Anti-CD40 monoclonal antibody ameliorates experimental autoimmune uveoretinitis in mice.

OBJECTIVE: To investigate the effects of CD40 on ocular inflammation in experimental autoimmune uveoretinitis (EAU) in B10.RIII mice. ANIMALS STUDIED: EAU-susceptible B10.RIII mice were subcutaneously immunized with interphotoreceptor retinoid-binding protein (IRBP) 161-180 in complete Freund's adjuvant and evaluated clinically and pathologically on days 7, 14, 21, 28, and 35 postimmunization. Anti-CD40 antibody was intraperitoneally injected into mice every other day from days 7 to 14 postimmunization. Phosphate-buffered saline (PBS)-injected EAU mice were used as the controls. PROCEDURES: The frequencies of CD11c+ CD40+ dendritic cells (DCs), CD11c+ MHC-II+ DCs, and CD11c+ CD40+ MHC-II+ DCs in splenocytes were evaluated by flow cytometry on days 0, 7, 14, and 21 after immunization. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in CD11c+ DCs was assessed by ELISA. IRBP-specific lymphocyte proliferation was assessed using a modified MTT cell proliferation assay. RESULTS: The number of CD11c+ CD40+ DCs, CD11c+ MHC-II+ DCs, and CD11c+ CD40+ MHC-II+ DCs increased at the onset of EAU, peaked at the height of disease severity, and was sustained at a high level until day 21. Treatment with anti-CD40 antibody significantly alleviated clinical and pathological activities related to EAU. Compared with the control mice, antibody-treated EAU mice showed few CD11c+ CD40+ DC and CD11c+ CD40+ MHC-II+ DC frequencies in splenocytes. The anti-CD40 antibody significantly suppressed IRBP-specific lymphocyte proliferation and TNF-α and IL-6 production by DCs in EAU mice. CONCLUSIONS: The increased expression of CD40 and major histocompatibility complex (MHC) class II molecules in the splenocytes of EAU mice were correlated with inflammatory activity. Anti-CD40 treatment can significantly attenuate EAU activity by inhibiting systemic IRBP-specific immune responses.

Clinical and Pathologic Features of a Suspected Selenium Deficiency in Captive Plains Zebras.

Previous studies have shown that selenium (Se) deficiency is associated with nutritional myopathy, known as white muscle disease (WMD), in horses. However, correlations between Se deficiency and clinical findings, such as hematologic biochemical values and pathological features, have not been evaluated in captive plains zebras. The purpose of the present study was to investigate the clinical and pathologic features that may be caused by a Se deficiency in the captive plains zebra. Clinical findings, feed analyses, hematologic biochemical analyses, response to treatment, and pathologic examination were assessed in six affected plains zebras. The dietary concentration of Se in feed was also tested. Sudden death occurred in two cases during the first day of the onset of symptoms. Two zebras died at 4 days and two zebras survived after treatment. The clinical signs in affected animals were characterized by general weakness, astasia, and abnormal postural positions. The Se concentration in hay from the breeding stable was low, based on the reference value. Glutathione peroxidase (GSH-Px) activity was lower compared with the equine reference value. Multiple areas of subcutaneous steatitis and pale skeletal muscle and myocardium were revealed at gross necropsy. Degeneration and necrosis of myocardial and skeletal muscles, as well as congestion of the liver, lung, and kidney were found via histopathological examination. No suspected bacterial infections were found. Feed analyses, response to treatment, serum GSH-Px activity, and pathological features suggest that Se deficiency may have caused the disease in the six affected captive plains zebra.

Treatment of rats with Jiangzhi Capsule improves liquid fructose-induced fatty liver: modulation of hepatic expression of SREBP-1c and DGAT-2.

BACKGROUND: Jiangzhi Capsule is an Australian listed patented traditional Chinese medicine and has been used for management of lipid abnormalities over the past 10 years. To obtain a better understanding regarding Jiangzhi Capsule, the present study investigated the effects and underlying mechanisms of Jiangzhi Capsule on chronic fructose overconsumption-induced lipid abnormalities. METHODS: Male rats were treated with liquid fructose in their drinking water over 14 weeks. Jiangzhi Capsule was co-administered (once daily, by oral gavage) during the last 7 weeks. Indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by real-time PCR, Western blot and/or immunohistochemistry. RESULTS: Treatment with Jiangzhi Capsule (100 mg/kg) attenuated fructose-induced excessive triglyceride accumulation and Oil Red O-stained area in the liver. This effect was accompanied by amelioration of hyperinsulinemia. There was no significant difference in intakes of fructose and chow, and body weight between fructose control and fructose Jiangzhi Capsule-treated groups. Mechanistically, Jiangzhi Capsule downregulated fructose-stimulated hepatic overexpression of sterol regulatory element binding protein (SREBP)-1/1c at the mRNA and protein levels. Accordingly, the SREBP-1c downstream genes, acetyl-CoA carboxylase-1 and stearoyl-CoA desaturase-1, were also inhibited. In addition, acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver was also inhibited after Jiangzhi Capsule treatment. In contrast, Jiangzhi Capsule affected neither carbohydrate response element binding protein, peroxisome proliferator-activated receptor (PPAR)-gamma and DGAT-1, nor PPAR-alpha and its target genes. CONCLUSIONS: These findings demonstrate the anti-steatotic action of Jiangzhi Capsule in fructose-fed rats, and modulation of hepatic SREBP-1c and DGAT-2 involved in hepatic de novo synthesis of fatty acids and triglyceride, respectively. Our findings provide an evidence-based and mechanistic understanding of Jiangzhi Capsule supporting its application for the prevention and/or treatment of fatty liver and its associated disorders in clinical practice.

[Protective effects of total alkaloids from rhizoma Coptis chinensis on alcohol-induced gastric lesion in rats].

OBJECTIVE: To study the effects of total alkaloids(TA) from rhizoma Coptis chinensis on alcohol-induced gastric lesion in rats and the possible mechanisms. METHOD: The experimental gastric damges were established by intragastric(ig) absolute ethanol, and possible protective effects of TA given orally previously were evaluated by following parameters: gastric damage indexes, gastric juice volume, acidity, and mucus quantity. The contents of NO, MDA, *OH, and SOD activity were also measured in gastric mucosa. RESULT: TA showed significantly inhibitive effects on gastric damages induced by ig ethanol in a dose dependent manner. The effects of TA (120 mg x kg(-1)) were stronger than that of both cimitidine(70 mg x kg(-1)) and berberine(100 mg x kg(-1)), the quantity of later was equal to TA as calculated with berberine. TA significantly suppressed secretion of gastric acid caused by ethanol without clear influences on gastric juice volume and mucus secretion. TA obviously blunted ethanol-induced elevation of MDA and *OH, as well as decrease of NO level and SOD activity from gastric mucosa. CONCLUSION: It is suggested that the TA is a potent protective agent against ethanol-induced gastric damages. The mechanism of actions may be related with inhibiting the secretion of gastric acid and blunting the increase of MDA and *OH, as well as the decrease of NO level and SOD activity from gastric mucus.