantes/farmacologia , Hipocampo/efeitos dos fármacos , Hipóxia Encefálica/prevenção & controle , Neurônios/efeitos dos fármacos , Oxigênio/administração & dosagem , Fenóis/farmacologia , Animais , Morte Celular , Hipóxia Celular , Células Cultivadas , Camundongos , Fatores de TempoRESUMO
Using primary cultures of cerebellar granule cells from 4-6-day old Wistar rats we showed the protective effect of vitamin E against kainate-induced neurotoxicity. The preincubation of 7-8-day old cultures with 5 x 10(-4) M alpha-tocopherol solution significantly (on 10-20%) reduces the number of damaged granule cells. As vitamin E takes part in stabilization of membrane lipids the data presented allows us to suggest that one of the possible mechanisms of neuronal injury includes lipid oxidation of the neuronal membranes which leads to additional influx of Ca2+ and results in neuronal death.
Assuntos
Cerebelo/efeitos dos fármacos , Ácido Caínico/toxicidade , Neurônios/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Cerebelo/citologia , Interações Medicamentosas , Neurônios/citologia , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Using the quenching effect of the fluorescence by nitroxyl radicals the lateral mobility of chromanols in the lipid bilayer was studied. The lateral mobility of the chromanols was shown to increase when the length of phytol chain was diminished. The result is consistent with the idea that antioxidant affect of the chromanols depends on their lateral mobility.
Assuntos
Cromanos/análise , Bicamadas Lipídicas/análise , Vitamina E/análise , Fluorescência , Peroxidação de Lipídeos , Lipídeos de Membrana/análise , Movimento , Fosfolipídeos/análiseRESUMO
The action of phospholipase A2 and alpha-tocopherol on adenylate cyclase system functioning and on the lipid bilayer microviscosity of the rat brain synaptosome membranes was investigated. It was shown that the exposure of the synaptosomes to phospholipase A2 increases the adenylate cyclase activity stimulated by guanylyl imidotriphosphate (GITP), decreases the adenylate cyclase activity stimulated both by isoproterenol and by isoproterenol with GITP. The preincubation of synaptosomes in medium containing alpha-tocopherol does not change the character of the phospholipase action on the adenylate cyclase activity stimulated by isoproterenol but normalizes the adenylate cyclase activity stimulated both by GITP and by GITP with isoproterenol. In the last case the normalizing action of alpha-tocopherol is not caused by alteration of the microviscosity of the lipid bilayer. It appears to be due to the modification of the lipid-protein interactions of annular lipids with activated complex of catalytic subunit and guanyl nucleotide-binding protein.