Treadmill Running Improves Spatial Learning Memory Through Inactivation of Nuclear Factor Kappa B/Mitogen-Activated Protein Kinase Signaling Pathway in Amyloid-β-Induced Alzheimer Disease Rats / 대한배뇨장애요실금학회지

Purpose@#Exercise is known to reduce proinflammatory cytokines production and apoptosis. We investigated the effect of treadmill running on spatial learning memory in terms of activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway in Alzheimer disease (AD) rats. We also evaluated the effect of treadmill running on proinflammatory cytokine production and apoptosis. @*Methods@#Using the stereotaxic frame, amyloid-β (Aβ) was injected into the lateral ventricle of the brain. The rats belong to treadmill running groups were forced to run on a motorized treadmill for 30 minutes per a day during 4 weeks, starting 3 days after Aβ injection. Morris water maze task was done for the determination of spatial learning memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry for cleaved caspase-3, and western blot for NF-κB, inhibitory protein of NF-κB (IκB), MAPK signaling pathway, tumor necrosis factor (TNF)-α, interleukin (IL)-1β were done. @*Results@#Induction of AD increased proinflammatory cytokine secretion by activating the NF-κB/MAPK signaling pathway. These changes induced apoptosis in the hippocampus and reduced spatial learning memory. In contrast, treadmill running inactivated the NF-κB/MAPK signaling pathway and suppressed proinflammatory cytokine production. These changes inhibited apoptosis and improved spatial learning memory. @*Conclusions@#Current results showed that treadmill running promoted spatial learning memory through suppressing proinflammatory cytokine production and apoptosis via inactivation of NF-κB/MAPK signaling pathway. Treadmill exercise can be considered an effective intervention for symptom relieve of AD.

Treadmill Running Improves Spatial Learning Memory Through Inactivation of Nuclear Factor Kappa B/Mitogen-Activated Protein Kinase Signaling Pathway in Amyloid-β-Induced Alzheimer Disease Rats / 대한배뇨장애요실금학회지

Purpose@#Exercise is known to reduce proinflammatory cytokines production and apoptosis. We investigated the effect of treadmill running on spatial learning memory in terms of activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway in Alzheimer disease (AD) rats. We also evaluated the effect of treadmill running on proinflammatory cytokine production and apoptosis. @*Methods@#Using the stereotaxic frame, amyloid-β (Aβ) was injected into the lateral ventricle of the brain. The rats belong to treadmill running groups were forced to run on a motorized treadmill for 30 minutes per a day during 4 weeks, starting 3 days after Aβ injection. Morris water maze task was done for the determination of spatial learning memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry for cleaved caspase-3, and western blot for NF-κB, inhibitory protein of NF-κB (IκB), MAPK signaling pathway, tumor necrosis factor (TNF)-α, interleukin (IL)-1β were done. @*Results@#Induction of AD increased proinflammatory cytokine secretion by activating the NF-κB/MAPK signaling pathway. These changes induced apoptosis in the hippocampus and reduced spatial learning memory. In contrast, treadmill running inactivated the NF-κB/MAPK signaling pathway and suppressed proinflammatory cytokine production. These changes inhibited apoptosis and improved spatial learning memory. @*Conclusions@#Current results showed that treadmill running promoted spatial learning memory through suppressing proinflammatory cytokine production and apoptosis via inactivation of NF-κB/MAPK signaling pathway. Treadmill exercise can be considered an effective intervention for symptom relieve of AD.

