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1.
Braz. j. med. biol. res ; 53(4): e8993, 2020. tab, graf
Article in English | LILACS | ID: biblio-1089353

ABSTRACT

The central nervous system shows limited regenerative capacity after injury. Spinal cord injury (SCI) is a devastating traumatic injury resulting in loss of sensory, motor, and autonomic function distal from the level of injury. An appropriate combination of biomaterials and bioactive substances is currently thought to be a promising approach to treat this condition. Systemic administration of valproic acid (VPA) has been previously shown to promote functional recovery in animal models of SCI. In this study, VPA was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microfibers by the coaxial electrospinning technique. Fibers showed continuous and cylindrical morphology, randomly oriented fibers, and compatible morphological and mechanical characteristics for application in SCI. Drug-release analysis indicated a rapid release of VPA during the first day of the in vitro test. The coaxial fibers containing VPA supported adhesion, viability, and proliferation of PC12 cells. In addition, the VPA/PLGA microfibers induced the reduction of PC12 cell viability, as has already been described in the literature. The biomaterials were implanted in rats after SCI. The groups that received the implants did not show increased functional recovery or tissue regeneration compared to the control. These results indicated the cytocompatibility of the VPA/PLGA core-shell microfibers and that it may be a promising approach to treat SCI when combined with other strategies.


Subject(s)
Animals , Male , Rats , Spinal Cord Injuries/therapy , Central Nervous System/drug effects , Valproic Acid/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Materials Testing , Microscopy, Electron, Scanning , Rats, Wistar , Microfibrils/chemistry , Tissue Engineering/methods , Disease Models, Animal , Tissue Scaffolds
2.
Prensa méd. argent ; 105(1): 16-23, mar 2019. graf, fig
Article in Spanish | LILACS, BINACIS | ID: biblio-1026319

ABSTRACT

En el presente trabajo se seleccionaron pacientes adultos HIV en tratamiento antirretroviral que contenían efavirenz de más de tres años de duración que hubieron tenido efectos adversos del sistema nervioso central iniciales, comprobando la desaparición completa de los mismos en el 94% de los pacientes evaluados al cabo de 36 meses de tratamiento. Se empleó como método el análisis observacional retrospectivo, utilizando una encuesta de valoración de frecuencia temporal de efectos adversos del sistema nervioso central. Se tuvieron en cuenta los siguientes: mareos: depresión; trastornos del sueño; pesadillas e ideación suicida. De los efectos adversos del sistema nervioso central investigados, los más frecuente fue pesadillas 100% y mareos 81%. Esta frecuencia decreciente hasta su desaparición, fortalece la hipótesis del "fenómeno de tolerancia" similar al observado con ciertas indolaminas, debido a que efavirenz presenta una similitud estructural con estas e interacciona con algunos receptores de la superfamilia de receptores de 5 hidroxitriptamina (5HT). Además las diferencias interindividuales de efectos adversos del SNC podrían estar dadas por las diferencias alélicas en citocromo p 450 que determinan niveles plasmáticos de metabólitos hidroxilados neurotóxicos


In the present study, adult HIV patients were selected on antiretroviral treatment that contained efavirenz for more than three years that had adverse effects on the initial central nervous system, proving their complete disappearance in 94% of the patients evaluated after 36 months of treatment. A retrospective observational analysis was used as a method, using a survey of temporal frequency assessment of adverse effects of the central nervous system. The following were taken into account: dizziness; anxiety; depression; sleep disorders; nightmares and suicidal ideation. Of the adverse effects of the central nervous system investigated, the most frequent was nightmares 100% and dizziness 81%. This decreasing frequency until its disappearance, strengthens the hypothesis of the "tolerance phenomenon" similar to that observed with certain indolamines, because efavirenz has a structural similarity with these and interacts with some receptors of the superfamily of 5-hydroxytryptamine (5HT) receptors. In addition, the interindividual differences of CNS adverse effects could be due to allelic differences in cytochrome p 450 that determine plasma levels of neurotoxic hydroxylated metabolites.


Subject(s)
Humans , Adult , Middle Aged , Central Nervous System/drug effects , Retrospective Studies , HIV/drug effects , Antiretroviral Therapy, Highly Active/adverse effects , Drug-Related Side Effects and Adverse Reactions/therapy , Time-to-Treatment , Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/adverse effects
3.
Bol. latinoam. Caribe plantas med. aromát ; 18(2): 95-105, mar. 2019. tab
Article in English | LILACS | ID: biblio-1007685

ABSTRACT

The Lippia alba species consists of an aromatic plant used in Brazilian traditional medical practice and in the medical practice of several countries as well. Presenting a wide variability in its essential oil chemical composition, the Lippia alba is classified in chemotypes, or chemical races, according to the major constituents contained in its essential oil. Considering the quali and quantitative distribution of the components in the essential oil affect directly its pharmacological properties, which are presented in the medicinal species, this paper proposes a scientific literature review to correlate both biological and pharmacological properties presented by L. alba according to its chemical constitution.


