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1.
Clin Microbiol Infect ; 26(6): 784.e1-784.e5, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31972317

RESUMEN

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.


Asunto(s)
Antifúngicos/uso terapéutico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Terbinafina/uso terapéutico , Voriconazol/uso terapéutico , Adulto , Anciano , Quimioterapia Combinada , Femenino , Humanos , Infecciones Fúngicas Invasoras/sangre , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Scedosporium/efectos de los fármacos , Resultado del Tratamiento
2.
Ann N Y Acad Sci ; 1012: 94-114, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15105258

RESUMEN

There is evidence suggesting that oxidative stress contributes to kainate neurotoxicity. Since iron promotes oxidative stress, the present study explores how change in nutritional iron content modulates kainate-induced neurotoxicity. Rats received an iron-deficient diet (ID) from 22 days of age for 4 weeks. One control group received the same diet supplemented with iron and another control group received standard rodent diet. Cellular damage after subcutaneous kainate (10 mg/kg) was assessed by silver impregnation and gliosis by staining microglia. ID reduced cellular damage in piriform and entorhinal cortex, in thalamus, and in hippocampal layers CA1-3. ID also attenuated gliosis, except in the hippocampal CA1 layer. Given involvement of zinc in hippocampal neurotransmission and in oxidative stress, we tested for a possible interaction of nutritional iron with nutritional zinc. Rats were made iron-deficient and then assigned to supplementation with iron, zinc, or iron + zinc. Controls were continued on ID diet. After 2 weeks, rats were treated with kainate. Iron supplementation abolished the protective effect of ID in piriform and entorhinal cortex. In hippocampal CA1 and dorsal thalamus, neither iron nor zinc supplementation alone abolished the protective effect of ID against cellular damage. Iron + zinc supplementation abolished ID protection in dorsal thalamus, but not in reuniens nucleus. Kainate-induced gliosis in CA1 remained unaffected by nutritional treatments. Thus, in piriform and entorhinal cortex, nutritional iron has a major impact on cellular damage and gliosis. In hippocampal CA1, gliosis may associate with synaptic plasticity not modulated by nutritional iron, while cellular damage is sensitive to nutritional iron and zinc.


Asunto(s)
Antígenos CD , Antígenos de Neoplasias , Antígenos de Superficie , Proteínas Aviares , Proteínas Sanguíneas , Deficiencias de Hierro , Ácido Kaínico , Degeneración Nerviosa/prevención & control , Síndromes de Neurotoxicidad/prevención & control , Animales , Animales Recién Nacidos , Basigina , Conducta Animal , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Química Encefálica , Recuento de Células/métodos , Suplementos Dietéticos , Modelos Animales de Enfermedad , Hematócrito/métodos , Inmunohistoquímica/métodos , Hierro/farmacología , Masculino , Glicoproteínas de Membrana/metabolismo , Microglía/metabolismo , Microglía/patología , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/metabolismo , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Ratas , Ratas Sprague-Dawley , Tinción con Nitrato de Plata/métodos , Zinc/farmacología
3.
J Neural Transm (Vienna) ; 109(10): 1241-56, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12373558

RESUMEN

Iron deficiency (ID), the most prevalent nutritional disorder in the world, impairs cognition in early development. The involvement of hippocampus in cognition has prompted investigation into distribution of the iron storage protein ferritin (FER) in rat hippocampus. (a) In normal rats, FER positive cells appeared first in lateral CA3 and hilus of dentate gyrus and then spread over the entire mossy fiber (MF) system. No such spread was observed in CA1 field. (b) Nutritional iron deficiency retarded development of FER in the MF system. No change in FER was observed in CA1 field. (c) Zinc distribution can be altered by iron deficiency. Thus, the effect of zinc added to iron supplementation was tested in iron-deficient rats. Significant FER recovery was observed only in hippocampal MF of rats receiving both zinc and iron. It is apparent that for accelerating recovery of hippocampal function in iron deficiency, both zinc and iron are required.


Asunto(s)
Ferritinas/metabolismo , Hipocampo/metabolismo , Deficiencias de Hierro , Hierro de la Dieta/farmacología , Zinc/farmacología , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Recuento de Células , Dieta , Hipocampo/anatomía & histología , Hipocampo/efectos de los fármacos , Inmunohistoquímica , Masculino , Fibras Musgosas del Hipocampo/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tinción con Nitrato de Plata , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología
4.
Biol Psychiatry ; 49(10): 876-85, 2001 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-11343684

RESUMEN

BACKGROUND: Facilitation of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission via administration of glycine site agonists of the NMDA receptor (e.g., glycine, D-serine), and glycine transport inhibitors may represent an innovative pharmacologic strategy in schizophrenia; however, given the potential involvement of NMDA receptors in the neurotoxicity of excitatory amino acids, possible neurotoxic effects of glycinergic compounds need to be explored. Furthermore, studying brain adaptations to chronic administration of glycine site agonists may provide insights into the therapeutic mechanisms of these drugs. METHODS: Adult rats were randomized to one of three nutritional regimens (no glycine supplementation, 1 g/kg/day, or 5 g/kg/day glycine supplementation) and to one of three treatment durations (1, 3, or 5 months). Serum glycine and serine levels at sacrifice and brain sections were examined using histologic markers of neurodegeneration (cresyl violet and silver impregnation staining) and immunohistochemical staining of glial fibrillary acidic protein, microtubule-associated protein, and neurofilament 200. To explore additional neural adaptations to high-dose glycine treatment, immunostaining was also performed for class B, N-type Ca(2+) channels. RESULTS: Serum glycine levels increased dose dependently during glycine nutrition, whereas serine levels were not changed. In hippocampal dentate gyrus, the percentage of hypertrophied astrocytes transiently increased at 1 month. At 3 and 5 months of glycine treatment, the density of class B, N-type Ca(2+) channels was reduced in parietal cortex and hippocampus. No evidence of neuronal or glial cell excitotoxic damage or degeneration was registered at either of the treatment intervals studied. CONCLUSIONS: These findings demonstrate for the first time that in vivo administration of high-dose glycine may induce brain morphological changes without causing neurotoxic effects. A reduction in density of class B, N-type Ca(2+) channels in specific brain regions may represent one general adaptation to long-term, high-dose glycine treatment.


