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1.
Encephale ; 49(2): 205-208, 2023 Apr.
Artigo em Francês | MEDLINE | ID: mdl-36253179

RESUMO

Despite being one of the most common complaints of people with schizophrenia, fatigue remains largely unexplored in this population. The lack of knowledge regarding this complex symptom makes it often underdiagnosed and undertreated in schizophrenia. The aim of this brief perspective review is to outline the potential origins (distinguishing primary and secondary fatigue) and consequences of fatigue and to explore some potential treatments in this population. The current literature in schizophrenia has mainly investigated fatigue as a trait, using a self-administered questionnaire. Beyond this observational approach, which does not allow to capture the symptom in real life situations where high levels of fatigue can emerge rapidly, we propose to consider the state level of fatigue, for instance occurring after a prolonged period of cognitive activity (i.e. mental fatigue). We elaborate on the potential relationships between mental fatigue and negative symptoms of schizophrenia and propose some research avenues to test the effects of acute fatigue on effort intentions and behaviours. The consideration of the multidimensional aspects of fatigue will allow to move beyond the sole pharmacological approach to treat fatigue in schizophrenia. Targeting the cognitive as well as the performance components of fatigue through interventions such as concomitant aerobic exercise - mental training offers attractive prospects to reduce fatigue in this population and minimize its functional negative impact.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/terapia , Exercício Físico
2.
Radiologe ; 60(4): 342-350, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-31932955

RESUMO

BACKGROUND: As part of the reform of medical education with a stronger focus on clinical-practical skills, a restructured seminar on interventional radiology was evaluated using a newly developed questionnaire. OBJECTIVES: Because knowledge in medical education is increasingly transferred by means of application-based teaching formats, a suitable evaluation tool is essential to assess the quality of newly implemented teaching courses. The aim of this study was to evaluate the seminar on interventional radiology and to validate the "Radio-Prak" questionnaire psychometrically in the process. MATERIALS AND METHODS: In the summer semester of 2018, 123 students participating in the newly established seminar were asked to document their satisfaction using the "Radio-Prak" questionnaire with 23 items employing a 5-point Likert scale. We evaluated the questionnaire psychometrically by performing exploratory factor (EFA) and reliability analysis and examined differential validity by group differences. RESULTS: The newly structured seminar on interventional radiology was met with great approval by students (mean global rating = 1.31, on a grading scale where 1 = very good, 5 = insufficient). EFA revealed that the questionnaire consisted of two main factors "didactic quality" and "practical quality" (five items each, α = 0.68). The seminar was rated more positively when students perceived the time for practice as sufficient (p < 0.05). Furthermore, female students demonstrated significantly less self-esteem, identified by the item "I have improved my spatial ability through the seminar," (p < 0.05). CONCLUSION: The "Radio-Prak" questionnaire is both reliable and valid as an instrument to evaluate the quality of a clinical-practical seminar. The students assessed the didactic dimension, but also rated the practical component as important in the assessment.


Assuntos
Difusão de Inovações , Educação Médica/organização & administração , Radiologia Intervencionista/educação , Inquéritos e Questionários , Ensino , Humanos , Psicometria , Reprodutibilidade dos Testes
3.
Klin Monbl Augenheilkd ; 235(7): 820-829, 2018 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-28187469

RESUMO

Intraoperative optical coherence tomography (iOCT) represents another milestone in ocular imaging technologies. Now, for the first time, high resolution OCT images are available not only pre- or postoperatively, but also intraoperatively. In recent years, there have been significant advances in iOCT technology - from hand-held probes and mounted systems towards iOCT systems which are fully integrated into the surgical microscope and which provide seamless integration into the workflow. These systems offer high-resolution, intraoperative OCT scans in real-time and provide additional information on microstructures of the retina or the cornea. These findings may even lead to a modification of surgical strategies. Like any other new technology, iOCT technology still has some limitations, such as shadowing from instruments and the lack of eye tracking systems. Therefore, the current state of iOCT technology still requires some skill to track surgical maneuvers in real time. Further research and development will help to solve these limitations in the future. However, even if not required for all surgical procedures, iOCT imaging can already improve safety and control in many surgical procedures on the anterior and posterior segments. This has already been shown in several studies and case series. Particularly in the surgery of vitreomacular traction, peeling of epiretinal membranes (ERM peeling) and macular hole surgery, iOCT offers significant added value. It improves the visualisation of transparent structures and helps to avoid the usage of dyes. In addition the success of the surgical maneuvers can be investigated intraoperatively. In lamellar keratoplasty and glaucoma surgery too, iOCT improves precision and safety. Moreover, iOCT technology may help to achieve further insight into ocular pathologies and a better understanding of the impact of surgical maneuvers on visual rehabilitation. Further prospective studies are however required to evaluate the usefulness of iOCT in various surgical procedures on both, the anterior and posterior segments.