Lippia alba es una planta aromática utilizada en la medicina tradicional de Brasil y de varios países. Con una gran variabilidad en la composición química de su aceite esencial, se clasifica en quimiotipos, o razas químicas, de acuerdo con los constituyentes mayoritarios presentes en el aceite esencial. Dado que la distribución cualitativa y cuantitativa de los componentes del aceite esencial afecta directamente a las propiedades farmacológicas presentadas por la especie medicinal, este trabajo propone realizar una revisión en la literatura científica para correlacionar las propiedades biológicas y farmacológicas de los quimiotipos presentes en el aceite essencial de la L. alba.


Subject(s)
Oils, Volatile/pharmacology , Lippia , Bacteria/drug effects , Brazil , Oils, Volatile/chemistry , Cardiovascular System/drug effects , Central Nervous System/drug effects , Monoterpenes/pharmacology , Gastrointestinal Tract/drug effects , Medicine, Traditional
4.
Int. j. morphol ; 35(3): 942-949, Sept. 2017.
Article in English | LILACS | ID: biblio-893078

ABSTRACT

Prolonged alcohol consumption has consequences on the liver, producing necrotic precipitates and fibrosis, on the pancreas, causing the pancreatic acini to atrophy and destroying insulin-producing cells, and on the central nervous system (CNS), causing the gray and white matter in the frontal lobes of the brain and cerebellum to atrophy. Generally, alcohol is metabolized via oxidative pathways, where the enzymes alcohol dehydrogenase and aldehyde dehydrogenase participate during its metabolization in the liver and CNS, or via non-oxidative pathways during its metabolization in the pancreas. Ethanol metabolism can produce oxidative stress and tissue damage mediated by free radicals, causing morphological and functional alterations in the liver. In the pancreas, it can cause progressive and irreversible damage affecting the endocrine and exocrine functions, a result of the activation of the stellate cells, which are activated directly by alcohol, causing pancreatic fibrosis. In the CNS ethanol can bind directly to proteins, nucleic acids and phospholipids to develop its pathogenesis. The effects produced by alcohol can be counteracted by supplementation with antioxidants, which reduce the inflammation and areas of focal necrosis in the liver, inhibit the activation of pancreatic stellate cells, and reduce oxidative stress in the CNS. Additionally, in order to reduce the negative effects associated with alcohol consumption, recent studies have suggested the administration of antioxidants as a treatment strategy.


El consumo prolongado de alcohol tiene consecuencias en hígado, produciendo precipitados necróticos y fibrosis; en páncreas, provocando atrofia del acino pancreático y destrucción de las células productoras de insulina, y en Sistema Nervioso Central (SNC) generando atrofia de la sustancia gris y blanca en lóbulos frontales del cerebro y cerebelo. En general, el metabolismo del alcohol se consigue mediante las vías oxidativas, donde participan las enzimas alcohol-deshidrogenasa y aldehído deshidrogenasa durante su metabolización en hígado y SNC; o bien, mediante las vías no oxidativas durante su metabolización en páncreas. El metabolismo del etanol es capaz de producir estrés oxidativo y daño tisular mediado por radicales libres, causando alteraciones morfológicas y funcionales del hígado; en el páncreas, puede causar daño progresivo e irreversible afectando las funciones endocrinas y exocrinas de este órgano producto de la activación de las células estrelladas que son activadas directamente por el alcohol generando fibrosis pancreática; mientras que, en SNC se puede unir directamente a proteínas, ácidos nucleicos y fosfolípidos para desarrollar su patogenia. Los efectos producidos por el alcohol pueden contrarrestarse mediante la suplementación con antioxidantes, que reducen la inflamación y las zonas de necrosis focal en el hígado, inhiben la activación de células pancreáticas estrelladas, y reducen el estrés oxidativo en SNC. Asimismo, para reducir los efectos negativos asociados al consumo de alcohol, estudios recientes han propuesto la administración de antioxidantes como estrategia terapéutica.


