Protective effect of etanercept, an inhibitor of tumor necrosis factor-α, in a rat model of retinal ischemia.

BACKGROUND: To assess the neuroprotective effect of etanercept (Enbrel®) which is a commercialized Tumor necrosis factor-α (TNF-α) inhibitor on axonal injury in an animal model of acute ischemia. METHODS: Acute ischemia was induced by intraocular pressure elevation in 36 rats. The treatment groups underwent subcutaneous injection of etanercept (0.3 or 1.0 mg/kg) three times per week up to 4 weeks. The control groups were treated in the same manner using the same volume of phosphate-buffered saline (PBS). Optic nerve damage was evaluated by counting the number of axons under a transmission electron microscope. Microglial cell activity was assessed using Iba1 and CD68. RESULTS: After induction of ischemia, the ratio of preserved axons was significantly greater in the 2-week 1.0-mg/kg etanercept-treated group than in the PBS-treated group (p = 0.062). The 4-week 0.3-mg/kg and 1.0-mg/kg etanercept-treated groups also showed significantly higher ratios of preserved axons than did the PBS-treated group (p = 0.021 and 0.003, respectively). The expression of Iba1 and CD68 in the optic nerve was lower in the etanercept-treated groups than in the PBS-treated groups. Immunohistochemical staining using rabbit anti-Iba1 antibody showed that the amount of microglia at the optic nerve head was noticeably lower in the etanercept-treated groups than in the PBS-treated groups. CONCLUSIONS: Etanercept significantly suppressed optic nerve injury in this rat model of acute ischemia. This in vivo study suggests that etanercept might be a novel neuroprotective treatment agent for TNF-α-related disease.

Effect of trabeculectomy on the accuracy of intraocular lens calculations in patients with open-angle glaucoma.

BACKGROUND: The objective of the study is to examine the effect of trabeculectomy on intraocular lens power calculations in patients with open-angle glaucoma (OAG) undergoing cataract surgery. DESIGN: The design is retrospective data analysis. PARTICIPANTS: There are a total of 55 eyes of 55 patients with OAG who had a cataract surgery alone or in combination with trabeculectomy. METHODS: We classified OAG subjects into the following groups based on surgical history: only cataract surgery (OC group), cataract surgery after prior trabeculectomy (CAT group), and cataract surgery performed in combination with trabeculectomy (CCT group). MAIN OUTCOME MEASURES: Differences between actual and predicted postoperative refractive error. RESULTS: Mean error (ME, difference between postoperative and predicted SE) in the CCT group was significantly lower (towards myopia) than that of the OC group (P = 0.008). Additionally, mean absolute error (MAE, absolute value of ME) in the CAT group was significantly greater than in the OC group (P = 0.006). Using linear mixed models, the ME calculated with the SRK II formula was more accurate than the ME predicted by the SRK T formula in the CAT (P = 0.032) and CCT (P = 0.035) groups. CONCLUSIONS: The intraocular lens power prediction accuracy was lower in the CAT and CCT groups than in the OC group. The prediction error was greater in the CAT group than in the OC group, and the direction of the prediction error tended to be towards myopia in the CCT group. The SRK II formula may be more accurate in predicting residual refractive error in the CAT and CCT groups.

Brimonidine reduces TGF-beta-induced extracellular matrix synthesis in human Tenon's fibroblasts.

BACKGROUND: Brimonidine is a highly selective α2 adrenergic agonist that has been widely used in anti-glaucoma eyedrops. The aim of this study was to investigate its putative anti-fibrotic role in the fibrosis caused by activated Tenon's fibroblasts. METHODS: Primary cultured human Tenon's fibroblasts were exposed to 2.0 ng/mL of transforming growth factor-ß1 (TGF-ß1) for up to 48 h. In the presence of various concentrations of brimonidine (from 0.0 to 10.0 µM), the expression levels of fibronectin, collagen types I and III, and ß-actin were determined by Western immunoblots. The expression of phosphorylated SMAD2/3 (p-SMAD2/3) was then evaluated using immunofluorescence. RESULTS: TGF-ß1 significantly increased the synthesis of fibronectin and collagens in human Tenon's fibroblasts; however brimonidine treatment distinctly attenuated the TGF-ß1-induced production of extracellular matrix (ECM) proteins. TGF-ß1 also changed the cellular morphology to be plump, while brimonidine treatment returned the cells to a spindle shape, similar to control fibroblasts. Regarding p-SMAD2/3, brimonidine treatment did not show any apparent changes in its expression. CONCLUSIONS: Our data revealed that brimonidine reduces TGF-ß-induced ECM synthesis in human Tenon's fibroblasts in vitro. This finding implies that topical administration of brimonidine may be helpful in reducing the fibrosis caused by the long-term use of topical anti-glaucoma medications.

