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1.
Semergen ; 50(4): 102172, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38160630

RESUMO

INTRODUCTION: Thyroid dysfunction during gestation impacts on maternal-fetal health and may influence the neurocognitive development of the child. Thyroid physiology changes during pregnancy and requires the establishment of specific reference levels per trimester and for each population and method. The objectives of our study were to analyse thyroid function throughout pregnancy and to establish reference levels for TSH and T4L in each trimester for our population and methodology. MATERIAL AND METHODS: Prospective analytical study of 598 pregnant women from March 2018 to October 2020. TSH, T4L, T3L, ATPO and ATG were determined in all of them. A total of 151 pregnant women were excluded due to positive thyroid immunity, previous thyroid disease in treatment with levothyroxine, twin pregnancy, diagnosis of hypothyroidism and hyperthyroidism in the request or absence of some of the parameters studied, with a reference population of 447 pregnant women. RESULTS: The reference levels for TSH were 0.07-3.14mIU/L for the first, 0.66-3.21mIU/L for the second and 0.52-2.97mIU/L for the third trimester. Reference levels for T4L were 0.81-1.19ng/dL for the first, 0.71-1.07ng/dL for the second and 0.69-1.06ng/dL for the third trimester. CONCLUSIONS: The reference levels for TSH and T4L obtained in this study differ from those used for the general population, which may have led to misclassification errors and unnecessary treatment in pregnant women.


Assuntos
Tireotropina , Tiroxina , Humanos , Feminino , Gravidez , Estudos Prospectivos , Adulto , Tireotropina/sangue , Valores de Referência , Tiroxina/sangue , Adulto Jovem , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/sangue , Hormônios Tireóideos/sangue , Trimestres da Gravidez , Testes de Função Tireóidea , Doenças da Glândula Tireoide/diagnóstico
2.
Neuroreport ; 34(1): 30-37, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36504039

RESUMO

OBJECTIVE: The aim of the current study was to evaluate the influence of HFD on the functionality of LepR by quantifying phosphorylated levels of 705Tyr-STAT3 in hippocampus astrocytes from mice that consumed an HFD either during the juvenile or the adult period. METHODS: Five- and eight-week-old male mice, fed during 8 weeks with either control chow or HFD, received a single dose of leptin and their brains were prepared for immunofluorescence to identify double-positive GFAP/p705Tyr-STAT3 cells. RESULTS: HFD intake led to increased pSTAT3 immunoreactivity in GFAP+ cells in the CA1/CA3 hippocampus areas. The effect was observed both in adolescent and adult mice. Leptin increased pSTAT3 immunoreactivity in control animals but was devoid of effect in HFD mice. HFD itself has no effect on the number of GFAP+ cells. CONCLUSIONS: Our data show that regular intake of HFD enhances STAT3 signaling in CA1/CA3 astrocytes, an effect that could be linked to the increase of leptin triggered by HFD. The increase of pSTAT3 might be integral to homeostatic mechanisms aimed at maintaining hippocampus function.


Assuntos
Astrócitos , Dieta Hiperlipídica , Masculino , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Fosforilação , Hipocampo , Encéfalo
3.
Psychoneuroendocrinology ; 133: 105429, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34624673

RESUMO

Consumption of high-fat diets (HFD) has been associated with neuronal plasticity deficits and cognitive disorders linked to the alteration of glutamatergic disorders in the hippocampus. As young individuals are especially vulnerable to the effects of nutrients and xenobiotics on cognition, we studied the effect of chronic consumption of saturated (SOLF) and unsaturated oil-enriched foods (UOLF) on: i) spatial memory; ii) hippocampal synaptic transmission and plasticity; and iii) gene expression of glutamatergic receptors and hormone receptors in the hippocampus of adolescent and adult mice. Our results show that both SOLF and UOLF impair spatial short-term memory. Accordingly, hippocampal synaptic plasticity mechanisms underlying memory, and gene expression of NMDA receptor subunits are modulated by both diets. On the other hand, PPARγ gene expression is specifically down-regulated in adolescent SOLF individuals and up-regulated in adult UOLF mice.


