Long-term efficacy and safety of sirolimus for retinal astrocytic hamartoma associated with tuberous sclerosis complex.

Mammalian target of rapamycin (mTOR) inhibitors (sirolimus or everolimus) have been demonstrated effective in reducing the size of tuberous sclerosis complex (TSC)-associated retinal astrocytic hamartoma (RAH) in short term. To investigate the long-term efficacy and safety of sirolimus on TSC-associated RAH, 13 TSC-associated RAH patients (59 RAH lesions) who received sirolimus therapy for at least 2 years were retrospectively enrolled in this study. Changes in the maximal thickness (MT) of RAH on optical coherence tomography and the longest base diameter (LBD) of RAH on color fundus photography were assessed. The results showed that for a mean follow-up of 39 months, sirolimus was associated with a mean reduction of 14.6% in MT and 6.8% in LBD of RAHs. The main impacts of sirolimus occurred within the first 6-12 months, with 14.8% reduction in MT and 4.7% reduction in LBD. Mouth ulceration (10 [76.9%]) and acne (9 [69.2%]) were the most common adverse events. These follow-up data support the long-term use of sirolimus in TSC-associated RAH patients, and persistent use of sirolimus possibly prevents tumor regrowth.

Discovery of a series of 5-phenyl-2-furan derivatives containing 1,3-thiazole moiety as potent Escherichia coli ß-glucuronidase inhibitors.

Gut microbial ß-glucuronidases have drawn much attention due to their role as a potential therapeutic target to alleviate some drugs or their metabolites-induced gastrointestinal toxicity. In this study, fifteen 5-phenyl-2-furan derivatives containing 1,3-thiazole moiety (1-15) were synthesized and evaluated for their inhibitory effects against Escherichia coli ß-glucuronidase (EcGUS). Twelve of them showed satisfactory inhibition against EcGUS with IC50 values ranging from 0.25 µM to 2.13 µM with compound 12 exhibited the best inhibition. Inhibition kinetics studies indicated that compound 12 (Ki = 0.14 ± 0.01 µM) was an uncompetitive inhibitor for EcGUS and molecular docking simulation further predicted the binding model and capability of compound 12 with EcGUS. A preliminary structure-inhibitory activity relationship study revealed that the heterocyclic backbone and bromine substitution of benzene may be essential for inhibition against EcGUS. The compounds have the potential to be applied in drug-induced gastrointestinal toxicity and the findings would help researchers to design and develop more effective 5-phenyl-2-furan type EcGUS inhibitors.

Engineering Lignin Nanomicroparticles for the Antiphotolysis and Controlled Release of the Plant Growth Regulator Abscisic Acid.

Lignin is the most abundant aromatic biopolymer in nature and is a major byproduct from the paper industry. The unlocking of lignin's potential for high-value applications has gained increasing attention in recent years. In this study, alkali lignin (AL), with a rigid conjugated structure and amphiphilic property, was used as a sustainable and eco-friendly encapsulation material for the protection and controlled release of photosensitive abscisic acid (ABA), an important and widely used plant growth regulator. Cetyltrimethylammonium bromide (CTAB) was used to induce the formation of AL-CTAB nanomicroparticles by self-assembly. The size and morphology of AL-CTAB particles were modified by changing the AL concentration and the dispersion agent. AL (0.3 M) dissolved in tetrahydrofuran could form a uniform size (300 nm) of particles with a regular spherical structure. Subsequently, ABA was loaded on the prepared nanomicroparticles to synthesize the capsule formulation of ABA@AL-CTAB. The controlled-release behavior and the antiphotolysis performance as well as the thermal stability of ABA@AL-CTAB were proved to be superior. Lasting inhibition of Arabidopsis and rice seed germination by ABA@AL-CTAB under light irradiations implied protection of ABA from photolysis. In addition, ABA@AL-CTAB could effectively regulate plant stomata, thereby increasing plant drought resistance. Overall, lignin is suitable for the preparation of agrochemical formulations with excellent controlled release and antiphotolysis performances.

Optic Nerve Sheath Measurements by Computed Tomography to Predict Intracranial Pressure and Guide Surgery in Patients with Traumatic Brain Injury.

