Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
1.
Org Biomol Chem ; 20(37): 7458-7466, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36094013

RESUMO

Herein, we introduce the first diphenylalanine dipeptide hydrogelator capped with the cinnamoyl functional group (Cin-L-F-L-F). We evaluate the effects of the cinnamoyl moiety on molecular self-assembly events and resultant physical properties of the hydrogel formed. In addition, we report our preliminary results of this dipeptide's cytotoxicity against glioblastoma (GBM) cancer cells.


Assuntos
Dipeptídeos , Hidrogéis , Dipeptídeos/química , Dipeptídeos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Fenilalanina/química , Fenilalanina/farmacologia
2.
Ann Oncol ; 30(12): 1925-1940, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31617564

RESUMO

BACKGROUND: Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. DESIGN: This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. RESULTS: Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. CONCLUSIONS: CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer.


Assuntos
Antineoplásicos/efeitos adversos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/epidemiologia , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Apolipoproteínas E/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Sobreviventes de Câncer , Catecol O-Metiltransferase/genética , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/genética , Disfunção Cognitiva/terapia , Citocinas/genética , Exercício Físico , Humanos , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/genética , Neurogênese/efeitos dos fármacos , Polimorfismo Genético , Qualidade de Vida
3.
BMC Anesthesiol ; 18(1): 96, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053804

RESUMO

BACKGROUND: Several hypnotic drugs have been previously identified as modulators of food intake, but exact mechanisms remain unknown. Feeding behavior implicates several neuronal populations in the hypothalamic arcuate nucleus including orexigenic neuropeptide Y and anorexigenic pro-opiomelanocortin producing neurons. The aim of this study was to investigate in mice the impact of different hypnotic drugs on food consumption and neuropeptide Y or pro-opiomelanocortine mRNA expression level in the hypothalamic arcuate nucleus. METHODS: Saline control, isoflurane, thiopental, midazolam or propofol were administered to C57Bl/6 mice. Feeding behavior was evaluated during 6 h. In situ hybridization of neuropeptide Y and pro-opiomelanocortine mRNAs in the hypothalamus brain region was also performed. Data were analyzed by Kruskal Wallis test and analysis of variance (p < 0.05). RESULTS: Midazolam, thiopental and propofol induced feeding behavior. Midazolam and thiopental increased neuropeptide Y mRNA level (respectively by 106 and 125%, p < 0.001) compared with control. Propofol and midazolam decreased pro-opiomelanocortine mRNA level by 31% (p < 0,01) compared with control. Isoflurane increased pro-opiomelanocortine mRNA level by 40% compared with control. CONCLUSION: In our murine model, most hypnotics induced food consumption. The hypnotic-induced regulation of neuropeptide Y and pro-opiomelanocortine hypothalamic peptides is associated with this finding. Our data suggest that administration of some hypnotic drugs may affect hypothalamic peptide precursor and neuropeptide expression and concomittantly modulate food intake. Thus, this questions the choice of anesthetics for better care management of patients undergoing major surgery or at risk of undernutrition.


Assuntos
Anestésicos/farmacologia , Núcleo Arqueado do Hipotálamo/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Neuropeptídeo Y/biossíntese , Pró-Opiomelanocortina/biossíntese , Animais , Masculino , Camundongos
4.
Neurochirurgie ; 62(2): 94-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26853800

RESUMO

PURPOSE: To assess long-term neurodevelopmental outcome in children with hydrocephalus requiring neurosurgical treatment during the neonatal period. METHODS: This prospective longitudinal population-based study included 43 children with neonatal shunted hydrocephalus. The 43 children were prospectively reviewed in the presence of their parents at the outpatient clinic. Cognitive and motor outcomes were assessed respectively using different Wechsler scales according to age and Gross Motor Function Classification System (GMFCS). Postoperative MRI was routinely performed. RESULTS: The mean gestational age at birth of the 43 consecutive children with neonatal hydrocephalus (sex ratio M/F: 1.39) was 34.5±5.4 weeks of gestation. At mean follow-up of 10.4±4 years, mean total IQ was 73±27.7, with equivalent results in mean verbal and mean performance IQ. Of the 33 children with IQ evaluation, 18 presented an IQ≥85 (41.9%). Efficiency in walking without a mobility device (GMFCS≤2) was obtained in 37 children (86%). Only severity of postoperative ventricular dilation was significantly associated with unfavorable outcome (Evans index>0.37; odds ratio: 0.16, P=0.03). CONCLUSION: This information could be provided to those families concerned who often experience anxiety when multi-disciplinary management of neonatal hydrocephalus is required.