Comparison of three types of images for the detection of retinal nerve fiber layer defects.

PURPOSE: To compare the clinical effectiveness of three types of images for detecting retinal nerve fiber layer (RNFL) defects. METHODS: Three image sets of 100 subjects (9 normal control subjects, 16 glaucoma suspects, and 75 glaucoma patients) were produced using color fundus photography, typical red-free RNFL photography, and blue reflectance RNFL photography with confocal scanning laser ophthalmoscopy (CSLO). A total of 300 images were rated twice in random order by five independent evaluators who were masked to the patient characteristics; each image was rated as normal, having a diffuse RNFL defect, or showing a wedge RNFL defect. Intraobserver and interobserver agreement, sensitivity, specificity, accuracy, and area under the curve were assessed. An additional analysis was performed for identifying differences in two black-and-white RNFL photographs. RESULTS: The results showed high intraobserver agreement, with relatively low interobserver agreements among the five evaluators. Blue reflectance RNFL photography with CSLO demonstrated the best performance in sensitivity, specificity, accuracy, and area under the curve. Blue reflectance RNFL images showed better accuracy than red-free RNFL images especially in subjects with wedge defects and in advanced glaucomatous cases. CONCLUSIONS: The RNFL images produced using blue reflectance with CSLO showed the best performance for the detection of RNFL defects, especially in cases with wedge defects and advanced glaucoma stages.

Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes.

BACKGROUND: In physiologic and pathologic conditions of the central nervous system (CNS), astrocytes are a double-edged sword. They not only support neuronal homeostasis but also contribute to increases in neuronal demise. A large body of experimental evidence has shown that impaired astrocytes play crucial roles in the pathologic process of cerebral ischemia; therefore, astrocytes may represent a breakthrough target for neuroprotective therapeutic strategies. Agmatine, an endogenous polyamine catalyzed from L-arginine by arginine decarboxylase (ADC), is a neuromodulator and it protects neurons/glia against various injuries. RESULTS: In this investigation, agmatine-producing mouse cortical astrocytes were developed through transduction of the human ADC gene. Cells were exposed to oxygen-glucose deprivation (OGD) and restored to a normoxic glucose-supplied condition. Intracellular levels of agmatine were measured by high performance liquid chromatography. Cell viability was evaluated by Hoechest/propidium iodide nuclear staining and lactate dehydrogenase assay. Expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase s (MMPs) were assessed by a reverse transcription polymerase chain reaction, Western immunoblots, and immunofluorescence. We confirmed that ADC gene-expressed astrocytes produce a great amount of agmatine. These cells were highly resistant to not only OGD but also restoration, which mimicked ischemia-reperfusion injury in vivo. The neuroprotective effects of ADC seemed to be related to its ability to attenuate expression of iNOS and MMPs. CONCLUSION: Our findings imply that astrocytes can be reinforced against oxidative stress by endogenous agmatine production through ADC gene transduction. The results of this study provide new insights that may lead to novel therapeutic approaches to reduce cerebral ischemic injuries.

Neuroprotective and neurite outgrowth effects of maltol on retinal ganglion cells under oxidative stress.