BACKGROUND: Research has shown that the optic nerve sheath diameter (ONSD) is a good predictor of intracranial pressure (ICP) and may predict the need for surgery in patients with head injury. The objective was to test the value of ONSD in predicting the requirement for surgery in patients with traumatic brain injury (TBI). METHODS: In this retrospective cohort study, we first verified the correlation between ICP and ONSD using data from 62 patients with TBI who had undergone ICP monitoring. Second, we analyzed head computed tomography images from patients with TBI who were admitted to the emergency department where patients had been divided into surgery or conservative treatment groups, dependent on the assessment of a neurosurgeon. The correlation between ICP and ONSD was measured using linear regression analysis. Biologistic and receiver operating characteristic curve analyses were used to test the diagnostic value of ONSD to predict surgery. RESULTS: ONSD was significantly correlated with ICP (r = 0.606; P < 0.01), and there was a significant linear regression equation (y = 0.071 × ICP + 3.533; P < 0.01), with ONSD predicting the requirement for surgery in patients with TBI (area under the curve, 0.920; P < 0.01; 95% confidence interval, 0.877-0.962). CONCLUSIONS: ONSD measured via head computed tomography correlates with ICP and can predict the requirement for surgery in patients with TBI following admission to the emergency department.

DNA Methylation and Uveal Melanoma.

OBJECTIVE: The objective of the study was to summarize the role of DNA methylation in the development and metastasis of uveal melanoma (UM). DATA SOURCES: The relevant studies in MEDLINE were searched. STUDY SELECTION: In this review, we performed a comprehensive literature search in MEDLINE using "uveal melanoma" AND ("DNA methylation" OR "epigenetics") for original research/review articles published before February 2018 on the relationship between DNA methylation and UM. References of the retrieved studies were also examined to search for potentially relevant papers. RESULTS: Previous studies on the relationship between DNA methylation and UM covered many genes including tumor suppressor genes (TSGs), cyclin-dependent kinase genes, and other genes. Among them, the TSG genes such as RASSF1A and p16INK4a, which encodes a cyclin-dependent kinase inhibitor, are relatively well-studied genes. Specifically, a high percentage of promoter methylation of RASSF1A was observed in UM cell lines and/or patients with UM. Promoter methylation of RASSF1A was also associated with the development of metastasis. Similarly, a high percentage of promoter hypermethylation of p16INK4a was found in UM cell lines. DNA promoter methylation can control the expression of p16INK4a, which affect cell growth, migration, and invasion in UM. Many other genes might also be involved in the pathogenesis of UM such as the Ras and EF-hand domain containing (RASEF) gene, RAB31, hTERT, embryonal fyn-associated substrate, and deleted in split-hand/split-foot 1. CONCLUSIONS: Our review reveals the complex mechanisms underlying the tumorigenesis of UM and highlights the great needs of future studies to discover more genes/5'-C-phosphate-G-3' sites contributing to the development/metastasis of UM and explore the mechanisms through which epigenetic changes exert their function in UM.

[Choroidal thickness in normal subjects measured by enhanced depth imaging optical coherence tomography].

OBJECTIVE: To evaluate the efficiency of enhanced depth imaging optical coherence tomography (EDI-OCT) on quantifying choroidal thickness (CT) in normal subjects. METHODS: This was a cross-sectional study. From June to November 2011, 129 eyes of 129 normal subjects were enrolled in this study and divided into three groups by age distribution. Group A, 43 eyes, 22 to 40 years old; group B, 42 eyes, 41 to 60 years old and group C, 44 eyes, 61 to 79 years old. They were examined with EDI-OCT for CT. The choroid was measured from the posterior edge of the retinal pigment epithelium to the choroid-scleral junction at 500 µm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. The paired t test was used to analyze differences in CT by location in the macula. One-way analysis of variance (ANOVA) was conducted to compare mean CT in different groups. Subsequently the data between two groups were analyzed by least significant difference (LSD-t). The reliability was evaluated by intraclass correlation coefficient (ICC). RESULTS: The choroid was thickest beneath the fovea (305.9 ± 78.2) µm. The mean CT decreased rapidly in the nasal direction and gradually in the temporal direction, reaching (159.0 ± 67.3) µm at 3 mm nasal to the fovea and (256.8 ± 73.6) µm at 3 mm temporal to the fovea. There was a significant difference between subfoveal CT and CT at all extrafoveal locations (t = 4.021 to 34.544, P < 0.05). There was also a significant difference of CT at all locations among three age groups (F = 34.122 to 72.239, P < 0.05). CT was significantly greater in group A than group B and C at all locations (P = 0.000, 0.000). It was also significantly greater in group B than group C (P = 0.000). The inter-examination ICC values ranged from 0.979 to 0.996. The intraobserver ICC values ranged from 0.981 to 0.997. The interobserver ICC values ranged from 0.971 to 0.995. CONCLUSIONS: Normal CT can be measured accurately by EDI-OCT. There are significant differences of CT between different age groups in normal subjects.

Spectral domain optical coherence tomography of Vogt-Koyanagi-Harada disease: novel findings and new insights into the pathogenesis.

