Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice

In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 µg each): mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25 percent cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD), respectively) compared to control (124.9 ± 13.2 µm²). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 ± 0.70 per field x 10) compared to controls (21.5 ± 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized: 1.0 ± 1.4; control: 20.5 ± 3.5 RLU), the amount of cholesterol oxides in plasma (immunized: 4.7 ± 2.7; control: 15.0 ± 2.0 pg COx/mg cholesterol) and liver (immunized: 2.3 ± 1.5; control: 30.0 ± 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized: 0.30 ± 0.020; control: 0.38 ± 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.

Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice.

In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 microg each): mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25% cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 +/- 9.7, 67.3 +/- 17.02, 56.9 +/- 8.02 microm(2) (mean +/- SD), respectively) compared to control (124.9 +/- 13.2 microm(2)). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 +/- 0.70 per field x 10) compared to controls (21.5 +/- 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized: 1.0 +/- 1.4; control: 20.5 +/- 3.5 RLU), the amount of cholesterol oxides in plasma (immunized: 4.7 +/- 2.7; control: 15.0 +/- 2.0 pg COx/mg cholesterol) and liver (immunized: 2.3 +/- 1.5; control: 30.0 +/- 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized: 0.30 +/- 0.020; control: 0.38 +/- 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.

Antiatherogenic effects of S-nitroso-N-acetylcysteine in hypercholesterolemic LDL receptor knockout mice.

BACKGROUND: The pathophysiology of the NO/NO synthase system and dysfunctional changes in the endothelium in the early phases of the atherogenic process are incompletely understood. In this study, we investigated the effects of the nitrosothiol NO donor S-nitroso-N-acetylcysteine (SNAC) in the early prevention of plaque development in the hypercholesterolemic LDLr-/- mice as well as the changes in endothelium-dependent relaxation and NO synthase expression. METHODS AND RESULTS: LDLr-/- mice were fed a 1.25% cholesterol-enriched diet for 15 days. Plasma cholesterol/triglyceride levels increased and this increase was accompanied by the development of aortic root lesions. Aortic vasorelaxation to acetylcholine was increased, although endothelium-independent relaxation in response to sodium nitroprusside did not change, which suggest stimulated NO release enhanced. This dysfunction was associated with enhanced aortic superoxide production and with increased levels of constitutive NOS isoform expression, particularly neuronal NOS. SNAC (S-nitroso-N-acetylcysteine) administration (0.51 micromol/kg/day i.p. for 15 days) decreased the extent of the plaque by 55% in hypercholesterolemic mice, but had no effects on vasomotor changes. It did, however, lead to a decrease in constitutive NOS expression. The SNAC induced only minor changes in plasma lipid profile. CONCLUSION: The present study has shown that, in early stages of plaque development in LDLr-/- mice, specific changes in NO/NO synthase system develop, that are characterized by increased endothelium-dependent vasorelaxation and increased constitutive NOS expression. Since the development of plaque and the indicator of endothelial cell dysfunction were prevented by SNAC, such treatment may constitute a novel strategy for the halting of progression of early plaque.

Steroid profiles in cultured female jundiá, the Siluridae Rhamdia quelen (Quoy and Gaimard, Pisces Teleostei), during the first reproductive cycle.

The jundiá Rhamdia quelen (Quoy and Gaimard) is a teleost species from the Siluridae family and is an important species for aquaculture in temperate and subtropical climates. Gonad and blood tissue samples were taken from cultured jundiá females between 1998 and 1999. Plasma concentrations of 17beta-estradiol (E(2)), testosterone (T), 11-ketotestosterone (11-KT), 17-hydroxy-4-pregnene-3,20-dione (17-P), 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S) were measured by radioimmunoassay and potential correlations with the stage of oogenesis and sexual maturation examined. During the experimental period two spawning episodes were observed. Plasma concentrations of E(2) increased progressively during oocyte development, simultaneously with the appearance of yolk vesicles and increasing amounts of deposited yolk. In female jundiá, the T peak occurred in October and was coincident with the peak in gonadosomatic index. Two distinct peaks of progestogens were detected, corresponding to the two spawning episodes, suggesting that one or more of these steroids might act as the "maturational-inducing steroid" in jundiá. Unusually large amounts of 11-KT were also measured in the plasma of mature jundiá females. The identity of 11-KT was confirmed by thin-layer chromatography. Although the profiles of the other steroids are compatible with the roles proposed for the action of these hormones in other teleosts, the role of 11-KT, normally found only in males, is unknown.

What's Wrong with Plastic Trees?: Rationales for preserving rare natural environments involve economic, societal, and political factors.

With some ingenuity, a transformation of our attitudes toward preservation of the environment will take place fairly soon. We will recognize the symbolic and social meanings of environments, not just their economic utility; we will emphasize their historical significance as well as the future generations that will use them. At the same time, we must realize that there are things we may not want to trade at all, except in the sense of letting someone else have his share of the environment also. As environments become more differentiated, smaller areas will probably be given greater significance, and it may be possible for more groups to have a share. It is likely that we shall want to apply our technology to the creation of artificial environments. It may be possible to create environments that are evocative of other environments in other times and places. It is possible that, by manipulating memory through the rewriting of history, environments will come to have new meaning. Finally, we may want to create proxy environments by means of substitution and simulation. In order to create substitutes, we must endow new objects with significance by means of advertising and by social practice. Sophistication about differentiation will become very important for appreciating the substitute environments. We may simulate the environment by means of photographs, recordings, models, and perhaps even manipulations in the brain (48). What we experience in natural environments may actually be more controllable than we imagine (49). Artificial prairies and wildernesses have been created, and there is no reason to believe that these artificial environments need be unsatisfactory for those who experience them. Rare environments are relative, can be created, are dependent on our knowledge, and are a function of policy, not only tradition. It seems likely that economic arguments will not be sufficient to preserve environments or to suggest how we can create new ones. Rather, conscious choice about what matters, and then a financial and social investment in an effort to create significant experiences and environments, will become a policy alternative available to us. What's wrong with plastic trees? My guess is that there is very little wrong with them. Much more can be done with plastic trees and the like (50) to give most people the feeling that they are experiencing nature. We will have to realize that the way in which we experience nature is conditioned by our society-which more and more is seen to be receptive to responsible interventions. Bentham, the father of utilitarianism, was very concerned about the uses of the dead to the living and suggested (51): If a country gentleman have rows of trees leading to his dwelling, the autoicons [embalmed bodies in an upright position] of his family might alternate with the trees; copal varnish would protect the face from the effects of rain-caoutchouc [rubber] the habiliments.