PURPOSE: To evaluate the neuroprotective and neurite outgrowth effects of maltol, a natural aroma compound, on retinal ganglion cells (RGCs) under oxidative stress in vitro. METHODS: Mouse primary RGCs were isolated using immunopanning-magnetic separation and exposed to H2O2 in the presence of maltol. The cell viability and apoptosis were determined by using adenosine 5'-triphosphate (ATP) assay and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. Neurite outgrowth was assessed by immunofluorescence for α-tubulin. The activation of nuclear factor-κB (NF-κB) was also evaluated using immunofluorescence. RESULTS: When the RGCs were exposed to 20 µM of H2O2 for 16 h, their viability dropped to 40.3±3.4%. However, the maltol treatment restored the cells in a dose-dependent manner. The viability recovered to 73.9±5.1% with 10 µM of maltol and even reached 175.1±11.3% with 2 mM of maltol, as measured by ATP assay. This oxidative stress significantly increased the number of TUNEL-positive RGCs, but the maltol drastically reduced the proportion of those apoptotic cells. The oxidative stress hampered the neurite outgrowth of the RGCs, whereas maltol restored their ability to sprout neurites. Regarding NF-κB, the active form of phosphorylated NF-κB (pNF-κB) increased the oxidative stress level but the maltol treatment again reduced it to an unstressful level. CONCLUSIONS: Our data revealed that maltol attenuated the oxidative stress-induced injury in the primary mouse RGCs. Its neuroprotective and neurite outgrowth effects seemed to be related to NF-κB signaling. Maltol has potential as a new neuroprotective therapeutic agent for oxidative stress-related ocular diseases, including glaucoma.

Is vitamin D status associated with open-angle glaucoma? A cross-sectional study from South Korea.

OBJECTIVE: Open-angle glaucoma (OAG) is one of the major chronic diseases involving the optic nerve. However, little is known about the association between vitamin D and OAG. The present study was conducted to test the hypothesis that lower vitamin D status is associated with greater prevalence of OAG. DESIGN: Cross-sectional study. Multivariable logistic regression was performed to examine the relationship between serum 25-hydroxyvitamin D (25(OH)D) and OAG after adjusting for traditional potential confounders. OAG was defined by the criteria of the International Society for Geographical and Epidemiological Ophthalmology. SETTING: The Fifth Korean National Health and Nutrition Examination Survey conducted in 2010-2011. SUBJECTS: Six thousand and ninety-four adult participants randomly selected from 192 surveys in 131 locations in South Korea. RESULTS: Multivariable-adjusted odds ratios of OAG across quintiles of decreasing 25(OH)D were 1.26, 1.00 (reference), 1.31, 1.36 and 1.69 (P for quadratic trend <0.01). The odds ratio for the lowest 25(OH)D quintile was significantly higher than that for the second quintile (P < 0.01). In addition, we discovered that the predictors for worsening of OAG, such as intraocular pressure or vertical and horizontal cup-to-disc ratios, had a significant relationship with 25(OH)D level. CONCLUSIONS: There was a reverse J-shaped association between 25(OH)D levels and the risk of OAG, with significantly elevated risk at lower 25(OH)D. The findings of this research suggest that vitamin D deficiency should be considered as a potential risk factor for the development of OAG. To our knowledge, the present study is the first one that shows an association between vitamin D status and OAG.

Instability of 24-hour intraocular pressure fluctuation in healthy young subjects: a prospective, cross-sectional study.

BACKGROUND: Elevated intraocular pressure (IOP) is a major risk factor for the development and/or progression of glaucoma, and a large diurnal IOP fluctuation has been identified as an independent risk factor of glaucoma progression. However, most previous studies have not considered the repeatability of 24-hour IOP measurements. The aim of this study was to evaluate the instability of 24-hour IOP fluctuations in healthy young subjects. METHODS: Ten healthy young volunteers participated in this prospective, cross-sectional study. Each subject underwent 24-hour IOP and systolic/diastolic blood pressure (SBP/DBP) assessments both in sitting and supine positions every 3 hours, once a week for 5 consecutive weeks. Mean ocular perfusion pressure (MOPP) was then calculated for both positions. The intraclass correlation coefficients (ICCs) of maximum, minimum, and fluctuation parameters were computed for IOP, SBP/DBP, and MOPP. Fluctuation was defined as the difference between maximum and minimum values during a day. RESULTS: Among the serial measurements taken over a 24-hour rhythm, the maximum/minimum values of IOP, as well as BP, showed excellent agreement: regardless of position, all ICC values were over 0.800. Most of the BP fluctuation values also showed excellent agreement. IOP fluctuation, however, did not show excellent agreement; the ICC of sitting IOP fluctuation was just 0.212. MOPP fluctuation also showed poor agreement, especially in the sitting position (ICC, 0.003). CONCLUSION: On a day to day basis, 24-hour IOP fluctuations were not highly reproducible in healthy young volunteers. Our results imply that a single 24-hour IOP assessment may not be a sufficient or suitable way to characterize circadian IOP fluctuations for individual subjects.

