[Anti-scarring effect of rapamycin following filtering surgery in rabbit eyes].

OBJECTIVE: To study the effect of rapamycin on scar formation in rabbit eyes following filtering operation and explore the possible mechanism. METHODS: Ninety-six healthy adult rabbits were subjected to trabeculectomy of the left eye and subsequently randomly divided into 4 groups (n=24) for treatment with castor oil (control) or rapamycin (1%, 3%, or 5%) eye drops of the operated eyes 4 times a day. The morphology and function of the filtering blebs of the rabbits were compared at 7, 14, 21 and 28 days after the operation; at each of the time points, 6 rabbits from each group were euthanized for detection of expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in the tissues in the surgical area using immunohistochemistry. Cultured rabbit subconjunctival fibroblasts (RTFSs) were treated with different concentrations of rapamycin (0.06, 0.25, 1, and 4 mg/L) and the cell apoptosis was detected using flow cytometry. RESULTS: In the first, second and third weeks after the operation, the rate of functional follicle formation was significantly higher in the 3 rapamycin groups than in the control group (P < 0.05), and the number of α- SMA-positive fibroblasts decreased over time in the 3 rapamycin groups. In cultured RTFSs, treatment with rapamycin at different concentrations resulted in increased apoptosis of the cells, and rapamycin above 0.25 mg/L significantly increased the cell apoptosis in a dose-dependent manner. CONCLUSIONS: Rapamycin can inhibit hyperplasia of the filtering passage tissue, helps to preserve the functional filtering blebs and prolong their life span, and induces apoptosis of RTFS.

Corneal differences between healthy and subclinical patients assessed using two diferente corneal tomographers / Diferenças entre as córneas de pacientes saudáveis e pacientes subclínicos avaliados com dois tipos de tomógrafos de córnea

ABSTRACT Purpose: To analyze subclinical keratoconus topography indexes using Pentacam and Orbscan-II measurements to identify evidences for seeking sensitive indexes to screen and diagnose subclinical keratoconus. Methods: Fifty healthy participants (50 eyes) and 40 patients with subclinical keratoconus (40 eyes) were included. Seven common parameters including corneal thickness at the thinnest point; minimum curvature of the front surface (minimum simulated keratometry value, SimK's Min); maximum curvature of the front surface (maximum simulated keratometry value, SimK's Max); the frontal corneal surface best-fit spherical radius of the curvature; the back corneal surface best-fit spherical radius of curvature; the anterior corneal surface height (anterior Diff value); and the posterior corneal surface height (posterior Diff value) measured by Pentacam and Orbscan-II between normal and subclinical keratoconus eyes were compared. Results: Statistical differences between the healthy and subclinical keratoconus groups (p<0.01) were found in all corneal parameters measured using both devices. Differences in the minimum curvature of the front surface (SimK's Min), thinnest point, anterior Diff value, and posterior Diff value were significant between Pentacam and Orbscan-II in the subclinical keratoconus group (p<0.05). Conclusion: The findings of this study identify the differences between normal and subclinical keratoconus eyes at the minimum curvature of the front surface, maximum curvature of the front surface, frontal corneal surface best-fit spherical radius of curvature, back corneal surface best-fit spherical radius of curvature, Anterior Diff value, and Posterior Diff value measures using Orbscan II and Pentacam that can help eye care practitioners clinically diagnose subclinical keratoconus.

RESUMO Objetivo: Analisar os índices subclínicos de to pografia de ceratocone utilizando as medidas feitas com Pentacam e com Orbscan-II para identificar evidências para a busca de índices sensíveis para triagem e diagnóstico de ceratocone subclínico. Métodos: Cinquenta participantes saudáveis (50 olhos) e 40 pacientes com ceratocone subclínico (40 olhos) foram incluídos. Sete parâmetros comuns, incluindo a espessura da córnea no ponto mais fino; a curvatura mínima da superfície frontal (valor mínimo da ceratometria simulada, Min de SimK); a curvatura máxima da superfície frontal (valor máximo da ceratometria simulada, Max de SimK); a superfície frontal e a superfície posterior da córnea de melhor ajuste ao raio da curvatura, a altura da superfície anterior da córnea (valor Diff anterior) e a altura da superfície corneana posterior (valor Diff posterior) medidos pelo Pentacam e pelo Orbscan-II entre os olhos normais e com ceratocone subclínico foram comparados. Resultados: As diferenças estatísticas entre os grupos saudável e com ceratocone subclínico (p<0,01) foram encontradas em todos os parâmetros corneanos medidos usando ambos os dispositivos. Diferenças na curvatura mínima da superfície frontal (Min de SimK) no ponto mais fino, no valor Diff anterior e no valor Diff posterior foram significativas entre Pentacam e Orbscan-II no grupo com ceratocone subclínico (p<0,05). Conclusão: Os achados deste estudo identificam as diferenças entre olhos normais e com ceratocone subclínico para a curvatura mínima da superfície frontal, a curvatura máxima da superfície frontal, a superfície corneana frontal e a superfície corneana posterior de melhor ajuste ao raio esférico da curvatura e as medidas de Diff anterior e posterior usando Orbscan II e o Pentacam que podem auxiliar os profissionais de oftalmologia a diagnosticar clinicamente o ceratocone subclínico.