Dendritic Cell Activation by Glucan Isolated from Umbilicaria Esculenta

BACKGROUND: Lichen-derived glucans have been known to stimulate the functions of immune cells. However, immunostimulatory activity of glucan obtained from edible lichen, Umbilicaria esculenta, has not been reported. Thus we evaluated the phenotype and functional maturation of dendritic cells (DCs) following treatment of extracted glucan (PUE). METHODS: The phenotypic and functional maturation of PUE-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. PUE-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity. Finally we detected the activation of MAPK and NF-kappaB by immunoblot. RESULTS: Phenotypic maturation of DCs was shown by the elevated expressions of CD40, CD80, CD86, and MHC class I/II molecules. Functional activation of DCs was proved by increased cytokine production of IL-12, IL-1beta, TNF-alpha, and IFN-alpha/beta, decreased endocytosis, and enhanced proliferation of allogenic T cells. Polymyxin B, specific inhibitor of lipopolysaccharide (LPS), did not affect PUE activity, which suggested that PUE was free of LPS contamination. As a mechanism of action, PUE increased phosphorylation of ERK, JNK, and p38 MAPKs, and enhanced nuclear translocation of NF-kappaB p50/p65 in DCs. CONCLUSION: These results indicate that PUE induced DC maturation via MAPK and NF-kappaB signaling pathways.

Relationship between Central Retinal Vein Occlusion and Axial Length of Eye

Central retinal vein occlusion (CRVO) is a common retinal vascular disorder, and it has been suggested to occur by the occlusion of the sclerotic central retinal vein by thrombo- sis in the lamina cribrosa. Various systemic and local conditions have been considered to be predisposing factors to the development of CRVO, and it has been reported that CRVO occurs more frequently in hypermetropic small eyes. We studied on several factors such as age, refractive error, axial length and the association with systemic diseases in 32 eyes of unilateral CRVO. In the CRVO group,the mean axial length of the affected eyes was 23.13 +/-0.99 mm in males and 22.64 +/-0.63 mm in females. That of the unaffected eyes was 23.36 +/-1.17 mm in males and 22.64 +/-0.53 mm in females, the differences were statistically insignificant in males and females (p=0.250,p=0.496). The mean axial length of normal comparison eyes was 23.81 +/-0.73 mm in males and 23.07 +/-0.69 mm in females. The differences between the mean axial lengths of both eyes with unilateral CRVO and that of normal comparison eyes were statistically significant in males and females (p<0.05). In conclusion,the short axial length may play as an important related factor in the development of CRVO.

Two Cases of Uveal Metastasis of Lung Cancer with Systemic Metastasis

Intraocular metastasis of metastatic carcinoma is relatively rare, although it is the most common malignancy affecting the eye. Choroid is the most commonly involved site, whereas iris is involved very infrequently. The most common primary tumor of the intraocular metastasis is the breast cancer in total and lung cancer in men.To our knowledge, intraocular metastasis of lung adenocarcinoma has not reported in Korea. We experienced two lung cancer patients who had developed a metastaticlesion to the iris and choroid,so we report these with the review of related literatures.

Axial Lenth of Eye as a Risk Factor of the Branch Retinal Vein Occlusion

Branch retinal vein occlusion(BRVO), along with central retinal vein occlusion, is second only to diabetic retinopathy as a cause of retinal vascular disease. It has been suggested that eyes with shorter axial length have smaller lamina cribrosa and a narrower scleral canal through which the central retinal vein and artery could pass, causing physical blockage in the vein which predisposes to thrombus formation. The subsequent narrowing of the venous lumen will lead to trubulence. reduced flow, venous stasis and thrombus formation at the level of the arteriovenous crossing. This study was conducted to determine whether there was any difference between the axial lengths of eyes with BRVO and those of control eyes. The axial lengths of the eyes in the group of 37 patients with a unilateral BRVO was compared with those of eyes in the control group. The BRVO group consisted of 23 male and 14 female patients and their mean ages were 61.5+/-7.0 years(51~75years) in male and 63.7+/-7.0 years(52~76years) in female. The control group consisted of 46 male and 28 female patients and their mean ages were 62.5+/-6.5 years(50~73years) in male and 63.9+/-6.1 years(52~75years) in female. The mean axial length of eyes of the BRVO group was 23.08+/-0.57mm(21.92~24.19mm) in male and 22.71+/-0.65mm(21.08~24.00mm) in female. The mean axial length of control eyes was 23.74+/-0.73mm(22.46~25.24mm) in male and 23.18+/-0.81mm(21.62~24.76mm) in female. The difference between the mean axial length of eyes of the BRVO group and that of control eyes was statistically significant(p<0.05). In conclusion, the short axial length may play as a risk factor in the occurrence of a BRVO.

