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1.
Artigo em Chinês | MEDLINE | ID: mdl-30929347

RESUMO

Objective: To explore the preventive effect and possible molecular mechanism of dietary supplementation of N-carbamylglutamate (NCG) in the implantation of carbon disulfide (CS(2)) into embryo implantation disorders. Methods: embryo implantation disorder model was established by single intraperitoneal exposure to CS(2) on the 3rd, 4th, and 5th days after pregnancy. Endometrial tissues were collected for 24h after exposure to CS(2) for western-blot and immunohistochemical staining. Results: The number of embryo implantation was increased in NCG+CS(2) group, compared with CS(2) alone group. Day 4 of pregnancy when CS(2)-exposed after 24 h, the expression of pAKT protein in NCG+CS(2) group was significantly increased (P<0.05), the expression level of pAMPK protein in NCG+CS(2) group was significantly decreased, compared with CS(2) alone group, respectively. Immunohistochemical results showed that pAKT, pAMPK, AKT and AMPK proteins were expressed in luminal epithelial cells, glandular epithelial cells and stromal cells of endometrium; Day 4 of pregnancy when CS(2)-exposed after 24 h, deep staining of ATK and pAKT protein in NCG+CS(2) group, the AMPK and pAMPK protein staining became lighter. Conclusion: Dietary supplementation of NCG can interfere with the embryo loss induced by CS(2) by altering the total amount of AKT/AMPK molecules.


Assuntos
Dissulfeto de Carbono/toxicidade , Suplementos Nutricionais , Perda do Embrião/prevenção & controle , Ácido Glutâmico/uso terapêutico , Perda do Embrião/induzido quimicamente , Feminino , Humanos , Gravidez , Resultado do Tratamento
2.
Molecules ; 24(3)2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30754620

RESUMO

Radio-ligand therapy (RLT) with177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53⁻85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16⁻24 h, 36⁻48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6⁻60.7) for PGs, 31.4 h (12.2⁻80.6) for kidneys, 8.2 h (2.5⁻14.7) for RM and 40.1 h (31.6⁻79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33⁻2.63) for PGs, 0.70 mGy/MBq (0.26⁻1.07) for kidneys, 0.044 mGy/MBq (0.023⁻0.067) for RM and 0.04 mGy/MBq (0.02⁻0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.


Assuntos
Dipeptídeos/administração & dosagem , Ácido Glutâmico/administração & dosagem , Compostos Heterocíclicos com 1 Anel/administração & dosagem , Lutécio/administração & dosagem , Manitol/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Radioisótopos/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/química , Dipeptídeos/química , Dipeptídeos/farmacocinética , Ácido Glutâmico/uso terapêutico , Meia-Vida , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/farmacocinética , Humanos , Infusões Intravenosas , Rim/química , Lutécio/farmacocinética , Masculino , Manitol/uso terapêutico , Pessoa de Meia-Idade , Glândula Parótida/química , Estudos Prospectivos , Doses de Radiação , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Comprimidos/administração & dosagem
3.
Rev. neurol. (Ed. impr.) ; 67(10): 387-393, 16 nov., 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-175272

RESUMO

La esclerosis múltiple es una enfermedad inflamatoria que hasta el día de hoy afecta a la población del hemisferio norte, generando una gran carga socioeconómica. Uno de los síntomas menos favorables en este fenómeno patológico crónico es la fatiga. En esta revisión, sustentamos y favorecemos una alteración principal en el complejo del eje hipotálamo-hipófiso-adrenal y sus consecuencias fisiopatológicas, relacionadas mayormente con el glutamato y los niveles de cortisol. Trataremos de sustentar nuestra hipótesis en lo que se ha notificado hasta el momento, corroborando que las células inflamatorias liberan mayormente glutamato, una sustancia neurotóxica que conlleva un efecto desmielinizante y como resultado principal fatiga como síntoma. Cuando esta hipótesis se demuestre, podríamos trazar dianas terapéuticas para detener la liberación de glutamato en estas células inmunológicas, de manera que podamos evitar la fatiga en la esclerosis múltiple


Multiple sclerosis is an inflammatory disease, which still today affects the Northern-hemisphere population, generating a socioeconomically burden. One of the most unfavorable symptoms in this chronic disorder is fatigue. In this review, we favor and sustain a main alteration of the hypothalamus-pituitary-axis complex and its physiopathologic consequences, mostly related to glutamate and corticoid levels. We try to sustain our hypothesis in what is already reported, corroborating that the inflammatory cells release mainly glutamate, a neuro-toxic substance which leads to a demyelinating effect and as a main result fatigue as a symptom. When this hypothesis is demonstrated, we could trace therapeutic targets to stop the release of glutamate of these immunologic cells, in order to avoid fatigue in multiple sclerosis patients