Adjusted color probability codes for peripapillary retinal nerve fiber layer thickness in healthy Koreans.

BACKGROUND: Though a newly developed spectral domain optical coherence tomography (OCT) is at the center of interests for many ophthalmologic researchers and clinicians, its own characteristics are not fully evaluated yet. The main purpose of this study was to establish the adjusted color probability codes for peripapillary retinal nerve fiber layer (RNFL) thickness in healthy Koreans and to compare them with original color codes provided by spectral domain OCT. METHODS: Two hundred ninety-five healthy Korean eyes were enrolled and their peripapillary RNFL thickness was measured by Cirrus OCT. For each decade of age, the normal thickness reference was determined on the basis of z-scores and the adjusted color probability codes were established. Then the agreements between adjusted and original color codes were calculated using weighted Kappa (Kw) coefficient. RESULTS: On the basis of Kw coefficient, the overall agreement between the adjusted and original probability color codes was not excellent (Kw range of 0.500 to 0.806). If the adjusted probability codes were assumed as a standard of comparison, the original color codes showed the false-negative in 11% of eyes and the false-positive in 0.3% of eyes for average RNFL thickness. CONCLUSIONS: Adjusted color probability codes judged by the Korean normative data showed a discrepancy with original codes. It implies that normal reference and adjusted probability codes for each ethnicity might be needed to determine whether a certain RNFL thickness is within normal range or not.

Visual fields and OCT role in diagnosis of glaucoma.

PURPOSE: To evaluate the clinical performance of visual field (VF) tests and optical coherence tomography (OCT) in diagnosing glaucoma. METHODS: One hundred sets of disc photographs, red-free fundus photographs, VF tests, and OCT images were presented progressively to seven ophthalmologists. Each set was provided in three steps: (1) the disc and red-free fundus photographs were shown first; (2) then, VF tests were also provided; and (3) finally, the OCT results were provided. The same process was repeated on another day. Kappa statistics were used to assess the intraobserver and interobserver agreement, as well as the agreement with the reference standard. RESULTS: The intraobserver agreement was almost perfect in this study and did not change markedly with the addition of diagnostic tools. The interobserver agreement increased from 0.54 to 0.61 when VF was added and increased slightly to 0.63 with OCT. The agreement with the reference standard also increased significantly from 0.48 to 0.61 after adding VF and increased slightly with additional OCT. CONCLUSIONS: An optic disc evaluation and VF test are sufficient to diagnose glaucoma in most cases. However, OCT can play an important role in detecting glaucoma in cases in which it cannot be identified by optic disc examination and VF.

Early rehabilitation versus conventional care after laparoscopic rectal surgery: a prospective, randomized, controlled trial.

BACKGROUND: Although early rehabilitation programs have been reported to be effective after laparoscopic colectomy, there is no report of the efficacy of rehabilitation programs after rectal cancer surgery. This study was designed to evaluate the efficacy of an early rehabilitation program after laparoscopic low anterior resection for mid or low rectal cancer in a randomized, controlled trial. METHODS: Ninety-eight patients who had undergone a laparoscopic low anterior resection with defunctioning ileostomy were randomized on a 1:1 basis to an early rehabilitation program (n = 52) or conventional care (n = 46). The primary endpoint was recovery rate at 4 days postoperatively. The secondary endpoints were recovery time, postoperative hospital stay, complications, readmission rates, pain on a visual analogue scale, and quality of life (QOL) according to Short Form 36. RESULTS: The recovery rates were not different in both groups (rehabilitation, 25 % vs. conventional, 13 %, p = 0.135). Recovery time and postoperative hospital stay was similar between the groups (rehabilitation, 137 h [107-188] vs. conventional, 146.5 h [115-183], p = 0.47; 7.5 days [7-11] vs. 8.0 days [7-10], p = 0.882). The complication rates did not differ between the two groups, but more complications were noted in the rehabilitation program group (42.3 vs. 24.0 %, p = 0.054), which was related to postoperative ileus (28.8 vs. 13.0 %, p = 0.057) and acute voiding difficulty (19.6 vs. 4.7 %, p = 0.032). There was no readmission within 1 month of surgery. Pain and QOL were similar in both groups. CONCLUSIONS: This randomized trial did not show that an early rehabilitation program is beneficial after laparoscopic low anterior resection. Our results confirm that postoperative ileus and acute voiding difficulty are major obstacles to fast-track surgery for mid or low rectal cancer. This study was registered (registration number NCT00606944).