Assuntos
Dieta Hiperlipídica , Hipocampo , Receptores de N-Metil-D-Aspartato , Animais , Dieta Hiperlipídica/efeitos adversos , Gorduras Insaturadas/efeitos adversos , Ácidos Graxos/efeitos adversos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Camundongos , Plasticidade Neuronal/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo
4.
Neurobiol Learn Mem ; 123: 179-86, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26103137

RESUMO

The use of Lewis (LEW) together with Fischer-344 (F344) rats has been proposed as an addiction model because of the addiction behavior differences of these two strains. We have previously suggested that these differences could be related to learning and memory processes and that they depend on the genetic background of these two strains of rats. Adolescence is a period of active synaptic remodeling, plasticity and particular vulnerability to the effects of environmental insults such as drugs of abuse. We have evaluated spatial memory using novel location recognition in LEW and F344 adult rats undergoing a chronic treatment with cocaine during adolescence or adulthood. In order to study whether synaptic plasticity mechanisms were involved in the possible changes in learning after chronic cocaine treatment, we carried out electrophysiological experiments in hippocampal slices from treated animals. Our results showed that, in LEW cocaine-treated rats, hippocampal memory was only significantly impaired when the drug was administered during adolescence whereas adult administration did not produce any detrimental effect in spatial memory measured in this protocol. Moreover, F344 rats showed clear difficulties carrying out the protocol even in standard conditions, confirming the spatial memory problems observed in previous reports and demonstrating the genetic differences in spatial learning and memory. Our experiments show that the effects in behavioral experiments are related to synaptic plasticity mechanisms. Long-term depression induced by the glutamate agonist NMDA (LTD-NMDA) is partially abolished in cocaine-treated animals in hippocampal slices from LEW rats. Hippocampal LTD-NMDA is partially inhibited in F344 animals regardless of whether saline or cocaine administration, suggesting the lack of plasticity of this strain that could be related to the inability of these animals to carry out the novel object location protocol.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína/efeitos adversos , Hipocampo/metabolismo , Transtornos da Memória , Plasticidade Neuronal/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Fatores Etários , Animais , Comportamento Animal/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/complicações , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/metabolismo , Reconhecimento Psicológico
5.
Arch. Soc. Esp. Oftalmol ; 90(5): 206-211, mayo 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-137693

RESUMO

OBJETIVO: Presentar nuestra experiencia con la intubación monocanalicular autoestable Masterka, sin recuperación nasal, en la obstrucción lagrimal congénita en niños mayores de un año. MÉTODOS: Un total de 40 niños con edad media de 2,6 años (rango 1-7 años) fueron intervenidos de forma consecutiva. La sonda de Masterka incluye una guía metálica flexible dentro del tubo de silicona que la cubre totalmente hasta su extremo distal. El extremo proximal se ancla a punto lagrimal tras presionarlo con el terminal de un dilatador o pinza. Hubo monitorización y comprobación visual endoscópica de su correcta ubicación en tiempo real en todos los casos. RESULTADOS: El tiempo medio de maniobras quirúrgicas, excluyendo el tiempo anestésico, fue 1,56 min (rango 1,05-4). Los éxitos finales fueron un 97,5%, entendiéndolos como ausencia de epífora, la desaparición del colorante en menisco lagrimal y de secreción mucopurulenta. El tiempo medio de seguimiento fue 15 meses (rango 7-21). CONCLUSIONES: La intubación con Masterka es un tratamiento primario efectivo. No ofrece más dificultad que el sondaje simple, puesto que la técnica quirúrgica es similar, sin embargo sus resultados funcionales son mejores, evita la posibilidad de tener que repetir el sondaje y es más fácil de realizar que la intubación bicanalicular clásica, al no precisar manipulaciones repetidas ni tener que introducir instrumental quirúrgico en el meato inferior, simplificando el proceso


OBJECTIVE: To present our work with the Masterka self-adjusting monocanalicular intubation without nasal recuperation in congenital lacrimal obstruction in children over 12-months old. METHODS: A total of 40 children between the ages of one and seven (average age 2.6 years) were consecutively operated on. The Masterka catheter has a flexible metal guide inside the silicone tube that covers it completely. The proximal end is fixed onto the lacrimal punctum by pushing it with a dilator or forceps. Its correct position was monitored and visually checked in real time during surgery in all cases. RESULTS: The average surgery time, excluding anaesthetic, was 1.56 min, ranging from 1.05 to 4 min. The final success was 97.5%, considering absence of epiphora, disappearance of colouring in lacrimal meniscus, and mucopurulent secretion. The average follow-up time was 15 months (ranging from 7 to 21 months). CONCLUSIONS: Masterka intubation is an effective primary treatment. It is no more difficult than a simple catheter, since the surgical technique is similar, but with better functional results. It avoids the possibility of having to repeat the catheterization and it is easier to carry out than bicanalicular intubation, since there is no need to manipulate repeatedly or use surgical instruments in the inferior meatus, thus simplifying the process


