Congenital diaphragmatic hernia and retinoids: searching for an etiology

Congenital diaphragmatic hernia (CDH) is a major life-threatening cause of respiratory failure in the newborn. Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the epidemiology and pathophysiology of human CDH, the metabolism of retinoids and the implications of retinoids in the development of the diaphragm and lung. Finally, we describe the existing evidence of a disruption of the retinoid-signaling pathway in CDH

The effect of a brinzolamide/brimonidine fixed combination on optic nerve head blood flow in rabbits.

PurposeThe purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits.MethodsA crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day's first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point.ResultsThere were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P ConclusionBBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF

A ginger extract improves ocular blood flow in rats with endothelin-induced retinal blood flow dysfunction

Abstract The aim of this study was to investigate the effect of a ginger extract on optic nerve head blood flow (ONH BF) under endothelin-1 (ET-1) stimulation. Using laser speckle flowgraphy, we measured ONH BF in brown Norway rats. To establish the ONH BF impairment profile under ET-1 stimulation, we administered an intravitreal injection of ET-1 under anesthesia. We then gave the ginger extract sublingually to assess its effect on ONH BF in both normal and ET-1-induced ischemic conditions. Post ET-1 injection, there were no significant changes in parameters including intraocular pressure or systemic factors. ONH BF showed a dose-dependent decline after ET-1 injection, with a significant reduction after a 2.50 pmol ET-1 dose. Sublingual administration of the ginger extract significantly improved ONH BF in both normal and ET-1-stimulated rats. This suggests that our newly developed supplement for improving ONH BF has a potential role in retinal ischemic diseases, including glaucoma

Sex differences in the association between systemic oxidative stress status and optic nerve head blood flow in normal-tension glaucoma.

PurposeTo investigate the association of systemic oxidative stress markers and optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients, as well as sex differences in this association.MethodsThis was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9±14.1 years). Laser speckle flowgraphy (LSFG) was used to measure ONH blood flow (mean blur rate in the tissue area of the ONH; MBR-T) and LSFG pulse-waveform parameters, including flow acceleration index in the tissue area of the ONH (FAI-T). Oxidative stress markers, diacron-reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) were measured with a free radical elective evaluator. Spearman's rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow.ResultsMBR-T was significantly correlated with age (rs = -0.28, p ConclusionA lower serum antioxidant level, as indicated by BAP, was associated with reduced ONH blood flow only in male NTG patients. Our findings suggest that there are sex differences in the involvement of oxidative stress in the pathogenesis of reduced ocular blood flow in NTG

Sex differences in the association between systemic oxidative stress status and optic nerve head blood flow in normal-tension glaucoma

Purpose To investigate the association of systemic oxidative stress markers and optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients, as well as sex differences in this association. Methods This was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9±14.1 years). Laser speckle flowgraphy (LSFG) was used to measure ONH blood flow (mean blur rate in the tissue area of the ONH; MBR-T) and LSFG pulse-waveform parameters, including flow acceleration index in the tissue area of the ONH (FAI-T). Oxidative stress markers, diacron-reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) were measured with a free radical elective evaluator. Spearman’s rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow. Results MBR-T was significantly correlated with age (rs = -0.28, p Conclusion A lower serum antioxidant level, as indicated by BAP, was associated with reduced ONH blood flow only in male NTG patients. Our findings suggest that there are sex differences in the involvement of oxidative stress in the pathogenesis of reduced ocular blood flow in NTG

Dysgerminoma with Estrogen-Producing Functioning Stroma Presenting Precocious Puberty

Dysgerminoma is a malignant ovarian germ cell tumor, and unlike sex-cord stromal tumors, endocrine manifestation is considered rare. Here, we report the first case of dysgerminoma presenting precocious puberty. The patient is a 7-year-old girl who presented with a breast development in Tanner stage 3. Serum estradiol (E2) was markedly elevated while luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were suppressed below the detection limit. Microscopically, the right ovarian mass displayed nests of large polygonal cells and fibrous septa which were focally concentrated by theca-like plump spindle cells. Immunohistochemistry revealed that the spindle cells expressed various steroidogenic enzymes involved in estrogen biosynthesis including P450 aromatase. The tumor was diagnosed with pure dysgerminoma with estrogen-producing functioning stroma. After the operation, serum E2 declined below the detection limit; LH and FSH returned within the normal range. This case demonstrates that even a conventional dysgerminoma can present endocrine manifestation through functioning stroma