Serodiagnosis of echinococcosis by ELISA using cystic fluid from Uzbekistan sheep.

According to increase of travel, the cases of imported echinococcosis have been increasing in Korea. The present study was undertaken to develop a serodiagnostic system for echinococcosis in Korea. For diagnosis of echinococcosis, the fluid of Echinococcus granulosus hydatid cysts was collected from naturally infected sheep in Uzbekistan. Also serum samples of infected patients who were surgically confirmed were collected in a hospital in Tashkent, Uzbekistan. According to the absorbance of 59 echinococcosis positive and 39 negative control serum samples, the cut-off value was determined as 0.27. The sensitivity and specificity of ELISA with hydatid fluid antigen were 91.5% and 96%, respectively. The antigen cross-reacted with the serum of some cysticercosis or clonorchiasis patients. However, immunoblot analysis on the cystic fluid recognized antigenic proteins of 7-, 16-, and 24-kDa bands in their dominant protein quantity and strong blotting reactivity. In conclusion, the present ELISA system using hydatid cyst fluid antigen from Uzbekistan sheep is sensitive and specific for diagnosis of echinococcosis cases.

Infection status of hydatid cysts in humans and sheep in Uzbekistan.

Uzbekistan is endemic of cystic echinococcosis (CE). In order to estimate endemicity of CE, we collected data from emergency surgery due to CE in 2002-2010 and also investigated the prevalence of hydatid cysts in the liver and lungs of sheep at an abattoir in Uzbekistan from July 2009 to June 2010. In 14 emergency hospitals, 8,014 patients received surgical removal or drainage of CE during 2002-2010, and 2,966 patients were found in 2010. A total of 22,959 sheep were grossly examined of their liver and lungs, and 479 (2.1%) and 340 (1.5%) of them were positive for the cyst in the liver and lungs, respectively. Echinococcus granulosus is actively transmitted both to humans and sheep, and CE is a zoonotic disease of public health priority in Uzbekistan.

Public effect of the 2022 Colorectal Cancer Awareness Campaign delivered through a metaverse platform.

Purpose: The Korean Society of Coloproctology has been conducting Colorectal Cancer Awareness Campaign, also known as the Gold Ribbon Campaign, every September since 2007. The 2022 campaign was held through a metaverse platform targeting the younger age group under the slogan of raising awareness of early-onset colorectal cancer (CRC). This study aimed to analyze the impact of the 2022 campaign on a metaverse platform. Methods: Anonymized survey data were collected from participants in the metaverse campaign from September 1 to 15, 2022. The satisfaction score of the participants was evaluated by sex, age group, and previous campaign participation status. Results: During the campaign, 2,770 people visited the metaverse. Among them, 455 people participated in the survey (response rate, 16.4%). Approximately 95% of the participants reported being satisfied with the information provided by the campaign, understood the necessity of undergoing screening for and prevention of early-onset CRC, and were familiar with the structure of the metaverse. The satisfaction score for campaign information tended to decrease as the participants' age increased. When the participants' overall level of satisfaction with the metaverse platform was assessed, teenagers scored particularly lower than the other age groups. The satisfaction scores for CRC information provided in the metaverse, as well as the scores for recognizing the seriousness and necessity of screening for early-onset CRC, indicated a high positive tendency (P<0.001). Conclusion: Most of the 2022 Gold Ribbon Campaign participants were satisfied with the metaverse platform. Medical society should pay attention to increasing participation in and satisfaction with future public campaigns.