Subject(s)
Humans , Central Nervous System/drug effects , Ethanol/toxicity , Alcoholic Intoxication/drug therapy , Antioxidants/therapeutic use , Pancreas/drug effects , Pancreas/pathology , Central Nervous System/pathology , Oxidative Stress , Ethanol/metabolism , Liver/drug effects , Liver/pathology
5.
An. acad. bras. ciênc ; 89(1,supl): 497-504, May. 2017. tab
Article in English | LILACS | ID: biblio-886661

ABSTRACT

ABSTRACT This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and evaluate its influence on central nervous system (CNS) side effect development in HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population from southern Brazil. Additionally, we performed a survey on the clinical and epidemiological characteristics of our sample. In addition to medical records evaluation, whole blood of 89 individuals was analyzed for viral load, T lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side effects of the CNS reported by individuals but without considering the genetic variables, no statistically significant association was noted between the adverse effects and the antiretroviral treatment (including or not EFV). In addition, no statistically significant difference was noted for the influence of genotype on the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals undergoing EFV treatment. This is the first study that investigated the impact of the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from southern Brazil. Its clinical significance indicates the need for prospective studies in this population.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Polymorphism, Genetic/genetics , HIV Infections/genetics , HIV Infections/drug therapy , Central Nervous System/drug effects , Reverse Transcriptase Inhibitors/adverse effects , Benzoxazines/adverse effects , Cytochrome P-450 CYP2B6/genetics , Prospective Studies , CD4-CD8 Ratio , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load , Benzoxazines/therapeutic use , Genotype
6.
Rev. bras. anestesiol ; 67(1): 1-5, Jan.-Feb. 2017. tab
Article in English | LILACS | ID: biblio-843365

ABSTRACT

Abstract Background: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. Methods: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n = 6), Group 1/10 (n = 6), and Group 1/100 (n = 6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. Results: The rocuronium bromide seizure threshold value was found to be 0.056 ± 0.009 µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286 µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. Conclusions: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.


Resumo Justificativa: O objetivo deste estudo foi investigar os efeitos do brometo de rocurônio administrado intracerebroventricularmente sobre o sistema nervoso central, determinar a dose do limiar convulsivo de rocurônio em ratos e investigar os efeitos de rocurônio no sistema nervoso central em diluições de 1/5, 1/10 e 1/100 da dose do limiar convulsivo determinada. Métodos: Uma cânula permanente foi colocada no ventrículo lateral do cérebro dos animais. O estudo foi projetado em duas fases. Na primeira, a dose do limiar convulsivo do brometo de rocurônio foi determinada. Na segunda, o Grupo R 1/5 (n = 6), o Grupo 1/10 (n = 6) e Grupo 1/100 (n = 6) foram formados com doses de 1/5, 1/10 e 1/100, respectivamente, da dose do limiar convulsivo de brometo de rocurônio obtida. Resultados: Descobrimos que o valor do limiar convulsivo de brometo de rocurônio é 0,056 ± 0,009 µmoL. O limiar convulsivo, como uma função do peso corporal dos ratos, foi calculado como 0,286 µmoL/kg-1. Uma dose de 1/5 da dose do limiar convulsivo causou principalmente abertura postural dos membros e tremores em todo o corpo, enquanto uma dose de 1/10 da dose do limiar convulsivo causou agitação e tremores. Uma dose de 1/100 da dose do limiar convulsivo foi associada à diminuição da atividade locomotora. Conclusões: Este estudo mostrou que o brometo de rocurônio tem efeitos deletérios relacionados com a dose sobre o sistema nervoso central e pode produzir efeitos excitatórios dependentes da dose e convulsões.


Subject(s)
Animals , Female , Dihydrotestosterone/pharmacology , Central Nervous System/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Epilepsy/drug therapy , Random Allocation , Rats, Wistar , Neuromuscular Nondepolarizing Agents/administration & dosage , Dose-Response Relationship, Drug , Rocuronium , Injections, Intraventricular , Androstanols/administration & dosage , Locomotion/drug effects
7.
Arq. neuropsiquiatr ; 74(9): 737-744, Sept. 2016. graf
Article in English | LILACS | ID: lil-796045

ABSTRACT

ABSTRACT Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein. Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation remained unchanged. This study demonstrated that aged Lewis rats exposed to a low dose of rotenone is a useful model to study cellular processes before protein aggregation, while the higher dose makes a good model to study the effects of protein inclusions.


RESUMO A fisiologia celular está prejudicada antes da agregação proteica podendo ser mais importante para a neurodegeneração do que as próprias inclusões. Assim, o objetivo deste estudo é caracterizar um modelo animal para analisar os mecanismos e efeitos da agregação proteica. Ratos Lewis com 10 meses de idade foram expostos a rotenona (1 ou 2 mg/kg/dia), administrada subcutaneamente, utilizando minibombas osmóticas. Os níveis de peptídeo beta-amiloide, TAU hiperfosforilada, alfa-sinucleína e proteínas carboniladas (indicativo de estresse oxidativo) foram avaliados por imunohistoquímica e western blot no hipocampo, substância negra e locus coeruleus. Foi demonstrado que 2 mg/kg/dia de rotenona promoveu aumento do peptídeo beta-amiloide, hiperfosforilação da TAU e alfa-sinucleína. Já 1 mg/kg/dia de rotenona não alterou os níveis dessas proteína nessas regiões. As proteínas carboniladas não se alteraram. Foi demonstrado que ratos Lewis idosos expostos a baixas doses de rotenona são modelo de estudo dos processos celulares antes da agregação proteica, enquanto 2 mg/kg/dia de rotenona permite estudos sobre os efeitos da agregação proteica.