Assuntos
Membrana Epirretiniana , Procedimentos Cirúrgicos Oftalmológicos , Tomografia de Coerência Óptica , Humanos , Cuidados Intraoperatórios , Estudos Prospectivos , Retina
4.
Klin Monbl Augenheilkd ; 233(1): 57-65, 2016 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-26797889

RESUMO

Pathological angiogenesis is a major characteristic of many diseases, such as cancer and retinal vascular disorders. Vascular diseases of the eye, such as diabetic retinopathy (DR) and neo-vascular age-related macular degeneration (nAMD), are the main cause of severe vision loss. The specific role of the cytokine VEGF-A in these pathologies has been proven in many ways. Thus, VEGF-A is still the major target for antiangiogenic therapy. Recently, another angiogenic factor, the placental growth factor (PlGF), has become a focal point for clinical research. This interest is based on the fact that the expression of PlGF is limited to embryonic development and PlGF can hardly be found in healthy tissues. During pathological angiogenetic processes, such as retinal vascular diseases, however, PlGF is increasingly expressed. Substances which inhibit the effect of PlGF and thus pathological angiogenesis, without simultaneously affecting healthy tissues, could significantly extend the therapeutic options for the treatment of retinal vascular diseases. Convincing results have recently been published from clinical trials in oncology, as well as preclinical investigations in animal models of retinal vascular diseases. The aim of this review is to summarise the role of PlGF in retinal vascular diseases and the available experimental data on the therapeutic potential of PlGF inhibitors.


Assuntos
Indutores da Angiogênese/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde , Fator de Crescimento Placentário/administração & dosagem , Doenças Retinianas/tratamento farmacológico , Vasos Retinianos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicina Baseada em Evidências , Humanos , Resultado do Tratamento
5.
Klin Monbl Augenheilkd ; 231(9): 901-8, 2014 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-24992237

RESUMO

Since the late 1980s implantation of UV-blocker intraocular lenses during cataract surgery has become an internationally accepted standard. Last year the Kassenärztliche Vereinigung Bayern (KVB) and statutory health insurance organisations proposed for the first time quality criteria for intraocular lenses (IOL), thereby including exact parameters for the amount of UV light transmission (≤10% at 400 nm). Since then, the discussion has been raised again as to what extent IOLs should filter or block UV light. In this article, exact definitions of spectral subbands within the optical radiation band are given. Today, 400 nm is the internationally accepted standard to distinguish UV light and visible light. Moreover, exposure of the eye to UV radiation is described as well as mechanisms of photooxidative damage to the retina. Comprehensive laboratory and animal experimental studies show that light of short wave lengths, i.e., above all UV light but also blue light, may induce photochemical damage to the retina. Primary sites of such damage are both the outer segments of the photoreceptors and the retinal pigment epithelium (RPE). Physiological protective mechanisms of the eye, such as filtering properties of different ocular media are described in detail. Cornea, aqueous and vitreous absorb UV radiation below 300 nm, while the natural adult lens absorbs UV radiation between 300 and 400 nm. This protection is lost when the lens is removed by cataract surgery and thus should be restored. UV light does not contribute to vision but damages retinal structures. Therefore, UV-blocking intraocular lenses with a 10% cut-off near 400 nm should be implanted during cataract surgery. This ensures sufficient retinal protection after surgery. These theoretical considerations are supported by results from animal and clinical studies.