Isolation of primary mouse retinal ganglion cells using immunopanning-magnetic separation.

PURPOSE: To establish an effective system for isolating primary retinal ganglion cells (RGCs) from newborn mice. METHODS: The retinas were separated from enucleated eyeballs of Crl:CD-1 mice on postnatal day 1 to 4. RGCs were purified using three different methods, including two-step immunopanning (TSI), direct magnetic separation (DMS), and immunopanning-magnetic separation (IMS). Harvested cells were maintained for 24 h in a defined medium and then examined with immunocytochemistry, western immunoblotting, and real-time reverse transcription polymerase chain reaction (RT-PCR) for glial cell-specific glial fibrillary acidic protein (GFAP) and amacrine cell-specific syntaxin 1. RESULTS: As determined with immunofluorescence staining, RGCs purified by TSI were sparsely mixed with GFAP-positive astrocytes, and RGCs isolated by DMS were frequently mixed with syntaxin 1-positive amacrine cells. However, RGCs collected by IMS were seldom contaminated by GFAP-positive or syntaxin 1-positive cells. On western immunoblots, TSI cells showed significant GFAP expression, and DMS cells showed apparent syntaxin 1 expression, but IMS cells did not. Results of the real-time RT-PCR showed a similar tendency to those of the immunocytochemistry and western immunoblots. CONCLUSION: Primary mouse RGCs were highly purified by the IMS method, combining the benefits of the TSI and DMS methods. This isolation method may provide a good experimental system for studying glaucoma in vitro.

Role of heat shock protein 47 in transdifferentiation of human tenon's fibroblasts to myofibroblasts.

BACKGROUND: Heat shock protein 47 (Hsp47) is a well-known molecular chaperone in collagen synthesis and maturation. The aim of this study is to investigate its putative role in the transdifferentiation of Tenon's fibroblasts to myofibroblasts. METHODS: Primary cultured human Tenon's fibroblasts were exposed to transforming growth factor-ß1 (TGF-ß1) for up to 48 hours. The mRNA levels of Hsp47 and α smooth muscle actin (αSMA) were determined by quantitative real time RT-PCR. After delivery of small interfering RNA (siRNA) molecules targeting Hsp47 into the cells, the expression of Hsp47 and αSMA proteins was determined by western immunoblotting. RESULTS: TGF-ß1 increased the mRNA expressions of both Hsp47 and αSMA in human Tenon's fibroblasts, as determined by quantitative real time RT-PCR. However, it induced the protein expression of only αSMA but not Hsp47, as determined by western immunoblots. When siRNAs specific for Hsp47 were introduced into those cells, the TGF-ß1-induced expression of αSMA was significantly attenuated on western immunoblots; after 48 hours of exposure to TGF-ß1, the relative densities of immunobands were 11.58 for the TGF-ß1 only group and 2.75 for the siRNA treatment group, compared with the no treatment control group (p < 0.001). CONCLUSIONS: Our data suggest that Hsp47 may be related to the TGF-ß1-induced transdifferentiation of human Tenon's fibroblasts to myofibroblasts.

Comparison of early mobilization and diet rehabilitation program with conventional care after laparoscopic colon surgery: a prospective randomized controlled trial.

