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1.
Neurosci Biobehav Rev ; 107: 492-504, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31163206

RESUMO

Increasing evidence suggests that childhood trauma (CT) is a major risk factor for schizophrenia but the underpinning mechanisms of their association remain unclear. Our aim is to review the literature on the association between CT and brain imaging measurements in adult schizophrenia subjects. We conducted a systematic review of the existing neuroimaging literature on CT and schizophrenia. We reviewed studies considering adult subjects with schizophrenia, schizoaffective disorder or first episode schizophrenia. A total of 15 studies were included. The most replicated result was the association in schizophrenia patients between CT and decreased total cerebral grey matter, particularly in the prefrontal cortex. In addition, studies suggest a different sensitivity to early stressors between schizophrenia subjects, their sibling and healthy unrelated subjects. In schizophrenia, CT is associated with alterations of white matter integrity in the inferior and superior longitudinal fasciculus, the inferior fronto-occipital fasciculus and the forceps major. Functional connectivity studies suggest an association between CT and a network including the amygdala, the anterior cingulate cortex, the precuneus/posterior cingulate cortex region and the temporo-parietal junction.

2.
PLoS One ; 14(1): e0210150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30615647

RESUMO

Male condoms are important to prevent transmission of HIV (and other STIs) and unwanted pregnancies. Research was conducted to evaluate the quality of male condoms available in the Dominican Republic market based on preliminary concerns of suspect product. Based on international testing standards (ISO 4074 and ASTM D 3492-08), condoms were sampled across ten prominent brands within the market and evaluated for airburst pressure / volume, freedom from holes, visual defects, package seal integrity, packaging and marking, lubricant quantity, and dimensions. Five of the brands were found to have extensive quality problems, where holes were found in 5.7% to 17.5% of the condoms (depending on the brand). Between 5.1% and 30.5% of these condoms failed to meet the requirements for airburst properties, and violations in regulatory labeling where observed. Three additional brands were compliant for the other tests, but were found to have the same challenges with labeling violations as the previous five brands. Two brands were found to be fully compliant with all aspects of the evaluation. The level of defects observed in these samples would greatly increase the risk of HIV transmission (and other STIs) and unwanted pregnancies. When projected on the annual market of male condoms sold in the Dominican Republic (~26 million), potentially over 1 million condoms could be estimated to adversely impact the health risk of the end-user. These results prompted action by the Dominican Republic regulatory authorities to investigate and remove poor quality product from the market. This research study emphasizes the need for continued vigilance towards increased regulatory and market surveillance efforts to better protect public health interests.


Assuntos
Preservativos/normas , Anticoncepção/instrumentação , Vigilância de Produtos Comercializados/normas , Controle de Qualidade , Doenças Sexualmente Transmissíveis/prevenção & controle , República Dominicana , Humanos , Cooperação Internacional , Látex , Masculino , Doenças Sexualmente Transmissíveis/transmissão , Estados Unidos , United States Agency for International Development
3.
Appetite ; 128: 242-254, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29906489

RESUMO

Every day, people are exposed to images of appetizing foods that can lead to high-calorie intake and contribute to overweight and obesity. Research has documented that manipulating the visual perspective from which eating is viewed helps resist temptation by altering the appraisal of unhealthy foods. However, the neural basis of this effect has not yet been examined using neuroimaging methods. Moreover, it is not known whether the benefits of this strategy can be observed when people, especially overweight, are not explicitly asked to imagine themselves eating. Last, it remains to be investigated if visual perspective could be used to promote healthy foods. The present work manipulated camera angles and tested whether visual perspective modulates activity in brain regions associated with taste and reward processing while participants watch videos featuring a hand grasping (unhealthy or healthy) foods from a plate during functional magnetic resonance imagining (fMRI). The plate was filmed from the perspective of the participant (first-person perspective; 1PP), or from a frontal view as if watching someone else eating (third-person perspective; 3PP). Our findings reveal that merely viewing unhealthy food cues from a 1PP (vs. 3PP) increases activity in brain regions that underlie representations of rewarding (appetitive) experiences (amygdala) and food intake (superior parietal gyrus). Additionally, our results show that ventral striatal activity is positively correlated with body mass index (BMI) during exposure to unhealthy foods from a 1PP (vs. 3PP). These findings suggest that unhealthy foods should be promoted through third-person (video) images to weaken the reward associated with their simulated consumption, especially amongst overweight people. It appears however that, as such, manipulating visual perspective fails to enhance the perception of healthy foods. Their promotion thus requires complementary solutions.