Assuntos
Humanos , Ácido Glutâmico/uso terapêutico , Fadiga/complicações , Fadiga/etiologia , Esclerose Múltipla/diagnóstico por imagem , Imagem por Ressonância Magnética , Microglia
4.
Prax Kinderpsychol Kinderpsychiatr ; 66(7): 516-525, 2017 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-29557312

RESUMO

A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954 Glutamic acid was commonly used in the treatment of intellectually disabled children in the 50s. Koch reported first results of an observation of 140 children treated with glutamic acid in 1952. In this line is the multi-arm placebo-controlled study reported here. The original study protocols were available. 58 children with speech problems who attending a school of special needs received glutamic acid, or vitamin B, or St.-John's-wort. The effect of glutamic acid was in few cases an improvement of attention. On the other hand restlessness and stutter increased. The majority of all reported a weight loss. The treatment with vitamin B showed a positive effect concerning concentration. The treatment with St.-John's wort was stopped caused by headache and vomiting in eight of nine cases. The results of the study reported here are unpublished. The reason may be that until the 60s the effects of glutamic acid in the treatment of intellectually disabled children were in generally overestimated.


Assuntos
Ensaios Clínicos Controlados como Assunto/história , Ácido Glutâmico/história , Ácido Glutâmico/uso terapêutico , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/história , Fitoterapia/história , Extratos Vegetais/história , Extratos Vegetais/uso terapêutico , Gagueira/tratamento farmacológico , Gagueira/história , Complexo Vitamínico B/história , Complexo Vitamínico B/uso terapêutico , Criança , Alemanha , História do Século XX , Humanos , Hypericum
5.
J Neurosci ; 36(29): 7727-39, 2016 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-27445149

RESUMO

UNLABELLED: The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Ácido Glutâmico/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , 4-Aminopiridina/toxicidade , Adulto , Idoso , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Neoplasias Encefálicas/complicações , Modelos Animais de Doenças , Método Duplo-Cego , Feminino , Glioblastoma/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/toxicidade , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Resultado do Tratamento
6.
Clin Exp Pharmacol Physiol ; 43(10): 951-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27279457

RESUMO

This study determined the effects of glutamate on the Ca(2+) paradoxical heart, which is a model for Ca(2+) overload-induced injury during myocardial ischaemia and reperfusion, and evaluated its effect on a known mediator of injury, calpain. An isolated rat heart was retrogradely perfused in a Langendorff apparatus. Ca(2+) paradox was elicited via perfusion with a Ca(2+) -free Krebs-Henseleit (KH) solution for 3 minutes followed by Ca(2+) -containing normal KH solution for 30 minutes. The Ca(2+) paradoxical heart exhibited almost no viable tissue on triphenyltetrazolium chloride staining and markedly increased LDH release, caspase-3 activity, cytosolic cytochrome c content, and apoptotic index. These hearts also displayed significantly increased LVEDP and a disappearance of LVDP. Glutamate (5 and 20 mmol/L) significantly alleviated Ca(2+) paradox-induced injury. In contrast, 20 mmol/L mannitol had no effect on Ca(2+) paradox. Ca(2+) paradox significantly increased the extent of the translocation of µ-calpain to the sarcolemmal membrane and the proteolysis of α-fodrin, which suggests calpain activation. Glutamate also blocked these effects. A non-selective inhibitor of glutamate transporters, dl-TBOA (10 µmol/L), had no effect on control hearts, but it reversed glutamate-induced cardioprotection and reduction in calpain activity. Glutamate treatment significantly increased intracellular glutamate content in the Ca(2+) paradoxical heart, which was also blocked by dl-TBOA. We conclude that glutamate protects the heart against Ca(2+) overload-induced injury via glutamate transporters, and the inhibition of calpain activity is involved in this process.


Assuntos
Cálcio/toxicidade , Calpaína/antagonistas & inibidores , Calpaína/metabolismo , Cardiotônicos/uso terapêutico , Ácido Glutâmico/uso terapêutico , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Cálcio/metabolismo , Cardiotônicos/farmacologia , Ácido Glutâmico/farmacologia , Coração/efeitos dos fármacos , Coração/fisiologia , Masculino , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley
7.
Rev. neurol. (Ed. impr.) ; 62(11): 516-523, 1 jun., 2016. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-153771