Subject(s)
Animals , Male , Rotenone/administration & dosage , Central Nervous System/drug effects , Central Nervous System/pathology , Disease Models, Animal , Protein Aggregation, Pathological/chemically induced , Protein Aggregation, Pathological/pathology , Rats, Inbred Lew , Substantia Nigra/drug effects , Immunohistochemistry , Central Nervous System/metabolism , Blotting, Western , Reproducibility of Results , Amyloid beta-Peptides/drug effects , Amyloid beta-Peptides/metabolism , Oxidative Stress , alpha-Synuclein/drug effects , alpha-Synuclein/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology
8.
Rev. Assoc. Med. Bras. (1992) ; 61(4): 381-387, July-Aug. 2015. tab
Article in English | LILACS | ID: lil-761716

ABSTRACT

SummaryIntroduction:alcohol is a psychotropic depressant of the central nervous system (CNS) that promotes simultaneous changes in several neuronal pathways, exerting a profound neurological impact that leads to various behavioral and biological alterations.Objectives:to describe the effects of alcohol on the CNS, identifying the signaling pathways that are modified and the biological effects resulting from its consumption.Methods:a literature review was conducted and articles published in different languages over the last 15 years were retrieved.Results:the studies reviewed describe the direct effect of alcohol on several neurotransmitter receptors (gamma-aminobutyric acid [GABA], glutamate, endocannabinoids AEA and 2-AG, among others), the indirect effect of alcohol on the limbic and opioid systems, and the effect on calcium and potassium channels and on proteins regulated by GABA in the hippocampus.Discussion and conclusion:the multiple actions of alcohol on the CNS result in a general effect of psychomotor depression, difficulties in information storage and logical reasoning and motor incoordination, in addition to stimulating the reward system, a fact that may explain the development of addiction. Knowledge on the neuronal signaling pathways that are altered by alcohol allows the identification of effectors which could reduce its central action, thus, offering new therapeutic perspectives for the rehabilitation of alcohol addicts.


ResumoIntrodução:o álcool é uma substância psicotrópica depressora do sistema nervoso central (SNC), que promove alteração simultânea de inúmeras vias neuronais, gerando profundo impacto neurológico e traduzindo-se em diversas alterações biológicas e comportamentais.Objetivos:descrever as ações do álcool sobre o SNC, identificando as vias de sinalização modificadas e os efeitos biológicos gerados pelo seu consumo.Métodos:revisão bibliográfica, priorizando trabalhos multilinguísticos publicados nos últimos 15 anos.Resultados:são descritas ação direta do álcool em inúmeros receptores de neurotransmissores (ácido gama-aminobutírico – GABA, glutamato, endocanabinoides AEA e 2-AG, entre outros), ação indireta do álcool no sistema límbico e opioide, ação sobre canais de cálcio, potássio e proteínas reguladas por GABA no hipocampo, além de ações centrais mediadas pela deficiência de vitamina B1.Conclusão:a ação multifocal do álcool sobre o SNC resulta em efeito geral de depressão psicomotora, dificuldades no armazenamento de informações e no raciocínio lógico, incoordenação motora, além da estimulação do sistema de recompensa, o que pode explicar o desenvolvimento da dependência química. O conhecimento das vias de sinalização neuronais alteradas pelo álcool permite reconhecer a descrição de efetores que possam reduzir sua ação central e, assim, vislumbrar novas perspectivas terapêuticas para a reabilitação de adictos a essa substância.


Subject(s)
Humans , Central Nervous System Depressants/pharmacology , Central Nervous System/drug effects , Ethanol/pharmacology , Receptors, Neurotransmitter/drug effects , Alcohol-Induced Disorders, Nervous System/physiopathology , Alcoholism/physiopathology , Central Nervous System Depressants/adverse effects , Ethanol/adverse effects , Receptors, Neurotransmitter/physiology
9.
Rev. latinoam. enferm ; 22(6): 911-917, 16/12/2014. tab
Article in English | LILACS, BDENF | ID: lil-732936

ABSTRACT

OBJECTIVE: to assess the quality of life of chronic kidney patients undergoing hemodialysis, using the WHOQOL-bref and WHOQOL-SRPB. METHOD: a descriptive and cross-sectional study was undertaken at a kidney replacement therapy service in the interior of the state of SP. The 110subjects who complied with the inclusion criteria answered the Subject Characterization Instrument, the WHOQOL-bref and WHOQOL-SRPB. RESULTS: most of the respondents were male (67.27%), with a mean age of 55.65 years, Catholic (55.45%), with unfinished primary education (33.64%) and without formal occupation (79.08%). The WHOQOL-bref domains with the highest and lowest mean score were, respectively, "psychological" (µ=74.20) and "physical" (µ=61.14). The WHOQOL-SRPB domains with the highest and lowest mean score were, respectively, "completeness and integration" (µ=4.00) and "faith" (µ=4.40). CONCLUSIONS: the respondents showed high quality of life scores, specifically in the dimensions related to spirituality, religion and personal beliefs. Losses were evidenced in the physical domain of quality of life, possibly due to the changes resulting from the chronic kidney disease and hemodialysis treatment. .