Heterogeneous HBV mutants coexist in Korean hepatitis B patients

Although many hepatitis B virus (HBV) mutants have been found in all open reading frames since the precore defective mutant was initially reported, systematic investigations of diverse HBV mutant populations in hepatitis B patients have not been performed. Therefore, we examined whether heterogeneous mutant populations simultaneously exist in Korean hepatitis B patients. In order to detect hepatitis B virus mutants, we amplified a conserved core region and a surface antigen region of HBV DNA by PCR from sera of 27 Korean chronic hepatitis B patients, and then performed single strand conformational polymorphism analysis followed by DNA sequencing analysis. The results showed that heterogeneous HBV mutants in both regions were present in a single as well as in various hepatitis B patients. Sequence analysis revealed a defective interfering particle with missense mutation in the core region. We also found that two subtypes of adr and adw coexisted in a single patient. In addition, a point mutation causing a stop codon in the surface antigen region was observed. We are further analyzing the clinical implications of HBV mutants to identify their roles in the pathogenesis of chronic hepatic disorders induced by HBV.

Pathologic Changes after Inferior Oblique Marginal Myotomy in Rabbits: The Effect of Triamcinolone

In the margial myotomy of inferior oblique muscle(IO myotomy), only the overaction of the muscle is eliminated and the normal action of the inferior oblique saved. Steroid is usually used to prevent the adhesion of the tissue after IO myotomy, subconjunctivally. The myotomy of IO was performed in 14 white rabbits which were divided into two groups, one group having local injection of triamcinolone after IO myotomy and the other not having it. At postoperative 1 month, there were edema of the muscle fibers and infiltration of the inflammatory cells. Three months postoperatively, ingrowth of fibrous tissue and atrophy of the muscle fibers were found. Those changes were less prominent in the group with triamcinolone injection. This study revealed that subconjunctival triamcinolone injection after the IO marginal myotomy produce a good effect on the prevention of postoperative adhesion in the long term.

The Effect of Mitomycin on the Experimental Filtering Surgery

In tiis study, an expenmental model of glaucoma filtering surgery in rabblts was used to evaluate the effect of single intraoperative application of Mitomycin Full-thickness filtering surgery, posterior lip sclerectomy, was performed after application of 0.5mg/ml Mitomycin-soaked Week-Cel(TM) sponge for 5 minutes in one eye of 15 pigmented rabbits and was irrigated copiously with balanced salt solution(BSS(TM)). The same procedure was done in the contralateral eye as a control, using BSS(TM). In Mitomycin-treated group, the filtering blebs were more prominent with sparse vascular tissues and were maintained through postoperative 8 weeks or more. Histologically, there loas was amount of inflammatory reactions in Mitomycin-treated group. The fibroblastic activity and proliferations of the collagen were also suppessed markedly in Mitomycin-treated group. These results suggest that a single intraoperative application of Mitomycin can be used adjunctively to improve the success rate of glaucoma filtering surgery.

Peripheral Scatter Treatment in Diabetic Retinopathy

Panretinal photocoagulation (PRP) has been known to be beneficial in preventing severe visual loss from diabetic retinopathy. Clinical effects of peripheral scatter treatment on diabetic retinopathies were compared with those of PRP in 40 eyes of each groups. In peripheral scatter treatment, equatorial and peripheral fundus was treated with argon blue-green laser or krypton red laser, in 2 sessions with interval of one week. The incidence of maculopathy causing decrease in visual acuity after laser treatment was higher in PRP-treated group than in peripheral scatter treatment group, but changes in visual acuity and fundus findings at last follow-up were not significantly different between PRP-treated and peripheral scatter treatment group (p>O.05). Peripheral scatter treatment was equally affective as PRP in treating diabetic retinopathy with less amount of laser bums and saving post-equatorial fundus.