Assuntos
Feminino , Humanos , Masculino , Intubação/instrumentação , Intubação/métodos , Obstrução dos Ductos Lacrimais/induzido quimicamente , Obstrução dos Ductos Lacrimais/metabolismo , Obstrução dos Ductos Lacrimais/patologia , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/metabolismo , Doenças da Laringe/patologia , Dacriocistite/metabolismo , Intubação/mortalidade , Intubação/enfermagem , Obstrução dos Ductos Lacrimais/complicações , Obstrução dos Ductos Lacrimais/diagnóstico , Obstrução dos Ductos Lacrimais/enfermagem , Doenças do Aparelho Lacrimal/complicações , Doenças do Aparelho Lacrimal/patologia , Doenças da Laringe/complicações , Dacriocistite/complicações
6.
Arch Soc Esp Oftalmol ; 90(5): 206-11, 2015 May.
Artigo em Espanhol | MEDLINE | ID: mdl-25616320

RESUMO

OBJECTIVE: To present our work with the Masterka self-adjusting monocanalicular intubation without nasal recuperation in congenital lacrimal obstruction in children over 12-months old. METHODS: A total of 40 children between the ages of one and seven (average age 2.6 years) were consecutively operated on. The Masterka catheter has a flexible metal guide inside the silicone tube that covers it completely. The proximal end is fixed onto the lacrimal punctum by pushing it with a dilator or forceps. Its correct position was monitored and visually checked in real time during surgery in all cases. RESULTS: The average surgery time, excluding anaesthetic, was 1.56min, ranging from 1.05 to 4min. The final success was 97.5%, considering absence of epiphora, disappearance of colouring in lacrimal meniscus, and mucopurulent secretion. The average follow-up time was 15 months (ranging from 7 to 21 months). CONCLUSIONS: Masterka intubation is an effective primary treatment. It is no more difficult than a simple catheter, since the surgical technique is similar, but with better functional results. It avoids the possibility of having to repeat the catheterization and it is easier to carry out than bicanalicular intubation, since there is no need to manipulate repeatedly or use surgical instruments in the inferior meatus, thus simplifying the process.


Assuntos
Dacriocistorinostomia/métodos , Intubação/métodos , Obstrução dos Ductos Lacrimais/terapia , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Humanos , Lactente , Intubação/instrumentação , Obstrução dos Ductos Lacrimais/congênito , Masculino , Ducto Nasolacrimal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
7.
Eur Neuropsychopharmacol ; 24(4): 621-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24268515

RESUMO

Cocaine addiction alters synaptic plasticity in many brain areas involved in learning and memory processes, including the hippocampus. Long-term potentiation (LTP) is one of the best studied examples of hippocampal synaptic plasticity and it is considered as one of the molecular basis of learning and memory. We previously demonstrated that in the presence of cocaine, a long lasting form of hippocampal LTP is induced by a single pulse of high frequency stimulation, which in normal conditions evokes only an early form of LTP. In this study, we further explore the molecular basis of this modulation of synaptic plasticity by cocaine. By performing pharmacological experiments on hippocampal slices, we were able to show that cocaine converts early LTP to a form of LTP dependent on protein synthesis, probably through the cAMP-dependent protein kinase and extracellular signal-regulated kinase signaling cascades. We also found that metabotropic glutamate receptors are involved in this phenomenon. These studies further clarify the molecular machinery used by cocaine to alter synaptic plasticity and modulate learning and memory processes.


Assuntos
Cocaína/farmacologia , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Modelos Neurológicos , Neurônios/efeitos dos fármacos , Psicotrópicos/farmacologia , Receptores de Glutamato Metabotrópico/agonistas , Animais , Cocaína/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Antagonistas de Dopamina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Técnicas In Vitro , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Psicotrópicos/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/metabolismo , Transmissão Sináptica/efeitos dos fármacos
8.
Neuroscience ; 187: 36-42, 2011 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-21565257