Assuntos
Traumatismos Oculares/prevenção & controle , Lentes Intraoculares/normas , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde/normas , Lesões por Radiação/prevenção & controle , Proteção Radiológica/instrumentação , Proteção Radiológica/normas , Raios Ultravioleta , Alemanha , Humanos , Desenho de Prótese/normas
6.
Sci Rep ; 13(1): 4590, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944652

RESUMO

Seafloor methane emissions can affect Earth's climate and ocean chemistry. Vast quantities of methane formed by microbial decomposition of organic matter are locked within gas hydrate and free gas on continental slopes, particularly in large areas with high sediment accumulations such as deep-sea fans. The release of methane in slope environments has frequently been associated with dissociation of gas hydrates near the edge of the gas hydrate stability zone on the upper slope, with discharges in greater water depths less understood. Here we show, using data from the Rio Grande Cone (western South Atlantic), that the intrinsic, gravity-induced downslope collapse of thick slope sediment accumulations creates structures that serve as pathways for gas migration, unlocking methane and causing seafloor emissions via giant gas flares in the water column. The observed emissions in the study region (up to 310 Mg year-1) are three times greater than estimates for the entire US North Atlantic margin and reveal the importance of collapsing sediment accumulations for ocean carbon cycling. Similar outgassing systems on the Amazon and Niger fans suggest that gravity tectonics on passive margins is a common yet overlooked mechanism driving massive seafloor methane emissions in sediment-laden continental slopes.

7.
J Exp Med ; 151(3): 587-601, 1980 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-6766981

RESUMO

C3H/HeJ T cells which specifically recognize B cell-surface antigens of the related, major histocompatibility complex-compatible C3H/Tif strain, can be substantially enriched in vitro by long-term exposure (2--6 wk) of primed lymph node cells to the relevant cellular antigens. These enriched T cells contain functional helper cells as demonstrated by their capacity to induce large numbers of Ig-secreting plaque-forming cells (PFC) in cultures of antigenic B cells. The cooperative interaction results in activation of a large fraction of all splenic B cells, with consequent exponential growth and maturation to high rate secretion of IgM, IgG1, and IgG2, but not IgG3. The IgM PFC response includes antibody specificities to a number of different antigens and can be considered, therefore, as polyclonal. The T helper cell-dependent B-cell response is insensitive to inhibition by anti-delta antibodies, and in contrast with lipopolysaccharide-induced PFC responses, is only partially sensitive to the inhibitory effects of anti-mu antibodies. Finally, B-cell activation to growth and maturation by helper T cells strictly required direct T-cell recognition of antigens on the surface of responding B cells, leading us to the conclusions that if any soluble factors are generated in the collaborative process, they are either antigen specific or incompetent to initiate B-cell growth.


Assuntos
Linfócitos B/imunologia , Cooperação Linfocítica , Linfócitos T/imunologia , Animais , Anticorpos Anti-Idiotípicos , Especificidade de Anticorpos , Antígenos de Superfície , Células Cultivadas , Células Clonais/imunologia , Cadeias mu de Imunoglobulina , Linfonodos/imunologia , Ativação Linfocitária , Complexo Principal de Histocompatibilidade
8.
J Exp Med ; 178(5): 1819-24, 1993 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8228828

RESUMO

gamma delta T cells participate in immune responses during viral, bacterial, and parasitic infections. However, it is not clear whether they recognize antigens produced by pathogens, or are actually reactive to self-ligands generated during the course of infection. In this paper, we report that the presence of the self-ligand that selectively expands a subset of gamma delta T cells correlates with the presence of an endogenous murine leukemia virus (MuLV) in inbred strains of mice. The implications of this observation for gamma delta T cell specificity and function is discussed.


