Distinct serum apolipoprotein A-I levels in neuromyelitis optica and acute transverse myelitis.

OBJECTIVE: NMO and ATM are intertwined both clinically and pathologically. Apolipoprotein (apo) A-I, the main apolipoprotein of HDL, plays an important role in lipid metabolism in the cerebrospinal fluid and is known to suppress pro-inflammatory cytokines generated by activated T cells in some autoimmune diseases as an immune regulator. However, the differences in the levels of serum apoA-I between NMO and ATM patients are unclear. METHODS: In the present study, serum apo A-I levels were measured in 53 NMO patients, 45 ATM patients and 49 healthy subjects. We tested serum apoA-I levels in all participants and investigated EDSS scores of patients with NMO and ATM. Statistical analyses were performed by using SPSS statistical software. RESULT: We found that serum apoA-I levels in patients with NMO were significantly lower in comparison to those with ATM. We also found that serum levels of apoA-I was lower in male subjects in comparison to the female subjects in all groups although these differences were not statistically significant in patients with NMO or ATM. It is also shown in our study that serum apoA-I levels in patients with NMO were significantly elevated after receiving a high dosage of intravenous corticosteroids over a period of one week. However, we did not find any correlation between the apoA-I levels and disease disability. CONCLUSION: From this study, we concluded that serum levels of apoA-I were lower in NMO patients compared to patients with ATM. Serum apoA-I studies might provide some useful clues to differentiate NMO cases from ATM cases.

Mitochondrial complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: protection by antioxidants.

PURPOSE: There is growing evidence that oxidative stress contributes to the progression of primary open-angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. The authors provide evidence that mitochondrial dysfunction is a possible mechanism for the loss of trabecular meshwork (TM) cells in persons with POAG. METHODS: TM from patients with POAG (GTM) and age-matched subjects without disease (NTM) were obtained by standard surgical trabeculectomy. Primary TM cultures were treated with one of the following mitochondrial respiratory chain inhibitors: rotenone (ROT, complex I inhibitor), thenoyltrifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM-complex III inhibitors); mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA); and antioxidants vitamin E (Vit E) or N-acetylcysteine (NAC). Mitochondrial function was determined by changes in mitochondrial membrane potential (DeltaPsim) and adenosine triphosphate (ATP) production with the fluorescent probes 5,5',6,6'-tetrachloro-1,1'3,3'-tetraethylbenzimid azolocarbocyanine iodide (JC-1) and a luciferin/luciferase-based ATP assay, respectively. Reactive oxygen species (ROS) level, determined by H(2)-DCF-DA, and cell death, measured by lactate dehydrogenase activity and Annexin V-FITC labeling, were also examined. RESULTS: GTM cells have higher endogenous ROS levels, lower ATP levels, and decreased Delta Psi m and they are more sensitive to mitochondrial complex I inhibition than their normal counterparts. ROT induces a further increase in ROS production, the release of cytochrome c, and decreases in ATP level and Delta Psi m in GTM cells, eventually leading to apoptosis. Complex II and III inhibition had little effect on the cells. Antioxidants protect against ROT-induced death by inhibiting ROS generation and cytochrome c release. CONCLUSIONS: The authors propose that a mitochondrial complex I defect is associated with the degeneration of TM cells in patients with POAG, and antioxidants and MPT inhibitors can reduce the progression of this condition.

[Establishment of human retinoblastoma model in human immune reconstruction non-obese diabetic-severe combine immunodeficient mice].