Corneal differences between healthy and subclinical patients assessed using two diferente corneal tomographers.

PURPOSE: To analyze subclinical keratoconus topography indexes using Pentacam and Orbscan-II measurements to identify evidences for seeking sensitive indexes to screen and diagnose subclinical keratoconus. METHODS: Fifty healthy participants (50 eyes) and 40 patients with subclinical keratoconus (40 eyes) were included. Seven common parameters including corneal thickness at the thinnest point; minimum curvature of the front surface (minimum simulated keratometry value, SimK's Min); maximum curvature of the front surface (maximum simulated keratometry value, SimK's Max); the frontal corneal surface best-fit spherical radius of the curvature; the back corneal surface best-fit spherical radius of curvature; the anterior corneal surface height (anterior Diff value); and the posterior corneal surface height (posterior Diff value) measured by Pentacam and Orbscan-II between normal and subclinical keratoconus eyes were compared. RESULTS: Statistical differences between the healthy and subclinical keratoconus groups (p<0.01) were found in all corneal parameters measured using both devices. Differences in the minimum curvature of the front surface (SimK's Min), thinnest point, anterior Diff value, and posterior Diff value were significant between Pentacam and Orbscan-II in the subclinical keratoconus group (p<0.05). CONCLUSION: The findings of this study identify the differences between normal and subclinical keratoconus eyes at the minimum curvature of the front surface, maximum curvature of the front surface, frontal corneal surface best-fit spherical radius of curvature, back corneal surface best-fit spherical radius of curvature, Anterior Diff value, and Posterior Diff value measures using Orbscan II and Pentacam that can help eye care practitioners clinically diagnose subclinical keratoconus.

Silibinin declines blue light-induced apoptosis and inflammation through MEK/ERK/CREB of retinal ganglion cells.

Purpose: This study aimed to assess the protective effects of silibinin on blue light-emitting diode (LED)-induced retinal ganglion cells (RGCs) damage. Methods: Silibinin was applied in RGCs damage in vitro model to test its protective effects. Cell viability was assessed with the MTT method and cell apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. The expressions of apoptosis related proteins and influenced signalling pathways were measured using western blotting and immunohistochemistry. Inflammatory factors induced by RGC damage were detected using ELISA method. Results: It was found that silibinin in 50 and 100 µM treatment showed a significant protective effect in RGCs under blue light damage. Apoptosis assay showed that silibinin treatment could significantly improve the apoptotic status of RGCs. When the potentially affected signal pathway was considered, blue light would down-regulate the expression of MEK1/ERK/CREB. The levels of inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-10) were significantly regulated by silibinin treatment. Conclusions: Silibinin pretreatment would demonstrate protective effect against blue light induced acute RGCs damage. Silibinin treatment has a direct suppression of apoptosis and inflammation through the activation of MEK/ERK/CREB pathway in vitro.

[Anti-scarring effect of rapamycin in rabbits following glaucoma filtering surgery].

OBJECTIVE: To study the anti- scarring effect of rapamycin in rabbits receiving glaucoma filtering surgery. METHODS: Ninety-six Chinchilla rabbits were randomized equally into 3 rapamycin treatment groups and one control group. All the rabbits underwent trabeculectomy, after which the rabbits in the 3 rapamycin groups were treated with eye drops containing 1%, 3%, or 5% rapamycin in the operated eyes, and those in the control groups were given castor oil 4 times a day. The intraocular pressure (IOP) and inflammatory reaction in the treated eyes were observed, and the PCNA-positive cells in the filtering bleb were detected using immunohistochemistry. RTFs isolated from the Tenon's capsule of the rabbits were cultured in vitro, and the expressions of caspase-3, caspase-8, and caspase-9 in the fibroblasts were detected after treatment with different concentrations of rapamycin. RESULTS: The IOP was significantly lower in rapamycin-treated group than in the control group after the surgery (P < 0.05). The counts of the PCNA-positive cells were significantly lower in rapamycin-treated rabbits than in the control group (P < 0.05). Rapamycin treatment dose-dependently increased the expressions of caspase-3 and caspase- 9 at both the mRNA (P < 0.001) and protein (P < 0.001) levels without causing significant changes in the expressions of caspase-8. CONCLUSIONS: Rapamycin can inhibit excessive proliferation of the fibroblasts in the filtering bleb to reduce scar formation after glaucoma filtration surgery in rabbits. Rapamycin also increases the expressions of caspase-3 and caspase-9 to induce apoptosis of the RTFs.