Asunto(s)
Encéfalo/citología , Encéfalo/efectos de los fármacos , Modelos Animales de Enfermedad , Glicina/farmacología , Adaptación Fisiológica/efectos de los fármacos , Animales , Anticuerpos Monoclonales/inmunología , Astrocitos/efectos de los fármacos , Astrocitos/patología , Canales de Calcio/efectos de los fármacos , Recuento de Células , Giro Dentado/efectos de los fármacos , Giro Dentado/patología , Relación Dosis-Respuesta a Droga , Proteína Ácida Fibrilar de la Glía/inmunología , Glicina/administración & dosificación , Glicina/efectos adversos , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipertrofia/inducido químicamente , Hipertrofia/patología , Inmunohistoquímica , Masculino , Lóbulo Parietal/efectos de los fármacos , Lóbulo Parietal/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Esquizofrenia/inmunología , Esquizofrenia/patología , Transmisión Sináptica/efectos de los fármacos
5.
Cell Mol Biol (Noisy-le-grand) ; 46(4): 743-60, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10875437

RESUMEN

In several neurodegenerative diseases, iron accumulates at sites of brain pathology. Since post-mortem examination cannot distinguish whether iron accumulation caused the damage or resulted from damage, it is necessary to manipulate iron in animal and tissue culture models to assess its causal role(s). However, only in models of Parkinson's disease and of global ischemia, iron deprivation (ID) or iron-chelators have been used to protect from damage. In these studies, documentation of microgliosis was not performed even though several lines of evidence converge to suggest that activation of microglia is an important source of oxidative stress. In the kainate model of epilepsy, we found that ID protected the olfactory cortex, thalamus and hippocampus and attenuated microgliosis, whereas iron supplementation to ID rats increased damage and microgliosis in the above regions. In the hilus of the hippocampal dentate gyrus, even though no cell loss was observed, ID attenuated microgliosis and iron-supplementation increased it. Thus there is a tight relationship between iron and microgliosis. In addition, iron+zinc supplementation dramatically increased damage to hippocampal CA1 whereas zinc supplementation alone had no effect. This study demonstrates an anatomically unique interaction of iron and zinc, which may lead to new insights to neurodegeneration in epilepsy.


Asunto(s)
Hierro/metabolismo , Microglía/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Neuronas/metabolismo , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Dieta , Epilepsia/metabolismo , Ataxia de Friedreich/metabolismo , Humanos , Enfermedad de Huntington/metabolismo , Masculino , Microglía/patología , Esclerosis Múltiple/metabolismo , Enfermedades Neurodegenerativas/etiología , Neuronas/patología , Neurodegeneración Asociada a Pantotenato Quinasa/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo
6.
Med Law ; 11(1-2): 19-31, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1522774

RESUMEN

This article deals with the thorny issue of official authority to search for drugs in the bodies of suspected drug offenders. Relevant Israeli cases and legislation are discussed and a draft bill proposed.


Asunto(s)
Derechos Humanos , Defensa del Paciente/legislación & jurisprudencia , Detección de Abuso de Sustancias/legislación & jurisprudencia , Enema , Humanos , Israel , Prisiones/legislación & jurisprudencia , Estómago/cirugía , Detección de Abuso de Sustancias/métodos
7.
Physiol Behav ; 28(2): 323-33, 1982 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7079346

RESUMEN

Following extensive bilateral lateral hypothalamic damage, rats appear "somnolent." Cortical EEG shows persistent high voltage delta, reinforcing the impression of sleep. Preoperatively and postoperatively, we simultaneously measured cortical and subcortical (hippocampal and pontine) EEG, muscular events (neck muscle EMG and eye movement EOG), and behavior, which, as aggregates, differentially define quiet sleep, active sleep, and waking. Postoperatively, though cortical activity was persistently slow, subcortical EEG, muscular events, and behavior, as aggregates, revealed quiet sleep, active sleep, and waking, organized subcortically, intact and alternating, but disconnected from the persistent slow cortical activity. For example, preoperatively, active sleep included cortical low voltage fast activity, hippocampal theta, episodic pontine spike bursts, flat EMG, nd rapid eye movements, without any organized behavior. Postoperatively, the same aggregate of subcortical and muscular events indicated the presence of active sleep. Similarly so, for subcortically organized quiet sleep and spontaneous waking. Such waking, termed "drowsy-wakefulness," is a low-arousal form, perhaps related to drowsiness in other species, and to human hypersomnia.


Asunto(s)
Corteza Cerebral/fisiología , Hipocampo/fisiología , Hipotálamo/fisiología , Puente/fisiología , Vigilia/fisiología , Animales , Nivel de Alerta/fisiología , Ingestión de Líquidos , Ingestión de Alimentos , Electroencefalografía , Potenciales Evocados , Masculino , Muridae , Vías Nerviosas/fisiología , Fases del Sueño/fisiología
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