Assuntos
Hidrocefalia/cirurgia , Doenças do Prematuro/cirurgia , Transtornos do Neurodesenvolvimento/etiologia , Complicações Pós-Operatórias/prevenção & controle , Derivação Ventriculoperitoneal , Ventriculostomia , Anormalidades Múltiplas , Neoplasias do Ventrículo Cerebral/complicações , Neoplasias do Ventrículo Cerebral/cirurgia , Feminino , Seguimentos , Idade Gestacional , Humanos , Hidrocefalia/complicações , Hidrocefalia/diagnóstico por imagem , Recém-Nascido , Recém-Nascido Prematuro , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/etiologia , Deficiência Intelectual/prevenção & controle , Imageamento por Ressonância Magnética , Masculino , Transtornos dos Movimentos/epidemiologia , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/prevenção & controle , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Neurochirurgie ; 62(1): 20-4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24210289

RESUMO

OBJECTIVES: Intracranial aneurysms are rare in children although giant aneurysms more commonly occur in adolescence. The aims of our study were to perform an extensive review of the literature over the past two decades and assess intracranial aneurysm management. METHODS: Based on a Pubmed search, we carried out a review of the literature from 1990 to 2012 regarding giant intracranial aneurysms diagnosed in the paediatric population. This descriptive study concerned clinical presentation, cerebral aneurysm characteristics, therapeutic management procedures and outcome. RESULTS: Forty-six cases were reported in 31 papers. The male/female sex ratio was 1.15, the clinical presentation was a tumour mass syndrome in 56.6%, followed by rupture in 30.4%. The aneurysm location was the posterior circulation in 41.3%, and microsurgical treatment (52.2%) predominated over endovascular coiling (28.3%). CONCLUSION: To date, no evidence-based medicine recommendation has been accepted for the management of rare intracranial aneurysms. Each reported patient was the object of a multidisciplinary clinical decision. Management of this challenging pathology should be performed on a case-to-case basis.


Assuntos
Angiografia Cerebral , Revascularização Cerebral , Embolização Terapêutica , Aneurisma Intracraniano/terapia , Procedimentos Neurocirúrgicos , Angiografia Cerebral/métodos , Revascularização Cerebral/métodos , Embolização Terapêutica/métodos , Humanos , Aneurisma Intracraniano/diagnóstico , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento
6.
Oncogene ; 34(39): 5080-94, 2015 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-25597409

RESUMO

Multiform glioblastomas (GBM) are the most frequent and aggressive primary brain tumors in adults. The poor prognosis is due to neo-angiogenesis and cellular invasion, processes that require complex chemotaxic mechanisms involving motility, migration and adhesion. Understanding these different cellular events implies identifying receptors and transduction pathways that lead to and promote either migration or adhesion. Here we establish that glioma express the vasoactive peptide urotensin II (UII) and its receptor UT and that UT-mediated signaling cascades are involved in glioma cell migration and adhesion. Components of the urotensinergic systems, UII and UT, are widely expressed in patient-derived GBM tissue sections, glioma cell lines and fresh biopsy explants. Interestingly, gradient concentrations of UII produced chemoattracting migratory/motility effects in glioma as well as HEK293 cells expressing human UT. These effects mainly involved the G13/Rho/rho kinase pathway while partially requiring Gi/o/PI3K components. In contrast, we observed that homogeneous concentrations of UII drastically blocked cell motility and stimulated cell-matrix adhesions through a UT/Gi/o signaling cascade, partially involving phosphatidylinositol-3 kinase. Finally, we provide evidence that, in glioma cells, homogeneous concentration of UII allowed translocation of Gα13 to the UT receptor at the plasma membrane and increased actin stress fibers, lamellipodia formation and vinculin-stained focal adhesions. UII also provoked a re-localization of UT precoupled to Gαi in filipodia and initiated integrin-stained focal points. Altogether, these findings suggest that UT behaves as a chemotaxic receptor, relaying a signaling switch between directional migration and cell adhesion under gradient or homogeneous concentrations, thereby redefining sequential mechanisms affecting tumor cells during glioma invasion. Taken together, our results allow us to propose a model in order to improve the design of compounds that demonstrate signaling bias for therapies that target specifically the Gi/o signaling pathway.