Assuntos
Dieta Saudável/psicologia , Ingestão de Alimentos/psicologia , Comportamento Alimentar/psicologia , Percepção Gustatória/fisiologia , Percepção Visual/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Sinais (Psicologia) , Feminino , Humanos , Imaginação , Imagem por Ressonância Magnética , Masculino , Estimulação Luminosa/métodos , Recompensa
4.
Soc Cogn Affect Neurosci ; 13(4): 381-390, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29069508

RESUMO

Functional dysconnection is increasingly recognized as a core pathological feature in schizophrenia. Aberrant interactions between regions of the cortico-limbic circuit may underpin the abnormal emotional processing associated with this illness. We used a functional magnetic resonance imaging (fMRI) paradigm designed to dissociate the various components of the cortico-limbic circuit (i.e. a ventral automatic circuit that is intertwined with a dorsal cognitive circuit), in order to explore bottom-up appraisal as well as top-down control during emotion processing. In schizophrenia patients compared to healthy controls, bottom-up processes were associated with reduced interaction between the amygdala and both the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). Contrariwise, top-down control processes led to stronger connectivity between the ventral affective and the dorsal cognitive circuits, i.e. heightened interactions between the ventral ACC and the DLPFC as well as between dorsal and ventral ACC. These findings offer a comprehensive view of the cortico-limbic dysfunction in schizophrenia. They confirm previous results of impaired propagation of information between the amygdala and the prefrontal cortex and suggest a defective functional segregation in the dorsal cognitive part of the cortico-limbic circuit.

5.
NPJ Schizophr ; 3(1): 25, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28883405

RESUMO

Hundreds of genetic loci participate to schizophrenia liability. It is also known that impaired cerebral connectivity is directly related to the cognitive and affective disturbances in schizophrenia. How genetic susceptibility and brain neural networks interact to specify a pathological phenotype in schizophrenia remains elusive. Imaging genetics, highlighting brain variations, has proven effective to establish links between vulnerability loci and associated clinical traits. As previous imaging genetics works in schizophrenia have essentially focused on structural DNA variants, these findings could be blurred by epigenetic mechanisms taking place during gene expression. We explored the meaningful links between genetic data from peripheral blood tissues on one hand, and regional brain reactivity to emotion task assayed by blood oxygen level-dependent functional magnetic resonance imaging on the other hand, in schizophrenia patients and matched healthy volunteers. We applied Sparse Generalized Canonical Correlation Analysis to identify joint signals between two blocks of variables: (i) the transcriptional expression of 33 candidate genes, and (ii) the blood oxygen level-dependent activity in 16 region of interest. Results suggested that peripheral transcriptional expression is related to brain imaging variations through a sequential pathway, ending with the schizophrenia phenotype. Generalization of such an approach to larger data sets should thus help in outlining the pathways involved in psychiatric illnesses such as schizophrenia. IMAGING: SEARCHING FOR LINKS TO AID DIAGNOSIS: Researchers explore links between the expression of genes associated with schizophrenia in blood cells and variations in brain activity during emotion processing. El Chérif Ibrahim and Eric Fakra at Aix-Marseille Université, France, and colleagues have developed a method to relate the expression levels of 33 schizophrenia susceptibility genes in blood cells and functional magnetic resonance imaging (fMRI) data obtained as individuals carry out a task that triggers emotional responses. Although they found no significant differences in the expression of genes between the 26 patients with schizophrenia and 26 healthy controls they examined, variations in activity in the superior temporal gyrus were strongly linked to schizophrenia-associated gene expression and presence of disease. Similar analyses of larger data sets will shed further light on the relationship between peripheral molecular changes and disease-related behaviors and ultimately, aid the diagnosis of neuropsychiatric disease.

6.
Psychiatry Res Neuroimaging ; 266: 146-152, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28667881

RESUMO

Recovery of stress-induced structural alterations in Posttraumatic Stress Disorder (PTSD) remains largely unexplored. This study aimed to determine whether symptoms improvement is associated with grey matter (GM) density changes of brain structures involved in PTSD. Two groups of PTSD patients were involved in this study. The first group was treated with Eye Movement Desensitization and Reprocessing (EMDR) therapy and recovered from their symptoms (recovery group) (n = 11); Patients were scanned prior to therapy (T1), one week (T2) and five months after the end of therapy (T3). The second group included patients which followed a supportive therapy and remained symptomatic (wait-list group) (n = 7). They were scanned at three time-steps mimicking the same inter-scan intervals. Voxel-based morphometry (VBM) was used to characterize GM density evolution. GM density values showed a significant group-by-time interaction effect between T1 and T3 in prefrontal cortex areas. These interaction effects were driven by a GM density increase in the recovery group with respect to the wait-list group. Symptoms removal goes hand-in-hand with GM density enhancement of structures involved in emotional regulation.