RESUMO

Introducción. El temblor esencial es el trastorno del movimiento más frecuente en el adulto. Se ha considerado una enfermedad benigna, pero puede ocasionar una importante discapacidad física y psicosocial. El tratamiento farmacológico sigue siendo poco satisfactorio. Su etiología, fisiopatología y anatomía siguen sin conocerse del todo. Objetivo. El conocimiento de las bases neuroquímicas es fundamental para el desarrollo de terapias más eficaces. Se revisan los conocimientos actuales en este campo a fin de incentivar nuevas investigaciones e ideas que permitan mejorar la comprensión de la enfermedad y que fomenten el desarrollo de nuevas terapias farmacológicas. Desarrollo. Se revisan los trabajos realizados hasta la fecha en humanos y en modelos animales de neurotransmisores (ácido gamma-aminobutírico, glutamato, noradrenalina, serotonina, adenosina), proteínas y otros fenómenos neuroquí- micos, como los canales de calcio de tipo T en el temblor esencial. Conclusiones. Se han descrito cuatro disfunciones neuroquímicas que acontecerían básicamente en el cerebelo y el núcleo olivar inferior: alteración del sistema gabérgico, aumento del rebote postinhibitorio mediante corrientes de calcio de tipo T, disminución de los mecanismos de inhibición neuronal y aumento de la actividad de los neurotransmisores excitatorios. Estas disfunciones neuroquímicas comportarían un aumento de la actividad de las neuronas profundas cerebelosas con actividad oscilatoria, que se trasladaría al núcleo del tálamo y a la corteza motora, y comportarían la aparición del temblor. Son necesarios nuevos estudios para poder confirmar estas hipótesis y seguir avanzando para conseguir tratamientos farmacológicos más eficaces para los pacientes con temblor esencial (AU)


Introduction. Essential tremor is the most frequent movement disorder in adults. It has been considered a benign disease, but can result in significant physical and psychosocial disability. Pharmacological treatment is still not very satisfactory. Its causation, pathophysiology and anatomy remain only partially understood. Aims. An understanding of its neurochemical basis is essential to be able to develop more efficient therapies. We review what is currently known in this field in order to motivate further research and ideas that allow an enhanced understanding of the disease and which foster the development of new pharmacological therapies. Development. We review the studies conducted to date in humans and in animal models of neurotransmitters (gammaaminobutyric acid, glutamate, noradrenalin, serotonin, adenosine), proteins and other neurochemical phenomena, such as T-type calcium channels, in essential tremor. Conclusions. Four neurochemical dysfunctions have been described that basically occur in the cerebellum and the inferior olivary nucleus: alteration of the GABAergic system, increased post-inhibitory rebound via T-type calcium currents, decreased neuronal inhibition mechanisms and an increase in excitatory neurotransmitter activity. These neurochemical dysfunctions would involve an increase in the activity of the deep neurons of the cerebellum with an oscillatory activity that would shift to the thalamic nucleus and the motor cortex, which in turn would lead to the appearance of tremor. Further research is needed to be able to confirm these hypotheses and to continue to advance towards achieving more efficient pharmacological treatments for patients with essential tremor (AU)


Assuntos
Humanos , Animais , Masculino , Feminino , Tremor Essencial/complicações , Tremor Essencial/diagnóstico , Neuroquímica/métodos , Receptores de Neurotransmissores/uso terapêutico , Neurotransmissores/análise , Ácido gama-Aminobutírico/análise , Ácido Glutâmico/análise , Ácido Glutâmico/uso terapêutico , Serotonina/análise , Serotonina/uso terapêutico , Modelos Animais , Neuropatologia/métodos , Neuropatologia/tendências , Eletrofisiologia/métodos , Neuroimagem/métodos , Norepinefrina/uso terapêutico
8.
Adv Gerontol ; 29(1): 116-122, 2016.
Artigo em Russo | MEDLINE | ID: mdl-28423256

RESUMO

The effect of the 24-hour immobilization-painful stress on myocardial contractility of young (6-month), middle-aged (12-month) and old (24-month) female rats was studied. It was identified a reduction of the functional reserve of the heart, which showed a smaller growth rates of contraction and relaxation of the myocardium (+ dP/dt max and -dP/dt max), left ventricular pressure (LVP) and the maximum intensity of the functioning of the structures (MIFS) under increased pre- afterload and adrenergic stimulation of the heart, especially pronounced in the group of 24-month old rats. The animals of all ages treated before and after stressing glufimet in a dose 29 mg/kg, have higher rates of growth + dP/dt max, -dP/dt max, LVP and MIFS during load tests, most significant rates of growth are noticed in older rats compared with the young and middle-aged. Phenibut improves studied parameters equally at 6, 12 and 24-month old females, subjected to stress.