Assuntos
Neoplasias Encefálicas/metabolismo , Quimiotaxia , Glioblastoma/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Urotensinas/metabolismo , Actinas/metabolismo , Biópsia , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Humanos , Polimerização
7.
Ann Fr Anesth Reanim ; 33(4): 256-65, 2014 Apr.
Artigo em Francês | MEDLINE | ID: mdl-24631003

RESUMO

During stress, the relationship between the central nervous system and the immune system is essential to maintain homeostasis. The main neuroendocrine system involved in this interaction is the hypothalamic-pituitary-adrenal axis (HPA), which via the synthesis of glucocorticoids will modulate the intensity of the inflammatory response. Anaesthetic agents could be interacting with the HPA axis during surgery. Although etomidate currently remains in the center of the discussions, it seems, at least experimentally, that most hypnotics have the capacity to modulate the synthesis of adrenal steroids. Nevertheless, with the large literature on this subject, etomidate seems to be the most deleterious hypnotic agent on the HPA axis function. Its use should be limited when HPA axis is already altered.


Assuntos
Hipnóticos e Sedativos/efeitos adversos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Complicações Intraoperatórias/induzido quimicamente , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Corticosteroides/biossíntese , Interações Medicamentosas , Humanos , Procedimentos Cirúrgicos Operatórios/efeitos adversos
8.
Neurochirurgie ; 60(1-2): 12-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24636403

RESUMO

BACKGROUND: Patients with brain metastasis (BM) from renal cell carcinoma (RCC) have a poorly known prognosis due to the rarity of this disease. The aim of our study was to assess the outcome of patients with a BM due to RCC, and to determine the predictive factors for survival. METHODS: Consecutive patients who underwent treatment between 1997 and 2012 were identified retrospectively from a database (n=28, median age of 57.8 years, sex ratio M/F: 3.7). Main criteria collected concerned survival time. Other data collected were relative to initial histology, clinical findings at the time of BM diagnosis (diagnosis circumstances, KPS), radiological findings and BM characteristics (number, size and localization), treatment of BM (including surgery, stereotactic radiosurgery [SRS], systemic treatments, whole brain radiotherapy [WBRT]) and the outcome of surgery if performed. Statistical analysis of survival was performed using the Kaplan-Meier method. RESULTS: Median survival was 13.3 months, 1-year survival was 60.2%, 2-year survival was 16.4%. Univariate analysis showed the existence of intracranial hypertension (P=0.01), other systemic metastasis (P=0.049), the absence of deep metastasis (P=0.03) which are all linked to shorter survival. Age, KPS, initial histology of RCC, number, size, localization, and hemorrhage in BM were not correlated to survival. The median survival in the surgical resection group was 25.3 months versus 8.6 months (P=0.02). The main criteria for the selection of the surgical group were a single BM (P=0.04), and superficial metastasis (P=0.02). CONCLUSIONS: Three predictive factors for longer survival in BMRCC were the absence of intracranial hypertension, the absence of acute metastasis and the absence of extracranial metastasis. Surgical removal, when possible, seems to benefit patient survival.


Assuntos
Neoplasias Encefálicas/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Radiocirurgia/métodos , Estudos Retrospectivos
9.
Neuropharmacology ; 79: 234-48, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24291465