RESUMO

Lewis (LEW) and Fischer 344 (F344) rats differ in their response to drugs and are frequently used as an experimental model to study vulnerability to drug addiction. We have previously reported that significant differences in hippocampal synaptic plasticity exist between LEW and F344 rats after non-contingent chronic cocaine administration. However, given the several biochemical differences between contingent and non-contingent administration of drugs, we have studied here the possible genetic differences in synaptic plasticity after contingent cocaine self-administration. LEW and F344 animals self-administered cocaine (1 mg/kg i.v.) or saline under a fixed ratio 1 schedule of reinforcement for 20 days. After self-administration, electrophysiological experiments were carried out in which hippocampal slices were tetanized with three high frequency pulses in order to induce long-term potentiation (LTP). After a 20 min period of LTP stabilization, a train of low frequency stimulation (LFS; 900 pulses, 1 Hz) was applied to induce depotentiation of LTP. Data showed no differences between cocaine self-administered LEW or F344 rats in the induction of saturated-LTP compared to saline animals. LEW saline self-administered rats showed normal LTP depotentiation whereas cocaine self-administration impaired depotentiation in this rat strain. In the F344 strain, depotentiation of saturated-LTP was impaired both in saline and cocaine self-administered rats. The present results corroborate previous findings showing differences in basal hippocampal synaptic plasticity between LEW and F344 rats. These differences seem to modulate cocaine effects in a manner independent of contingency of drug administration.


Assuntos
Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Animais , Transtornos Relacionados ao Uso de Cocaína/genética , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/genética , Hipocampo/fisiologia , Potenciação de Longa Duração/genética , Depressão Sináptica de Longo Prazo/genética , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Autoadministração
9.
Neurobiol Learn Mem ; 95(1): 80-5, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21093599

RESUMO

It has been suggested that hyperglycemia and insulin resistance triggered by energy-dense diets can account for hippocampal damage and deficits of cognitive behaviour. We wonder if the impairment of learning and memory processes detected in diet-induced obese (DIO) mice is linked to diet composition itself. With this purpose we have evaluated learning performance in mice undergoing a short-term high-fat (HF) treatment, which leads to a pre-obese state characterized by increased adiposity without significant changes of glucose and insulin plasma levels. C57BL/6J mice were fed either a HF (45 kcal% from fat) or control diet (10 kcal% from fat) during 8 weeks. Learning performance was evaluated by using the four-arm baited version of the eight-arm radial maze test (RAM). Mice were trained to learn the RAM protocol and then memory was tested at different time-points. Time spent to consume food placed in baited arms and errors committed to find them were measured in all sessions. DIO mice significantly spent more time in learning the task and made a greater number of errors than controls. Moreover, retention tests revealed that both working and total memory errors were also more numerous in DIO mice. The current results show that short-term DIO impairs spatial learning and suggest that impairment of hippocampal learning elicited by HF diets might be perceptible before metabolic alterations linked to obesity develop.


Assuntos
Adiposidade/fisiologia , Dieta , Gorduras na Dieta , Aprendizagem em Labirinto/fisiologia , Obesidade/fisiopatologia , Comportamento Espacial/fisiologia , Análise de Variância , Animais , Peso Corporal/fisiologia , Ingestão de Alimentos/fisiologia , Insulina/sangue , Leptina/sangue , Masculino , Camundongos , Radioimunoensaio , Percepção Espacial/fisiologia
10.
Pharmacol Biochem Behav ; 93(4): 482-90, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19576923

RESUMO

Pubertal and adolescent exposure to cannabinoids is associated with enduring alterations in anxiety and memory. However, periadolescence virtually remains unexplored. Here, we measured anxiety in the Elevated Plus Maze (EPM) in adult Wistar rats treated at periadolescence (P28-P38) with the cannabinoid agonist CP 55,940 (CP) (0.4 mg/kg; 2 ml/kg i.p., 1 daily injection), and we also defined their recognition memory in the novel object paradigm and spatial learning and memory in the water maze. Additionally, we measured the expression of hippocampal PSA-NCAM (Polysialic Acid-Neural Cell Adhesion Molecule) and long-term potentiation (LTP) as well as, given their role in mnemonic processing, the levels of plasma corticosterone and estradiol. We found that CP had no robust effects on anxiety or in recognition memory. In the water maze, only a slight decreased percentage of failed trials in the reference memory task and an improvement in an indirect index of attention were observed. However, we detected an up-regulation of hippocampal PSA-NCAM expression, only in CP-males, although this effect was not related to changes in LTP. No hormonal alterations were evident. Based on our data, minimal long-term effects on anxiety, learning and memory appear to result from cannabinoid exposure during the periadolescent period.