Assuntos
Cardiotônicos/uso terapêutico , Ácido Glutâmico/uso terapêutico , Animais , Feminino , Coração , Frequência Cardíaca , Contração Miocárdica , Miocárdio , Ratos
9.
Psych J ; 4(4): 226-30, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26663628

RESUMO

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a disease occurring when antibodies produced by the body's own immune system attack NMDA-type glutamate receptors in the brain. Most anti-NMDAR encephalitis cases are associated with paraneoplastic syndrome. We analyze the case of a 15-year-old girl who was hospitalized in a child psychiatry clinic in Riga, Latvia, with de novo acute polymorphic psychotic disorder gradually progressing to a catatonic state. The patient received antipsychotic and electroconvulsive therapy with no beneficial effect. The council of doctors discussed differential diagnoses of schizophrenia-induced catatonia and the autoimmune limbic encephalitis-induced catatonic condition. When the diagnosis of anti-NMDAR autoimmune encephalitis was finally confirmed by repeated immunological assays (specific immunoglobulin [Ig] G and IgM in her blood serum and cerebrospinal fluid), and a paraneoplastic process was ruled out, she was started on immunomodulating therapy (methylprednisolone, Ig, plasmapheresis, rituximab), which changed the course of her disease. On immunomodulating treatment, her physical and mental health have gradually improved to almost complete reconvalescence. Psychiatrists should consider anti-NMDAR encephalitis as a differential diagnosis in first-episode psychosis patients presenting with disorientation, disturbed consciousness, pronounced cognitive deficits, movement disorder, dysautonomia, or rapid deterioration, and test for specific IgG NR1 autoantibodies, even if there are no specific findings on routine neuroimaging, electroencephalography (EEG), or cerebrospinal fluid tests.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Transtornos Psicóticos/etiologia , Receptores de N-Metil-D-Aspartato/imunologia , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Autoanticorpos/sangue , Catatonia/diagnóstico , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Ácido Glutâmico/uso terapêutico , Humanos , Imunoglobulina G/uso terapêutico , Letônia , Receptores de Glutamato
10.
Bull Exp Biol Med ; 159(3): 365-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26212811

RESUMO

We studied in vitro and in vivo neuroprotective and antioxidant properties of neuroglutam, a new glutamic acid derivative. In experiments on immortalized mouse hippocampal cell line HT22, neuroglutam exhibited a neuroprotective effect in the model of oxidative stress after its introduction, both before and after H2O2. In vivo study on animals treated with neuroglutam against the background of cerebral ischemia modeled by irreversible occlusion of the common carotid arteries showed that plasma level of TBA-active products was significantly lower and activities of cell antioxidant enzymes (superoxide dismutase and catalase) were higher than in control animals receiving saline under the same conditions.


Assuntos
Antioxidantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Ácido Glutâmico/análogos & derivados , Ácido Glutâmico/uso terapêutico , Linhagem Celular , Humanos , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos
11.
Nutr Res ; 35(9): 774-83, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26144993

RESUMO

Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of γ-aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency-induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)-positive human osteoblast-like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER-ß messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal-regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER-ß mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells.


Assuntos
Estrogênios/deficiência , Ácido Glutâmico/uso terapêutico , Menopausa/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Receptores Estrogênicos/metabolismo , Vagina/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , Fosfatase Alcalina/sangue , Animais , Atrofia , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Proliferação de Células/efeitos dos fármacos , Estrogênios/sangue , Estrogênios não Esteroides/farmacologia , Estrogênios não Esteroides/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Ácido Glutâmico/farmacologia , Humanos , Antígeno Ki-67/metabolismo , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Obesidade/sangue , Obesidade/prevenção & controle , Osteoblastos/efeitos dos fármacos , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/metabolismo , Ovariectomia
12.
Pesqui. vet. bras ; 35(7): 691-699, jul. 2015. tab, graf
Artigo em Português | LILACS | ID: lil-766200

RESUMO

The aim of this study was to evaluate the effect of phytogenic additives and glutamine plus glutamic acid, associated or not, on histomorphometry of bursa of Fabricius and small intestine, oocyst count and lesion scores, and carbon turnover of duodenal mucosa of broiler chickens infected with Eimeria acervulina. A total of 450 male broiler chickens was distributed into a completely randomized design with six treatments and three replications. Treatments consisted of control diet (CD); CD + coccidiosis vaccine; CD + antibiotic performance enhancers and anticoccidial (APE/AC); CD + glutamine and glutamic acid (Gln/Glu); CD + phytogenic additives (PA); CD + Gln/Glu + PA. Birds on treatment CD + vaccine were vaccinated via drinking water at three days of age against coccidiosis. At 16 days of age all birds of all treatments were inoculated orally and individually with 500,000 oocysts of Eimeria acervulina. There was no treatment effect on lesion score in the intestinal epithelium of birds. The smaller number of excreted oocysts was observed in groups of birds fed diets containing APE/AC and PA. Were observed better results of villus height and crypt depth for duodenum and ileum of birds of treatments containing Gln/Glu at 7 days of age, and Gln/Glu and PA at 21 days of age. Higher percentage of cortical area from bursa follicles was observed in birds fed diets supplemented with Gln/Glu and PA at 7, 14 and 21 days of age. Increased turnover of intestinal mucosa was observed in treatments containing Gln/Glu, indicating acceleration in development and regeneration of damaged tissue. Glutamine plus glutamic acid and phytogenic additives can provide improvements to structure, and thus to intestinal function, as well as to better immune response against the infectious challenges. Phytogenic additives can be used for coccidiosis control of broiler chickens where the use of antibiotic performance enhancers and anticoccidials is prohibited...