RESUMO

In patients, cancer and treatments provoke cognitive impairments referred to "chemofog". Here a validated neurobehavioral animal model, the unique way to explore causal direct links between chemotherapy used in clinical practices and brain disorders, allowed investigation of the direct long-term impact of colo-rectal cancer chemotherapy on cognition and cerebral plasticity. Young and aged mice received three injections every 7 days during 2 weeks of 5-fluorouracil either alone (5-FU, 37.5 mg/kg) or in combination with oxaliplatin (3 mg/kg) or with glucose (5%). The long-term effects (from day 24 to day 60) of chemotherapy were tested on emotional reactivity, learning and memory, behavioral flexibility and hippocampal cell plasticity. 5-FU (in saline)-treated aged and also young mice exhibited specific altered cognitive flexibility and behavioral hyper-reactivity to novelty, whereas the combination 5-FU (in saline)/oxaliplatin (in glucose) did not provoke any cognitive dysfunction. We thus observed that glucose counteracted 5-FU-induced altered executive functions and hippocampal cell proliferation in vivo, and protected neural stem cells in vitro from toxicity of 5-FU or oxaliplatin. In conclusion, these data suggest that the lasting chemotherapy-induced selective impairment of executive functions, whatever the age, and associated with a reduced number of hippocampal proliferating cells, can be counteracted by co-administration with glucose.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Glucose/uso terapêutico , Nootrópicos/uso terapêutico , Compostos Organoplatínicos/efeitos adversos , Fatores Etários , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimioterapia Adjuvante , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Função Executiva/efeitos dos fármacos , Função Executiva/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/fisiologia , Testes Neuropsicológicos , Oxaliplatina , Fatores de Tempo
10.
Horm Metab Res ; 45(13): 955-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24062091

RESUMO

The hypothalamus senses hormones and nutrients in order to regulate energy balance. In particular, detection of hypothalamic glucose levels has been shown to regulate both feeding behavior and peripheral glucose homeostasis, and impairment of this regulatory system is believed to be involved in the development of obesity and diabetes. Several data clearly demonstrate that glial cells are key elements in the perception of glucose, constituting with neurons a "glucose-sensing unit". Characterization of this interplay between glia and neurons represents an exciting challenge, and will undoubtedly contribute to identify new candidates for therapeutic intervention. The purpose of this review is to summarize the current data that stress the importance of glia in central glucose-sensing. The nature of the glia-to-neuron signaling is discussed, with a special focus on the endozepine ODN, a potent anorexigenic peptide that is highly expressed in hypothalamic glia.


Assuntos
Comunicação Celular/fisiologia , Glucose/metabolismo , Hipotálamo , Neuroglia , Neurônios , Transdução de Sinais/fisiologia , Animais , Humanos , Hipotálamo/citologia , Hipotálamo/metabolismo , Neuroglia/citologia , Neuroglia/metabolismo , Neurônios/citologia , Neurônios/metabolismo
11.
Neurochirurgie ; 59(3): 121-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23806761

RESUMO

OBJECTIVES: Based on a cohort of patients treated on distal middle cerebral artery (MCA) aneurysm by microsurgical approach, the objectives were to assess the following: the postoperative functional outcome, study the causes of early neurological deterioration and to determine the predictive factors of favourable outcome. PATIENTS AND METHODS: From a neurovascular prospective database, this retrospective longitudinal study included all the patients treated for cerebral aneurysm located on the distal segment of the MCA over two decades (January 1990-December 2011). The patients were all treated by microsurgical clipping exclusion. Any aneurysm was associated to infectious angiopathy. Data were retrieved from the patient's medical charts. The outcome was analysed twice: during the immediate postoperative period and at 6 months according to the modified Rankin scale. The relative risk was estimated for each variable and the prognostic factors were assessed using a multivariate logistic regression model (P<0.05). RESULTS: Twenty-eight patients, mean age 40±13.3 years (median: 43 years; range 6-70 years) were divided into the ruptured group (n=20) and unruptured group (n=8). In the ruptured group, the initial clinical status was good (WFNS I-III) in 12 patients (60%) and poor in eight (40%) with an intracerebral haematoma (ICH) in 11 (55%). For both groups, the aneurysm location on the distal MCA decreased at a rate from 64.8% of the insular segment to 25% of the opercular then 10.7% to the cortical. During the hospital stay, neurological deterioration occurred in 16 patients (57.2%). The diagnosed causes were cerebral ischaemia in 10 (35.6%), initial ICH in three (10.7%), hydrocephalus in two (7.1%) and epilepsy in one (7.1%). At 6 months, a favourable outcome (mRS 0-2) was observed in 19 patients (68.1%), a definitive morbidity in seven (24.9%) and death in two (7.2%). Based on the prognostic factors, only the absence of immediate postoperative neurological deterioration was identified as significant for a favourable outcome. CONCLUSION: These rare cerebral aneurysms resulted in a high proportion of poor initial status related to a frequent ICH. Cerebral ischaemia was a major cause of the immediate neurological deterioration and the absence of immediate neurological deterioration was the single identified prognostic factor.