Assuntos
Vírus da Leucemia Murina/isolamento & purificação , Camundongos Endogâmicos BALB C/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/biossíntese , Animais , Sequência de Bases , Clonagem Molecular , DNA/química , DNA/isolamento & purificação , Primers do DNA , Expressão Gênica , Camundongos , Camundongos Pelados , Camundongos Endogâmicos/imunologia , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Especificidade da Espécie , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
9.
J Exp Med ; 178(5): 1713-24, 1993 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-7693855

RESUMO

T lymphocytes generated in the fetal and neonatal period are characterized by T cell receptor (TCR) gene rearrangements that lack N region nucleotides (fetal-type TCR). Using fetal-type TCR as a lineage marker, we show that such T cells are long-lived and persist in the periphery of adult mice. Moreover, in both neonatal and adult environments, upon encounter with self-antigens, they are less likely to be deleted. Inefficient clonal deletion could be due to the intrinsic properties of the T cells generated during this period, or to yet unknown properties of the perinatal thymus. Such anergic T cells constitute a subset that can further expand in vivo in an antigen-independent fashion, leaving open the possibility for self-aggression under the appropriate triggering conditions.


Assuntos
Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Antígenos Secundários de Estimulação de Linfócitos/imunologia , Linfócitos T/imunologia , Animais , Animais Recém-Nascidos , Sequência de Bases , Células Cultivadas , Primers do DNA , Feto , Ionomicina/farmacologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Dados de Sequência Molecular , Oligonucleotídeos Antissenso , Reação em Cadeia da Polimerase/métodos , RNA/isolamento & purificação , Receptores de Antígenos de Linfócitos T gama-delta/genética , Baço/imunologia , Linfócitos T/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Timectomia
10.
Klin Monbl Augenheilkd ; 227(8): 617-23, 2010 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-20706969

RESUMO

Data from both experimental and epidemiological trials have suggested a potential correlation between extraction of the natural lens associated with exposure to photo-oxidative stress to the retina and a progression of diseases such as AMD. A fundamental factor could be the unchecked exposure to blue light. This is why in the past years so-called blue light-filtering intraocular lenses have been implanted to serve as a protection to the retina. The following contribution is based on a data base research (Pub Med, National Library of Medicine, USA) and summarises information currently available on the use of blue light-filtering lenses. Experimental modeling has shown that, compared to regular UV lenses, blue light-filtering lenses block a considerable part of blue light transmission to the retina and reduce damage to retinal cells and production of inflammatory markers such as VEGF. The majority of the clinical data demonstrate that blue light-filtering lenses are compatible in terms of visual acuity, contrast sensitivity and colour perception as well as patient-rated quality of vision. But a few additional studies report reduced contrast sensitivity and limitations in mesopic vision.This is also true for the circadian rhythm. However, the evaluation of this parameter in connection with blue light-filtering lenses has only been done on a theoretical basis. Long-term data showing that blue light-filtering lenses actually do reduce the incidence of retinal diseases such as AMD are currently not available.


Assuntos
Filtração/instrumentação , Lentes Intraoculares , Luz/efeitos adversos , Degeneração Macular/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Proteção Radiológica/instrumentação , Retina/efeitos da radiação , Ritmo Circadiano , Humanos , Mediadores da Inflamação/metabolismo , Satisfação do Paciente , Desenho de Prótese , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Klin Monbl Augenheilkd ; 227(2): 90-8, 2010 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-20155652

RESUMO

Oxidative stress is defined as an overflow of oxidative metabolites either in the human body or in a compartment of the body. Today this chemical definition has been slightly modified and encompasses an elevation of oxidative metabolites or a relative deficiency of anti-oxidants. Molecular oxygen is the basis of many highly reactive oxidative species which are able to directly damage or lead to the generation of secondary reactions which then initiate oxidative processes. The cell has established numerous mechanisms and strategies to antagonise those oxidative processes at different steps. Many diseases have been shown to be either related to or even be initiated by oxidative processes. The eye is at high risk to be damaged by oxidative mechanisms. One major reason is its permanent exposition to oxidative stimuli. The biochemical composition of ocular structures, especially that of the retina (unsaturated fatty acids), is an important factor making the eye more susceptible as compared to other organs. Ocular ischaemia, ischaemia or hypoxia of the retina, diabetic retinopathy and glaucoma are important disease entities that are initiated or propagated by oxidative processes. Ischaemic processes lead to classical reactions of the oxidative pathway. This is no longer believed to be the case in diabetic retinopathy. Here, advanced glycation end products (AGE's) and related species are able to induce oxidative reactions and the expression of growth factors. In age-related macular degeneration, photodynamic processes that already occur in childhood are believed to be a major factor contributing to the pathogenesis of the disease process. In addition, the expression of growth factors and new vessel growth can be initiated via inflammatory reactions or oxidative metabolites.