O objetivo deste trabalho foi avaliar o efeito dos aditivos fitogênicos e da glutamina mais ácido glutâmico, associados ou não, sobre a histomorfometria da Bursa de Fabricius e intestino delgado, sobre contagem de oocistos e escores de lesão e sobre o turnover do carbono da mucosa intestinal de frangos de corte experimentalmente infectadas com Eimeria acervulina. Para isso foram utilizados 450 pintos de corte machos distribuídos em delineamento inteiramente casualisado, com seis tratamentos e três repetições. Os tratamentos consistiram de dieta controle (DC); DC + Vacina de coccidiose; DC + antibióticos melhoradores de desempenho e anticoccidiano (AMD/AC); DC + glutamina e ácido glutâmico (Gln/Glu); DC + sditivos fitogênicos (AFs); DC + Gln/Glu + AFs. As aves do tratamento DC + Vacina foram vacinadas via água de bebida, aos três dias de idade, contra coccidiose. Aos 16 dias de idade todas as aves de todos os tratamentos foram inoculadas oralmente e individualmente com 500.000 oocistos de Eimeria acervulina. Não houve efeito dos tratamentos para escore de lesão no epitélio intestinal das aves. O menor número de oocistos excretados foi observado nos grupos de aves alimentadas com dieta contendo AMD/AC e AFs. Foram observados melhores resultados para altura das vilosidades e profundidade das criptas do duodeno e ílio das aves dos tratamentos contendo Gln/Glu, aos 7 dias de idade e Gln/Glu e AFs aos 21 dias de idade. Maior porcentagem de área cortical dos folículos bursais foi observada em aves alimentadas com dieta suplementada com Gln/Glu e AFs aos 7, 14 e 21 dias de idade. Maior turnover da mucosa intestinal foi observada em aves dos tratamentos contendo Gln/Glu, indicando aceleração do desenvolvimento e regeneração do tecido lesado. Glutamina mais ácido glutâmico e aditivos fitogênicos podem oferecer melhorias à estrutura e, consequentemente, à função do intestino, bem como melhores condições para resposta imune frente à desafios infecciosos...


Assuntos
Animais , Ácido Glutâmico/uso terapêutico , Bolsa de Fabricius/anatomia & histologia , Galliformes/microbiologia , Glutamina/uso terapêutico , Contagem de Ovos de Parasitas/veterinária , Eimeria/parasitologia , Intestino Delgado/microbiologia , Mucosa Intestinal/lesões
13.
Acta Odontol Scand ; 73(8): 569-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25772193

RESUMO

OBJECTIVE: The purpose of this systematic review and meta-analysis was to evaluate the reliability of the Carisolv system with respect to drilling regarding the full removal of decayed hard tissues in primary dentition. A systematic review of the literature was conducted to identify controlled trails, randomized controlled trials and clinical trials that compared the Carisolv system to the traditional mechanical caries removal in the primary dentition. MATERIALS AND METHODS: The main relevant databases were searched: MEDLINE via PUBMED, Web of Science and SCOPUS. Complete caries removal, length of working time and need of local anesthesia were the outcomes evaluated. RESULTS: A total of 195 studies were identified and complete analysis of 28 studies was performed; finally, 10 papers were included. The trials included involved a total of 348 patients for 532 treated teeth. There was no significant difference in terms of clinical efficacy between the Carisolv and the rotary instrument (z = 0.68, p = 0.50), whereas the treatment with Carisolv was significantly longer in terms of time with respect to the rotary instruments (z = 10.49, p < 0.01). The chemo mechanical technique reduces the need for local anesthesia, with a difference between two types of treatment near to statistical significance (z = 1.91 p = 0.06). CONCLUSIONS: This systematic review indicates that the clinical efficacy of chemo-mechanical removal with Carisolv seems as reliable as the rotary instruments. However, the results should be interpreted cautiously due to the heterogeneity among study designs and to the shortage of available data. Further large-scale, well-designed randomized controlled trials are needed.