OBJECTIVE: To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease. METHODS: Detailed SD OCT and fluorescein angiography (FA) findings of 18 consecutive VKH patients (11 women and 7 men) from December 2007 to April 2009 who were in acute uveitic stage at presentation were reviewed. All the patients had been followed up for at least 6 months with reevaluation(s) of SD OCT performed in 10 patients. RESULTS: Intraretinal cysts were found to be located in various layers of the outer retina. In addition to the photoreceptor layer, they could also be found between the outer plexiform layer and the outer nuclear layer, or spanning the external limiting membrane. On FA, intraretinal cysts could be hypofluorescent, normofluorescent, or hyperfluorescent. Some intraretinal cysts had a characteristic FA pattern, in which a small round hypofluorescent area was surrounded by a ring of hyperfluorescence (donut-shaped dye pooling). Subretinal fibrinoid deposit appeared in acute uveitic stage in two severe VKH patients and seemed to develop from subretinal exudates and evolved into typical subretinal fibrosis. Gradual transfiguration/migration and progressive proliferation/pigmentation of the subretinal fibrinoid deposit/subretinal fibrosis was observed in one patient. CONCLUSIONS: Intraretinal cysts could form in various layers of the outer retina and may result from extension of choroidal inflammation. Subretinal fibrosis may develop from subretinal exudates in VKH patients and may cause substantial visual impairment.

[Analysis of fundus fluorescein angiography, indocyanine green angiography and choroidal thickness in central serous chorioretinopathy].

OBJECTIVE: To evaluate the characteristics of choroidal thickness changes and abnormalities in choroidal circulation in cases of central serous chorioretinopathy (CSC). METHODS: This was a case control study, we measured the bilateral choroidal thickness in 21 patients with unilateral CSC and 24 eyes of 24 age- and sex-matched normal subjects using enhanced depth imaging optical coherence tomography (EDI-OCT). The choroid was measured from the posterior edge of the retinal pigment epithelium (RPE) to the choroid-scleral junction at 500 µm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Paired-samples t-test was conducted to compare mean choroidal thicknesses between symptomatic eyes and fellow eyes of patients. The datum between patients and normal subjects were analyzed by independent-samples t-test. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed and the digital images were analyzed in CSC patients. RESULTS: The 21 CSC patients had a mean age of 45.6 years, and 12 patients (57.1%) were male. The choroid in symptomatic eyes was thickest beneath the fovea (519.0 ± 102.5) µm. It was significantly thicker than that in the fellow eyes (439.3 ± 94.1) µm (t = 4.171, P < 0.05). Choroidal thickness in both groups was significantly greater than that in the eyes of age- and sex-matched normal subjects (332.0 ± 67.3) µm (t = 7.125, 4.441; P < 0.05). Choroidal thickness at each of the other 12 points showed a similar tendency (t = 2.544 to 3.819, 4.799 to 7.816, 2.487 to 5.236; P < 0.05). ICGA showed a choroidal filling delay (100%), vessels dilation (90.5%), and focal choroidal hyperfluorescence (100%) surrounding leakage from the RPE in symptomatic eyes. Pigment epithelium detachment with abnormal choroidal circulation was observed in 6 fellow eyes. In 4 symptomatic eyes and 11 fellow eyes, ICGA revealed choroidal hyperfluorescence but FFA showed normal appearance. CONCLUSIONS: CSC seems to be a bilateral eye disease with choroidal focal ischemia followed by vessels congestion and hyperpermeability. EDI OCT is a useful tool for monitoring choroidal thickness changes caused by choroidal vascular hyperpermeability.

[Features of vitreomacular traction syndrome assessed with three-dimensional spectral-domain optical coherence tomography].

OBJECTIVE: To describe features of vitreomacular traction syndrome (VMT) on three-dimensional (3D) spectral-domain optical coherence tomography (SD OCT). METHODS: Eighteen eyes of 18 patients with VMT were diagnosed by SD OCT. SD OCT images were obtained and retrospectively analyzed. These VMT cases were defined as focal type or broad type by the region of the vitreous attachment to the macula. The relationship between the logMAR best corrected visual acuity (BCVA) and the retinal thickness of macular fovea was evaluated by linear regression analysis. RESULTS: SD OCT provided detailed 3D images of VMT and revealed information about the extent of vitreomacular traction. Focal VMT was seen in 14 eyes. Broad VMT was seen in four eyes. Eight cases had concurrent epiretinal membrane in the areas surrounding the fovea. Two cases had concurrent full thickness macular hole and two cases had concurrent lamellar macular hole. LogMAR BCVA correlated with the retinal thickness of macular fovea (r = 0.616, P = 0.007, linear regression analysis). CONCLUSIONS: SD OCT allows good visualization of the architectural morphology of the vitreous and retina in vitreomacular traction syndrome. It is useful and irreplaceable for the diagnosis and follow-up of VMT.