Assuntos
Glaucoma/fisiopatologia , Estresse Oxidativo/fisiologia , Doenças Retinianas/fisiopatologia , Antioxidantes/metabolismo , Retinopatia Diabética/fisiopatologia , Ácidos Graxos Insaturados/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hipóxia/fisiopatologia , Isquemia/fisiopatologia , Degeneração Macular/fisiopatologia
12.
Eye (Lond) ; 31(5): 684-690, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28085139

RESUMO

PurposeLimited data are available on the efficacy of the 0.2 µg/day fluocinolone acetonide (FAc) implant in eyes with prior vitrectomy. Here, we present a collection of 26 vitrectomized eyes treated with the 0.2 µg/day FAc implant.MethodsRetrospective study involving six centers from four European countries analyzing the safety and efficacy data from patients (26 eyes from 25 patients) with DME and a prior vitrectomy that had been treated with one 0.2 µg/day FAc implant.ResultsPrior intravitreal therapies included anti-VEGF (mean, 3.8 injections) and steroids (mean, 1.9 injections). Pars plana vitrectomy (PPV) was performed in these eyes primarily for abnormalities of vitreoretinal interface, followed by proliferative diabetic retinopathy and vitreous hemorrhage. The 0.2 µg/day FAc implant was injected 24.2 months, on average, after PPV and the mean duration of follow-up after injection was 255 days (range, 90 to 759 days). The mean change in BCVA was +11.7 ETDRS letters (range, -19 to +40 letters; P<0.0004) and the mean change in central foveal thickness (CFT) was -233.5 µm (range, -678 to 274 µm; P<0.0001). The mean change in IOP from baseline at the last visit was +1.4 mm Hg (range, -9 to +8 mm Hg; P=0.0090). Eight eyes initiated or continued IOP lowering medications.ConclusionsThese data suggest the 0.2 µg/day FAc implant is effective in vitrectomized patients with an acceptable safety profile. Further studies are still required to confirm the current findings and to assess the effect of the 0.2 µg/day FAc implant over a longer period of follow-up.


Assuntos
Retinopatia Diabética/terapia , Fluocinolona Acetonida/administração & dosagem , Macula Lutea/patologia , Edema Macular/terapia , Vitrectomia , Idoso , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Relação Dose-Resposta a Droga , Implantes de Medicamento , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
13.
Sci Rep ; 7: 46543, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28440309

RESUMO

Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in adult human CSF, and first pilot experiments with a longitudinal cohort indicate a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult neurogenesis in both animal and human physiology and disease, warranting future studies.


Assuntos
Células-Tronco Adultas/metabolismo , Glipicanas/líquido cefalorraquidiano , Hipocampo/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese , Adulto , Células-Tronco Adultas/citologia , Animais , Biomarcadores/líquido cefalorraquidiano , Diferenciação Celular , Proliferação de Células , Hipocampo/citologia , Humanos , Masculino , Camundongos , Células-Tronco Neurais/citologia
14.
Eur J Ophthalmol ; 16(6): 824-34, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17191188