OBJECTIVE: To develop a novel immunotherapy model of retinoblastoma (RB) in human PBL non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice, and to investigate its biological features. METHODS: Twenty NOD-SCID mice were randomly divided into 4 groups: group A, subcutaneous injection of phosphate buffered saline; group B, intraperitoneal injection of human peripheral blood lymphocyte (hu-PBL) for immune reconstruction; group C, subcutaneous injection of SO-RB50 cells and group D, intraperitoneal injection of hu-PBL with subcutaneous injection of SO-RB50 cells. The physical status of NOD-SCID mice and the tumor growth were observed. Human IgG in mouse serum was assayed by ELISA. Human T lymphocytes in murine spleen and peripheral blood were evaluated by flow cytometry. Histopathological examination and immunohistochemical studies were also performed. RESULTS: In groups C and D, the latent period of tumor growth was 12 - 19 days, and the taken rates of RB were 100%. Histological and immunohistochemical results showed that the tumor cells of the two groups retained the characteristics of human low differentiation RB. More interesting, some human lymphocytes stained by human LCA presented in transplanted tumors and murine spleens. Human IgG and T lymphocytes were detected in humanized groups (groups B and D). CONCLUSIONS: The RB model in the human PBL NOD-SCID mice has been successfully established, which simulates the biological behavior of human spontaneous RB. This model may be useful for the studying of immune regression and immunotherapy of human RB.

Serum uric acid levels in patients with infections of central nervous system.

The lower levels of serum uric acid (UA) correlated with meningitis have been reported. However, comparison of UA levels among different kinds of infections of central nervous system (CNS) and changes of UA levels before and after treatment are unknown. Our study aimed to investigate the antioxidant status of serum UA in five common types of CNS infections. We retrospectively evaluated serum UA levels of 399 patients with different types of CNS infections including viral meningitis or meningoencephalitis (VM), brain cysticercosis (BC), tuberculous meningitis or meningoencephalitis (TM), cryptococcus meningitis or meningoencephalitis (CM) and bacterial meningitis or meningoencephalitis (BM), and 119 healthy controls. The changes of serum UA were examined and analyzed. The serum levels of UA in patients with CNS infections were significantly lower than those in normal subjects and among in TM, CM and BM groups were apparently lower when compared with VM and BC groups; otherwise, after effective therapy, serum UA levels were obviously higher than before. Our findings showed that patients with CNS infections had lower serum UA levels, which was independent of the classification and the serum UA levels increased obviously after valid treatment, the variation of UA levels might be considered as an indicator of clinical curative effect in patients with CNS infections.

[Histopathological and ultrastructural characteristics of oil-associated complications in silicone oil-filled human eyes].

OBJECTIVE: To observe morphological changes of oil-associated complications in silicone oil-filled human eyes, and to further explore their pathogenesis. METHODS: The morphology analysis and immunohistochemistrical study were performed in 25 specimens including 8 eyeballs, 1 ocular content, 4 preretinal membranes, 4 corneal buttons and 8 lens from human eyes with silicone oil tamponade. Two of preretinal membranes acquired freshly were also evaluated by transmission electron microscopy (TEM). RESULTS: Endothelium cell loss (90%) and band keratopathy (83%) were the most typical changes in silicone oil-associated keratopathy;while epithelial cell fibrosis was the most frequent histopathological features in silicone oil-associated cataract. In 8 eyeballs and 1 ocular content, it was found that damages to normal retinal layers and formation of preretinal or subretinal membrane with extensive silicone bubbles were obvious in the cases of silicone oil-associated retinopathy, which included loss and degeneration of neuron cells. Moreover, in 3 eyeballs with silicone oil for more than 60 months, retinas were completely replaced by fibril membranes, and the oil vacuoles were also found in sclerocorneal scar, trabecula, iris, ciliary body, choroid, optic nerve and its tunica vaginalis. These finding demonstrated that the longer the silicone oil was retained in eyeballs, the more severe its complications were. Different sizes of silicone bubbles in 2 preretinal membranes were noted easier by TEM than light microscopy. There were some macrophages marker (CD68) positive staining cells in the tissues filled with silicone bubbles, such as preretinal or subretinal membrane and optic nerve. Partial of the membranes surrounding the oil bubbles was positive for GFAP staining, and other part was positive stained for Vimentin. CONCLUSIONS: Intraocular silicone oil can damage the normal tissue structures and function if it is retained in eyeballs too long. This results suggest that silicone oil should be removed timely after the retinal reattachment stabilized and can not be used as a kind of long term intraocular tamponade.