Assuntos
Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Avaliação de Resultados em Cuidados de Saúde , Córtex Pré-Frontal/patologia , Transtornos de Estresse Pós-Traumáticos , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/patologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto Jovem
7.
Schizophr Res ; 184: 69-72, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27979699

RESUMO

Childhood trauma strongly impacts emotional responses in schizophrenia. We have explored an association between early trauma and the amygdala functional connectivity using generalized psychophysiological interaction during an emotional task. Twenty-one schizophrenia patients and twenty-five controls were included. In schizophrenia patients, higher levels of sexual abuse and physical neglect during childhood were associated with decreased connectivity between the amygdala and the posterior cingulate/precuneus region. Additionally, patients showed decreased coupling between the amygdala and the posterior cingulate/precuneus region compared to controls. These findings suggest that early trauma could impact later connectivity in specific stress-related circuits affecting self-consciousness and social cognition in schizophrenia.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância , Tonsila do Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Conectoma/métodos , Emoções/fisiologia , Esquizofrenia/fisiopatologia , Adulto , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Tonsila do Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Reconhecimento Visual de Modelos/fisiologia , Adulto Jovem
8.
Contraception ; 92(4): 350-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26142619

RESUMO

OBJECTIVES: Measuring the amount of progestin remaining in contraceptive implants used for different lengths of time provides useful information on in vivo release kinetics including change over time. We compared estimated in vivo levonorgestrel (LNG) release rates derived from Sino-implant (II) explants with similar data from removed Jadelle. STUDY DESIGN: We measured LNG remaining in 44 sets of Sino-implant (II) used for up to 7 years and removed in four Chinese clinics. Results were compared with published data for Jadelle explants used for up to 36 months. We estimated and compared monthly and daily LNG release rates for the two products using prediction models for drug release. We also estimated the dissolution profile similarity factor, f2, for LNG release. RESULTS: Both Sino-implant (II) and Jadelle release approximately 30% of total LNG load after 3 years. Results of fitting the data to a biologically plausible modified Higuchi prediction model indicate comparable release through 3 years. An estimated similarity factor of 80.6 (90% confidence interval: 70.8-85.7) indicates similarity in the dissolution profiles of the two implants. CONCLUSIONS: LNG release in vivo measured through explant analysis suggest that Sino-implant (II) and Jadelle may perform similarly through 3 years of use and could remain highly effective beyond this time point. These results align with published data for Jadelle and Sino-implant (II) showing high effectiveness for 5 years. Ongoing clinical studies comparing the products over 5 years present an opportunity to verify this supportive measure of clinical effectiveness. IMPLICATIONS: This innovative approach provides evidence that Sino-implant (II) may perform clinically similarly to Jadelle over 3 years and remain a highly effective contraceptive beyond this time point. Data from explant analyses show promise for investigating the equivalence of elusion profiles of contraceptive implants.


Assuntos
Anticoncepcionais Femininos/farmacocinética , Levanogestrel/farmacocinética , Anticoncepcionais Femininos/administração & dosagem , Feminino , Humanos , Levanogestrel/administração & dosagem
9.
Hum Brain Mapp ; 36(6): 2207-14, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25664956

RESUMO

Converging evidence points to a link between anxiety proneness and altered emotional functioning, including threat-related biases in selective attention and higher susceptibility to emotionally ambiguous stimuli. However, during these complex emotional situations, it remains unclear how trait anxiety affects the engagement of the prefrontal emotional control system and particularly the anterior cingulate cortex (ACC), a core region at the intersection of the limbic and prefrontal systems. Using an emotional conflict task and functional magnetic resonance imaging (fMRI), we investigated in healthy subjects the relations between trait anxiety and both regional activity and functional connectivity (psychophysiological interaction) of the ACC. Higher levels of anxiety were associated with stronger task-related activation in ACC but with reduced functional connectivity between ACC and lateral prefrontal cortex (LPFC). These results support the hypothesis that when one is faced with emotionally incompatible information, anxiety leads to inefficient high-order control, characterized by insufficient ACC-LPFC functional coupling and increases, possibly compensatory, in activation of ACC. Our findings provide a deeper understanding of the pathophysiology of the neural circuitry underlying anxiety and may offer potential treatment markers for anxiety disorders.