RESUMO

PURPOSE: Choroidal neovascularization associated with age-related macular degeneration is the primary cause of blindness in the elderly in developed countries, due to a number of pathogenic effects, including angiogenesis, cell-mediated inflammation, leukocyte adhesion and extravasation, and matrix remodeling. METHODS: By producing photochemical effects at the site of target tissue (lesion), photodynamic therapy (PDT) can induce vascular damage and blood flow stasis, leading to occlusion of vascularization and lesion leakage. RESULTS: PDT with verteporfin (Visudyne, Novartis) has been shown to be safe and effective in reducing the risk of vision loss in patients with classic containing subfoveal CNV and occult with no classic CNV. However, in predominantly occult CNV, the treatment may be most effective in smaller lesions, and less in larger lesions. Most important, visual acuity rarely is improved. CONCLUSIONS: Pilot studies and large case series suggest that a combination of PDT and intravitreal triamcinolone acetonide has the potential to improve visual outcomes and reduce the need for additional treatments. Randomized, prospective clinical trials are underway to confirm the efficacy and safety of this novel treatment modality.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Degeneração Macular/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Triancinolona Acetonida/uso terapêutico , Quimioterapia Combinada , Humanos , Injeções , Verteporfina , Corpo Vítreo
15.
Indian J Nephrol ; 26(2): 134-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27051139

RESUMO

Two cases are described of previously unreported false positivity on the Luminex crossmatch assay due to non HLA specific antibodies directed against the beads. In both cases the Luminex crossmatch indicated the presence of donor specific antibodies to class II HLA antigens, which was not substantiated by the clinical scenario or other assays. We could demonstrate the non specificity of these antibodies through using the same assay in a modified form where beads were unexposed to cell lysate and therefore did not carry HLA antigens at all. These cases further serve to emphasize the absolute necessity of correlating positive results with the priming history, and confirming their relevance using other platforms.

16.
J Comp Neurol ; 398(3): 359-72, 1998 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-9714149

RESUMO

The sequence of events leading to the chemical matching of presynaptic neurotransmitters and postsynaptic transmitter receptors is investigated here in vivo for the spinal glycine receptor (GlyR) by using immunocytochemical methods. In the ventral horn of adult rat spinal cord, GlyRs are only present at glycinergic postsynaptic differentiations where they are stabilized by the associated protein gephyrin. With quantitative confocal microscopy, we found that gephyrin is detected before GlyRs at embryonic day (E)13-E14 and at E15, respectively, inside the cytoplasm and at plasmalemmal loci. Around the time of birth, the number of cell surface gephyrin-immunoreactive (-IR) spots exceeds that of GlyR. They first match 10 days after birth. The densities of postsynaptic gephyrin- and GlyR-IR were quantified between birth and the adult stage with post-embedding immunogold staining. Immunostaining for gephyrin and GlyR was not detected in the extrasynaptic membrane. The density of staining in postsynaptic membrane increased progressively with development. The inhibitory amino-acid content of the presynaptic terminal boutons opposed to gephyrin-IR sites was also analyzed. In the newborn, postnatal day 10, and adult, more than 90% of these boutons were immunostained for glycine. As seen with serial sections, 38% and 51.2% of the terminals also contained gamma-aminobutyric acid (GABA) in neonate and adult, respectively. These data indicate that around the time of birth, most glycine-containing boutons, some also containing GABA, are opposed to gephyrin-IR postsynaptic densities, whereas GlyRs are not present. Our results suggest that gephyrin determines subsynaptic loci on the plasma membrane where GlyR will subsequently accumulate.


Assuntos
Glicina/fisiologia , Medula Espinal/fisiologia , Sinapses/fisiologia , Animais , Proteínas de Transporte/metabolismo , Imunofluorescência , Imuno-Histoquímica , Proteínas de Membrana/metabolismo , Microscopia Confocal , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Receptores de GABA/metabolismo , Receptores de Glicina/biossíntese , Receptores de Glicina/genética , Receptores Pré-Sinápticos/metabolismo , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/ultraestrutura , Sinapses/ultraestrutura
17.
Invest Ophthalmol Vis Sci ; 35(11): 3897-904, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7928187