Assuntos
Aneurisma Intracraniano/cirurgia , Microcirurgia/métodos , Artéria Cerebral Média , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Idoso , Aneurisma Roto/patologia , Aneurisma Roto/cirurgia , Angiografia Digital , Isquemia Encefálica/etiologia , Criança , Progressão da Doença , Epilepsia/etiologia , Feminino , Humanos , Hidrocefalia/etiologia , Aneurisma Intracraniano/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
12.
Natl Med J India ; 25(2): 80-2, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22686713

RESUMO

BACKGROUND: Responding to psychosocial needs of patients is an important element of medical practice and is dependent on the psychosocial abilities of the physician. One of the aims of teaching doctor-patient communication in medical schools is to strengthen these qualities. We assessed changes in the psychosocial abilities of first-year medical students participating in a year-long clinical communication course. METHODS: Sixty-eight first-year medical students and 49 students from the Medical Laboratories School (control group) participated in the study. The students completed, once each at the beginning (October) and at the end (July) of the course, a structured questionnaire that included a psychosocial abilities measure and sociodemographic details. RESULTS: No significant differences were found between the two groups of students regarding their sociodemographic characteristics. Furthermore, the medical students and the control group did not differ significantly in their psychosocial abilities mean scores at the beginning of the communication course (baseline). At the end of the course, a significant improvement in mean scores was found among medical students compared with an insignificant decline among the control group. CONCLUSION: Participation in an extensive clinical doctor-patient communication course guided by multidisciplinary teams may strengthen psychosocial abilities of medical students. The study needs to be replicated with a larger sample size.


Assuntos
Comunicação , Educação de Graduação em Medicina , Relações Médico-Paciente , Estudantes de Medicina , Competência Clínica , Feminino , Humanos , Masculino , Inquéritos e Questionários
13.
Neurochirurgie ; 58(2-3): 140-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22464899

RESUMO

The ageing of the population in good health or without severe morbidity expose them to the occurrence of a subarachnoid hemorrhage (SAH) and requires effective management. Currently, the pertinence of cerebral aneurysm treatment by clipping or coiling is accepted for patients in the 8th or 9th decade of life, and the risk of postoperative morbidity induced by our therapeutic alternative must be carefully assessed. In these decades, the female/male sex ratio for aneurysmal SAH was greater in female who had a 1.6 times higher ratio than in male. The initial clinical status did not appear worse with age despite the frequent severity of bleeding observed on CT scan probably due to the large subarachnoid space. The aneurysm distribution and size were similar to those classically reported in the global population. The endovascular (EV) coiling appears as the first option with a favorable outcome rate estimated at 48% to 63%. Nevertheless, the benefit of EV coiling compared to microsurgical clipping for treatment of ruptured aneurysm in the elderly has not been demonstrated in a large randomized study. This is the reason why the vascular section of the French Society of Neurosurgery developed a prospective and randomized study of the aneurysmal SAH (PHRC 2007-042/HP) on the elderly patients.


Assuntos
Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Hemorragia Subaracnóidea/terapia , Envelhecimento , Procedimentos Endovasculares/métodos , Humanos , Aneurisma Intracraniano/complicações , Hemorragia Subaracnóidea/etiologia , Resultado do Tratamento
14.
Curr Med Chem ; 19(8): 1110-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22300045

RESUMO

Class A or rhodopsin-like G-protein-coupled receptors (GPCRs) constitute the largest transmembrane receptor family of the human genome. Because of their biological and pharmaceutical importance, the evolutionary history of these receptors has been widely studied. Most studies agree on the classification of the 700 members of this family into a dozen of sub-families. However, the relationship between these sub-families remains controversial and the molecular processes that drove the evolution and diversification of such a large family have still to be determined. We review here the evolutionary analyses carried out on class A GPCRs either by phylogenetic methods or by multidimensional scaling (MDS). We detail the key molecular events driving the evolution of this receptor family. We analyze these events in view of the recently resolved crystal structures of GPCRs and we discuss the usefulness of evolutionary information to help molecular modeling.