OBJETIVO: avaliar a qualidade de vida de pacientes renais crônicos em hemodiálise, por meio do WHOQOL-bref e WHOQOL-Spirituality, Religion and Personal Beliefs. MÉTODO: trata-se de um estudo descritivo, de corte transversal, realizado em uma unidade de terapia renal substitutiva do interior do Estado de São Paulo. Os 110 sujeitos que atenderam os critérios de inclusão responderam ao Instrumento de Caracterização dos Sujeitos, ao WHOQOL-bref e WHOQOL-Spirituality, Religion and Personal Beliefs. RESULTADOS: a maioria dos respondentes era do sexo masculino (67,27%), com idade média de 55,65 anos, católica (55,45%), com ensino fundamental incompleto (33,64%) e sem ocupação formal (79,08%). Os domínios do WHOQOL-bref com maior e menor pontuação média foram, respectivamente, "psicológico" (µ=74,20) e "físico" (µ=61,14). Os domínios do WHOQOL-Spirituality, Religion and Personal Beliefs de menor e maior pontuação média foram, respectivamente, "totalidade e integração" (µ=4,00) e "fé" (µ=4,40). CONCLUSÕES: os respondentes apresentaram elevados escores de qualidade de vida, especificamente nas dimensões referentes à espiritualidade, religião e crenças pessoais. Evidenciaram-se prejuízos no domínio físico da qualidade de vida, possivelmente em decorrência das alterações resultantes da doença renal crônica e do tratamento hemodialítico. .


OBJETIVO: evaluar la calidad de vida de pacientes renales crónicos en hemodiálisis, por medio del WHOQOL-bref y WHOQOL-SRPB. MÉTODO: se trata de un estudio descriptivo, de corte transversal, realizado en una unidad de terapia renal substitutiva del interior del estado de SP. Los 110 sujetos que atendieron a los criterios de inclusión respondieron al Instrumento de Caracterización de los Sujetos, al WHOQOL-bref y WHOQOL-SRPB. RESULTADOS: la mayoría de los entrevistados era del sexo masculino (67,27%), con edad promedio de 55,65 años, católicos (55,45%), con enseñanza fundamental incompleta (33,64%) y sin ocupación formal (79,08%). Los dominios del WHOQOL-bref con mayor y menor puntuación promedio fueron, respectivamente: "psicológico" (µ=74,20) y "físico" (µ=61,14). Los dominios del WHOQOL-SRPB de menor y mayor puntuación promedio fueron, respectivamente: "totalidad e integración" (µ=4,00) y "fe" (µ=4,40). CONCLUSIONES: los entrevistados presentaron elevados puntajes de calidad de vida, específicamente en las dimensiones referentes a espiritualidad, religión y creencias personales. Se evidenciaron perjuicios en el dominio físico de la calidad de vida, posiblemente en consecuencia de las alteraciones resultantes de la enfermedad renal crónica y del tratamiento de hemodiálisis. .


Subject(s)
Humans , Antineoplastic Agents/adverse effects , Bone Marrow/drug effects , Floxuridine/adverse effects , Administration, Oral , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/metabolism , Central Nervous System/drug effects , Floxuridine/administration & dosage , Floxuridine/metabolism , Heart/drug effects , Infusions, Intravenous , Leukopenia/chemically induced , Thrombocytopenia/chemically induced
10.
Indian J Exp Biol ; 2013 Oct; 51(10): 828-832
Article in English | IMSEAR | ID: sea-149388

ABSTRACT

Methanolic and ethyl acetate extract of A. galanga showed significant central nervous system (CNS) stimulant activity in mice using actophotometer and rotarod test. CNS stimulation at a dose of 500 mg/kg was comparable with standard drugs caffeine and amphetamine derivative modalart. The extracts did not shown any depressant effect in forced swim or tail suspension tests. It can be concluded that A. galanga rhizome may have stimulant activity in mice and the active constituents responsible for this effect is present both in crude methanolic extract as well as in ethyl acetate fraction of methanolic extract of this plant species.