Metabolic memory in mitochondrial oxidative damage triggers diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a microvascular complication induced by high blood glucose. This study was conducted to investigate the effect of metabolic memory on mitochondrial oxidative damage-induced DR. METHODS: Rat retinal endothelial cells (rRECs) were isolated from SD rats and treated with high glucose (20 mM) for various times and then cultured in normal glucose (5.6 mM) medium for 2 days. The cells were assayed for the expression of respiratory chain complexes cytochrome c oxidase subunit 1 (CO1) and NADPH-1 using RT-PCR, mitochondrial membrane potentials and reactive oxygen species (ROS) production using flow cytometry and apoptosis using Annexin V/PI flow cytometry. RESULTS: rRECs displayed like short spindles after cultured for 9-10 days and reached 100% confluency. Compared with the control grown in normal glucose (5.6 mM) medium, rRECs exposed to high glucose medium for 3, 12 and 24 h had significantly increased mRNA levels of CO1 and NAPDH-1 even after being shifted back to normal glucose medium. They also had lower mitochondrial membrane potential (89.13% vs 78.21%, p < 0.05), cytochrome C level (1 in control vs 0.25 after 24 h exposure to high glucose, p < 0.05 and higher ROS production (2.77% in control vs 9.00% after 12 h exposure to high glucose, p < 0.05) and apoptosis (7.15% in control vs and 29.91% after 24 h exposure to high glucose, p < 0.05). CONCLUSION: It is likely that mitochondrial oxidative damage triggers metabolic memory via ROS overproduction, leading to diabetic retinopathy.

[The metastatic pattern of thoracic lymph nodes in 306 patients with lung cancer].

BACKGROUND: To study the metastatic pattern of thoracic lymph nodes in patients with resectable lung cancer. METHODS: From January 1992 to December 2000, radical lobectomy or pneumonectomy and systemic lymphadenectomy were performed in 306 patients with lung cancer. Number, size, colour and hardness of lymph nodes in each region were recorded and neoplastic metastasis was examined by pathology. RESULTS: Out of 4 614 resected lymph nodes from 2 456 regions, 954 lymph nodes from 521 regions were confirmed to have metastasis. The metastatic rates of thoracic lymph nodes and mediastinal lymph nodes were 61.8% and 43.5% , respectively. The metastatic frequencies in regions around the hilar or root of lung (11,10,7,5,4) were higher than those of regions far from the root of lung (9,6,3,2,1). There was a remarkably higher metastatic rate of lymph nodes in small cell lung cancer than that in non small cell lung cancer (P < 0.01 ). The metastatic rate was closely related to size, colour and hardness of lymph nodes (P < 0.001, P < 0.001 , P < 0.001 ). CONCLUSIONS: Most of neoplastic metastasis of lymph nodes spreads from proximal to distal areas, lower to upper regions, and from the hilar to the mediastinal. A few mediastinal lymph nodes show a skipping pattern. It is necessary to perform systemic lymphadenectomy during pulmonary resection.

[Carinal resection and bronchial sleeve lobectomy in the treatment of central lung cancer: A report of 105 cases].

BACKGROUND: To summarize the experience of carinal resection and bronchial sleeve lobectomy in the treatment of 105 patients with central lung cancer from November, 1991, to November, 2001. METHODS: A total of 105 patients with central lung cancer underwent pulmonary resection. Carinal resection and reconstruction was performed in 19 patients, bronchial sleeve resection in 81, and bronchial sleeve combined with pulmonary artery sleeve lobectomy in 5. RESULTS: There was no operative mortality. Postoperative complications such as anastomotic leakage, cardiac arrhythmia, asthma, pulmonary atelectasis occurred in 10.5% of total group. The 1-, 3- and 5- year survival rates were 89.9%, 60.0% and 47.2%, respectively. CONCLUSIONS: Bronchial sleeve lobectomy and double-sleeve lobectomy are capable of excising pulmonary tumor as much as possible while remaining healthy lung tissues. Carinal resection and reconstruction is helpful to extend the surgical indication.