Assuntos
Ansiedade/psicologia , Canabinoides/farmacologia , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Moléculas de Adesão de Célula Nervosa/biossíntese , Presenilina-1/biossíntese , Animais , Corticosterona/metabolismo , Sinais (Psicologia) , Cicloexanóis/farmacologia , Ensaio de Imunoadsorção Enzimática , Estradiol/metabolismo , Feminino , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
11.
Neuroscience ; 161(2): 342-6, 2009 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-19336250

RESUMO

Synaptic plasticity is considered a physiological substrate for learning and memory [Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84:87-136] that contributes to maladaptive learning in drug addiction [Schoenbaum G, Roesch MR, Stalnaker TA (2006) Orbitofrontal cortex, decision-making and drug addiction. Trends Neurosci 29:116-124]. Many studies have revealed that drug addiction has a strong hereditary component [Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35-69; Uhl GR (2004) Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. Neuropharmacology 47 (Suppl 1):140-147], however the contribution of the genetic background to drug-induced changes in synaptic plasticity has been scarcely studied. The present study reports on an analysis of long-term potentiation (LTP) and depotentiation in Lewis (LEW) and Fischer-344 (F344) rats, two inbred rat strains that show different proneness to drugs of abuse and are considered an experimental model of genetic vulnerability to addiction [Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35-69]. The induction of saturated-LTP was similar in LEW and F344 rats treated with saline or cocaine. However, only slices from LEW saline-treated rats showed the reversal of LTP; thus, the depotentiation of saturated-LTP was not observed in cocaine-injected LEW rats and in F344 animals (treated either with cocaine or saline). These results suggest significant differences in hippocampal synaptic plasticity between Lewis and Fischer 344 rats.


Assuntos
Potenciação de Longa Duração/genética , Sinapses/fisiologia , Animais , Transtornos Relacionados ao Uso de Cocaína/genética , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Hipocampo/fisiopatologia , Técnicas In Vitro , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Especificidade da Espécie
12.
Mol Cell Biol ; 28(15): 4665-74, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18541673

RESUMO

Annexin A1 is a member of a phospholipid and calcium binding family of proteins; it is involved in anti-inflammation and in the regulation of differentiation, proliferation, and apoptosis. Here, we show the existence of a functional binding site for the tumor suppressor p53 near the proximal CCAAT box and the fact that the basal expression of annexin A1 in human colon adenocarcinoma cells is driven by p53 at the transcriptional level. Posttranscriptional mechanisms may also play an important role in maintaining constitutive annexin A1 expression. In addition, a p53/NF-Y complex is detected bound to the p53 binding site on its promoter. Butyrate is a natural product of fiber degradation in the colon and a key regulator of colonic epithelium homeostasis. We show that butyrate, a class I and II histone deacetylase inhibitor, induces transcriptional activation of annexin A1 expression correlated with differentiation. The effect of butyrate is mediated through a release of NF-Y from the proximal CCAAT box and an enhancement of p53 binding. The interaction of p53 with the promoter is dependent on p38 MAPK activity either in the absence or in the presence of butyrate. Further, activation of p38 MAPK by this agent is required to increase annexin A1 promoter activity and to increase protein expression.


Assuntos
Anexina A1/genética , Butiratos/farmacologia , Fator de Ligação a CCAAT/metabolismo , Neoplasias do Colo/enzimologia , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Sequência de Bases , Sítios de Ligação , Biomarcadores Tumorais/metabolismo , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Ácidos Hidroxâmicos/farmacologia , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
13.
Psychopharmacology (Berl) ; 196(2): 303-13, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17940751

RESUMO

RATIONALE: Accumbal excitatory amino acid (EAA) transmission has been implicated in cocaine addiction. However, the time course effects of extinction of cocaine self-administration on EAAs are unknown. OBJECTIVES: The objective of this study was to define the time course of cocaine self-administration and extinction effects on glutamate and aspartate levels in the nucleus accumbens. MATERIALS AND METHODS: Rats were trained to self-administer cocaine for 20 days, and the levels of extracellular glutamate and aspartate were measured by in vivo microdialysis both during cocaine self-administration and after a priming cocaine injection at different time points after extinction (1, 5, or 10 days). A food-reinforced control group was also included in this study. Furthermore, the effect of acute i.v. cocaine administration (0, 1, 2, or 4 mg/kg) on glutamate and aspartate levels was also evaluated. RESULTS: At any of the dose tested, acute i.v. cocaine did not affect the levels of glutamate or aspartate in the Nacc. In contrast, glutamate levels were reduced in animals trained to self-administer cocaine, although they augmented substantially during a subsequent session of cocaine self-administration, and similar changes were not observed in food-reinforced controls. After 1 or 5, but not after 10 days of extinction, the glutamate levels were also reduced, and the ability of i.v. cocaine priming injections to increase glutamate levels followed a similar time course. These effects were specific, as aspartate levels were not affected by any administration protocol. CONCLUSIONS: These data suggest that glutamatergic transmission could be involved in the maintenance of cocaine self-administration and in the early phases of abstinence.