RESUMO

PURPOSE: In addition to the inhibition of xanthine oxidase, allopurinol is known to act, dependent on the dose, as a free radical scavenger, an antioxidant, and a "scavenger" of hypochlorous acid. This activity was investigated using a model of lens-induced uveitis. METHODS: Lipid peroxides (LPO) were determined in aqueous humor and in retinal tissue. Reduced and oxidized glutathione (GSH and GSSG) of the aqueous humor and myeloperoxidase (MPO) activity in the iris-ciliary body complex were analyzed. Allopurinol and oxypurinol concentrations were determined by high-performance liquid chromatography in aqueous humor and retinal tissue of both control eyes and eyes with uveitis. These measurements were performed 6 hours after intravenous application of allopurinol. RESULTS: In lens-induced uveitis, LPO are significantly elevated, GSH is reduced, and GSSG and MPO are increased. A xanthine oxidase inhibition dose (< 10 mg/kg body weight) of allopurinol showed no effects on oxidative tissue damage in the model used in this study. Higher doses, however, were able to reduce the oxidative damage. Allopurinol (20 mg/kg body weight) had slight effects on GSH and GSSG. All parameters improved using a dose of 50 mg/kg body weight; a dose of 100 mg/kg body weight only showed additional improvement in GSH and GSSG. There was no further change in the other parameters. Allopurinol and oxypurinol concentrations in aqueous humor and retinal tissue showed a dose dependency reaching scavenger concentrations after application of 50 mg/kg body weight of allopurinol. CONCLUSIONS: These results suggest that the xanthine oxidase mechanism plays a minor role in the oxidative tissue damage due to lens-induced uveitis. Free radicals and oxidants are generated by activated leukocytes; therefore, the effect of higher doses of allopurinol is due to its free radical scavenging and antioxidative activity.


Assuntos
Alopurinol/farmacologia , Oxipurinol/farmacologia , Uveíte/metabolismo , Animais , Segmento Anterior do Olho/metabolismo , Antioxidantes , Cromatografia Líquida de Alta Pressão , Cristalinas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres , Glutationa/metabolismo , Cristalino , Peróxidos Lipídicos/metabolismo , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Retina/metabolismo , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico
18.
Int J Epidemiol ; 18(4 Suppl 2): S20-32, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2621045

RESUMO

The provision of simple health technologies in less developed countries has far outpaced the capabilities to evaluate their impact on health in general, and early childhood survival in particular. In rural Haiti, attempts to monitor the impact of health care delivery programmes have been frustrated by some of the same problems encountered elsewhere; ie lack of practicable yet scientifically sound methodologies that interface well with ongoing service delivery programmes. The 'preceding birth' technique, originally advanced by Brass and Macrae, holds promise as just such a method. Its practical appeal derives largely from simple data requirements. In its simplest form, the method requires only responses to a single question put to mothers at delivery regarding the survival status of her previous child. They have shown that the proportion of immediately preceding births dying before the 'index' birth date provides a good approximation of the standard life table probability of death before the second birthday. Given that in rural Haiti, as in much of the less developed world, few women deliver in clinic or hospital where such data could be systematically obtained, exploitation of the preceding birth method would require identification of a convenient and unobtrusive point of contact between questioner and mothers who have recently delivered. In Haiti, two options arose: (1) interview women at home after childbirth, and (2) interview women when they bring the 'index' child seeking vaccination or some other child survival intervention. Both of these deviate from the original technique of Brass and Macrae with respect to the timing and method of data collection, and could therefore introduce serious complications to the interpretation of trends in child mortality. To study this, we examined the effects of adapting the preceding birth method to a rural less developed country setting in Mirebalais, where since 1983 primary health care activities have been administered by MARCH (Management and Resources for Community Health), a private voluntary health organization. The Mirebalais study used a pregnancy register, originally developed for targeting of services, to identify women who were expected to have given birth during the 12-month period before each of two survey rounds. Brief interviews with these women would provide direct life table estimates of child mortality level and trend with which to compare estimates produced from use of the preceding birth method in modified form. Direct estimates of the probability of dying before the second birthday were 138/1000 from first round data and 134/1000 from second round data, indicating a 3% decline.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Mortalidade Infantil , Coleta de Dados , Países em Desenvolvimento , Estudos de Avaliação como Assunto , Feminino , Haiti/epidemiologia , Humanos , Funções Verossimilhança , Densidade Demográfica , População Rural
19.
Int J Epidemiol ; 18(4 Suppl 2): S33-7, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2621046