Assuntos
Ansiedade/psicologia , Conflito Psicológico , Emoções/fisiologia , Personalidade/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Giro do Cíngulo/fisiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
10.
Contraception ; 87(4): 473-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22921687

RESUMO

BACKGROUND: The importance of the distribution of safe, effective and cost-effective pharmaceutical products in resource-constrained countries is the subject of increasing attention. FHI 360 has developed a program aimed at evaluating the quality of a contraceptive implant manufactured in China, while the product is being registered in an increasing number of countries and distributed by international procurement agencies. The program consists of (1) independent product testing; (2) ongoing evaluation of the manufacturing facility through audits and inspections; and (3) post-marketing surveillance. STUDY DESIGN: This article focuses on the laboratory testing of the product. The various test methods were chosen from the following test method compendia, the United States Pharmacopeia (USP), British Pharmacopeia (BP), International Organization for Standardization (ISO), the American Society for Testing and Materials (ASTM), or lot release tests mandated by Chinese regulatory requirements. Each manufactured lot is independently tested prior to its distribution to countries supported by this program. In addition, a more detailed annual testing program includes evaluation of the active ingredient (levonorgestrel), the final product and the packaging material. RESULTS: Over the first 4 years of this 5-year project, all tested lots met the established quality criteria. CONCLUSIONS: The quality assurance program developed for this contraceptive implant has helped ensure that a safe product was being introduced into developing country family planning programs. This program provides a template for establishing quality assurance programs for other cost-effective pharmaceutical products that have not yet received stringent regulatory approval and are being distributed in resource-poor settings.


Assuntos
Anticoncepcionais Femininos/normas , Levanogestrel/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , China , Anticoncepcionais Femininos/administração & dosagem , Levanogestrel/administração & dosagem , Vigilância de Produtos Comercializados , Reino Unido , Estados Unidos
11.
Regul Toxicol Pharmacol ; 56(2): 156-65, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19631709

RESUMO

This study investigated if quinacrine can induce a tumorigenic response in rats when administered in a manner similar to the intended human use for female non-surgical sterilization. Young sexually mature female rats received two doses of quinacrine (or 1% methylcellulose control) into each uterine horn approximately 21 days apart, and were observed for 23 months after the second dose administration. Dose levels were 0/0, 0/0, 10/10, 70/70, and 70/250-350 mg/kg (first dose/second dose), which represent local doses in the uterus at approximate multiples of 1x, 8x and 40x the human dose (mg quinacrine/g uterine weight) used for female non-surgical sterilization. Rats were observed for viability, clinical signs of toxicity, and changes in body weight and food consumption. At necropsy, selected organs were weighed, macroscopic observations were recorded, and tissues were collected, fixed, processed, and examined for microscopic pathologic findings. Acute quinacrine toxicity was evident during the dosing period but did not affect long-term survival. Non-neoplastic findings were more common in treated animals than controls, providing evidence of the appropriateness of the bioassay. The incidence of uncommon tumors of the reproductive tract was similar to controls at doses of 10/10mg/kg but increased with dose level and was significantly greater than controls at >or=70/70 mg/kg. We conclude that two doses of quinacrine administered approximately 21 days apart into the uterus of young sexually mature rats at a local dose approximately 8 times the human dose used for non-surgical female sterilization increased the lifetime risk of tumor development in the reproductive tract.


Assuntos
Longevidade , Quinacrina/administração & dosagem , Quinacrina/toxicidade , Neoplasias Uterinas/induzido quimicamente , Útero/efeitos dos fármacos , Fatores Etários , Animais , Relação Dose-Resposta a Droga , Tubas Uterinas/efeitos dos fármacos , Tubas Uterinas/patologia , Feminino , Ratos , Neoplasias Uterinas/patologia , Útero/patologia
13.
Int J Toxicol ; 25(2): 109-18, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16597549

RESUMO

Quinacrine is an acridine derivative under investigation for its use in nonsurgical female sterilization. Safety issues regarding the carcinogenic potential of quinacrine have been raised because it is mutagenic and clastogenic in vitro. The objective of the study was to evaluate the carcinogenic potential of quinacrine dihydrochloride (quinacrine) in neonatal mice treated with single intraperitoneal doses on postpartum days 8 and 15 and observed for 52 weeks. Neonatal Crl: CD-1 mice of each sex were randomly allocated into four treatment groups (0, 10, 50, and 150 mg/kg), dosed twice with quinacrine suspended in carboxymethylcellulose, observed for 52 weeks post dose, and then euthanized, necropsied, and subjected to a full histopathological examination. In male mice, tumor incidence was not significantly increased at any site at any dose level. In female mice, the incidence of benign uterine endometrial stromal polyps was slightly greater at the mid and high dose (> or = 50 mg/kg), as was the incidence of endometrial hyperplasia. The incidence of polyps in these groups was not significantly greater than in controls by pair-wise comparison but was significantly greater (p = .042) by the linear trend test. The authors conclude that quinacrine administered twice to neonatal mice may have enhanced or accelerated the development of endometrial hyperplasia and uterine stromal polyps at higher doses. Because uterine stromal polyps are a commonly observed benign tumor in older mice, the significance of this finding is unclear and will require a weight of evidence evaluation for a conclusion on the carcinogenic potential of quinacrine.


Assuntos
Quinacrina/toxicidade , Esterilização Reprodutiva/métodos , Animais , Animais Recém-Nascidos , Testes de Carcinogenicidade , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos
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