Subject(s)
Alpinia/chemistry , Animals , Central Nervous System/drug effects , Central Nervous System Stimulants/pharmacology , Locomotion/drug effects , Male , Mice , Pilot Projects , Plant Extracts/pharmacology , Psychomotor Performance/drug effects , Rhizome/chemistry
11.
IJPM-International Journal of Preventive Medicine. 2013; 4 (Supp. 2): 222-228
in English | IMEMR | ID: emr-127457

ABSTRACT

Previous studies have shown that morphine consumption during pregnancy may cause delay or defect of embryo development or abnormal nervous system function in the human and animal models. In the present study, the highest density of morphine accumulation in the central nervous system of rat embryos was evaluated using C14-morphine. Female Wistar rats [W 170-200 g] used and were crossed with male rats and coupling time was recorded [Embryonic day 0-E0]. Experimental groups received 0.05 mg/ml of C14-morphine in drinking water daily. On the 10[th] and 17[th] days of pregnancy, pregnant rats were anesthetized and the embryos with these uterus and placenta were surgically removed and were fixed in formalin 10% for 4 week. Then the embryos were processed, sectioned in 25 micro m and 5 micro m thicknesses, fixed on the glasses for further evaluations. The sectioned in 25, the glasses were fixed on the Blanc black and white film for 6 h. Then, the films were appeared and their negatives were prepared. The sectioned in five staining hematoxylin and eosin by light microscope and MOTIC software. Our results indicated that the highest C14-morphine accumulation was observed in the vesicles and the ventricular choroid plexus [CP] of [E17] embryos, whereas, in the [E10] embryos. Highest concentration was observed in the brain vesicles and the ventricular CP. In addition, this study showed the surface area of lateral, 3[rd] and 4[th] ventricular CP in the experimental groups were increased in compared to control groups. Our results indicated that effects of morphine on reduction of embryos brain development may be due to the highest accumulation of C14-morphine in the CP and brain vesicles


Subject(s)
Animals, Laboratory , Rats, Wistar , Central Nervous System/drug effects , Embryonic Structures , Choroid Plexus , Embryonic Development
12.
Medicina (B.Aires) ; 73 Suppl 1: 93-102, 2013.
Article in Spanish | LILACS, BINACIS | ID: biblio-1165142

ABSTRACT

Neurodevelopmental disorders are the result of a disturbance of brain function. They are frequent, with varied symptomatology, manifest themselves at different times of life and tend to be persistent with impact at the individual, family and social level. The association of these disorders with genetic entities is low. Although the research supports a mode of genetic inheritance, epigenetic factors and environmental factors can play an important role. In recent years there was a striking increase of these disorders especially attention deficit hyperactivity disorders and pervasive development disorder. Environmental factors such as the intoxication of the fetus by especially heavy metals lead and mercury are to blame in some children, of these disorders. Other substances of wide use, little degradation and maintenance in the food chain as pesticides, polychlorinated biphenyls and now the recycling of electronic waste put especially infants and children at risk, and even more so in the developing countries.


Subject(s)
Developmental Disabilities/chemically induced , Central Nervous System Diseases/chemically induced , Environmental Exposure/adverse effects , Hazardous Substances/toxicity , Arsenic/toxicity , Polychlorinated Biphenyls/toxicity , Child , Female , Humans , Male , Pesticides/toxicity , Electronic Waste/adverse effects , Central Nervous System/drug effects
13.
Braz. j. med. biol. res ; 45(3): 250-255, Mar. 2012. ilus
Article in English | LILACS | ID: lil-618045

ABSTRACT

Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP8-37) and ADM receptor antagonist (ADM22-52) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.


Subject(s)
Animals , Female , Rats , Adrenomedullin/pharmacology , Blood Pressure/drug effects , Cholinergic Neurons/physiology , Heart Rate/drug effects , Vasodilator Agents/pharmacology , Vasopressins/drug effects , Adrenomedullin/administration & dosage , Central Nervous System/drug effects , Central Nervous System/physiology , Cholinergic Neurons/drug effects , Consciousness/drug effects , Consciousness/physiology , Injections, Intraventricular , Rats, Sprague-Dawley , Receptors, Calcitonin Gene-Related Peptide/drug effects , Receptors, Calcitonin Gene-Related Peptide/physiology , Vasodilator Agents/administration & dosage , Vasopressins/physiology
14.
Braz. j. med. biol. res ; 44(9): 933-938, Sept. 2011. ilus
Article in English | LILACS | ID: lil-599668

ABSTRACT

Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na+ pump, inhibiting its activity. Inhibition of this pump increases intracellular Na+, which reduces the activity of the sarcolemmal Na+/Ca2+ exchanger and thereby reduces Ca2+ extrusion. Consequently, intracellular Ca2+ increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.