Assuntos
Cárie Dentária/terapia , Preparo da Cavidade Dentária/métodos , Ácido Glutâmico/uso terapêutico , Leucina/uso terapêutico , Lisina/uso terapêutico , Dente Decíduo/patologia , Anestesia Local , Preparo da Cavidade Dentária/instrumentação , Humanos , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
14.
Pediatr Blood Cancer ; 62(6): 1004-10, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25545757

RESUMO

BACKGROUND: Vincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known. PROCEDURE: We performed a randomized, placebo-controlled, double-blind trial of oral glutamic acid as a preventive agent in pediatric patients with cancer who would be receiving vincristine therapy for at least 9 consecutive weeks (Stratum 1 = Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2 = Acute lymphoblastic leukemia and non-Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity. RESULTS: Between 2007 and 2012, 250 patients were enrolled (Stratum 1 = 50, Stratum 2 = 200). The glutamic acid treated group did not have a significantly lower percentage of neurotoxicity compared to placebo treated group either overall or within stratum or age subgroups. The only subgroup which was suggestive of treatment effect was for age. Patients 13 years or older showed a larger benefit in favor of glutamic acid (P = 0.055) compared to patients less than 13 years (P = 1.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity. CONCLUSION: Vincristine-associated neurotoxicity in pediatric oncology remains a frequent complication of chemotherapy for multiple diagnoses with an approximate 30% of patients affected. Glutamic acid is not effective for prevention in pre-adolescents. There is a suggestion of benefit in patients 13 years or older, but the study was not designed to provide adequate power to test the treatment effect within this age group alone.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Ácido Glutâmico/uso terapêutico , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/prevenção & controle , Vincristina/efeitos adversos , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino
15.
Eur Arch Paediatr Dent ; 16(1): 19-26, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25391222

RESUMO

AIM: The aim of the study was to compare the efficacy of caries removal, time taken and to evaluate the pain threshold experienced by children during various caries removal methods. METHODS: One hundred and twenty patients aged between 4 and 14 years requiring dental restorations were selected. Caries removal was completed using an air-rotor, hand instruments, Carisolv and polymer burs. The efficacy, time taken and pain thresholds were evaluated during caries removal by Ericsson et al. scale, visual analogue scale and verbal pain scale, respectively. STATISTICAL ANALYSIS: Data was collected and statistically analysed using one-way analysis of variance followed by Post Hoc comparison by Bonferroni method. The skewed data was analysed amongst groups by applying Kruskal-Wallis test followed by probability adjustment by Mann-Whitney test. RESULT: These results indicated that the efficacy of caries removal was highest with air-rotor and was least by the hand instrument, whilst Carisolv® was least painful and the most time-consuming method. CONCLUSIONS: Caries removal with polymer burs and Carisolv were found to be as effective in caries removal and could be considered as alternatives to painful procedures as air-rotor in management of caries especially in children.


Assuntos
Cárie Dentária/terapia , Preparo da Cavidade Dentária/métodos , Adolescente , Criança , Pré-Escolar , Corantes , Preparo da Cavidade Dentária/instrumentação , Equipamentos Odontológicos de Alta Rotação , Materiais Dentários/química , Dentina/patologia , Desenho de Equipamento , Ácido Glutâmico/uso terapêutico , Humanos , Leucina/uso terapêutico , Lisina/uso terapêutico , Dente Molar/patologia , Medição da Dor/métodos , Limiar da Dor/fisiologia , Polímeros/química , Distribuição Aleatória , Fatores de Tempo , Dente Decíduo/patologia , Resultado do Tratamento
16.
J Adhes Dent ; 16(6): 507-16, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25516887

RESUMO

PURPOSE: To evaluate the effect of enzyme-based (Papacárie) and sodium-hypochlorite-based (Carisolv) chemomechanical caries removal methods on bonding of self-etching adhesives to caries-affected dentin, in comparison to the standard rotary-instrument caries removal method. MATERIALS AND METHODS: Seventy-eight carious permanent molars exhibiting frank cavitation into dentin were used. Forty-eight teeth were randomly divided into three groups, according to the caries excavation methods: (i) Papacárie, (ii) Carisolv and (iii) a round steel bur. After caries removal, each group was subdivided into two groups for two-step (Clearfil SE Bond) or one-step (Clearfil S3 Bond) self-etching adhesive application and resin composite buildups. Bonded specimens were sectioned into beams for microtensile bond strength testing. Bond strength data were analyzed using three-way ANOVA and Tukey's test. For interfacial nanoleakage evaluation using a field-emission scanning electron microscope, caries was similarly removed from the remaining thirty carious molars, bonding was performed as for bond strength testing, and the teeth were sectioned. RESULTS: RESULTS of three-way ANOVA revealed that bond strength was significantly affected by "adhesive" (p<0.001) and "dentin" (p<0.001), but not "caries excavation methods" (p>0.05). The bond strength of the two-step self-etching adhesive was significantly higher than that of the one-step self-etching adhesive (p<0.001). Conversely, the bond strength of self-etching adhesives to sound dentin was significantly higher than to residual caries-affected dentin (p<0.001). Greater silver penetration was observed in the bonded interfaces of residual caries-affected dentin and in interfaces bonded with the one-step self-etching adhesive vs those bonded with the two-step self-etching adhesive. CONCLUSION: Chemomechanical caries removal did not affect the bonding of self-etching adhesives to caries-affected dentin as compared to caries excavation with rotary instruments.