The Effect of Vertical Transposition of Horizontal Muscles on Vertical Deviation Associated with Horizontal Strabismus

The authors performed vertical transposition of the horizontal rectus muscles during monocular recession-resection surgery to correct the comitant vertical deviation associated with the horizontal strabismus. When the eye was hypertropic, infratransposition of horizontal rectus muscles was performed and when the eye was hypotropic, supratransposition of the insertions of the horizontal muscles was performed. For vertical strabisumus with 4 delta-12 delta(mean 7.7 delta) angle deviation, each medial and lateral rectus muscles were vertically transposed 2mm-4.5mm(mean 3.1mm) in 51 eyes. Fourty four eyes(86.3%) were vertically aligned, 4 eyes(7.8%) were undercorrected, and 3 eyes(5.9%) were overcorrected with 19.1 months of follow-up periods in average. By one millimeter vertical transposition of horizontal recti, vertical deviation was corrected by 1.21 delta in average. The vertical transposition of horizontal recti can be an effective method for correcting vertical deviation associated with horizontal strabismus not associated with any cyclovertical muscle dysfunction.

The Effect of Vertical Transposition of Horizontal Muscles on Vertical Deviation Associated with Horizontal Strabismus

The authors performed vertical transposition of the horizontal rectus muscles during monocular recession-resection surgery to correct the comitant vertical deviation associated with the horizontal strabismus. When the eye was hypertropic, infratransposition of horizontal rectus muscles was performed and when the eye was hypotropic, supratransposition of the insertions of the horizontal muscles was performed. For vertical strabisumus with 4 delta-12 delta(mean 7.7 delta) angle deviation, each medial and lateral rectus muscles were vertically transposed 2mm-4.5mm(mean 3.1mm) in 51 eyes. Fourty four eyes(86.3%) were vertically aligned, 4 eyes(7.8%) were undercorrected, and 3 eyes(5.9%) were overcorrected with 19.1 months of follow-up periods in average. By one millimeter vertical transposition of horizontal recti, vertical deviation was corrected by 1.21 delta in average. The vertical transposition of horizontal recti can be an effective method for correcting vertical deviation associated with horizontal strabismus not associated with any cyclovertical muscle dysfunction.

Myopia in premature infants at the age of 6 months

>The authors performed cycloplegic refractions in 180 eyes of 99 premature infants at the age of 6 months to evaluate the incidence and the degree of myopia according to the development and disease course of retinopathy of prematurity (ROP) and to investigate the effect of cryotherapy on the refractive error. The incidences of myopia were not different between premature infants without ROP and premature infants with spontaneously and totally regressed ROP (36.3%, 25.5%),and the degrees of myopia were low in both groups (-1.76 D, -2.25 D). In premature infants with totally regressed ROP after cryotherapy, the incidence of myopia was high (75.5%) but the degree of myopia was low (-3.03 D). In premature infants with cicatricial ROP, cryotreated or not, both the incidence and the degree of myopia were high (93.9%, -5.50 D). It is suggested that cryotherapyincreases the incidence of myopia but the degree of myopia induced by cryotherap y is low.

Surgical Correction of Senile Entropion

Senile entropion is caused by following pathophysiology: 1) Dehiscence or disinsertion of lower lid retractors from lower tarsus, 2) Preseptal orbicularis overriding pretarsal orbicularis, 3) Horizontal lid laxity from involutional changes of medial canthal ligament, lateral canthal ligament and tarsal plate, 4) Relative enophthalmos from absorption of orbital fat. There have been numerous procedures to correct senile entropion, but lack of adequate correction of all of the underlying anatomic defects resulted in high recurrence rate. Authors performed a combined procedure including the reinsertion of disinserted or dehisced lower lid retractor to lower tarsus, the excision of overriding preseptal orbicularis, and the correction of the lower lid laxity using lateral tarsal strip procedure all at once Among 11 cases of 10 patients, 10 cases had cosmetically and functionally good lid position during the mean follow up periods of 13.4 months. There was one case of ectropion as a complication which was corrected by further lateral tarsal strip procedure.