Subject(s)
Animals , Humans , Rats , Blood Pressure/drug effects , Cardiotonic Agents/pharmacology , Hypertension/chemically induced , Ouabain/pharmacology , Angiotensin II/biosynthesis , Calcium/metabolism , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/metabolism , Central Nervous System/drug effects , Hypertension/metabolism , Injections, Intravenous , Norepinephrine , Ouabain/administration & dosage , Ouabain/metabolism , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/drug effects , Sodium-Potassium-Exchanging ATPase/drug effects , Sodium-Potassium-Exchanging ATPase/physiology
15.
Journal of Rafsanjan University of Medical Sciences. 2011; 9 (4): 273-280
in Persian | IMEMR | ID: emr-103731

ABSTRACT

Central nervous system is one of the primary targets of the detrimental effects of narcotics. Although opiates are among the most drugs of abuse, little is known about their side effects on the brain structures. Most investigations in this field are about their biochemical or psychological side effects. In this study pathologic changes in morphine dependent rats have been investigated. In this experimental study, 48 male wistar rats were divided into 6 groups. The dependent groups received 0.4mg/ml morphine in drinking water for 7, 28 and 56 days. The control groups received a solution of saccharose in drinking water for the same periods and then the histological studies of the brain samples were done. Significant neuronal loss in frontal and parietal lobes and hippocampus was observed. Results also showed a significant relationship between the duration of morphine intake and neuronal loss. The results of this study, in line with the other studies in this field indicate that opiate drugs might induce neuronal damage after long term exposure. These changes could be more significant in chronic addiction. Since brain atrophy is the most common pathology in dementia, further investigations for finding probable relations between dementia and opiate dependency is suggested


Subject(s)
Male , Animals, Laboratory , Opium , Morphine Dependence , Brain/pathology , Rats, Wistar , Brain/drug effects , Double-Blind Method , Central Nervous System/drug effects , Neurons/drug effects
16.
Medical Principles and Practice. 2011; 20 (1): 71-74
in English | IMEMR | ID: emr-111001

ABSTRACT

Our purpose was to study whether or not intravenous [IV] administration of lidocaine reduces propofol dose requirement as intramuscular [IM] lidocaine in a placebo-controlled manner. Seventy-five adult patients with American Society of Anesthesiologists physical status I and II, aged 20-60 years who were scheduled for surgery under general anaesthesia were included in the study. The patients were randomly allocated to 3 groups: IM: intramuscular administration; IV: intravenous administration and C: control. There were 25 patients in each group. The patients in group IM received lidocaine 1.5 mg kg-1 administered into the deltoid muscle 10 min before anaesthesia induction. In group IV, the patients received IV lidocaine 1.5 mg kg-1, 2 min before anaesthesia induction. Group C patients served as control group who received only propofol injection. Hypnosis after propofol administration was measured with response to verbal commands. There were no statistical differences between group IM [100.8 +/- 26.1 mg] and group IV [110.8 +/- 30.1 mg] regarding the induction dose of propofol [p > 0.05]. In group C, the required propofol dose [151.2 +/- 27.4 mg] for anaesthesia induction was significantly higher than in the other groups [p < 0.001]. No side effect was observed in any patients. In this study, both IV and IM lidocaine administration were effective in reducing the hypnotic dose of propofol without any side effects. In addition, IV lidocaine may be more comfortable for awake patients


Subject(s)
Humans , Male , Female , Lidocaine/administration & dosage , Propofol , Injections, Intramuscular , Injections, Intravenous , Anesthesia, Intravenous , Anesthetics, Intravenous , Anesthetics, Local/administration & dosage , Heart Rate/drug effects , Central Nervous System/drug effects
17.
Behbood Journal. 2011; 14 (4): 283-289
in Persian | IMEMR | ID: emr-122335

ABSTRACT

Morphine consumption during pregnancy could lead to defect and delay in nervous system development in the embryos. In the present study, development of the tongue of embryos whom their mothers received oral morphine during pregnancy have been studied. Female Wistar rats [200-220 g] after pregnancy were divided randomly into the experimental and control groups. The control group received tap water whereas the experimental group received morphine [0.05 mg/ml] in their drinking waters. On the day 19, the pregnant rats were killed by chloroform overdose and the embryos were removed surgically and were fixed in formalin 10%. Simultaneously, the rats' bloods were collected for corticosterone measurement. Weight and length of the embryos were determined. Then the embryos' heads were removed for tissue processing, cutting and Hematoxylin- Eosin staining. The subjects were evaluated using light microscope and MOTIC software. Number of the cells also counted. Un-paired t-test applied for statistical analysis. Plasma corticosterone level, embryos' weight and length did not show any significant differences between control and experimental groups. The large diameter of the tongue of the experimental group was decreased but the small diameter in two groups did not differ. Tongue cells numbers in the experimental group were increased but their size decreased. Decrease in the large diameter of tongue, increase in the cell number and decrease in cell size indicate the influence of morphine consumption during pregnancy on tongue development in the embryos