Assuntos
Colagem Dentária , Cárie Dentária/patologia , Preparo da Cavidade Dentária/métodos , Adesivos Dentinários/química , Dentina/ultraestrutura , Resinas Compostas/química , Preparo da Cavidade Dentária/instrumentação , Infiltração Dentária/classificação , Materiais Dentários/química , Restauração Dentária Permanente/métodos , Desenho de Equipamento , Ácido Glutâmico/uso terapêutico , Humanos , Leucina/uso terapêutico , Lisina/uso terapêutico , Teste de Materiais , Microscopia Eletrônica de Varredura , Dente Molar/ultraestrutura , Papaína/uso terapêutico , Cimentos de Resina/química , Coloração pela Prata , Estresse Mecânico , Resistência à Tração
17.
Actas esp. psiquiatr ; 42(5): 234-241, sept.-oct. 2014.
Artigo em Espanhol | IBECS | ID: ibc-128690

RESUMO

Actualmente se considera que tanto los síntomas positivos como en negativos de la esquizofrenia podrían deberse a una hipofunción glutamatérgica que tendría como consecuencia la alteración de la actividad de la neurotransmisión dopaminérgica. Concretamente, podría haber una disminución de la señalización glutamatérgica a nivel de los receptores NMDA, pero los agonistas directos de estos receptores no tienen utilidad clínica por ser inespecíficos y sus muchos efectos indeseables. Dados los problemas de falta de eficacia o de efectos secundarios que presentan los fármacos que actúan directamentesobre los receptores ionotrópicos y mGlu2-3, se han ensayado otros que actúan por otros mecanismos, especialmente indirectos, como es la administración co-agonistas de los receptores NMDA (glicina o D-serina), inhibidores del transportador de la glicina (sarcosina, Bitopertin), AMPAkinas (CX-516) y agonistas de los receptores mGlu5. Sin embargo, a pesar de los constantes fracasos, el enfoque glutamatérgico en el tratamiento de la esquizofrenia no está agotado y es necesario revisar todos los aspectos teóricos que relacionan estos mecanismos neuroquímicos con la compleja sintomatología esta patología hasta que logremos moléculas que sean realmente eficaces y que tengan un perfil de efectos secundarios aceptable


It is accepted that both positive and negative symptoms of schizophrenia may be due to hypofunction of glutamatergic pathways leading to altered dopaminergic neurotransmission activity. Specifically, there may be diminished glutamatergic signaling at the level of the NMDA receptors, but direct receptor agonists have no clinical utility due to their nonspecific actions and undesirable side effects. Given the problems of ineffectiveness or side effects of drugs that act directly on ionotropic and metabotropicmGlu2-3 receptors, clinical trials have been conducted with other drugs that have other mechanisms of action, especially indirect mechanisms, such as the co-administration of NMDA agonists (glycine or D-serine), glycine transporter inhibitors (sarcosine bitopertin), ampakines (CX-516), andmGlu5 receptor agonists. However, despite repeated failures, the glutamatergic approach to the treatment of schizophrenia has not been exhausted and all theoretical aspects that relate these complex neurochemical mechanisms with symptoms of schizophrenia should be reviewed until we find truly effective molecules with an acceptable side effect profile


Assuntos
Humanos , Masculino , Feminino , Ácido Glutâmico/uso terapêutico , Esquizofrenia/tratamento farmacológico , Receptores de Neurotransmissores/metabolismo , Neurotransmissores/metabolismo , Neurotransmissores/farmacocinética , N-Metilaspartato/uso terapêutico , Receptores de N-Metil-D-Aspartato/uso terapêutico , Glicina/uso terapêutico , Sarcosina/uso terapêutico , Neuroquímica/métodos , Neuroquímica/tendências
18.
J Endod ; 40(12): 1972-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25190603