Assuntos
Ácido Aspártico/metabolismo , Cocaína/farmacologia , Extinção Psicológica/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/administração & dosagem , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Líquido Extracelular/química , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Feminino , Injeções Intravenosas , Masculino , Microdiálise/métodos , Núcleo Accumbens/metabolismo , Ratos , Ratos Endogâmicos Lew , Autoadministração/métodos , Fatores de Tempo
14.
Psychopharmacology (Berl) ; 195(1): 19-25, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17641875

RESUMO

RATIONALE: Long-term potentiation (LTP) is considered to be a cellular substrate of learning and memory. Indeed, the involvement of LTP-like mechanisms in spatial learning has consistently been demonstrated in the Morris water maze test. We have previously shown that hippocampal LTP in Lewis rats was modulated by cocaine self-administration, although the performance of cocaine-self-administered rats in the Morris water maze was not altered. OBJECTIVE: Given that the ease of the task previously used could have masked any possible effects of the cocaine-induced LTP enhancement on spatial learning, a new and more difficult water maze task was devised to address this issue. MATERIALS AND METHODS: Animals self-administered cocaine (1 mg/kg) or saline under a fixed ratio 1 schedule of reinforcement for 22 days. Spatial learning was assessed in a difficult water maze task (four sessions, two trials per session with a 90-min intertrial interval), and spatial memory was also evaluated 48 h after training (a 90-s test). Additionally, reversal learning and perseverance were also studied. RESULTS: There was a reduced latency in finding the hidden platform during training, as well as improved memory of the platform location in cocaine-self-administered rats with respect to animals that self-administered saline. No differences were observed in reversal learning or perseverance between groups. CONCLUSIONS: Our data suggest that cocaine self-administration facilitates learning and memory in the water maze test only when animals are submitted to highly demanding tasks, involving working memory or consolidation-like processes during the intertrial interval.


Assuntos
Cocaína/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Análise e Desempenho de Tarefas , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/administração & dosagem , Injeções Intravenosas , Masculino , Rememoração Mental/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Esquema de Reforço , Autoadministração/métodos , Comportamento Espacial/efeitos dos fármacos , Natação , Fatores de Tempo , Vasoconstritores/administração & dosagem , Vasoconstritores/farmacologia
15.
Toxicol In Vitro ; 21(2): 262-70, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17084582

RESUMO

The effect of butyrate has been analyzed on human colon adenocarcinoma cell lines with different properties regarding tumorigenicity, differentiation and resistance to apoptosis induced by this agent. Butyrate reduces cell proliferation, induces differentiation (according to alkaline phosphatase activity) and apoptosis, being these effects time- and concentration-dependent. The susceptibility to the cytotoxic effects of butyrate depends on the cell line considered and it is not directly related to tumorigenicity or differentiation. We show that 2mM butyrate treatment of non-tumorigenic BCS-TC2 cells for four days strongly influences the transcriptional activity, causing extensive modification in gene expression patterns (69 up-regulated and 109 down-regulated genes). Some of these genes are involved in the modulation of cell cycle progression, apoptosis and differentiation. We have analyzed the effect of butyrate in spontaneous or induced multicellular spheroids. The more stable spheroids (spontaneous or induced from butyrate-resistant cells) increase the resistance of cells to the effects of butyrate probably due to an impaired accessibility. This in vitro model could be useful to study the resistance of tumors to the effect of natural regulators (i.e. butyrate) as well as to develop and test new therapeutic approaches.


Assuntos
Adenocarcinoma/tratamento farmacológico , Butiratos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Fosfatase Alcalina/metabolismo , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Perfilação da Expressão Gênica , Humanos , Esferoides Celulares
16.
Toxicol In Vitro ; 21(2): 254-61, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17084587

RESUMO

Butyrate, naturally produced by anaerobic fermentation of diet-fiber, is the major nutrient of colonocytes and also an important regulator of colonic epithelium renewal and physiology. Other luminal components, such as bile acids or bacterial products, influence these processes. The model system we used to analyze the influence of several luminal stressors is composed of a previously established cell line resistant to the apoptotic effects of butyrate and their parental butyrate-sensitive cells. Viability of butyrate-resistant cells is unaffected by mild heat-shock (2h, 42 degrees C) and only slightly reduced by severe heat-shock (2h, 45 degrees C) in contrast to their butyrate-sensitive counterparts. The higher constitutive expression of HSP70 and HSP60 could contribute to this resistance. In addition, expression of HSP70 follows a different pattern after heat-shock in both cell lines. Butyrate-resistant cells are quite unaffected by treatment with deoxycholic acid but apoptosis is induced by chenodeoxycholic acid although to a lower extent than in butyrate-sensitive cells. These resistant cells are also less sensitive to lipopolysaccharide and show differences regarding the activation of ERK following osmotic stress. Thus, the cell model herein reported is a useful tool for investigating the molecular mechanisms of resistance to apoptosis, as well as to analyze specific targets for butyrate-resistant tumors.