Assuntos
Modelos Moleculares , Receptores Acoplados a Proteínas G/química , Animais , Humanos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Alinhamento de Sequência
15.
Neurochirurgie ; 57(3): 105-13, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21907362

RESUMO

BACKGROUND: For suprasellar meningioma, the fronto-basal exposure is considered the standard approach. The superior interhemispheric (IH) approach is less described in the literature. OBJECTIVE: To assess the surgical complications, functional outcome (visual, olfaction), morbidity and mortality rates and late recurrence, after resection by superior IH approach of midline skull base meningioma. METHODS: Between 1998 and 2008, 52 consecutive patients with midline meningioma on the anterior portion of the skull base (mean age: 63.8 ± 13.1; sex ratio F/M: 3.7) were operated on via the superior IH approach. After a mean follow-up of 56.9 ± 32.9 months, an independent neurosurgeon proposed a prospective examination of functional outcome to each patient, as well as a visual and olfactory function assessment. RESULTS: Fifty-two patients were divided into a group with olfactory groove meningioma (n=34) and another with tuberculum sellae meningioma (n=18). The outcome was characterized by postoperative complications in 13 patients (25%), mortality rate in two (3.8%) and long-term morbidity at in 17 (37%) of 50 surviving patients. Based on multivariate analysis, no prognosis factor was significant as regards the favorable outcome. The mean postoperative KPS score (86.6 ± 9.4) was significantly improved. However, dysexecutive syndrome was observed in four patients (8%), hyposmia-anosmia in 34 (68%) and visual acuity deteriorated in one (2%). CONCLUSION: The superior IH approach could be considered a safe anteriorly orientated midline approach for removal OGM and TSM meningioma.


Assuntos
Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/cirurgia , Base do Crânio/cirurgia , Idoso , Função Executiva/fisiologia , Feminino , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Meningioma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Transtornos do Olfato/etiologia , Percepção Olfatória/fisiologia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Base do Crânio/anatomia & histologia , Neoplasias da Base do Crânio/mortalidade , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Testes Visuais , Acuidade Visual/fisiologia
16.
Aliment Pharmacol Ther ; 34(4): 454-61, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21682756

RESUMO

BACKGROUND: In end-stage renal disease (ESRD) patients, hepatitis C virus (HCV) eradication improves patient and graft survival. AIM: To determine optimal use of erythropoietin (EPO) and ribavirin, to compare ribavirin concentrations with those of HCV patients having normal renal function and to evaluate sustained virological response (SVR) in a prospective observatory of ESRD candidates for renal transplantation. METHODS: Thirty-two naïve patients were treated with Peg-IFN-α2a and ribavirin. Two different schedules of ribavirin and EPO administration were used: starting ribavirin at 600mg per week and adapting EPO when haemoglobin (Hb) fell below 10g/dL (adaptive strategy) or starting ribavirin at 1000mg per week while increasing EPO from the start of treatment (preventive strategy). RESULTS: Patients treated with the adaptive strategy had lower median Hb levels (9.6 vs. 10.9g/dL, P=0.02) and more frequent median Hb levels below 10g/dL (58 vs. 5%, P=0.0007) despite lower median ribavirin doses (105 vs. 142mg/day, P<0.0001) than patients treated with the preventive strategy. There was a trend for more frequent transfusion in patients treated with the adaptive strategy than in patients treated with preventive strategy (50 vs. 20%, P=0.08). Compared to patients with normal renal function, ESRD patients had lower ribavirin concentrations during the first month (0.81 vs. 1.7mg/L, P=0.007) and similar concentrations thereafter. SVR was reached in 50%. CONCLUSIONS: Pegylated interferon (Peg-IFN) and an adapted schedule of ribavirin are effective in ESRD patients. Increasing EPO from the start of treatment provides better haematological tolerance. The optimal dosage of ribavirin remains unresolved, in light of frequent side effects.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Falência Renal Crônica/terapia , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Antivirais/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes , Diálise Renal , Ribavirina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga Viral
17.
Educ Health (Abingdon) ; 23(1): 305, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20589602

RESUMO

CONTEXT: The Psychological Medicine Inventory (PMI) was first developed to measure physicians' reported interest level, confidence and perceived ability to address the psychological aspects of patient care. A student version of this scale has since been proposed (PMI-S). OBJECTIVE: To further examine the psychometric properties of responses to this student version and to confirm a 2-factor response structure. METHODS: A total of 213 first-year medical students at Ben-Gurion University of the Negev participated in this study. They completed the PMI-S (translated into Hebrew) and a socio-demographic questionnaire. The viability of the 2-factor structure of PMI-S responses was assessed using confirmatory factor analysis (CFA). FINDINGS: Consistent with the original English language version, CFA supported a 2-factor solution (i.e., psychological abilities and psychological sensitivity). All goodness-of-fit indices were found to be within ideal parameters. DISCUSSION AND CONCLUSIONS: Results of this study suggest that the PMI-S can be used to assess psychosocial competence and abilities of medical students and to evaluate the effectiveness of psycho-educational programs aimed at improving their psychosocial abilities.


