RESUMEN
La queratitis numular es un proceso inflamatorio de la córnea que se caracteriza por múltiples depósitos subepiteliales y para la cual se han propuesto diversas aproximaciones terapéuticas. Se realizó una revisión retrospectiva de las historias clínicas de pacientes diagnosticados con queratitis numular entre los años 2009 y 2017, que incluyó 21 ojos de 16 pacientes tratados con una inyección intraestromal combinada de ganciclovir y betametasona de depósito. Al finalizar el tratamiento, 18 ojos (85,71%) estaban asintomáticos. Esta mejora se mantuvo durante un tiempo medio de seguimiento de 22,90 meses. La combinación de betametasona de depósito mezclada con ganciclovir mediante aplicación intraestromal es una buena alternativa para el tratamiento de la queratitis numular
Nummular keratitis is an inflammatory process of the cornea that is characterised by multiple sub-epithelial deposits, for which a variety of therapeutic approaches have been proposed. A retrospective review was performed using the medical records of patients diagnosed with nummular keratitis and treated with a combined intrastromal injection of ganciclovir and depot betamethasone between the years 2009 and 2017. A total of 21 eyes of 16 patients were finally included. Upon termination of the treatment, 18 eyes (85.71%) were asymptomatic. This improvement was maintained during a mean follow-up time of 22.90 months. Depot betamethasone mixed with ganciclovir by intrastromal application is a good alternative for the treatment of nummular keratitis
Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Betametasona/uso terapéutico , Ganciclovir/uso terapéutico , Queratitis/tratamiento farmacológico , Betametasona/administración & dosificación , Sustancia Propia , Preparaciones de Acción Retardada , Evaluación de Medicamentos , Quimioterapia Combinada , Estudios de Seguimiento , Ganciclovir/administración & dosificación , Inyecciones Intraoculares , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Nummular keratitis is an inflammatory process of the cornea that is characterised by multiple sub-epithelial deposits, for which a variety of therapeutic approaches have been proposed. A retrospective review was performed using the medical records of patients diagnosed with nummular keratitis and treated with a combined intrastromal injection of ganciclovir and depot betamethasone between the years 2009 and 2017. A total of 21 eyes of 16 patients were finally included. Upon termination of the treatment, 18 eyes (85.71%) were asymptomatic. This improvement was maintained during a mean follow-up time of 22.90 months. Depot betamethasone mixed with ganciclovir by intrastromal application is a good alternative for the treatment of nummular keratitis.
Asunto(s)
Betametasona/uso terapéutico , Ganciclovir/uso terapéutico , Queratitis/tratamiento farmacológico , Adulto , Anciano , Betametasona/administración & dosificación , Sustancia Propia , Preparaciones de Acción Retardada , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Ganciclovir/administración & dosificación , Humanos , Inyecciones Intraoculares , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: The calcium-sensitizing drug levosimendan increases myocardial contractility and, by activating K(+)-channels, dilates pulmonary vessels. In the acute setting, levosimendan is clinically used to treat right heart failure in pulmonary hypertension. As K(+)-channel activation elicits several beneficial effects in the vascular system, we hypothesized that levosimendan also attenuates the remodeling process in the monocrotaline model of rat pulmonary hypertension. METHODS AND RESULTS: Animal subgroups received levosimendan, the K(+)-channel opener nicorandil, or levosimendan together with the K(+)-adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) blocker glibenclamide. Morphometric analyses revealed that levosimendan and nicorandil attenuated the increased pulmonary vascular medial wall thickness after monocrotaline challenge. Accordingly, in vivo BrdU assays revealed that levosimendan significantly diminished proliferation of pulmonary arterial smooth muscle cells (PASMCs), and this effect was attenuated by glibenclamide. Levosimendan also reduced right ventricular hypertrophy, but this effect was not glibenclamide sensitive and not recapitulated by nicorandil. In cell culture, levosimendan had a direct inhibitory effect on the platelet-derived growth factor (PDGF)-induced proliferation of PASMCs, which however required high concentrations of the compound, pointing towards an endothelial effect. Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-α (TNF-α)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1). In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-α-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1α (HIF-1α), and nuclear factor-κB (NF-κB). CONCLUSIONS: Levosimendan attenuates pulmonary vascular remodeling, presumably by an antiproliferative and anti-inflammatory effect which is mediated by cellular hyperpolarization. The compound also has a direct inhibitory effect on cardiac hypertrophy, which is however K(+)-channel independent.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Hidrazonas/farmacología , Hipertensión Pulmonar/tratamiento farmacológico , Circulación Pulmonar/efectos de los fármacos , Piridazinas/farmacología , Animales , Cardiotónicos/administración & dosificación , Cardiotónicos/farmacología , Modelos Animales de Enfermedad , Alemania , Gliburida/administración & dosificación , Gliburida/farmacología , Hidrazonas/administración & dosificación , Hipertensión Pulmonar/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Contracción Miocárdica/efectos de los fármacos , Nicorandil/administración & dosificación , Nicorandil/farmacología , Canales de Potasio/efectos de los fármacos , Piridazinas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Simendán , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND AND PURPOSE Arachidonic acid derivatives play a central role in inflammation processes. Arachidonic acid is metabolized by several enzymes, particularly cyclooxygenases (COX), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E-synthase-1 (mPGES-1) to pro-inflammatory mediators. EXPERIMENTAL APPROACH We determined the effect of LP105, a pirinixic acid derivative which acts as inhibitor of 5-LOX, COX and mPGES-1, on aortic aneurysm development in mice and on 5-LOX activity in murine monocytes. KEY RESULTS In a monocyte cell line (RAW264.7), LP105 inhibited 5-LOX in whole cells (IC(50) : 1-3 µM) and in supernatants (IC(50) : â¼10 µM). Oral administration of LP105 to mice resulted in therapeutic tissue and plasma levels. Aortic aneurysms were induced in ApoE(-/-) mice by angiotensin II (AngII) and LP105 (5 mg·day(-1) per animal) was co-administered to a subgroup. Compared with animals receiving AngII alone, the LP105+AngII group showed a lower heart rate, a trend towards reduced heart to body weight ratio but similar hypertensive responses. AngII alone significantly increased aortic weight and diameter but co-treatment with LP105+AngII prevented these changes. LC/MS-MS studies revealed increased 15-hydroxytetraenoic acid (15-HETE) and 14,15-epoxyeicosatrienoic acid (14,15-EET) plasma levels in LP105-treated animals. In the murine kidney, mRNAs of EET-generating or metabolizing enzymes and of 5-LOX and 15-LOX were unaffected by LP105. LP105 also did not inhibit the EET-metabolizing soluble epoxide hydrolase. CONCLUSIONS AND IMPLICATIONS LP105 was a potent inhibitor of monocyte 5-LOX and reduced AngII-induced vascular remodelling in mice. A shift of arachidonic acid metabolism to the protective EET pathway may contribute to the beneficial effects of LP105.