Myopia in Premature Infants

The authors performed cycloplegic refraction in premature infants at the 6 months and 3 years of age to evaluate the incidence and degree of myopia and the changes of refractive errors according to the development, disease course and cryotherapy of retinopathy of prematurity (ROP). In 180 eyes of 99 infants at the 6 months of age, the incidences of myopia were not different between eyes with no ROP and eyes with spontaneously regressed ROP (36.3%, 25.5%), and the degrees of myopia were low in both groups (-1.76D, - 2.25D). In eyes with regressed ROP after cryotherapy, the incidence of myopia was high (75.5%) but the degree of myopia low (-3.0:3D). In eyes with cicatrical ROP, cryotreated or not, both of the incidence and the degree of myopia were high(93.9%, -5.50D). It is suggested that the incidence of myopia is increased after cryotherapy but the degree of myopia occurring after cryotherapy is low. In eyes with spontaneously regressed ROP, the degrees of refractive errors did not change from 6 months to 3 years of age, whereas in eyes cryotreated or with cicatrical ROP, the degrees of refractive errors were progressively changed to myopic side.

Morphological Changes of the Corneal Endothelial Cells and Central Corneal Thickness in Neovascular Glaucoma

Morphometric variables of the corneal endothelial cells and central corneal thickness were evaluated in 12 neovascular glaucoma eyes and 12 normal contralateral eyes. Cell area and density was 611.50 micrometer2, 2,065 cells/mm2 respectively in neovasualar glauloma eyes and 441.33 micrometer2, 2,313cells/mm2 respectively in normal contralateral eyes and there were no significant diffeernce between two groups (p>O.1). Hexagonality was 55.69% in neovascular glaucoma eyes and 62.01 % in normal contralateral eyes and the decrease in hexagonality in the former was statistically significant (P0.05). It can be concluded that neovascular glaucoma induces morphological changes of the corneal endothelial cens which might bring corneal edema.

Morphological Changes of the Corneal Endothelial Cells and Central Corneal Thickness in Neovascular Glaucoma

Morphometric variables of the corneal endothelial cells and central corneal thickness were evaluated in 12 neovascular glaucoma eyes and 12 normal contralateral eyes. Cell area and density was 611.50 micrometer2, 2,065 cells/mm2 respectively in neovasualar glauloma eyes and 441.33 micrometer2, 2,313cells/mm2 respectively in normal contralateral eyes and there were no significant diffeernce between two groups (p>O.1). Hexagonality was 55.69% in neovascular glaucoma eyes and 62.01 % in normal contralateral eyes and the decrease in hexagonality in the former was statistically significant (P0.05). It can be concluded that neovascular glaucoma induces morphological changes of the corneal endothelial cens which might bring corneal edema.

Clinical Evaluations of Penetration Ocular Injuries

The authors retrospectively analyzed 188 eyes of 188 patients with penetrating ocular injuries who visited Seoul National University Hospital and Kim's Eye Clinic from 1986 to 1989. Clinical pictures of injuries and factors influencing visual outcome were evaluated. The patients were mostly male (93.0%) and in third decade were 42.0%, and second and fourth decades was 17.0% respectively. Industrial injuries (70.0%) was the most common type of injury and among the vectors of injuries, sharp objects (83.0%) were more commonly found than blunt objects (17.0%). The sites of injury were in cornea, sclera, corneosclera and among them the cornea was most frequently involved (61.2%). Lens damage (51.6%), hyphema (38.4%), intraocular foreign body (34.6%) were most commonly associated. 60.9% of patients underwent operation within first 24 hours. Primary closures (67.6%) were the leading procedures among the operations. Postoperative visual acuity was better in corneal laceration, anterior segment injury, and injury by sharp objects than in corneoscleral or scleral laceration, posterior segment injury, injury due to blunt trauma. Complications included corneal opacity (55.3%), cataract (11.2%), retinal degeneration (11.2%), vitreous opacity (7.4%), retinal detachment (5.3%), secondary glucoma (2.1 %), endophthalmitis, phthisis, preretinal membrane (1.6%).