Assuntos
Atitude do Pessoal de Saúde , Educação Médica , Psicometria , Faculdades de Medicina , Estudantes de Medicina/psicologia , Adolescente , Adulto , Coleta de Dados , Demografia , Análise Fatorial , Feminino , Humanos , Idioma , Masculino , Modelos Estatísticos , Médicos/psicologia , Inquéritos e Questionários , Adulto Jovem
18.
J Mol Endocrinol ; 44(5): 295-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20219854

RESUMO

In the central nervous system of mammals, the gene encoding diazepam-binding inhibitor (DBI) is exclusively expressed in glial cells. Previous studies have shown that central administration of a DBI processing product, the octadecaneuropeptide ODN, causes a marked inhibition of food consumption in rodents. Paradoxically, however, the effect of food restriction on DBI gene expression has never been investigated. Here, we show that in mice, acute fasting dramatically reduces DBI mRNA levels in the hypothalamus and the ependyma bordering the third and lateral ventricles. I.p. injection of insulin, but not of leptin, selectively stimulated DBI expression in the lateral ventricle area. These data support the notion that glial cells, through the production of endozepines, may relay peripheral signals to neurons involved in the central regulation of energy homeostasis.


Assuntos
Inibidor da Ligação a Diazepam/metabolismo , Jejum , Neuroglia/metabolismo , Neuropeptídeos/metabolismo , Fragmentos de Peptídeos/metabolismo , Animais , Regulação para Baixo , Epêndima/metabolismo , Hipotálamo/metabolismo , Injeções Intraperitoneais , Insulina/administração & dosagem , Ventrículos Laterais/metabolismo , Leptina/administração & dosagem , Masculino , Camundongos , Neuropeptídeos/genética , Fragmentos de Peptídeos/genética , Ligação Proteica , Terceiro Ventrículo/metabolismo , Transcrição Gênica
19.
Am J Transplant ; 10(2): 354-63, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19775311

RESUMO

Hepatopulmonary syndrome (HPS) is present in 10-32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO(2)) < or =50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow-up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO(2) or SaO(2) were recorded. PaO(2) increased from 52.2 +/- 13.2 to 90.3 +/- 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal.


Assuntos
Síndrome Hepatopulmonar/mortalidade , Síndrome Hepatopulmonar/terapia , Transplante de Fígado/mortalidade , Adulto , Síndrome Hepatopulmonar/diagnóstico , Humanos , Doadores Vivos , Pessoa de Meia-Idade , Oxigênio , Oxigenoterapia/mortalidade , Período Pós-Operatório , Resultado do Tratamento
20.
J Nutr Health Aging ; 12(5): 313-8, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18443713

RESUMO

OBJECTIVES: To explore the association between depressive symptoms and risk for malnutrition in hospitalized elderly people. METHODS: 195 hospitalized medical patients older than 65 years of age were studied in a cross-sectional design. Depression was assessed by 30-item Geriatric Depression Scale (GDS), nutritional status was evaluated by the Mini-Nutritional Assessment (MNA). Eating and digestive problems were assessed using selected items of Nutrition Risk Index (NRI), cognitive and functional status by Folstein and Barthel indices respectively; demographic data, diagnoses and medications were obtained from medical records. RESULTS: The prevalence of depression in the studied population was 28%. MNA scores were significantly lower among depressed patients as compared with non-depressed (22.86 vs. 24.96, p < 0.001), indicating a higher risk for undernutrition among depressed persons. After controlling for age, cognitive status, functional ability, and number of illnesses, undernutrition was significantly associated with depression (OR = 2.23; 95% CI: 1.04-4.8). CONCLUSIONS: Nutritional risk is associated with depression in aged inpatients. Close case management of the elderly hospitalized patients that include assessment and treatment for both disorders may be beneficial.


Assuntos
Depressão/epidemiologia , Hospitalização , Desnutrição/epidemiologia , Estado Nutricional , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Avaliação Nutricional , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...