Subject(s)
Animals , Female , Tongue/embryology , Prenatal Exposure Delayed Effects , Central Nervous System/drug effects , Rats, Wistar , Organ Size/drug effects , Maternal Exposure
18.
Arab Journal of Pharmaceutical Sciences. 2009; 4 (1): 76-69
in Arabic | IMEMR | ID: emr-134509

ABSTRACT

In this work [+]-dihydroperfamine was isolated from Haplophyllum tuberculatum and several derivatives, namely, anhydroperforine, dihydroperfaminole, haplophyllidine, [-]-perforine and [+]-perforine were prepared. Dihydroperfamine and its derivatives were investigated for prolongation of sleeping time of pentobarbitone. Their cytotoxic activity was performed using a mechanism-based bioassay utilizing genetically engineered mutants of the yeast Saccharomyces cerevisiae. In addition, their antimicrobial activity was also tested using agar dilution method. The results showed that dihydroperfamine and its derivatives except haplophyllidine prolonged the hypnotic duration of pentobarbital. Dihydroperfamine was the only compound that possessed cytotoxic activity against strain I. On the other hand, all compounds were antimicrobially inactive


Subject(s)
Male , Animals, Laboratory , Perforin , Central Nervous System/drug effects , Anti-Infective Agents , Cytotoxins , Saccharomyces cerevisiae/drug effects , Phenobarbital
19.
IJMS-Iranian Journal of Medical Sciences. 2009; 34 (1): 72-75
in English | IMEMR | ID: emr-91307

ABSTRACT

Rheumatoid arthritis is a chronic systemic inflammatory disease that affects approximately 0.5-1% of the world population. The current approach to this disease is to start an intensive treatment without delay once the disease has developed. Various studies in the literature have shown that combination of disease modifying antirheumatic drugs such as sulfasalazine and chloroquine offers a more advantageous treatment. Although these drugs may cause central nervous system adverse effects such as serious psychiatric problems including mania and psychosis, these symptoms have been reported to occur only infrequently. The present case study reports a female patient who was hospitalized due to bipolar affective disorder-mixed episode. She had been receiving 250 mg/day chloroquine for 9 months for rheumatoid arthritis without exhibiting any adverse psychiatric effects. However, upon receiving a combination of 250 mg/day chloroquine and 2 gr/day sulfasalazine, she developed serious psychiatric symptoms


Subject(s)
Humans , Female , Chloroquine/adverse effects , Arthritis, Rheumatoid/drug therapy , Mood Disorders/etiology , Antirheumatic Agents , Bipolar Disorder , Psychotic Disorders , Affective Disorders, Psychotic , Mood Disorders/diagnosis , Mood Disorders/therapy , Central Nervous System/drug effects
20.
Article in English | IMSEAR | ID: sea-16749

ABSTRACT

Manganese (Mn) is an essential element present in all living organisms and is naturally present in rocks, soil, water, and food. Exposure to high oral, parenteral, or ambient air concentrations of Mn can result in elevations in Mn tissue levels and neurological effects. However, current understanding of the impact of Mn exposure on the nervous system leads to the hypothesis that there should be no adverse effects at low exposures, because Mn is an essential element; therefore, there should be some threshold for exposure above which adverse effects may occur and adverse effects may increase in frequency with higher exposures beyond that threshold. Data gaps regarding Mn neurotoxicity include what the clinical significance is of the neurobehavioural, neuropsychological, or neurological endpoints measured in many of the occupational studies that have evaluated cohorts exposed to relatively low levels of Mn. Specific early biomarkers of effect, such as subclinical neurobehavioural or neurological changes or magnetic resonance imaging (MRI) changes have not been established or validated for Mn, although some studies have attempted to correlate biomarkers with neurological effects. Experimental studies with rodents and monkeys provide valuable information about the absorption, bioavailability, and tissue distribution of various Mn compounds with different solubilities and oxidation states in different age groups. Studies have shown that rodents and primates maintain stable tissue manganese levels as a result of homeostatic mechanisms that tightly regulate absorption and excretion. In addition, physiologically based pharmacokinetic (PBPK) models are being developed to provide for the ability to conduct route-to-route extrapolations, evaluate nasal uptake to the CNS, and evaluate lifestage differences in Mn pharmacokinetics. Such models will facilitate more rigorous quantitative analysis of the available pharmacokinetic data for Mn and will be used to identify situations that may lead to increased brain accumulation related to altered Mn metabolism in different human populations, and develop quantitatively accurate predictions of increased Mn levels that may serve as a basis of dosimetry-based risk assessments. Such assessments will permit for the development of more scientifically refined and robust recommendations, guidelines, and regulations for Mn levels in the ambient environment and occupational settings.


Subject(s)
Animals , Central Nervous System/drug effects , Humans , Manganese/physiology
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