Assuntos
Adenocarcinoma/tratamento farmacológico , Butiratos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Ácidos e Sais Biliares/farmacologia , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Resistencia a Medicamentos Antineoplásicos , Proteínas de Choque Térmico/biossíntese , Humanos , Lipopolissacarídeos/farmacologia , Pressão Osmótica , Estresse Fisiológico
17.
Ann N Y Acad Sci ; 1074: 427-37, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17105941

RESUMO

Previously, we have shown that long-term potentiation (LTP) in hippocampus of Lewis rats was significantly modulated by cocaine self-administration. Using a single train of high-frequency stimulation of 100 Hz for 1s (HFS), we found an enhancement of LTP after cocaine self-administration that was maintained even during the extinction of this behavior. However, the effects of cocaine self-administration on a hippocampal-dependent spatial learning task were unknown. Therefore, in the present study our first objective was to analyze if cocaine self-administration might affect the performance in a hippocampus-dependent task, such as the Morris water maze test. Male adult Lewis (LEW) rats self-administered cocaine (1 mg/kg/injection) or saline (0.9% NaCl) for 3 weeks. Three hours after finishing the last self-administration session, animals were submitted to Morris water maze training for 3 consecutives days. A memory test was carried out 24 h after the last training session. No significant differences were found in escape latencies and time spent in the quadrant where the platform was located during training. Given that we did not find any cocaine effect on this spatial learning task, our second objective was to estimate indirectly if brain cocaine levels have failed to modulate LTP in animals that were performing the water maze trials. To this end, we tested if cocaine application to hippocampal slices of naïve subjects was able to evoke LTP. The results indicated that cocaine produced an enhanced LTP in these hippocampal slices. Taking together, the results of the present study suggest that hippocampal LTP-like processes generated after cocaine self-administration are not related to spatial learning hippocampal-dependent tasks, such as the water maze test.


Assuntos
Cocaína/administração & dosagem , Hipocampo/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Comportamento Animal , Masculino , Plasticidade Neuronal , Ratos , Ratos Endogâmicos Lew , Autoadministração , Água
18.
An Pediatr (Barc) ; 65(2): 123-8, 2006 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-16948975

RESUMO

OBJECTIVE: To determinate the chief complaints in neonates presenting to a pediatric emergency service and their management. MATERIAL AND METHODS: We performed a retrospective study of patients younger than 28 days old who presented to the pediatric emergency department in 2003. Patients directly admitted to the neonatal unit and those attended by the surgery and orthopedic surgery departments were excluded. Information on sex, age, time and date, waiting time, visit duration, source of referral, presenting complaint, complementary examinations, final diagnosis, and hospital admission were analyzed. RESULTS: There were 1,481 neonatal visits. The mean chronological age was 15.8 days and 57.3 % were boys. Visits were most frequent on Fridays, evening shifts, and in July and December. The most frequent chief complaints were crying/irritability (16.3 %), fever (13.6 %), vomiting (11 %), and influenza (10.8 %). The most frequent final diagnoses were feeding problems (12.6 %), infantile colic (12.4 %), and upper respiratory tract infections (12 %). No abnormalities were detected in 11.7 % of the patients and complementary examinations were not required in 45.9 %. The admission rate was 26 %, most commonly due to fever and bronchiolitis. CONCLUSIONS: Many visits were due to minor problems that did not require complementary examinations and could have been resolved in primary care. Because of the greater vulnerability of this age group, thorough investigation is required to rule out severe disease. This phenomenon was reflected by the large number of complementary examinations and admissions.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Doenças do Recém-Nascido/terapia , Hospitais Pediátricos , Humanos , Recém-Nascido , Estudos Retrospectivos
19.
An. pediatr. (2003, Ed. impr.) ; 65(2): 123-128, ago. 2006. ilus, tab
Artigo em Es | IBECS | ID: ibc-050838