RESUMO

INTRODUCTION: The aim of this study was to assess the effect on bacterial viability within dentinal tubules after the application of sodium hypochlorite (NaOCl)- or enzyme-based chemomechanical caries removal agents. METHODS: Twenty-five caries-free dentin discs prepared from 25 sound maxillary premolars were used. The discs were then infected with Streptococcus mutans suspension and randomly divided into the following 6 groups according to the dentin treatments: the negative control group: noninfected sound dentin discs, the positive control group: infected discs were left untreated; the NaOCl group: treated with 5% NaOCl solution, the chlorhexidine (CHX) group: 2% CHX solution, the Carisolv group: Carisolv gel (Medi Team Dentalutveckling AB, Savedalen, Sweden), and the Papacarie group: Papacarie gel (Formula & Acao, São Paulo, Brazil). All the agents were applied for 5 minutes. The dentin discs were fractured into 2 halves and stained with fluorescent LIVE/DEAD Stain (Molecular Probes, Eugene, OR). Each specimen was observed using confocal laser scanning microscopy at 5 different randomly selected sites. RESULTS: The results of 1-way analysis of variance revealed that 5% NaOCl solution achieved the highest intratubular antibacterial effect, whereas Carisolv gel had the lowest antibacterial effect (P < .05). No significant difference in antibacterial effect was observed between the Papacarie gel and 2% CHX solution (P > .05). CONCLUSIONS: The enzyme-based chemomechanical caries removal (Papacarie) was effective in the reduction of residual cariogenic bacteria in the dentinal tubules of coronal dentin.


Assuntos
Cárie Dentária/microbiologia , Preparo da Cavidade Dentária/métodos , Dentina/microbiologia , Viabilidade Microbiana/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Clorexidina/uso terapêutico , Cárie Dentária/terapia , Desinfetantes de Equipamento Odontológico/uso terapêutico , Corantes Fluorescentes , Géis , Ácido Glutâmico/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Leucina/uso terapêutico , Lisina/uso terapêutico , Teste de Materiais , Microscopia Confocal , Microscopia Eletrônica de Varredura , Papaína/uso terapêutico , Distribuição Aleatória , Hipoclorito de Sódio/uso terapêutico , Fatores de Tempo
19.
Actas Esp Psiquiatr ; 42(5): 234-41, 2014 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25179095

RESUMO

It is accepted that both positive and negative symptoms of schizophrenia may be due to hypofunction of glutamatergic pathways leading to altered dopaminergic neurotransmission activity. Specifically, there may be diminished glutamatergic signaling at the level of the NMDA receptors, but direct receptor agonists have no clinical utility due to their nonspecific actions and undesirable side effects. Given the problems of ineffectiveness or side effects of drugs that act directly on ionotropic and metabotropic mGlu2-3 receptors, clinical trials have been conducted with other drugs that have other mechanisms of action, especially indirect mechanisms, such as the co-administration of NMDA agonists (glycine or D-serine), glycine transporter inhibitors (sarcosine bitopertin), ampakines (CX-516), and mGlu5 receptor agonists. However, despite repeated failures, the glutamatergic approach to the treatment of schizophrenia has not been exhausted and all theoretical aspects that relate these complex neurochemical mechanisms with symptoms of schizophrenia should be reviewed until we find truly effective molecules with an acceptable side effect profile.


Assuntos
Antipsicóticos/uso terapêutico , Ácido Glutâmico/uso terapêutico , Receptores de Glutamato/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Antipsicóticos/farmacologia , Ácido Glutâmico/farmacologia , Humanos
20.
Braz Oral Res ; 282014.
Artigo em Inglês | MEDLINE | ID: mdl-25141016

RESUMO

The aim of this study was to compare the efficacy of chemochemical methods (Carisolv™ and Papacárie®) versus the manual method (excavators) in reducing the cariogenic microbiota in dentine caries of primary teeth. Forty-six healthy children (5 to 9 years old) having at least one primary tooth with a cavitated dentine carious lesion were included in the study. The teeth presented no clinical or radiographic signs of pulpal involvement. The sample of 74 teeth was randomly divided into three different groups: Papacárie® (n = 25), Carisolv™ (n = 27) and Manual (n = 22). Samples of carious and sound dentine were collected with sterile excavators before and after caries removal in the three groups. The dentine samples were transferred to glass tubes containing a 1mL thioglycollate medium used as a carrier and enriched for microbiological detection of mutans streptococci and Lactobacillus spp, after incubation for 6h at room temperature. The minimum detection value for colony forming units (CFU) was 3.3 x 102 CFU/ml, and the results were converted into scores from 0 to 4. A significant difference was observed in relation to the microbiological scores before and after caries removal for all methods (Wilcoxon test; p < 0.001). The use of chemomechanical methods for caries removal did not improve the reduction of cariogenic microorganisms in dentine caries lesions, in comparison with manual excavation.


Assuntos
Cárie Dentária/microbiologia , Cárie Dentária/terapia , Preparo da Cavidade Dentária/métodos , Ácido Glutâmico/uso terapêutico , Leucina/uso terapêutico , Lisina/uso terapêutico , Papaína/uso terapêutico , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Dentina/efeitos dos fármacos , Dentina/microbiologia , Feminino , Humanos , Lactobacillus/isolamento & purificação , Masculino , Estatísticas não Paramétricas , Streptococcus mutans/isolamento & purificação , Resultado do Tratamento
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