RESUMO

A rapid ethnographic assessment of barriers to health service utilization was conducted to identify maternal factors predicting use of child immunizations in Haiti. Methods included four focus group interviews, four natural group interviews, individual interviews with 14 health care providers and participant observation at vaccination posts. Analysis of qualitative data identified five categories of maternal factors associated with immunization use: competing priorities, low motivation, socioeconomic constraints, perceived accessibility of services, fears about health or social consequences and knowledge and folk beliefs related to vaccines. Selected variables among these factors were incorporated into a survey instrument designed to compare mothers of completely vaccinated children (cases) with mothers of incompletely vaccinated children (controls). The questionnaire was administered to 299 randomly selected mothers (217 cases, 82 controls). Bivariate and multivariate analyses found that of the factors identified through ethnographic research, only vaccine-related knowledge was significantly associated with immunization status. The utility and constraints of using ethnographic research for instrument development in epidemiological studies are discussed.


PIP: A rapid ethnographic assessment consisting of 4 focus groups, 4 natural group interviews, 14 provider interviews and participant observation rally posts was combined into a questionnaire which was tested by chi square for use in predicting which Haitian mothers utilize immunization services. The study population were mothers of 1800 children 12-23 months old in the Mirebalais Area Community Health program in the central highlands of Haiti. The program uses the rally post system, with teams visiting villages at 6-week intervals. Audio tapes and written notes were reduced to lists of all possible barriers to maternal utilization, and then regrouped into 16 categories, under 5 topics: competing priorities, lack of motivation, socioeconomic constraints, perceived accessibility of posts, fears of health consequences and knowledge of folk beliefs about vaccines. 22 questionnaire items were then developed, which were edited by the overall project director without input from the ethnographer. The questions were administered to 299 mothers, 82 with incompletely immunized, and 217 with completely immunized children. The questions which significantly predicted complete vaccination by bivariate analysis were knowledge of the name of 1 or more vaccines or illnesses, the recommended number of doses, and the correct age to begin vaccinations. It was likely that time demands from subsistence farming and income generating activities also affected service utilization, but the women probably interpreted the question on employment incorrectly.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Imunização/estatística & dados numéricos , Mães , Estudos de Casos e Controles , Etnologia , Feminino , Haiti , Indicadores Básicos de Saúde , Humanos , Entrevistas como Assunto , Projetos de Pesquisa , População Rural
20.
Surv Ophthalmol ; 42 Suppl 1: S118-26, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9603297

RESUMO

The intravascular oxygen tension (pO2) of the pig retina was determined by measuring the phosphorescence lifetime of an intravenously injected dye. Pseudocolor images of the intravascular retinal pO2 were obtained. The method is noninvasive except for the application of the dye. The measurement system was adapted to a fundus camera. The systemic arterial oxygen pressure (PaO2) as well as the intraocular pressure (IOP) were altered. In the measurements the pO2 of the choriocapillaris was close to the systemic PaO2. Under normoxia, the retinal veins showed a lower pO2 of about 40 mm Hg. We found evidence of an autoregulation of the retinochoroidal pO2. The retina and the optic nerve head showed an autoregulation of the intravascular pO2 at low IOP, but were more sensitive to a moderate elevation of the IOP of about 40 mm Hg, as compared to the choroidal pO2. The pO2 of the choriocapillaris seemed to change little until the considerably high IOP value of about 50 mm Hg was attained. This behavior is due to either the high perfusion reserve capacity of the choroid or to autoregulation. Although our experiments refer to the perfusion of the pig eye, the results provide indirect evidence that even during a glaucoma attack the human choroid might be able to maintain a reasonable oxygen supply to the retina, whereas the intravascular pO2 of the retinal vessels and of the optic nerve head decrease strongly. The adaptation to a fundus camera facilitates a future clinical application if a nontoxic dye can be developed.


Assuntos
Pressão Intraocular , Oxigênio/metabolismo , Retina/metabolismo , Vasos Retinianos/metabolismo , Animais , Gasometria , Corantes , Homeostase , Medições Luminescentes , Mesoporfirinas , Metaloporfirinas , Consumo de Oxigênio , Paládio , Pressão Parcial , Suínos
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