PURPOSE: Although laparoscopic surgery may permit earlier recovery compared with open surgery, no published randomized controlled trial has investigated the benefit of a multimodal rehabilitation program after laparoscopic colonic resection. This study aimed to evaluate the efficacy of a rehabilitation program after laparoscopic colon surgery in the context of a randomized controlled trial. METHODS: Between September 2007 and October 2009, 100 patients who had received laparoscopic colon surgery were selected for the study and randomly assigned on a 1:1 basis to a rehabilitation program group with early mobilization and diet (n = 46) or conventional care group (n = 54). The rehabilitation program group received early oral feeding, early ambulation, and regular laxative. The primary outcome was recovery time, measured with criteria of tolerable diet for 24 hours, safe ambulation, analgesic-free, and afebrile status without major complications. Secondary outcomes were postoperative hospital stay, complications, quality of life by Short Form 36, pain by visual analog scale, and readmission. This study was registered (ID number NCT00606944, http://register.clinicaltrials.gov). RESULTS: Recovery time was shorter in the rehabilitation program group than in the conventional care group (median (interquartile range), 4 (3-5) d vs 6 (5-7) d, respectively; P < .0001). There was no difference in postoperative hospital stay between the 2 groups (rehabilitation program group, 7 (6-8) d vs conventional care group, 8 (7-9) d; P = .065). There was no difference in complication rates between the rehabilitation program group and conventional care group (10.9% vs 20.4%, respectively; P = .136). Quality of life and pain were similar in both groups. There were no readmissions or mortality. CONCLUSIONS: A rehabilitation program with early mobilization and diet after laparoscopic colon surgery results in reduced recovery time without increased complications. These results suggest that a multimodal rehabilitation program may increase the short-term benefits after laparoscopic colon surgery.

Ocular hypotensive effects of topically administered agmatine in a chronic ocular hypertensive rat model.

Agmatine, a primary polyamine and potential neuromodulator, exhibits a high affinity to the alpha2-adrenergic receptor as well as imidazoline receptors. As alpha2-adrenergic receptor agonists display positive ocular hypotensive effects, we assessed whether agmatine effectively lowers intraocular pressure (IOP) using a chronic ocular hypertensive rat model. We raised IOP in unilateral eyes of Sprague-Dawley rats by cauterizing three episcleral veins per eye. Four weeks later, we topically administered 10(-3) M agmatine solution 4 times a day for 6 consecutive weeks. After confirming the recovery of IOP to pretreatment level at 13 weeks after cauterization, the retinal ganglion cells (RGCs) were retrogradely labeled and counted. Eyes subjected to episcleral vein cauterization (EVC) demonstrated significant increases in IOP (48.39% increase over baseline IOP), and the elevated IOP was well maintained until 12 weeks. Topically administered agmatine powerfully lowered IOP to 30.29% of its pretreatment level, and the associated washout period was about two weeks. EVC was associated with a 55.44% loss of RGCs in the control group, but agmatine appeared to attenuate this RGC loss to 18.65%. Overall, topically administered agmatine appeared to effectively lower IOP and rescue RGCs in a chronic ocular hypertensive rat model. Although the mechanism underlying these effects is not yet established, it is possible that agmatine offers a powerful new ocular hypotensive agent for eyes with chronic ocular hypertension and/or glaucoma.

TGF-beta-induced interleukin-6 participates in transdifferentiation of human Tenon's fibroblasts to myofibroblasts.

PURPOSE: To gain a better understanding of the roles of interleukins (ILs) in subconjunctival fibrosis, we investigated their expression in transforming growth factor-beta1 (TGF-beta1)-stimulated Tenon's fibroblasts and examined their association with the transdifferentiation of fibroblasts to myofibroblasts. METHODS: After primary culture, fibroblasts derived from human Tenon's capsule were exposed to TGF-beta1. The expression of alpha-smooth muscle actin (alpha-SMA) protein was assessed by western immunoblots and immunofluorescence. The mRNA levels of various ILs were also evaluated by multiplex reverse transcription (RT)-PCR. Using the small interfering RNAs (siRNAs) specific for IL-6 and IL-11 and the promoter deletion assay, the contributions of IL-6 and IL-11 to TGF-beta1-induced induction of alpha-SMA were determined. RESULTS: In human Tenon's fibroblasts, TGF-beta1 stimulated the expression of alpha-SMA protein determined by western blot analysis and also increased the mRNA levels of IL-6 and IL-11 determined by multiplex RT-PCR. On the western immunoblots and immunofluorescence, the increased expression of alpha-SMA was attenuated only by the siRNAs specific for IL-6 but not by the siRNAs specific for IL-11. When the activator protein-1 binding sites of the IL-6 promoter region were deleted, the stimulation effects of TGF-beta1 decreased. CONCLUSIONS: Our data show that autocrine IL-6 may participate in the TGF-beta1-induced transdifferentiation of human Tenon's fibroblasts to myofibroblasts, which is known to be an essential step for subconjunctival fibrosis.