Comparisons of presentations and outcomes of cryptococcal meningitis between patients with and without hepatitis B virus infection.

OBJECTIVE: The clinical characteristics and outcomes in cryptococcal meningitis (CM) have been shown to vary depending on the underlying condition. The purpose of this study was to investigate these differences in patients with and without hepatitis B virus (HBV) infection. METHODS: We performed a retrospective study at the Third Affiliated Hospital of Sun Yat-Sen University from January 2006 to June 2012. Thirty-two HBV-positive patients and 58 HBV-negative patients were included. RESULTS: Among the 90 patients with CM, 32 (35.6%) were HBV-infected. CM occurred in a younger population in the HBV-positive group, with a higher Charlson comorbidity score than the HBV-negative group. The HBV-positive group presented with lower initial complaints of visual symptoms, lower cerebrospinal fluid (CSF) white blood cell counts, lower percentages of the total protein in the CSF exceeding 0.45 g/l, higher glucose levels in the CSF, a higher percentage of positive results for Cryptococcus culture in the CSF, more extraneural involvement sites, and a higher proportion of normal brain images than the HBV-negative group. Factors for a poor prognosis in the HBV-positive group included liver cirrhosis and HBV DNA >10³ copies/ml. In the HBV-uninfected group, lower glucose in the CSF and hydrocephalus were the indicators of an unsatisfactory outcome. CONCLUSIONS: Certain clinical features of CM were found to be significantly different between HBV-infected and HBV-uninfected patients, including age and initial laboratory findings, as well as the indicators of an unsatisfactory outcome. Host defense defects in the HBV-infected group may lead to a lower intensity of inflammation in the pathogenesis of CM compared with the HBV-uninfected patients and may account for these divergences between the two groups.

Histological and ultrastructural study on the medial canthal ligament of blepharophimosis, ptosis and epicanthus inversus syndrome.

BACKGROUND: Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a rare congenital ophthalmic disorder, characterized by congenital eyelid malformation including bilateral ptosis, shortening of the horizontal eyelid fissure, epicanthus inversus, and increased distance between the inner canthi. In this research, we studied the histological structure and ultrastructure of medial canthal ligament of patients with BPES. METHODS: Thirty patients with BPES who received plastic surgery at the Zhongshan Ophthalmic Center from March 2006 to January 2008 were studied. There were 17 males and 13 females with an average age of (8.73 +/- 3.37) years (3 - 31 years). The medial canthal ligaments of patients were collected during the plastic surgery to analyze the histological structure by hematoxylin and eosin (HE), Congo red, van Gieson's (VG), Masson trichrome and aldehyde-fuchsin staining. The ultrastructures of the medial canthal ligaments were also analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fifteen samples of medial canthal ligament from healthy persons with an average age of (9.02 +/- 3.12) years (6 - 30 years) were collected as a control group. RESULTS: Morphological and histological study showed that the medial canthal ligaments of BPES patients were composed of collagen fibers, a few elastic fibers and striated muscles. The collagen fibers assemblies were disorganized and the fibrous connective tissues were undergoing hyaline degeneration. The karyopycnosis of fibroblasts was located among the collagen fibrils and the numbers of fibroblasts were decreased. Ultrastructural study with SEM showed that the collagen fibers were larger than normal, irregular and loose. Parts of the collagen fibers were broken and had a coarse surface. Ultrastructural study with TEM showed that the fibroblasts had less cytoplasm, fewer organelles and the nucleus displayed pyknosis. CONCLUSIONS: The medial canthal ligament in BPES patients is composed chiefly of collagen fibers. The collagen fibers of medial canthal ligaments in BPES patients are disorganized and hyaline degeneration is present. The study revealed that the medial canthal ligament of BPES patients might have congenital dysplasia.