Regulation of macrophage functions by L-arginine

Sites of inflammation with prominent macrophage infiltration, such as wounds and certain tumors, are uniquely deficient in free arginine. The effects of arginine availability on macrophage physiology were investigated. When cultured in media containing less than 0.1 mM L-arginine, rat resident peritoneal macrophages exhibited enhanced spreading, tumor cytotoxicity, superoxide production, phagocytosis, and protein synthesis. Thus, arginine concentrations similar to those found in sites of inflammation can augment macrophage functions, while those found in plasma (approximately 0.1 mM) and in commonly used culture media (0.4 to 1.2 mM) are inhibitory. Culture in homoarginine, but not D-arginine, ornithine, citrulline, urea, histidine, or lysine also inhibited macrophage tumor cytotoxicity, indicating the specificity of the effect. In contrast to resident macrophages, the tumor cytotoxicity of peritoneal macrophages obtained after C. parvum injection was suppressed by culture in arginine-deficient media. However, L-arginine-deficient media enhanced all other activation-associated functions in C. parvum-elicited macrophages as in resident cells. Arginine-free wound fluid promoted resident macrophage tumoricidal activity when compared with rat serum, and again, the addition of L-arginine was inhibitory. The marked effects of L-arginine availability on macrophage functions, together with the knowledge that these cells modify the extracellular arginine concentration in sites of inflammation through arginase, provide evidence for an autoregulatory mechanism of macrophage activation.     

Lack of protective effects of dietary silicon on aluminium-induced maternal and developmental toxicity in mice.

In recent years, it has been demonstrated that oral aluminium (Al) exposure can produce growth retardation, delayed ossification and an increased incidence of foetal abnormalities in rats and mice. On the other hand, it has been also suggested that silicon may have a protective effect in limiting oral Al absorption. The aim of the present study was to assess whether dietary silicon could prevent against Al-induced maternal and developmental toxicity in mice. On gestation days 6-15, Al nitrate nonahydrate (398 mg/kg/day) was given by gavage to three groups of pregnant animals, which also received silicon in drinking water at concentrations of 0, 118 and 236 mg/l on days 7-18 of gestation. Three additional groups of pregnant mice received respectively: 270.6 mg/kg of sodium nitrate (gavage), and silicon in drinking water at 118 and 236 mg/l. Although silicon administration at 236 mg/l significantly reduced the percentage of Al-induced deaths, abortions and early deliveries, neither 118 nor 236 mg/l of silicon produced significant ameliorations on Al-induced foetotoxicity. Under the current experimental conditions dietary silicon was not effective in protecting against Al-induced developmental toxicity.     

Use of retinol-binding protein and prealbumin as indicators of the response to nutrition therapy

There is no single available measurement for evaluating the short-term response to nutrition therapy. The ideal parameter should have high sensitivity and specificity and should be unaffected by non-nutritional factors. A literature review suggested that plasma retinol-binding protein and prealbumin concentrations change earlier than albumin and transferrin levels and appear to correlate better with nitrogen balance during nutrition therapy. That conclusion was supported by our own findings in patients receiving total parenteral nutrition and following the transition to oral or enteral feedings. Although concentrations of these plasma proteins have been shown to be affected by stress and renal and hepatic disease, they appear to be more sensitive indicators of the adequacy of nutrition support than other more commonly used assessment parameters.     

Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine

Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD). In this study, the changes in endogenous antioxidant capacity and oxidative damage in liver and kidney of SASP-treated rats were investigated. Adult male Sprague–Dawley rats were orally given 0, 300, or 600 mg SASP/kg body weight for 14 days. One half of the animals in each group remained 14 additional days without SASP treatment. At the end of the experimental period, rats were euthanized and liver and kidney were removed. In both organs, the following stress markers were determined: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substances (TBARS). Moreover, histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in renal tissue. Oral SASP administration induced a significant increase in TBARS levels in both liver and kidney. After 2 weeks without SASP administration, a recovery of these levels was noted. SOD activity was significantly reduced, while CAT activity significantly increased at 600 mg SASP/(kg day). In kidney, GPx activity significantly increased, while GST activity and GSH levels were significantly reduced at 600 mg SASP/(kg day). These results suggest that in male rats, oxidative damage can be a mechanism for nephro- and hepatotoxicity related with SASP treatment.     

Ankle-brachial index and ocular diseases in a Russian population

BackgroundTo assess potential associations between the ankle-brachial blood pressure index (ABI) and ocular disorders.MethodsIn the population-based cross-sectional Russian Ural Eye and Medical Study including 5,899 (80.5%) out of 7328 eligible participants aged 40+ years, the participants underwent a series of ocular and medical examinations including measurement of ABI.ResultsBlood pressure measurements of both arms and ankles were available for 3187 (54.0%) individuals. The mean ABI was 1.26 ± 0.19 (median:1.20; range: 0.61, 2.20). In multivariate analysis, a higher ABI was associated with younger age (P < 0.001; non-standardized regression coefficient B: −0.001; 95% confidence interval (CI): −0.002, −0.001), female sex (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04), lower body mass index (P < 0.001; B: −0.004; 95% CI: −0.006, −0.003), lower waist-to-hip ratio (P = 0.01; B: −0.10; 95% CI: −0.17, −0.02), lower glucose serum concentration (P = 0.008; B: −0.005; 95% CI: −0.009, −0.001), lower prevalence of arterial hypertension (P < 0.001; B: −0.14; 95% CI: −0.16, −0.12), higher mean systolic blood pressure (P < 0.001; B: 0.003; 95% CI: 0.002, 0.003), and higher prevalence of any alcohol consumption (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04). In that multivariate model, prevalence of glaucoma (P = 0.67) as a whole, open-angle glaucoma (P = 0.86) and angle-closure glaucoma (P = 0.54), stage of glaucomatous optic neuropathy (P = 0.57), prevalence of age-related macular degeneration (P = 0.88), prevalence and stage of diabetic retinopathy (P = 0.30, and P = 0.29, respectively), nuclear cataract (P = 0.32, and P = 0.41, resp.), cortical cataract (P = 0.33, and P = 0.92, resp.), subcapsular cataract (P = 0.74 and P = 0.60, resp.), and pseudoexfoliation (P = 0.44 and P = 0.47, resp.), intraocular pressure (P = 0.52), axial length (P = 0.20), and peripapillary retinal nerve fibre layer thickness (P = 0.55) were not significantly associated with the ABI.ConclusionsIn this ethnically mixed population from Russia, none of the major ocular diseases was associated with ABI suggesting that subclinical atherosclerosis is not markedly associated with the aetiology of these ocular disorders.Subject terms: Retinal diseases, Lens diseases