RESUMO

Objetivo Conocer qué problemas motivan las consultas de neonatos a un servicio de urgencias y determinar las características de la atención que se les ofrece. Material y métodos Revisión retrospectiva de los informes de urgencias de los neonatos atendidos durante el año 2003. Se excluyen los pacientes que ingresaron directamente en el Servicio de Neonatología y los atendidos por las secciones de Cirugía y Traumatología. Se analizan edad, sexo, hora y fecha de llegada, tiempo de espera y asistencia, derivación por otro médico/centro, motivo de consulta, exploraciones complementarias, diagnóstico final y destino del paciente. Resultados Se realizaron 1.481 visitas, con edad media de 15,8 días. El 53,7 % eran varones. La mayor presión asistencial se registró en viernes, en el turno de tarde y en los meses de julio y diciembre. El principal motivo de consulta fue llanto/irritabilidad (16,3 %), seguido de fiebre (13,6 %), vómitos (11 %) y cuadro catarral (10,8 %). Los diagnósticos más frecuentes fueron: dudas de puericultura (12,6 %), cólico del lactante (12,4 %) e infección de vías respiratorias altas (12 %). En el 11,7 % de los casos no se objetivó ninguna patología y el 45,9 % no precisó exploraciones complementarias. La proporción de ingresos fue del 26 %, principalmente por fiebre sin foco y bronquiolitis. Conclusiones Muchas consultas corresponden a patología menor que no precisan exploraciones complementarias y podrían ser resueltas en centros de atención primaria. La alta vulnerabilidad de la etapa neonatal requiere de una valoración minuciosa por la posibilidad de procesos graves, dato reflejado en la elevada proporción de pruebas diagnósticas e ingresos


Objective To determinate the chief complaints in neonates presenting to a pediatric emergency service and their management. Material and methods We performed a retrospective study of patients younger than 28 days old who presented to the pediatric emergency department in 2003. Patients directly admitted to the neonatal unit and those attended by the surgery and orthopedic surgery departments were excluded. Information on sex, age, time and date, waiting time, visit duration, source of referral, presenting complaint, complementary examinations, final diagnosis, and hospital admission were analyzed. Results There were 1,481 neonatal visits. The mean chronological age was 15.8 days and 57.3 % were boys. Visits were most frequent on Fridays, evening shifts, and in July and December. The most frequent chief complaints were crying/irritability (16.3 %), fever (13.6 %), vomiting (11 %), and influenza (10.8 %). The most frequent final diagnoses were feeding problems (12.6 %), infantile colic (12.4 %), and upper respiratory tract infections (12 %). No abnormalities were detected in 11.7 % of the patients and complementary examinations were not required in 45.9 %. The admission rate was 26 %, most commonly due to fever and bronchiolitis. Conclusions Many visits were due to minor problems that did not require complementary examinations and could have been resolved in primary care. Because of the greater vulnerability of this age group, thorough investigation is required to rule out severe disease. This phenomenon was reflected by the large number of complementary examinations and admissions


Assuntos
Recém-Nascido , Humanos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Doenças do Recém-Nascido/terapia , Hospitais Pediátricos , Estudos Retrospectivos
20.
Acta Biomater ; 2(4): 445-55, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16765884

RESUMO

Vitreous coatings of the SiO(2)-CaO system have been prepared on Ti6Al4V substrates by the sol-gel method. The textural parameters (porosity and roughness) and thickness of the films obtained increase when the concentration of the precursor solutions is raised. In vitro studies of these coatings have been performed using two approaches: soaking in simulated body fluid, and by growing osteoblasts on these materials. The results of both studies show differences in terms of chemical reactivity. While in simulated body fluid the coatings were dissolved without forming a bioactive surface, when osteoblast-like cells grew on the coatings they were more stable. Furthermore, cell culture assays show biocompatible behavior of these coatings making them of potential interest for clinical applications. The effect of the textural parameters of the obtained coatings on the cell functions (attachment, spreading, proliferation and differentiation) has also been studied. The results show an increase in these cell parameters as the roughness and porosity of the coatings increase.


Assuntos
Líquidos Corporais/química , Compostos de Cálcio/química , Materiais Revestidos Biocompatíveis/química , Simulação por Computador , Vidro/química , Osteoblastos/metabolismo , Óxidos/química , Titânio/química , Fosfatase Alcalina/análise , Fosfatase Alcalina/metabolismo , Ligas , Biomarcadores/metabolismo , Adesão Celular , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Materiais Revestidos Biocompatíveis/síntese química , Humanos , Cinética , Osteoblastos/citologia , Osteoblastos/enzimologia , Osteoblastos/fisiologia , Osteoblastos/ultraestrutura , Difração de Raios X
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